DE VELASCO Marco A.

Department of MedicineLecturer

Last Updated :2024/10/10

■Researcher comments

List of press-related appearances

1

■Researcher basic information

Degree

  • Ph.D.(2017/06 Kindai University)

ORCID ID

0000-0002-4011-6572

Research Keyword

  • Personalized therapy   Urological cancers   Tumor biology   Biomarker discovery   Immunotherapy   Molecular Targeting   Prostate cancer   Preclincal models   Preclinical Testing   前立腺癌   動物モデル   ノックアウトマウス   ペプチド   腎細胞癌   分子標的治療   ペプチドワクチン   ワクチン療法   免疫療法   腫瘍   尿路上皮癌   

Research Field

  • Life sciences / Tumor biology
  • Life sciences / Molecular biology
  • Life sciences / Tumor diagnostics and therapeutics
  • Life sciences / Urology
  • Life sciences / Immunology / Cancer immunology, Immunotherapy,

■Career

Career

  • 2023/04 - Today  Kindai University Faculty of MedicineDepartment of Gemone BiologyLecturer
  • 2006 - 2022/03  Kindai University Faculty of MedicineGenome Biology助教

■Research activity information

Paper

  • Marco A. De Velasco; Kazuko Sakai; Seiichiro Mitani; Yurie Kura; Shuji Minamoto; Takahiro Haeno; Hidetoshi Hayashi; Kazuto Nishio
    International Journal of Clinical Oncology 1341-9625 2024/09 
    Abstract Background Genome DNA methylation profiling is a promising yet costly method for cancer classification, involving substantial data. We developed an ensemble learning model to identify cancer types using methylation profiles from a limited number of CpG sites. Methods Analyzing methylation data from 890 samples across 10 cancer types from the TCGA database, we utilized ANOVA and Gain Ratio to select the most significant CpG sites, then employed Gradient Boosting to reduce these to just 100 sites. Results This approach maintained high accuracy across multiple machine learning models, with classification accuracy rates between 87.7% and 93.5% for methods including Extreme Gradient Boosting, CatBoost, and Random Forest. This method effectively minimizes the number of features needed without losing performance, helping to classify primary organs and uncover subgroups within specific cancers like breast and lung. Conclusions Using a gradient boosting feature selector shows potential for streamlining methylation-based cancer classification.
  • Yurie Kura; Marco A De Velasco; Kazuko Sakai; Hirotsugu Uemura; Kazutoshi Fujita; Kazuto Nishio
    Human cell 2024/08 [Refereed]
     
    Chronic systemic inflammation caused by diseases such as ulcerative colitis (UC) and Crohn's disease (CD) increases the risk of developing colorectal cancer (CRC). Recent evidence indicates that patients with UC are more susceptible to prostate cancer (PCa), and individuals with PCa may also be at a higher risk of developing CRC. However, these relationships are not well defined. A better understanding of this phenomenon could improve the identification of high-risk populations. In this study, we characterized these relationships with experiments using preclinical mouse models of dextran sulfate sodium (DSS)-induced colitis (DSS-UC) and DSS/azoxymethane (AOM)-induced CRC (DSS/AOM-CRC) in wild-type and conditional transgenic mice of PCa. We showed that DSS-induced UC was more severe in mice with PCa and resulted in the development of CRC in the absence of AOM. We further showed that PCa-free mice that developed DSS-induced UC also showed histological changes in the normal prostate that resembled proliferative inflammatory atrophy. Finally, we used immunohistochemical immune profiling to show that mice with PCa-induced chronic systemic inflammation accumulated Gr1+ myeloid cells in the normal colon and exposure to DSS further enriched these cells in active colitis regions and colon tumors. Our study provides evidence to support a link between systemic chronic inflammation and cancer.
  • Chisato Wakamori; Marco A. De Velasco; Kazuko Sakai; Yurie Kura; Makoto Matsushita; Saizo Fujimoto; Koji Hatano; Norio Nonomura; Kazutoshi Fujita; Kazuto Nishio; Hirotsugu Uemura
    The Prostate 2024/08 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Kazutoshi Fujita; Hirotsugu Uemura
    International Journal of Urology 2024/04 [Refereed]
  • Terufumi Yoshida; Kazuko Sakai; Masaki Kaibori; Mitsuaki Ishida; Shogo Tanaka; Shoji Kubo; Takuya Nakai; Marco De Velasco; Hideyuki Matsushima; Koji Tsuta; Mitsugu Sekimoto; Kazuto Nishio
    Oncology Letters Spandidos Publications 27 (3) 1792-1074 2024/01 [Refereed]
  • Pten欠損前立腺癌進展における骨髄由来抑制細胞のプロファイリング(Profiling myeloid-derived suppressor cells during mouse prostate cancer progression)
    野澤 昌弘; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 安富 正悟; 西本 光寿; 南 高文; 森 康範; 藤田 和利; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 82回 803 - 803 0546-0476 2023/09
  • 前立腺癌と大腸癌そして潰瘍性大腸炎の関連性の探索(Systemic inflammation as a link between prostate cancer, colorectal cancer, and ulcerative colitis)
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 藤田 和利; 安富 正悟; 森 康範; 南 高文; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 82回 1416 - 1416 0546-0476 2023/09
  • Pten欠損前立腺癌マウスモデルにおいてクルクミンモノグルクロニドは腫瘍免疫微小環境を改善する(Curcumin monoglucuronide reprograms the tumor micro-immune environment in mouse Pten-null prostate cancer)
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 橋本 士; 西本 光寿; 安富 正悟; 森 康範; 南 高文; 野澤 昌弘; 藤田 和利; 吉村 一宏; 西尾 和人; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 110回 PP62 - 04 2023/04
  • Makoto Matsushita; Kazutoshi Fujita; Koji Hatano; Marco A De Velasco; Akira Tsujimura; Hirotsugu Uemura; Norio Nonomura
    The world journal of men's health 2023/02 [Refereed]
     
    The human gut microbiota changes under the influence of environmental and genetic factors, affecting human health. Extensive studies have revealed that the gut microbiome is closely associated with many non-intestinal diseases. Among these, the influence of the gut microbiome on cancer biology and the efficacy of cancer therapy has attracted much attention. Prostate cancer cells are affected by direct contact with the microbiota of local tissues and urine, and a relationship between prostate cancer cells and the gut microbiota has been suggested. In the human gut microbiota, bacterial composition differs depending on prostate cancer characteristics, such as histological grade and castration resistance. Moreover, the involvement of several intestinal bacteria in testosterone metabolism has been demonstrated, suggesting that they may affect prostate cancer progression and treatment through this mechanism. Basic research indicates that the gut microbiome also plays an important role in the underlying biology of prostate cancer through multiple mechanisms owing to the activity of microbial-derived metabolites and components. In this review, we describe the evidence surrounding the emerging relationship between the gut microbiome and prostate cancer, termed the "gut-prostate axis."
  • Kazutoshi Fujita; Makoto Matsushita; Marco A De Velasco; Koji Hatano; Takafumi Minami; Norio Nonomura; Hirotsugu Uemura
    Cancers 15 (5) 2023/02 [Refereed]
     
    Obesity and a high-fat diet are risk factors associated with prostate cancer, and lifestyle, especially diet, impacts the gut microbiome. The gut microbiome plays important roles in the development of several diseases, such as Alzheimer's disease, rheumatoid arthritis, and colon cancer. The analysis of feces from patients with prostate cancer by 16S rRNA sequencing has uncovered various associations between altered gut microbiomes and prostate cancer. Gut dysbiosis caused by the leakage of gut bacterial metabolites, such as short-chain fatty acids and lipopolysaccharide results in prostate cancer growth. Gut microbiota also play a role in the metabolism of androgen which could affect castration-resistant prostate cancer. Moreover, men with high-risk prostate cancer share a specific gut microbiome and treatments such as androgen-deprivation therapy alter the gut microbiome in a manner that favors prostate cancer growth. Thus, implementing interventions aiming to modify lifestyle or altering the gut microbiome with prebiotics or probiotics may curtail the development of prostate cancer. From this perspective, the "Gut-Prostate Axis" plays a fundamental bidirectional role in prostate cancer biology and should be considered when screening and treating prostate cancer patients.
  • Marco Antonio De Velasco
    Cancer Research 2023
  • 腸内細菌叢由来LPSはヒスタミンH1受容体シグナル経路を介して前立腺癌増殖を促進する(Lipopolysaccharide from gut microhiota promotes prostate cancer growth through histamine III receptor signaling)
    藤田 和利; 松下 慎; 元岡 大祐; 長谷 拓明; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 南 高文; マルコ・デベラスコ; 吉村 一宏; ジョージ・ネットー; 辻川 和丈; 中村 昇太; 森井 英一; 植村 天受; 野々村 祝夫
    日本癌学会総会記事 (一社)日本癌学会 81回 E - 3077 0546-0476 2022/09
  • マウス前立腺癌におけるアンドロゲン除去による腸内細菌叢の一時的変化について(Temporal changes in gut microbial composition in response to androgen deprivation in mouse prostate cancer)
    若森 千怜; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 藤田 和利; 坂野 恵里; 橋本 士; 西本 光寿; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 81回 J - 1001 0546-0476 2022/09
  • 橋本 士; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 藤田 和利; 坂野 恵里; 西本 光寿; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 81回 E - 1056 0546-0476 2022/09
  • マウス前立腺癌モデルを用いた抗アンドロゲン受容体治療による分子および免疫学的反応の検討(Use of a mouse model of prostate cancer to assess molecular and immune responses to anti-androgen receptor therapy)
    坂野 恵里; デベラスコ・マルコ; 倉 由吏恵; 藤田 和利; 坂井 和子; 橋本 士; 西本 光寿; 吉村 一宏; 野澤 昌弘; 西尾 和人
    日本癌学会総会記事 (一社)日本癌学会 81回 J - 2061 0546-0476 2022/09
  • クルクミンモノグルクロニドのPten欠損前立腺癌マウスに対する化学予防の可能性(Chemopreventive potential of curcumin monoglucuronide in mouse Pten-null prostate cancer)
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 藤田 和利; 坂野 恵里; 藤田 至彦; 橋本 士; 西本 光寿; 野澤 昌弘; 吉村 一宏; 掛谷 秀昭; 植村 天受; 西尾 和人
    日本癌学会総会記事 (一社)日本癌学会 81回 P - 2387 0546-0476 2022/09
  • 細胞外アデノシンを標的とした治療は前立腺癌の抗腫瘍免疫を高める(Targeting extracellular adenosine to enhance antitumor immunity in prostate cancer)
    デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 藤田 和利; 坂野 恵里; 橋本 士; 西本 光寿; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 81回 E - 3011 0546-0476 2022/09
  • PTEN KOマウス前立腺癌におけるabiraterone+capivasertib併用治療による抗腫瘍効果および免疫反応についての検討(Profiling antitumor and immune responses of abiraterone plus capivasertib in mouse Pten-deficient prostate cancer)
    植村 天受; 倉 由吏恵; 坂井 和子; 藤田 和利; 坂野 恵里; 西本 光寿; 橋本 士; 野澤 昌弘; 吉村 一宏; 西尾 和人; デベラスコ・マルコ
    日本癌学会総会記事 (一社)日本癌学会 81回 P - 3286 0546-0476 2022/09
  • Yusuke Makutani; Kazuko Sakai; Masahiro Yamada; Toshiaki Wada; Takaaki Chikugo; Takao Satou; Yoko Iwasa; Hidekazu Yamamoto; Marco A de Velasco; Kazuto Nishio; Junichiro Kawamura
    International journal of clinical oncology 27 (7) 1180 - 1187 2022/04 [Refereed]
     
    BACKGROUND: The Biocartis Idylla™ platform is a fully automated, real-time PCR-based diagnostic system. The Idylla™ KRAS and NRAS-BRAF Mutation Tests have been developed for the qualitative detection of mutations in KRAS, NRAS and BRAF genes, facilitating the genomic profiling of patients with colorectal cancer. The aim of the present study was to evaluate clinical performances of these tests in Japan. METHODS: The RAS and BRAF mutation statuses of 253 formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissues were analyzed using the Investigational Use Only Idylla™ KRAS Mutation Test and the Idylla™ NRAS-BRAF Mutation Test and an in vitro diagnostics (IVD) kit (MEBGEN RASKET™-B kit). RESULTS: The success rate for obtaining a valid mutational data without retest of the Idylla tests was 97.6% (247/253): 111 KRAS mutations (43.8%), 9 NRAS mutations (3.6%), and 36 BRAF V600E mutations (14.2%) were detected using the Idylla tests. Compared with the MEBGEN RASKET-B results, the positive concordance rate was 97.4%, the negative concordance rate was 95.7%, and the overall concordance rate was 95.3% (κ = 0.919, 95% CI 0.871-0.967). The average turnaround time to Idylla™ KRAS and NRAS-BRAF Mutation Test was 5.6 working days (range: 3-11 days). CONCLUSION: This result demonstrates a high concordance between the Idylla™ KRAS and NRAS-BRAF Mutation Tests and an existing IVD kit. In this manner, the Idylla™ mutation tests were validated for the detection of clinically significant KRAS, NRAS, and BRAF mutations in FFPE samples from colorectal cancer patients.
  • Kazutoshi Fujita; Makoto Matsushita; Eri Banno; Marco A De Velasco; Koji Hatano; Norio Nonomura; Hirotsugu Uemura
    International journal of urology : official journal of the Japanese Urological Association 29 (8) 793 - 798 2022/04 [Refereed]
     
    The gut microbiome is linked to several diseases such as Alzheimer's disease, rheumatoid arthritis, and colon cancer. The gut microbiome is also associated with the modulation of immune function, resulting in a different response to immune checkpoint therapy. The gut microbiome differs according to lifestyle, diet, sex, race, genetic background, and country. Lifestyle, especially diet, plays an important role in the development and progression of prostate cancer. Recent studies have revealed a connection between the gut microbiome and prostate cancer. A high-fat diet causes gut dysbiosis and gut bacterial metabolites, such as short-chain fatty acids and phospholipids that enter systemic circulation result in promoting prostate cancer growth. Additionally, the gut microbiota can serve as a source of testosterone, which affects prostate cancer progression. Men with castration-resistant prostate cancer have an increased abundance of gut bacteria with androgenic functions. Men with high-risk prostate cancer share a specific gut microbial profile and profiling gut microbiota could be a potentially effective tool to screen men with high-risk prostate cancer. Lifestyle modifications can improve the gut microbiome. Furthermore, altering the gut microbiome using prebiotic or probiotic interventions may prevent or delay prostate cancer development. Further study into the "Gut-Prostate Axis" would help in the discovery of new strategies for the prevention, screening, and treatment of prostate cancer.
  • Masaki Kaibori; Kazuko Sakai; Hideyuki Matsushima; Hisashi Kosaka; Kosuke Matsui; Marco A De Velasco; Mitsugu Sekimoto; Kazuto Nishio
    Hepatology international 16 (1) 135 - 147 2022/02 [Refereed]
     
    BACKGROUND/PURPOSE OF THE STUDY: Tumor heterogeneity based on copy number variations is associated with the evolution of cancer and its clinical grade. Clonal composition (CC) represents the number of clones based on the distribution of B-allele frequency (BAF) obtained from a genome-wide single nucleotide polymorphism (SNP) array. A higher CC number represents a high degree of heterogeneity. We hypothesized and evaluated that the CC number in hepatocellular carcinoma (HCC) tissues might be associated with the clinical outcomes of patients. METHODS: Somatic mutation, whole transcriptome, and CC number based on copy number variations of 36 frozen tissue samples of operably resected HCC tissues were analyzed by targeted deep sequencing, transcriptome analysis, and SNP array. RESULTS: The samples were classified into the heterogeneous tumors as poly-CC (n = 26) and the homogeneous tumors as mono-CC (n = 8). The patients with poly-CC had a higher rate of early recurrence and a significantly shorter recurrence-free survival period than the mono-CC patients (7.0 months vs. not reached, p = 0.0084). No differences in pathogenic non-synonymous mutations, such as TP53, were observed between the two groups when targeted deep sequencing was applied. A transcriptome analysis showed that cell cycle-related pathways were enriched in the poly-CC tumors, compared to the mono-CC tumors. Poly-CC HCC is highly proliferative and has a high risk of early recurrence. CONCLUSION: CC is a possible candidate biomarker for predicting the risk of early postoperative recurrence and warrants further investigation.
  • Makoto Matsushita; Kazutoshi Fujita; Koji Hatano; Marco A De Velasco; Hirotsugu Uemura; Norio Nonomura
    Frontiers in endocrinology 13 852382 - 852382 2022 [Refereed]
     
    Prostate cancer (PCa) is the most common malignancy in men worldwide, thus developing effective prevention strategies remain a critical challenge. Insulin-like growth factor 1 (IGF-1) is produced mainly in the liver by growth hormone signaling and is necessary for normal physical growth. However, several studies have shown an association between increased levels of circulating IGF-1 and the risk of developing solid malignancies, including PCa. Because the IGF-1 receptor is overexpressed in PCa, IGF-1 can accelerate PCa growth by activating phosphoinositide 3-kinase and mitogen-activated protein kinase, or increasing sex hormone sensitivity. Short-chain fatty acids (SCFAs) are beneficial gut microbial metabolites, mainly because of their anti-inflammatory effects. However, we have demonstrated that gut microbiota-derived SCFAs increase the production of IGF-1 in the liver and prostate. This promotes the progression of PCa by the activation of IGF-1 receptor downstream signaling. In addition, the relative abundance of SCFA-producing bacteria, such as Alistipes, are increased in gut microbiomes of patients with high-grade PCa. IGF-1 production is therefore affected by the gut microbiome, dietary habits, and genetic background, and may play a central role in prostate carcinogenesis. The pro-tumor effects of bacteria and diet-derived metabolites might be potentially countered through dietary regimens and supplements. The specific diets or supplements that are effective are unclear. Further research into the "Gut-IGF-1-Prostate Axis" may help discover optimal diets and nutritional supplements that could be implemented for prevention of PCa.
  • アンドロゲン除去療法とJAK1/2およびPD-L1阻害による前立腺特異的Ptenノックアウトマウスモデルにおける抗腫瘍効果の改善について
    倉 由吏恵; 西本 光寿; 清水 信貴; 南 高文; 坂井 和子; 藤田 和利; 野澤 昌弘; 吉村 一宏; デベラスコ・マルコ; 西尾 和人; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP71 - 01 2021/12
  • A2aRの阻害はPten欠損前立腺癌マウスにおいてCTLA4抗体の抗腫瘍活性を高める
    デベラスコ・マルコ; 倉 由吏恵; 西本 光寿; 坂井 和子; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP71 - 02 2021/12
  • 前立腺特異的Ptenノックアウトマウスにおけるアパルタミドの短期免疫反応について
    植村 天受; 倉 由吏恵; 西本 光寿; 南 高文; 坂井 和子; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; デベラスコ・マルコ
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP71 - 03 2021/12
  • マウスPTEN欠失前立腺癌に対するJAK1/2標的療法が腸内細菌叢に与える影響について
    橋本 士; De Velasco Marco; 坂野 恵里; 清水 信貴; 森 康範; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP12 - 01 2021/12
  • 倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 橋本 士; 藤田 和利; 野澤 昌弘; 吉村 一宏; 植村 天受; 西尾 和人
    近畿大学医学雑誌 近畿大学医学会 46 (3-4) 19A - 19A 0385-8367 2021/12
  • 異種間遺伝子発現解析から免疫療法のための免疫表現型解析への応用
    坂野 恵里; 橋本 士; 安富 正悟; 西本 光寿; 倉 由吏恵; 藤田 和利; 野澤 昌弘; 吉村 一宏; De Velasco Marco; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP12 - 07 2021/12
  • Kazuko Sakai; Toshiharu Sakurai; Marco A. De Velasco; Tomoyuki Nagai; Takaaki Chikugo; Kazuomi Ueshima; Yurie Kura; Takayuki Takahama; Hidetoshi Hayashi; Kazuhiko Nakagawa; Masatoshi Kudo; Kazuto Nishio
    Frontiers in Oncology Frontiers Media SA 11 763468 - 763468 2021/10 [Refereed]
     
    Immune checkpoint inhibitors (ICIs) have become the standard of care for several cancers. However, ICI therapy has also been associated with various immune-related adverse events (irAEs). Clinical manifestations of immune-related colitis resemble those of inflammatory bowel diseases such as ulcerative colitis (UC). The composition of the bowel microflora is thought to influence the development of inflammatory bowel disease and irAE colitis. We profiled the gene expressions and microbe compositions of colonic mucosa from patients with solid cancers receiving anti-PD-L1 antibody treatment; we then compared the expression profiles associated with irAE colitis with those associated with UC. The pathway enrichment analysis revealed functional similarities between inflamed regions of irAE colitis and UC. The common enriched pathways included leukocyte extravasation and immune responses, whereas non-inflamed mucosa from patients with irAE colitis was distinct from patients with UC and was characterized by the recruitment of immune cells. A similarity between the microbiota profiles was also identified. A decreased abundance of Bacteroides species was observed in inflamed regions from both irAE colitis and UC based on a microbiota composition analysis of 16S rDNA sequencing. Pathways associated with molecule transport systems, including fatty acids, were enriched in inflamed and non-inflamed irAE colitis and inflamed UC, similar to Piphillin-inferred KEGG pathways. While UC is characterized by local regions of inflammation, ICI treatment extends to non-inflammatory regions of the colonial mucosa where immune cells are reconstituted. This analysis of the similarity and heterogeneity of irAE colitis and UC provides important information for the management of irAE colitis.
  • Pten欠損前立腺癌マウスにおける糞便中の微生物とアンドロゲン除去の関係について
    若森 千怜; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 橋本 士; 坂野 恵里; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 80回 [E3 - 4] 0546-0476 2021/09
  • A2aR阻害はPten欠損前立腺癌マウスモデルにおいてCTLA4阻害薬の抗腫瘍活性を増強する
    デベラスコ・マルコ; 倉 由吏恵; 坂野 恵里; 坂井 和子; 清水 信貴; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 80回 [E12 - 1] 0546-0476 2021/09
  • クルクミンモノグルクロニドはPten欠損前立腺癌の腫瘍微小環境を調節し抗腫瘍活性を示す
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 藤田 至彦; 橋本 士; 森 康範; 南 高文; 藤田 和利; 掛谷 秀昭; 植村 天受; 西尾 和人
    日本癌学会総会記事 (一社)日本癌学会 80回 [E17 - 3] 0546-0476 2021/09
  • アパルタミドが惹起する短期免疫反応の前臨床評価について
    植村 天受; 倉 由吏恵; 坂野 恵里; 橋本 士; 坂井 和子; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; デベラスコ・マルコ
    日本癌学会総会記事 (一社)日本癌学会 80回 [J14 - 3] 0546-0476 2021/09
  • 前立腺癌マウスにおける抗PD-L1免疫療法およびJAK1/2阻害と糞便中の細菌について
    坂野 恵里; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 橋本 士; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 80回 [E14 - 4] 0546-0476 2021/09
  • Mamoru Hashimoto; Takahito Nakayama; Saizo Fujimoto; Shunsuke Inoguchi; Mitsuhisa Nishimoto; Takashi Kikuchi; Shogo Adomi; Eri Banno; Marco A. De Velasco; Yoshitaka Saito; Nobutaka Shimizu; Yasunori Mori; Takafumi Minami; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Hirotsugu Uemura
    Anti-Cancer Drugs Ovid Technologies (Wolters Kluwer Health) Publish Ahead of Print (1) e818-e821  0959-4973 2021/08 [Refereed]
     
    Recently, combination therapy including immune checkpoint inhibition (ICI) has proven to be effective as first-line therapy for patients with metastatic renal cell carcinoma. Although the first-line combination therapies with ICI have shown clinical benefit, a number of patients require second-line treatment. We report a 60-year-old man with metastatic renal cell carcinoma who was treated with pazopanib soon after nivolumab plus ipilimumab combination therapy. He experienced Grade 3 disseminated intravascular coagulation (DIC). We suspect that this was caused by an interaction between pazopanib and nivolumab even though ICI therapy was discontinued. He was treated with thrombomodulin and platelet transfusion and recovered from DIC. Treatment with pazopanib was subsequently restarted. No evidence of DIC was observed thereafter. This severe adverse reaction may have been induced by an interaction between activated proinflammatory immune cells and cytokines from an exacerbated inflammatory state and pazopanib. This report highlights the need to perform careful monitoring of patients who receive molecular targeted therapy after ICI-based immunotherapy.
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Noriko Sako; Eri Banno; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    Cancers MDPI AG 13 (16) 3975 - 3975 2021/08 [Refereed]
     
    Significant improvements with apalutamide, a nonsteroidal antiandrogen used to treat patients suffering from advanced prostate cancer (PCa), have prompted evaluation for additional indications and therapeutic development with other agents; however, persistent androgen receptor (AR) signaling remains problematic. We used autochthonous mouse models of Pten-deficient PCa to examine the context-specific antitumor activity of apalutamide and profile its molecular responses. Overall, apalutamide showed potent antitumor activity in both early-stage and late-stage models of castration-naïve prostate cancer (CNPC). Molecular profiling by Western blot and immunohistochemistry associated persistent surviving cancer cells with upregulated AKT signaling. While apalutamide was ineffective in an early-stage model of castration-resistant prostate cancer (CRPC), it tended to prolong survival in late-stage CRPC. Molecular features associated with surviving cancer cells in CRPC included upregulated aberrant-AR, and phosphorylated S6 and proline-rich Akt substrate of 40 kDa (PRAS40). Strong synergy was observed with the pan-AKT inhibitor GSK690693 and apalutamide in vitro against the CNPC- and CRPC-derived cell lines and tended to improve the antitumor responses in CNPC but not CRPC in vivo. Upregulation of signal transducer and activator of transcription 3 (STAT3) and proviral insertion in murine-1 (PIM-1) were associated with combined apalutamide/GSK690693. Our findings show that apalutamide can attenuate Pten-deficient PCa in a context-specific manner and provides data that can be used to further study and, possibly, develop additional combinations with apalutamide.
  • Toshiharu Sakurai; Marco A De Velasco; Kazuko Sakai; Tomoyuki Nagai; Hiroki Nishiyama; Kentaro Hashimoto; Hirotsugu Uemura; Hisato Kawakami; Kazuhiko Nakagawa; Hiroyuki Ogata; Kazuto Nishio; Masatoshi Kudo
    Molecular Oncology Wiley 1574-7891 2021/07 [Refereed]
     
    Immune checkpoint inhibitors (ICIs) are widely used to treat various malignancies. Although the gut microbiome is known to influence the efficacy of ICIs on epithelial tumors, the functional interactions between gut taxa and colonic mucosa remain poorly understood. Here we performed transcriptomic profiling and 16S rRNA sequencing to investigate the relationships between mucosal gene expression and microbial composition with ICI responses and gastrointestinal immune-related adverse events (GI irAEs). In responders, genes related to DNA repair and cell cycle signatures were enriched in responders whereas signatures related to innate immune response, NFAT and IFN-γ signaling pathways were enriched in nonresponders. Gut microbial composition revealed an association between moderate GI irAE and favorable response to ICI therapy. Favorable therapeutic responses to ICI and GI irAE treatments were associated with taxa classified as Enterobacteriaceae and were related to ribonucleoprotein complex biogenesis, cytokine-mediated signaling pathway, tRNA metabolic process, and ribonucleoprotein complex assembly in the colon. These findings open new perspectives for improving the efficacy and safety of cancer immunotherapy.
  • Kazuko Sakai; Marco A. De Velasco; Yurie Kura; Kazuto Nishio
    Cancers MDPI AG 13 (15) 3683 - 3683 2021/07 [Refereed]
     
    Colitis is a risk factor for colorectal cancer (CRC) and can change the dynamics of gut microbiota, leading to dysbiosis and contributing to carcinogenesis. The functional interactions between colitis-associated CRC and microbiota remain unknown. In this study, colitis and CRC were induced in BALB/c mice by the administration of dextran sodium sulfate (DSS) and/or azoxymethane (AOM). Whole transcriptome profiling of normal colon was then performed, and gene set enrichment analysis (GSEA) revealed enriched fatty acid metabolism, oxidative phosphorylation, and PI3K-Akt-mTOR signaling in the tissues from DSS/AOM mice. Additionally, immunohistochemical staining showed increased expression levels of phosphorylated S6 ribosomal protein, a downstream target of the PI3K-Akt-mTOR pathway in the inflamed mucosa of DSS/AOM mice. Fecal microbes were characterized using 16S rDNA gene sequencing. Redundancy analysis demonstrated a significant dissimilarity between the DSS/AOM group and the others. Functional analysis inferred from microbial composition showed enrichments of the sphingolipid signal and lipoarabinomannan biosynthetic pathways. This study provides additional insights into alterations associated with DSS/AOM-induced colitis and associates PI3K-Akt-mTOR, sphingolipid-signaling and lipoarabinomannan biosynthetic pathways in mouse DSS/AOM-induced colitis.
  • Marco A. De Velasco; Kazuko Sakai; Yurie Kura; Eri Banno; Naomi Ando; Noriko Sako; Nobutaka Shimizu; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Cancer Research American Association for Cancer Research 2021/07
  • Marco A. De Velasco; Yurie Kura; Noriko Sako; Naomi Ando; Kazuko Sakai; Alwin Schuller; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Cancer Research American Association for Cancer Research 2021/07
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Kazuko Sakai; Nobutaka Shimizu; Eri Banno; Masahiro Nozawa; Kazuhiro Fujita; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Cancer Research American Association for Cancer Research 2021/07
  • Marco A. De Velasco; Kazuko Sakai; Yurie Kura; Naomi Ando; Noriko Sako; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Cancer Research American Association for Cancer Research 2021/07
  • Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Cancer Research American Association for Cancer Research 2021/07
  • Mamoru Hashimoto; Kazutoshi Fujita; Takahito Nakayama; Saizo Fujimoto; Mamoru Hamaguchi; Mitsuhisa Nishimoto; Takashi Kikuchi; Shogo Adomi; Eri Banno; Marco A. De Velasco; Yoshitaka Saito; Nobutaka Shimizu; Yasunori Mori; Takafumi Minami; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Hirotsugu Uemura
    Translational Andrology and Urology AME Publishing Company 10 (7) 2838 - 2847 2223-4683 2021/01 [Refereed]
     
    Background: Inflammatory cytokines and immature myeloid derived suppressor cells (MDSCs), which increase during cancer progression, could lead to a neutrophil increase and lymphocyte reduction. Thus, the neutrophil-lymphocyte ratio (NLR) was used to predict survival of patients suffering from urological cancers including upper urinary tract carcinoma. We further determined whether the NLR during the first cycle of first-line chemotherapy could predict cancer specific survival.Methods: We recruited patients with locally advanced or metastatic upper urinary tract urothelial carcinoma (UTUC) who received chemotherapy between January 2014 and July 2019. We investigated the impact of various clinical variables, including age, sex, performance status, and estimated creatinine clearance (CCr), and NLR before and after the first cycle of the first-line chemotherapy on prognosis.Results: A total of 41 patients were included in our study. Cancer specific survival of the patients with lower NLR was significantly better than that of the patients with higher NLR measured after the first cycle of the first-line chemotherapy (log-rank test P=0.005, median 29.2 vs. 11.9 months, respectively). Cox proportional regression analysis showed that higher NLR after the first cycle of the first-line chemotherapy was a significant predictor of cancer specific survival.Conclusions: The NLR after the first cycle of the first-line chemotherapy could be an indication for patients with locally advanced or metastatic UTUC to maintain their first-line chemotherapy treatment.
  • リアルタイムPCRは前立腺癌の腫瘍免疫プロファイルと免疫反応性の評価を可能とする
    植村 天受; 倉 由吏恵; 坂井 和子; 清水 信貴; 森 康則; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; デベラスコ・マルコ
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 108回 1159 - 1159 2020/12
  • 前立腺癌特異的Ptenノックアウトマウスモデルを用いたマルチチロシンキナーゼ阻害薬であるTAS-115の免疫調節について
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 清水 信貴; 森 康範; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 108回 1161 - 1161 2020/12
  • Sakurai, T.; Nishiyama, H.; Sakai, K.; De Velasco, M.A.; Nagai, T.; Komeda, Y.; Kashida, H.; Okada, A.; Kawai, I.; Nishio, K.; Ogata, H.; Kudo, M.
    Scientific Reports 10 (1) 1 - 12 2045-2322 2020/11 [Refereed]
  • Pten欠損前立腺癌におけるJAK1/2標的治療が糞便中のマイクロバイオームに与える影響について
    デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 79回 OE3 - 5 0546-0476 2020/10
  • 前立腺癌特異的Ptenノックアウトマウスにおけるマイクロバイオームについての検討
    倉 由吏恵; 坂井 和子; 藤田 至彦; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 79回 OJ3 - 8 0546-0476 2020/10
  • 大腸炎誘発大腸癌と微生物叢の多様性のインタラクトーム解析
    西尾 和人; 坂井 和子; 倉 由吏恵; 竹ヶ原 京志郎; デベラスコ・マルコ
    日本癌学会総会記事 (一社)日本癌学会 79回 OJ3 - 10 0546-0476 2020/10
  • アンドロゲン除去療法は前立腺特異的Ptenノックアウトマウスにおいて免疫療法の抗腫瘍効果を増強する
    植村 天受; 倉 由吏恵; 坂井 和子; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ
    日本癌学会総会記事 (一社)日本癌学会 79回 OE12 - 5 0546-0476 2020/10
  • 異種間遺伝子発現解析による免疫プロファイリングへの応用について
    坂野 恵理; 倉 由吏恵; 坂井 和子; 藤田 至彦; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 79回 OE15 - 6 0546-0476 2020/10
  • Pten欠損前立腺癌におけるJAK1/2標的治療が糞便中のマイクロバイオームに与える影響について
    デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 79回 OE3 - 5 0546-0476 2020/10
  • 前立腺癌特異的Ptenノックアウトマウスにおけるマイクロバイオームについての検討
    倉 由吏恵; 坂井 和子; 藤田 至彦; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 79回 OJ3 - 8 0546-0476 2020/10
  • 大腸炎誘発大腸癌と微生物叢の多様性のインタラクトーム解析
    西尾 和人; 坂井 和子; 倉 由吏恵; 竹ヶ原 京志郎; デベラスコ・マルコ
    日本癌学会総会記事 (一社)日本癌学会 79回 OJ3 - 10 0546-0476 2020/10
  • アンドロゲン除去療法は前立腺特異的Ptenノックアウトマウスにおいて免疫療法の抗腫瘍効果を増強する
    植村 天受; 倉 由吏恵; 坂井 和子; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ
    日本癌学会総会記事 (一社)日本癌学会 79回 OE12 - 5 0546-0476 2020/10
  • 異種間遺伝子発現解析による免疫プロファイリングへの応用について
    坂野 恵理; 倉 由吏恵; 坂井 和子; 藤田 至彦; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 79回 OE15 - 6 0546-0476 2020/10
  • Marco A De Velasco; Yan Lu; Yurie Kura; Toshiyuki China; Yasuyuki Inoue; Akinori Nakayama; Hiroshi Okada; Shigeo Horie; Hirotsugu Uemura; Hisamitsu Ide
    Human cell 33 (3) 730 - 736 2020/07 [Refereed]
     
    The present study investigated the antitumor activity and chemopreventive effects of a nanoparticle formulation of curcumin in preclinical models of mouse Pten-deficient prostate cancer. The antitumor activity of the nanoparticle curcumin was evaluated in mouse castration-naïve (7113-D3) and castration-resistant prostate cancer (2945-E10) derived cell lines in vitro. Cell viability was reduced in both cell lines in a dose and time-dependent manner. The effects of long-term dietary supplementation with the nanoparticle curcumin formulation were evaluated in a conditional Pten-deficient mouse model. Prostate tissues from Pten-deficient prostate cancers were obtained after sixteen weeks of dietary supplementation of 76 mg/kg/day or 380 mg/kg/day nanoparticle curcumin. Daily supplementation of nanoparticle curcumin did not affect mouse bodyweights or spleen size but did result in enlargement of the liver. Dietary supplementation did not influence tumor burden, however, mice fed high-dose curcumin had lower cancer cell proliferation rates at 12 and 16 weeks of age. Together, these results show that daily supplementation of a nanoparticle formulation of curcumin is tolerable and suggest that curcumin could have chemopreventive activity in early-stage prostate cancer.
  • Marco A De Velasco; Yurie Kura; Kazuko Sakai; Yuji Hatanaka; Barry R Davies; Hayley Campbell; Stephanie Klein; Youngsoo Kim; A Robert MacLeod; Koichi Sugimoto; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    JCI insight 4 (17) e122688  2019/09 [Refereed]
     
    Sustained therapeutic responses from traditional and next-generation antiandrogen therapies remain elusive in clinical practice due to inherent and/or acquired resistance resulting in persistent androgen receptor (AR) activity. Antisense oligonucleotides (ASO) have the ability to block target gene expression and associated protein products and provide an alternate treatment strategy for castration-resistant prostate cancer (CRPC). We demonstrate the efficacy and therapeutic potential of this approach with a Generation-2.5 ASO targeting the mouse AR in genetically engineered models of prostate cancer. Furthermore, reciprocal feedback between AR and PI3K/AKT signaling was circumvented using a combination approach of AR-ASO therapy with the potent pan-AKT inhibitor, AZD5363. This treatment strategy effectively improved treatment responses and prolonged survival in a clinically relevant mouse model of advanced CRPC. Thus, our data provide preclinical evidence to support a combination strategy of next-generation ASOs targeting AR in combination with AKT inhibition as a potentially beneficial treatment approach for CRPC.
  • 腫瘍免疫環境プロファイルと抗腫瘍免疫反応(Profiling the tumor immune milieu to assess and predict immune responses)
    デベラスコ・マルコ; 倉 由吏恵; 森 康範; 清水 信貴; 大關 孝之; 坂井 和子; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 78回 E - 2067 0546-0476 2019/09
  • アパルタミドによる前立腺腫瘍内の免疫環境の変化(Apalutamide reworks the tumor immune microenvironment of prostate tumors)
    清水 信貴; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 78回 P - 2267 0546-0476 2019/09
  • TAS-115マルチキナーゼ阻害薬のマウス前立腺癌モデルにおける免疫調整について(Immunomodulation of the multi-tyrosine kinase inhibitor TAS-115 in a mouse Pten-deficient prostate cancer)
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 78回 P - 2360 0546-0476 2019/09
  • イソフラボン摂取はマウス前立腺癌転移モデルにおいて癌の進行を抑制し生存期間を延長させる(Chemopreventive effects of dietary isoflavone in conditional Pten/Trp53-deficient mouse model of prostate cancer)
    森 康範; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 78回 J - 3030 0546-0476 2019/09
  • リアルタイムPCRを用いた腫瘍免疫プロファイルと免疫反応性の評価について(A real-time PCR-based approach to quantitatively assess tumor immune profiles and immune responses)
    野澤 昌弘; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 78回 J - 3035 0546-0476 2019/09
  • Yuji Hatanaka; Marco A de Velasco; Takashi Oki; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    The Prostate 79 (5) 554 - 563 2019/04 [Refereed]
     
    BACKGROUND: HOX genes encode transcription factors that play key roles in modulating normal tissue morphogenesis, differentiation and homeostasis. Disruption of normal HOX gene expression occurs frequently in human cancers and is associated with both tumor promoting and suppressing activities. Among these is, HOXA10, a pleiotropic gene that is critical for normal prostate development. In this study we characterized HOXA10 expression in human and mouse PCa to gain insights into its clinical significance. METHODS: A meta-analysis of HOXA10 mRNA expression was carried out across several publicly available data sets. Expression of HOXA10 protein expression was assessed by immunohistochemistry (IHC) using human radical prostatectomy (RP) cases. We correlated HOXA10 expression to clinicopathological features and investigated its relationship to biochemical recurrence (BCR) after RP by the Kaplan-Meier method. HOXA10 mRNA and IHC protein expression was also examined in a mouse model of Pten-null PCa. RESULTS: A meta-analysis of HOXA10 gene expression indicated dysregulated expression of HOXA10 in human PCa. IHC profiling of HOXA10 revealed inverse correlations between HOXA10 expression and Gleason pattern, Gleason score, and pathological stage (P < 0.01). Patients with low expression profiles of HOXA10 were associated with a higher risk of BCR, (OR, 3.54; 95%CI, 1.21-16.14; P = 0.049) whereas patients with high HOXA10 expression experienced longer times to BCR (P = 0.045). However, HOXA10 was not an independent predictor of BCR (OR, 1.52; 95%CI, 0.42-5.54; P = 0.52). Evaluation of expression patterns of HOXA10 in mouse prostate tumors mimicked that of humans. CONCLUSIONS: Our findings show that HOXA10 expression is inversely associated with tumor differentiation and high HOXA10 expression is associated with improved BCR-free survival. This study provides human and mouse evidence to suggest tumor suppressive roles for HOXA10 in the context of prostate cancer.
  • Akiko Takao; Kazuhiro Yoshikawa; Sivasundaram Karnan; Akinobu Ota; Hirotsugu Uemura; Marco A De Velasco; Yurie Kura; Susumu Suzuki; Ryuzo Ueda; Tokiko Nishino; Yoshitaka Hosokawa
    Oncology reports 40 (5) 2455 - 2466 2018/11 [Refereed]
     
    Phosphatase and tensin homolog (PTEN) deficiency is associated with development, progression, and metastasis of various cancers. However, changes in gene expression associated with PTEN deficiency have not been fully characterized. To explore genes with altered expression in PTEN‑deficient cells, the present study generated a PTEN‑knockout cell line (ΔPTEN) from a mouse prostate cancer‑derived cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‑associated protein 9 (CRISPR/Cas9) gene editing system. Following transfection of the CRISPR/Cas9 construct, DNA sequencing was performed to identify deletion of the Pten locus and PTEN inactivation was verified by western blotting. The ΔPTEN cell line exhibited enhanced RAC‑alpha serine/threonine‑protein kinase phosphorylation and cyclin D1 expression. In addition, an increase in cell proliferation and colony formation was observed in the ΔPTEN cell line. Gene expression profiling experiments were analyzed with microarray and microRNA (miRNA) arrays. In the microarray analysis, 111 genes exhibited ≥10‑fold increased expression compared with the parent strain and mock cell line and 23 genes were downregulated. The only miRNA with increased expression of 10‑fold or more was mmu‑miR‑210‑3p. Genes with enhanced expression included genes involved in the development, progression, and metastasis of cancer such as Tet methylcytosine dioxygenase 1, twist family BHLH transcription factor 2, C‑fos‑induced growth factor and Wingless‑Type MMTV Integration Site Family, Member 3, and genes involved in immunosuppression such as Arginase 1. The results of the present study suggest that PTEN deficiency mobilizes a variety of genes critical for cancer cell survival and host immune evasion.
  • Marco A De Velasco; Hirotsugu Uemura
    Current opinion in urology 28 (1) 15 - 24 2018/01 [Refereed][Invited]
     
    PURPOSE OF REVIEW: In this review, we present the progress and current landscape for prostate cancer immunotherapy and overview recent scientific findings that shed novel insights into immunoresistance and discuss potential therapeutic strategies. RECENT FINDINGS: Prostate cancer immunogenicity is hampered by a highly immunosuppressive microenvironment and low mutation burden. Complex interactions between resident immunosuppressive cells such regulatory T cells, macrophages, myeloid-derived suppressor cells, and cancer cells cooperate to suppress antitumor immune responses and promote disease progression. A biphasic approach that boosts tumor immunogenicity and blockade of immunosuppressive pathways will most likely be required in order to produce meaningful therapeutic responses. SUMMARY: Significant advances have shed new light on prostate cancer immunology. These findings should enhance the development of immunotherapeutic strategies, especially when used in combination with other cancer treatments.
  • Kazuko Sakai; Masayo Ukita; Jeanette Schmidt; Longyang Wu; Marco A. De Velasco; Alan Roter; Luis Jevons; Kazuto Nishio; Masaki Mandai
    CANCER LETTERS ELSEVIER IRELAND LTD 405 22 - 28 0304-3835 2017/10 [Refereed]
     
    Intratumoral heterogeneity of cancer cells remains largely unexplored. Here we investigated the composition of ovarian cancer and its biological relevance. A whole-genome single nucleotide polymorphism array was applied to detect the clonal composition of 24 formalin-fixed, paraffin-embedded samples of human ovarian cancer. Genome-wide segmentation data consisting of the log2 ratio (log2R) and B allele frequency (BAF) were used to calculate an estimate of the clonal composition number (CC number) for each tumor. Somatic mutation profiles of cancer-related genes were also determined for the same 24 samplesby next-generation sequencing. The CC number was estimated successfully for 23 of the 24 cancer samples. The mean +/- SD value for the CC number was 1.7 +/- 1.1 (range of 0-4). A somatic mutation in at least one gene was identified in 22 of the 24 ovarian cancer samples, with the mutations including those in the oncogenes KRAS (29.2%), PIK3CA (12.5%), BRAF (8.3%), FGFR2 (4.2%), andJAK2 (4.2%) as well as those in the tumor suppressor genes TP53 (54.2%), FBXW7 (8.3%), PTEN (4.2%), and RB1 (4.2%). Tumors with one or more oncogenic mutations had a significantly lower CC number than did those without such a mutation (1.0 +/- 0.8 versus 2.3 +/- 0.9, P = 0.0027), suggesting that cancers with driver oncogene mutations are less heterogeneous than those with other mutations. Our results thus reveal a reciprocal relation between oncogenic mutation status and clonal composition in ovarian cancer using the established method for the estimation of the CC number. (C) 2017 The Author(s). Published by Elsevier B.V.
  • Lei L. Chen; Jing Zhu; Jonathan Schumacher; Chongjuan Wei; Latha Ramdas; Victor G. Prieto; Arnie Jimenez; Marco A. Velasco; Sheryl R. Tripp; Robert H. I. Andtbacka; Launce Gouw; George M. Rodgers; Liansheng Zhang; Benjamin K. Chan; Pamela B. Cassidy; Robert S. Benjamin; Sancy A. Leachman; Marsha L. Frazier
    PLOS ONE PUBLIC LIBRARY SCIENCE 12 (9) e0184154  1932-6203 2017/09 [Refereed]
     
    We demonstrate that SCF-KIT signaling induces synthesis and secretion of endothelin-3 (ET3) in human umbilical vein endothelial cells and melanoma cells in vitro, gastrointestinal stromal tumors, human sun-exposed skin, and myenteric plexus of human colon post-fasting in vivo. This is the first report of a physiological mechanism of ET3 induction. Integrating our finding with supporting data from literature leads us to discover a previously unreported pathway of nitric oxide (NO) generation derived from physiological endothelial NO synthase (eNOS) or neuronal NOS (nNOS) activation (referred to as the KIT-ET3-NO pathway). It involves: (1) SCF-expressing cells communicate with neighboring KIT-expressing cells directly or indirectly (cleaved soluble SCF). (2) SCF-KIT signaling induces timely local ET3 synthesis and secretion. (3) ET3 binds to ETBR on both sides of intercellular space. (4) ET3-binding-initiated-ETBR activation increases cytosolic Ca2+, activates cell-specific eNOS or nNOS. (5) Temporally-and spatially-precise NO generation. NO diffuses into neighboring cells, thus acts in both SCF-and KIT-expressing cells. (6) NO modulates diverse cell-specific functions by NO/cGMP pathway, controlling transcriptional factors, or other mechanisms. We demonstrate the critical physiological role of the KIT-ET3-NO pathway in fulfilling high demand (exceeding basal level) of endothelium-dependent NO generation for coping with atherosclerosis, pregnancy, and aging. The KIT-ET3-NO pathway most likely also play critical roles in other cell functions that involve dual requirement of SCF-KIT signaling and NO. New strategies (e.g. enhancing the KIT-ET3-NO pathway) to harness the benefit of endogenous eNOS and nNOS activation and precise NO generation for correcting pathophysiology and restoring functions warrant investigation.
  • Marco De Velasco
    International Journal of Oncology 2017/04 [Refereed]
  • Masato Chiba; Yosuke Togashi; Eri Bannno; Yoshihisa Kobayashi; Yu Nakamura; Hidetoshi Hayashi; Masato Terashima; Marco A. De Velasco; Kazuko Sakai; Yoshihiko Fujita; Tetsuya Mitsudomi; Kazuto Nishio
    BMC CANCER BIOMED CENTRAL LTD 17 (281) 1471-2407 2017/04 [Refereed]
     
    Background: Non-small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor (EGFR) gene mutations (exon 19 deletion or exon 21 L858R) respond to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The secondary T790 M mutation in exon 20 of the EGFR gene is the most common type of acquired resistance mutation. Several reports have also shown that other secondary mutations (L747S, D761Y and T854A), while uncommon, can induce acquired resistance to first-generation EGFR-TKIs. However, little is known about the anticancer activities of second-or third-generation EGFR-TKIs. Methods: Uncommon secondary mutations were introduced into Ba/F3 cells along with the sensitive EGFR L858R mutation (Ba/F3-L858R/L747S, Ba/F3-L858R/D761Y, and Ba/F3-L858R/T854A), and the sensitivities to various EGFR-TKIs were then investigated. Results: Both the Ba/F3-L858R/L747S and Ba/F3-L858R/D761Y cell lines exhibited weak resistances to first-generation reversible EGFR-TKIs, while the Ba/F3-L858R/T854A cell line exhibited a strong resistance. In contrast, irreversible EGFR-TKIs, especially third-generation EGFR-TKIs, were capable of overcoming these resistances. Western blot analyses demonstrated that gefitinib (first-generation) inhibited the phosphorylation of EGFR to a lesser extent in cells with these secondary mutations than in cells with the sensitive L858R mutation alone. In contrast, afatinib and osimertinib (second-and third-generation) inhibited the phosphorylation of EGFR in cells with these secondary mutations to a similar extent as that seen in cells with the sensitive L858R mutation alone. Conclusions: Our experimental findings suggest that irreversible EGFR-TKIs, especially third-generation EGFR-TKIs, can be effective against uncommon secondary mutations and that switching to third-generation EGFR-TKIs could be a promising treatment strategy for patients with acquired resistance because of these uncommon secondary mutations.
  • Minami, Takafumi; Matsumura, Naold; Sugimoto, Koichi; Shimizu, Nobutaka; De Velasco, Marco; Nozawa, Masahiro; Yoshimura, Kazuhiro; Harashima, Nanae; Harada, Mamoru; Uemura, Hirotsugu
    INTERNATIONAL IMMUNOPHARMACOLOGY ELSEVIER SCIENCE BV 44 197 - 202 1567-5769 2017/03 [Refereed]
     
    Hypoxic tumor microenvironment makes cancer cells to be therapy-resistant and hypoxia-inducing factors (HIFs) play a central role in hypoxic adaptation. Especially, renal cell carcinoma (RCC) is often associated with von Hippel-Lindau (VHL) gene mutations, leading to up-regulation of HIFs. However, from a different point of view, this suggests the possibility that HIFs could be promising targets in anti-cancer therapy. In this study, we searched for HIF-l alpha-derived peptides that are able to induce RCC-reactive cytotoxic T lymphocytes (CTLs) from HLA-A24(+) RCC patients. Among five peptides derived from HIF-1 alpha, which were prepared based on the binding motif to the HLA-A24 allele, a HIF-1 alpha(278-287) peptide induced peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24(+) RCC patients most effectively. In immunoblot assays, the expression of HIF-l alpha was lowly detected in whole and nuclear lysates of RCC cell lines even under normoxia (20% O-2), and their expression in whole lysates was increased under hypoxia (1% O-2). Additionally, HIP-1 alpha(278-287) peptide stimulated T cells showed a higher cytotoxicity against HLA-A24(+) HIF-l alpha-expressing RCC cells than against HLA-A24-HIF-l alpha-expressing RCC cells. The cytotoxicity was inhibited by the addition of HIF-1 alpha(278-287) peptide-pulsed cold target cells. Altogether, these results indicate that the HIF-1 alpha(278-287) peptide could be a candidate for peptide-based anti-cancer vaccines for HLA-A24(+) RCC patients. (C) 2017 Published by Elsevier B.V.
  • 海堀昌樹; 坂井和子; 石崎守彦; 松島英之; デベラスコ・マルコ; 松井康輔; 飯田洋也; 北出浩章; 櫂雅憲; 和田浩志; 永野浩昭; 土師誠二; 塚本忠司; 金沢景繁; 武田裕; 竹村茂一; 久保正二; 西尾和人
    The Liver Cancer Journal 9 (2) 182 - 185 1883-9347 2017/02 [Refereed]
  • Masato Chiba; Yosuke Togashi; Shuta Tomida; Hiroshi Mizuuchi; Yu Nakamura; Eri Banno; Hidetoshi Hayashi; Masato Terashima; Marco A. De Velasc; Kazuko Sakai; Yoshihiko Fujita; Tetsuya Mitsudomi; Kazuto Nishio
    INTERNATIONAL JOURNAL OF ONCOLOGY SPANDIDOS PUBL LTD 49 (6) 2236 - 2244 1019-6439 2016/12 [Refereed]
     
    Several receptor tyrosine kinases (RTKs) including EGFR, ALK, and MET have been identified as therapeutic targets in non-small cell lung cancer (NSCLC). Among the downstream pathways of RTKs, the MAPK pathway is particularly important for cancer cell proliferation, differentiation, and survival. In this study, the effects of MEK inhibitors (trametinib and PD0325901) in several NSCLC cell lines with driver gene alterations, especially RTK genes, were tested in vitro using an MTT assay, and a wide range of sensitivities was found. In particular, all the EGFR-mutated cell lines were resistant to MEK inhibitors, whereas all the MET-amplified cell lines were sensitive. A bioinformatics technique and western blot analyses showed that the PI3K/AKT pathway is more activated in EGFRmutated NSCLC than in MET-amplified NSCLC, and a PI3K inhibitor enhanced the sensitivity to trametinib in the EGFR-mutated cell lines, suggesting that this pathway is associated with resistance to MEK inhibitors. Although the HCC827 cell line (EGFR mutation) was resistant to MEK inhibitors, the HCC827CNXR cell line, whose driver gene shifts from EGFR to MET, exhibited enhanced sensitivity to MEK inhibitors, indicating the biological importance of the MAPK pathway for MET-amplified NCSLC. Furthermore, a synergistic effect of crizotinib (a MET inhibitor) and trametinib was observed in MET-amplified NCLC cell lines. Our findings indicate that the MAPK pathway is biologically important for MET-amplified NSCLC and strongly encourage the development of combination therapy with a MET inhibitor and a MEK inhibitor against MET-amplified NSCLC.
  • Masaaki Hibi; Hiroyasu Kaneda; Junko Tanizaki; Kazuko Sakai; Yosuke Togashi; Masato Terashima; Marco Antonio De Velasco; Yoshihiko Fujita; Eri Banno; Yu Nakamura; Masayuki Takeda; Akihiko Ito; Tetsuya Mitsudomi; Kazuhiko Nakagawa; Isamu Okamoto; Kazuto Nishio
    CANCER SCIENCE WILEY-BLACKWELL 107 (11) 1667 - 1676 1347-9032 2016/11 [Refereed]
     
    Fibroblast growth factor receptor (FGFR) gene alterations are relatively frequent in lung squamous cell carcinoma (LSCC) and are a potential targets for therapy with FGFR inhibitors. However, little is known regarding the clinicopathologic features associated with FGFR alterations. The angiokinase inhibitor nintedanib has shown promising activity in clinical trials for non-small cell lung cancer. We have now applied next-generation sequencing (NGS) to characterize FGFR alterations in LSCC patients as well as examined the antitumor activity of nintedanib in LSCC cell lines positive for FGFR1 copy number gain (CNG). The effects of nintedanib on the proliferation of and FGFR signaling in LSCC cell lines were examined invitro, and its effects on tumor formation were examined invivo. A total of 75 clinical LSCC specimens were screened for FGFR alterations by NGS. Nintedanib inhibited the proliferation of FGFR1 CNG-positive LSCC cell lines in association with attenuation of the FGFR1-ERK signaling pathway invitro and invivo. FGFR1 CNG (10.7%), FGFR1 mutation (2.7%), FGFR2 mutation (2.7%), FGFR4 mutation (5.3%), and FGFR3 fusion (1.3%) were detected in LSCC specimens by NGS. Clinicopathologic features did not differ between LSCC patients positive or negative for FGFR alterations. However, among the 36 patients with disease recurrence after surgery, prognosis was significantly worse for those harboring FGFR alterations. Screening for FGFR alterations by NGS warrants further study as a means to identify patients with LSCC recurrence after surgery who might benefit from nintedanib therapy.
  • Masaki Kaibori; Kazuko Sakai; Morihiko Ishizaki; Hideyuki Matsushima; Marco A. De Velasco; Kosuke Matsui; Hiroya Iida; Hiroaki Kitade; A-Hon Kwon; Hiroaki Nagano; Hiroshi Wada; Seiji Haji; Tadashi Tsukamoto; Akishige Kanazawa; Yutaka Takeda; Shigekazu Takemura; Shoji Kubo; Kazuto Nishio
    ONCOTARGET IMPACT JOURNALS LLC 7 (31) 49091 - 49098 1949-2553 2016/08 [Refereed]
     
    The multi-kinase inhibitor sorafenib is clinically approved for the treatment of patients with advanced hepatocellular carcinoma (HCC). We previously reported that fibroblast growth factor 3 and 4 (FGF3/FGF4) amplification is a predictor of a response to sorafenib. This study aims to analyze the relationship between FGF-FGF receptor (FGFR) genetic alterations and the response to sorafenib. Formalin-fixed, paraffin-embedded tissue specimens from HCC patients who had achieved a complete response (CR, N=6) or non-CR (N=39) to sorafenib were collected and were examined for FGF-FGFR gene alterations using next generation sequencing and copy number assay. FGFR mutations were detected in 5 of 45 (11.1%) cases. There was no significant association between FGFR mutation status and the response to sorafenib. We detected no increase in the FGF3/FGF4 copy number in CR cases. An FGF19 copy number gain was detected more frequently among CR cases (2/6, 33.3%) than among non-CR cases (2/39, 5.1%) (P = 0.024, Chi-squared test). In conclusion, a copy number gain for FGF19 may be a predictor of a response to sorafenib, in addition to FGF3/FGF4 amplification.
  • Yu Nakamura; Yosuke Togashi; Hirokazu Nakahara; Shuta Tomida; Eri Banno; Masato Terashima; Hidetoshi Hayashi; Marco A. de Velasco; Kazuko Sakai; Yoshihiko Fujita; Takatsugu Okegawa; Kikuo Nutahara; Suguru Hamada; Kazuto Nishio
    MOLECULAR CANCER THERAPEUTICS AMER ASSOC CANCER RESEARCH 15 (8) 1988 - 1997 1535-7163 2016/08 [Refereed]
     
    The prognosis for patients with advanced esophageal or head-and-neck squamous cell carcinoma (ESCC or HNSCC) remains poor, and the identification of additional oncogenes and their inhibitors is needed. In this study, we evaluated the sensitivities of several ESCC and HNSCC cell lines to HER inhibitors (cetuximab, erlotinib, and afatinib) in vitro and found two cell lines that were hypersensitive to afatinib. Sequence analyses for the afatinib-targeted HER family genes in the two cell lines revealed that one cell line had a previously reported activating EGFR L861Q mutation, whereas the other had an HER4 G1109C mutation of unknown function. No amplification of HER family genes was found in either of the two cell lines. The phosphorylation level of HER4 was elevated in the HER4 G1109C mutation-overexpressed HEK293 cell line, and the mutation had a transforming potential and exhibited tumorigenicity in an NIH3T3 cell line, indicating that this HER4 mutation was an activating oncogenic mutation. Afatinib dramatically reduced the phosphorylation level of EGFR or HER4 and induced apoptosis in the two cell lines. In vivo, tumor growth was also dramatically decreased by afatinib. In a database, the frequencies of HER family gene mutations in ESCC or HNSCC ranged from 0% to 5%. In particular, HER4 mutations have been found relatively frequently in HNSCC. Considering the addiction of cancer cells to activating oncogenic EGFR or HER4 mutations for proliferation, HNSCC or ESCC with such oncogenic mutations might be suitable for targeted therapy with afatinib. (C) 2016 AACR.
  • Eri Banno; Yosuke Togashi; Yu Nakamura; Masato Chiba; Yoshihisa Kobayashi; Hidetoshi Hayashi; Masato Terashima; Marco A. de Velasco; Kazuko Sakai; Yoshihiko Fujita; Tetsuya Mitsudomi; Kazuto Nishio
    CANCER SCIENCE WILEY-BLACKWELL 107 (8) 1134 - 1140 1347-9032 2016/08 [Refereed]
     
    Most patients with non-small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor (EGFR) mutations, such as deletions in exon 19 or the L858R mutation in exon 21, respond dramatically to EGFR tyrosine kinase inhibitors (EGFR-TKI), and their sensitivities to various EGFR-TKI have been well characterized. Our previous article showed the in vitro sensitivities of EGFR exon 18 mutations to EGFR-TKI, but little information regarding the sensitivities of other uncommon EGFR mutations is available. First, stable transfectant Ba/F3 cell lines harboring EGFR L858R (Ba/F3-L858R), L861Q (Ba/F3-L861Q) or S768I (Ba/F3-S768I) mutations were created and their drug sensitivities to various EGFR-TKI were examined. Both the Ba/F3-L861Q and Ba/F3-S768I cell lines were less sensitive to erlotinib, compared with the Ba/F3-L858R cell line, but their sensitivities to afatinib were similar to that of the Ba/F3-L858R cell line. The Ba/F3-L861Q cell line was similarly sensitive and the Ba/F3-S768I cell line was less sensitive to osimertinib, compared with the Ba/F3-L858R cell line. The results of western blot analyses were consistent with these sensitivities. Next, similar experiments were also performed using the KYSE270 (L861Q) and KYSE 450 (S768I) cell lines, and their results were compatible with those of the transfectant Ba/F3 cell lines. Our findings suggest that NSCLC harboring the EGFR L861Q mutation might be sensitive to afatinib or osimertinib and that NSCLC harboring the EGFR S768I mutation might be sensitive to afatinib. Overall, afatinib might be the optimal EGFR-TKI against these uncommon EGFR mutations.
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Takashi Oki; Kazuhiro Yoshimura; Masahiro Nozawa; Barry R. Davies; Dennis Huszdar; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 76 0008-5472 2016/07 [Refereed]
  • Marco A. De Velasco; Koichi Sugimoto; Yurie Kura; Yuji Hatanaka; Yutaka Yamamoto; Takashi Oki; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 76 0008-5472 2016/07 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Yuji Hatanaka; Takashi Oki; Yutaka Yamamoto; Koichi Sugimoto; Yasunori Mori; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 76 0008-5472 2016/07 [Refereed]
  • Masato Terashima; Yosuke Togashi; Katsuaki Sato; Hiroshi Mizuuchi; Kazuko Sakai; Kenichi Suda; Yu Nakamura; Eri Banno; Hidetoshi Hayashi; Marco A. De Velasco; Yoshihiko Fujita; Shuta Tomida; Tetsuya Mitsudomi; Kazuto Nishio
    CLINICAL CANCER RESEARCH AMER ASSOC CANCER RESEARCH 22 (14) 3663 - 3671 1078-0432 2016/07 [Refereed]
     
    Purpose: This study investigated whether mutations of receptor tyrosine kinase (RTK) genes detected using next-generation sequencing (NGS) are suitable therapeutic targets. Experimental design: Fifty surgically resected non-small cell lung cancer (NSCLC) samples were target resequenced using NGS. We then investigated the functions of the identified RTK gene mutations, including their oncogenic potential, in vitro. Results: Mutations in RTK genes were found in 20 samples (EGFR, 15; ERBB4, 1; ALK, 1; DDR2, 2; FGFR1, 1), mutations in MAPK pathway genes were found in nine samples (KRAS, 7; NRAS, 1; BRAF, 2), and mutations in PI3K pathway genes were found in three samples (PIK3CA, 1; PTEN, 3). Among the mutations in RTKs, the functions of four mutations were unclear (ERBB4 D245G; DDR2 H246R and E655K; FGFR1 A263V). These mutations did not exhibit any transformational activities. Neither the phosphorylation nor the protein expressions of RTKs were changed by the DDR2 H246R, ERBB4 D245G, and FGFR1 A263V mutations, although the expression level of the DDR2 protein harboring the E655K mutation was particularly low. Collagen stimulation decreased cellular proliferation through p38 activation in the DDR2 wild-type-overexpressed cell lines, whereas the growth-suppressive effect was weakened in DDR2 E655K-overex-pressed cell lines. Furthermore, the DDR2 E655K protein strongly bound to ubiquitin ligase E3 (Cbl-b), and the mutant protein expression was increased after treatment with a proteasome inhibitor. Conclusions: Our experimental findings suggest that RTK mutations are not always suitable as therapeutic targets. The DDR2 E655K mutation can play a role in cancer progression by reducing the growth-inhibitory effect of collagen. (C) 2016 AACR.
  • Preclinical studyに有用な遺伝子改変動物モデルの開発
    Kura Yurie; Yoshimura Kazuhiro; Nozawa Masahiro; Minami Takafumi; Sugimoto Kouichi; Yoshikawa Kazuhiro; Nishio Kazuhiro; De Velasco Marco; Uemura Hirotsugu
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 104回 AOP - 55 2016/04 [Refereed]
  • Marco A De Velasco; Yurie Kura; Kazuhiro Yoshikawa; Kazuto Nishio; Barry R Davies; Hirotsugu Uemura
    Oncotarget 7 (13) 15959 - 76 2016/03 [Refereed]
     
    The PI3K/AKT pathway is frequently altered in advanced human prostate cancer mainly through the loss of functional PTEN, and presents as potential target for personalized therapy. Our aim was to determine the therapeutic potential of the pan-AKT inhibitor, AZD5363, in PTEN-deficient prostate cancer. Here we used a genetically engineered mouse (GEM) model of PTEN-deficient prostate cancer to evaluate the in vivo pharmacodynamic and antitumor activity of AZD5363 in castration-naïve and castration-resistant prostate cancer. An additional GEM model, based on the concomitant inactivation of PTEN and Trp53 (P53), was established as an aggressive model of advanced prostate cancer and was used to further evaluate clinically relevant endpoints after treatment with AZD5363. In vivo pharmacodynamic studies demonstrated that AZD5363 effectively inhibited downstream targets of AKT. AZD5363 monotherapy significantly reduced growth of tumors in castration-naïve and castration-resistant models of PTEN-deficient prostate cancer. More importantly, AZD5363 significantly delayed tumor growth and improved overall survival and progression-free survival in PTEN/P53 double knockout mice. Our findings demonstrate that AZD5363 is effective against GEM models of PTEN-deficient prostate cancer and provide lines of evidence to support further investigation into the development of treatment strategies targeting AKT for the treatment of PTEN-deficient prostate cancer.
  • Yasumasa Yoshioka; Yosuke Togashi; Takaaki Chikugo; Akihiro Kogita; Masataka Taguri; Masato Terashima; Takuro Mizukami; Hidetoshi Hayashi; Kazuko Sakai; Marco A. de Velasco; Shuta Tomida; Yoshihiko Fujita; Tadao Tokoro; Akihiko Ito; Kiyotaka Okuno; Kazuto Nishio
    CANCER WILEY-BLACKWELL 121 (24) 4359 - 4368 0008-543X 2015/12 [Refereed]
     
    BACKGROUND: Although colorectal mucinous adenocarcinomas (MCs) are conventionally regarded as exhibiting high-grade differentiation, they can be divided by differentiation into 2 groups according to the glandular appearance: low-grade mucinous adenocarcinoma (low-MC) and high-grade mucinous adenocarcinoma (high-MC). METHODS: Patients with colorectal cancer (CRC) who underwent surgical resection between 2000 and 2012 were enrolled in this study. Among the cases with MC, the clinicopathological and genetic differences between low-MC and high-MC were investigated with next-generation sequencing. RESULTS: A total of 1373 patients with CRC were analyzed. Forty patients (2.9%) had MC, and 13 patients had high-MC. Patients with MC had significantly shorter disease-free survival (DFS) and overall survival (OS) periods than those with nonmucinous carcinoma. When low-MC patients and high-MC patients were compared, those with high-MC had significantly shorter DFS and OS periods than those with low-MC. Multivariate analyses revealed that high-MC was significantly associated with both shorter DFS and shorter OS, but low-MC was not. A genome analysis revealed that low-MC had a considerably larger number of mutations than high-MC, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and adenomatous polyposis coli mutations were particularly frequently found in low-MC. In contrast, SMAD family member 4 (SMAD4) mutations were frequently found in high-MC. CONCLUSIONS: High-MC is an independent prognostic factor in CRC (but low-MC is not), and it is genetically different from other CRCs, including low-MC. Both the clinicopathological differences and the genetic differences suggest that low-MC and high-MC should be distinguished in clinical settings. (C) 2015 American Cancer Society.
  • Minami, Takafumi; Minami, Tomoko; Shimizu, Nobutaka; Yamamoto, Yutaka; De Velasco, Marco; Nozawa, Masahiro; Yoshimura, Kazuhiro; Harashima, Nanae; Harada, Mamoru; Uemura, Hirotsugu
    JOURNAL OF IMMUNOTHERAPY LIPPINCOTT WILLIAMS & WILKINS 38 (7) 285 - 291 1524-9557 2015/09 [Refereed]
     
    Molecular therapy targeting tumor angiogenesis has been the standard treatment for metastatic renal cell carcinoma (mRCC). However, despite their significant antitumor effects, most of patients with mRCC have not been cured. Under such circumstances, anticancer immunotherapy has been considered a promising treatment modality for mRCC, and cancer-reactive cytotoxic T lymphocytes (CTLs) are the most powerful effectors among several immune cells. However, anticancer CTLs can be inhibited by several immune inhibitory mechanisms, including the interaction between programmed death 1 (PD-1) and its ligand PD-L1, on T cells and cancer cells, respectively. Alternatively, this also means that PD-L1 could be a promising target for anticancer immunotherapy. Therefore, we searched for PD-L1-derived peptides that are applicable for anticancer vaccine for HLA-A24(+) RCC patients. Among 5 peptides derived from PD-L1, which were prepared based on the binding motif to the HLA-A24 allele, both PD-L1(11-19) and PD-L1(41-50) peptides induced peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24(+) RCC patients. Such PD-L1 peptide-stimulated CD8(+) T cells showed cytotoxicity against HLA-A24(+) and PD-L1-expressing RCC cells. Although IFN- treatment increased PD-L1 expression on PD-L1(low) RCC cells, their sensitivity to cytotoxicity of PD-L1 peptide-stimulated CD8(+) T cells varied between patients. Altogether, these results indicate that both PD-L1(11-19) and PD-L1(41-50) peptides could be candidates for peptide-based anticancer vaccines for HLA-A24(+) mRCC patients.
  • Yurie Kura; Marco A. De Velasco; Naomi Ando; Emiko Fukushima; Barry R. Davies; Dennis Huzdar; Yutaka Yamamoto; Yuji Hatanaka; Takashi Oki; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 75 0008-5472 2015/08 [Refereed]
  • Marco A. De Velasco; Takashi Oki; Yurie Kura; Naomi Ando; Emiko Fukushima; Barry R. Davies; Dennis Huszar; Yutaka Yamamoto; Yuji Hatanaka; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 75 0008-5472 2015/08 [Refereed]
  • Marco A. De Velasco; Yuji Hatanaka; Yurie Kura; Emiko Fukushima; Naomi Ando; Barry R. Davies; Yutaka Yamamoto; Takashi Oki; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 75 0008-5472 2015/08 [Refereed]
  • Marco A. De Velasco; Yutaka Yamamoto; Yurie Kura; Emiko Fukushima; Naomi Ando; Barry Davies; Yuji Hatanaka; Takashi Oki; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 75 0008-5472 2015/08 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Barry R. Davies; Hayley Campbell; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 75 0008-5472 2015/08 [Refereed]
  • Takuro Mizukami; Yosuke Togashi; Shunsuke Sogabe; Eri Banno; Masato Terashima; Marco A. de Velasco; Kazuko Sakai; Yoshihiko Fujita; Shuta Tomida; Takako Eguchi Nakajima; Narikazu Boku; Kazuto Nishio
    INTERNATIONAL JOURNAL OF ONCOLOGY SPANDIDOS PUBL LTD 47 (2) 499 - 505 1019-6439 2015/08 [Refereed]
     
    Since the prognosis of unresectable advanced gastric cancer remains poor, novel therapeutic strategies are needed. Somatic MEKI gene mutations have been reported as oncogenic activating mutations in gastric cancer, and MEK inhibitors can be effective against such gastric cancers. In the present study, however, activated EGFR and HER2 signals after treatment with a MEK inhibitor (trametinib) were found in a MEK1-mutated gastric cancer cell line (OCUM-1 cell line) using a phospho-receptor tyrosine kinase array. The phosphorylation of EGFR and HER2 reactivated ERK1/2, which had been inhibited by trametinib, and EGF stimulation led to resistance to trametinib in this cell line. Lapatinib, an EGFR and an HER2 inhibitor, reversed the activation of ERK1/2 by inhibiting the phosphorylation of EGFR and HER2 and cancelled the resistance. The combination of trametinib and lapatinib synergistically inhibited the cell growth of the OCUM-1 cell line and strongly induced apoptosis by inhibiting the activated EGFR and HER2 signals. These results suggest that the EGFR and HER2 signals play a salvage role and are related to resistance to MEK inhibitors in MEK1-mutated gastric cancer. Moreover, combination therapy with trametinib and lapatinib can exhibit a synergistic effect and may contribute to overcoming the resistance to MEK inhibitors.
  • Y. Togashi; H. Mizuuchi; Y. Kobayashi; H. Hayashi; M. Terashima; K. Sakai; E. Banno; T. Mizukami; Y. Nakamura; M. A. de Velasco; Y. Fujita; S. Tomida; T. Mitsudomi; K. Nishio
    ANNALS OF ONCOLOGY OXFORD UNIV PRESS 26 (8) 1800 - 1801 0923-7534 2015/08 [Refereed]
  • Minami, Takafumi; Minami, Tomoko; Shimizu, Nobutaka; Yamamoto, Yutaka; De Velasco, Marco A.; Nozawa, Masahiro; Yoshimura, Kazuhiro; Harashima, Nanae; Harada, Mamoru; Uemura, Hirotsugu
    INTERNATIONAL IMMUNOPHARMACOLOGY ELSEVIER SCIENCE BV 26 (1) 133 - 138 1567-5769 2015/05 [Refereed]
     
    Analyses on reactivity of anti-cancer cytotoxic T lymphocytes (CTLs) and clinical application of peptide-based anti-cancer vaccine have been mainly focused on patients with HLA-A2 or -A24 alleles. In this study, we identified an enhancer of zeste homolog (EZH) 2-derived peptide applicable for anti-cancer vaccine for prostate cancer patients with HLA-A3 supertype alleles. Five EZH2-derived peptides that were prepared based on the binding motif to the HLA-A3 supertype alleles (HLA-A11, -A31, and -A33) were functionally screened for their potential to induce peptide-specific CTLs from peripheral blood mononuclear cells (PBMCs) of HLA-A3 supertype allele prostate cancer patients. As a result, EZH2(733-741) peptide was found to efficiently induce peptide-specific CTLs. The EZH2(733-741) peptide-stimulated and purified CD8(+) T cells from PBMCs of HLA-A3 supertype allele + prostate cancer patients showed higher cytotoxicity against HLA-A3 supertype allele-expressing LNCaP prostate cancer cells than against parental LNCaP cells. This cytotoxicity against HLA-A3 supertype allele-expressing LNCaP cells was partially but significantly inhibited by the addition of EZH2(733-741) peptide-pulsed competitive cells. These results indicate that the EZH2(733-741) peptide could be a promising candidate for peptide-based immunotherapy for HLAA3 supertype allele(+) prostate cancer patients. (C) 2015 Elsevier B.V. All rights reserved.
  • Kazuko Sakai; Junji Tsurutani; Takeharu Yamanaka; Azusa Yoneshige; Akihiko Ito; Yosuke Togashi; Marco A. De Velasco; Masato Terashima; Yoshihiko Fujita; Shuta Tomida; Takao Tamura; Kazuhiko Nakagawa; Kazuto Nishio
    PLOS ONE PUBLIC LIBRARY SCIENCE 10 (5) e0121891  1932-6203 2015/05 [Refereed]
     
    Somatic mutations in KRAS, NRAS, and BRAF genes are related to resistance to anti-EGFR antibodies in colorectal cancer. We have established an extended RAS and BRAF mutation assay using a next-generation sequencer to analyze these mutations. Multiplexed deep sequencing was performed to detect somatic mutations within KRAS, NRAS, and BRAF, including minor mutated components. We first validated the technical performance of the multiplexed deep sequencing using 10 normal DNA and 20 formalin-fixed, paraffin-embedded (FFPE) tumor samples. To demonstrate the potential clinical utility of our assay, we profiled 100 FFPE tumor samples and 15 plasma samples obtained from colorectal cancer patients. We used a variant calling approach based on a Poisson distribution. The distribution of the mutation-positive population was hypothesized to follow a Poisson distribution, and a mutation-positive status was defined as a value greater than the significance level of the error rate (alpha = 2 x 10(-5)). The cut-off value was determined to be the average error rate plus 7 standard deviations. Mutation analysis of 100 clinical FFPE tumor specimens was performed without any invalid cases. Mutations were detected at a frequency of 59% (59/100). KRAS mutation concordance between this assay and Scorpion-ARMS was 92% (92/100). DNA obtained from 15 plasma samples was also analyzed. KRAS and BRAF mutations were identified in both the plasma and tissue samples of 6 patients. The genetic screening assay using next-generation sequencer was validated for the detection of clinically relevant RAS and BRAF mutations using FFPE and liquid samples.
  • Yamamoto, Yutaka; De Velasco, Marco A.; Kura, Yurie; Nozawa, Masahiro; Hatanaka, Yuji; Oki, Takashi; Ozeki, Takayuki; Shimizu, Nobutaka; Minami, Takafumi; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    JOURNAL OF TRANSLATIONAL MEDICINE BMC 13 (1) 150  2015/05 [Refereed]
     
    Background: Despite recent advances in the treatment for advanced prostate cancer, outcomes remain poor. This lack of efficacy has prompted the development of alternative treatment strategies. In the present study we investigate the effects of the multikinase inhibitor sorafenib in a genetically engineered mouse model of prostate cancer and explore the rational combination with the mTOR inhibitor everolimus.Methods: Conditional prostate specific PTEN-deficient knockout mice were utilized to determine the pharmacodynamic and chemopreventive effects of sorafenib. This mouse model was also used to examine the therapeutic efficacy of sorafenib alone or in combination with everolimus. Preclinical efficacy was assessed by comparing the reduction of tumor burden, proliferation, angiogenesis and the induction of apoptosis. Molecular responses were assessed by immunohistochemical, TUNEL and western blot assays.Results: Pharmacodynamic analysis revealed that a single dose of sorafenib decreased activation of the PI3K/AKT/mTOR signaling axis at doses of 30-60 mg/kg, but activated JAK/STAT3 signaling. Levels of cleaved casapase-3 increased in a dose dependent manner. Chemoprevention studies showed that chronic sorafenib administration was capable of inhibiting tumor progression through the reduction of cancer cell proliferation, angiogenesis and the induction of apoptosis. In intervention models of established castration-naive and castration-resistant prostate cancer, treatment with sorafenib provided modest but statistically insignificant reduction in tumor burden. However, sorafenib significantly inhibited cancer cell proliferation and MVD but had minimal effects on the induction of apoptosis. Interestingly, the administration of sorafenib increased the expression levels of the androgen receptor, p-GSK3 beta and p-ERK1/2 in castration-resistant prostate cancers. In both intervention models, combination therapy demonstrated a clear tendency of enhanced antitumor effects over monotherapy. Notably, the treatment combination of sorafenib and everolimus overcame therapeutic escape from single agent therapy in castration-resistant prostate cancers.Conclusions: In summary, we provide insights into the molecular responses of sorafenib therapy in a clinically relevant model of prostate cancer and present preclinical evidence for the development of targeted treatment strategies based on the use of multikinase inhibitors in combination with mTOR inhibitors for the treatment of advanced prostate cancer.
  • Yosuke Togashi; Hidetoshi Hayashi; Kunio Okamoto; Soichi Fumita; Masato Terashima; Marco A. de Velasco; Kazuko Sakai; Yoshihiko Fujita; Shuta Tomida; Kazuhiko Nakagawa; Kazuto Nishio
    LUNG CANCER ELSEVIER IRELAND LTD 88 (1) 16 - 23 0169-5002 2015/04 [Refereed]
     
    Background: Some of patients with non-small cell lung cancer (NSCLC) harboring somatic activating mutations of the epidermal growth factor receptor gene (EGFR mutations) show poor responses to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) treatment. Cigarette smoking is the strongest documented risk factor for the development of lung cancer. Nicotine, while not carcinogenic by itself, has been shown to induce proliferation, angiogenesis, and the epithelial-mesenchymal transition; these effects might be associated with EGFR-TKI resistance. Materials and methods: PC-9 and 11-18 cell lines (EGFR-mutated NSCLC cell lines) were cultured with 1 mu M nicotine for 3 months and were designated as PC-9/N and 11-18/N cell lines, respectively. The sensitivities of these cell lines to EGFR-TKI were then tested in vitro. Moreover, the association between the smoking status and the progression-free survival (PFS) period was investigated in patients with EGFR-mutated NSCLC who were treated with gefitinib. Results: The PC-9/N and 11-18/N cell lines were resistant to EGFR-TKI, compared with controls. The phosphorylation of EGFR in these cell lines was reduced by EGFR-TKI to a smaller extent than that observed in controls, and a higher concentration of EGFR-TKI was capable of further decreasing the phosphorylation. Clinically, smoking history was an independent predictor of a poor PFS period on gefitinib treatment. Conclusions: Chronic nicotine exposure because of cigarette smoking mediates resistance to EGFR-TKI via an EGFR signal. Smoking cessation is of great importance, while resistance may be overcome through the administration of high-dose EGFR-TKI. (c) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Akihiro Kogita; Yosuke Togashi; Hidetoshi Hayashi; Eri Banno; Masato Terashima; Marco A. De Velasco; Kazuko Sakai; Yoshihiko Fujita; Shuta Tomida; Yoshifumi Takeyama; Kiyotaka Okuno; Kazuhiko Nakagawa; Kazuto Nishio
    INTERNATIONAL JOURNAL OF ONCOLOGY SPANDIDOS PUBL LTD 46 (3) 1025 - 1030 1019-6439 2015/03 [Refereed]
     
    Non-small cell lung cancer (NSCLC) carrying echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements is hypersensitive to ALK inhibitors, including crizotinib and alectinib. Crizotinib was initially designed as a MET inhibitor, whereas alectinib is a selective ALK inhibitor. The MET signal, which is inhibited by crizotinib but not by alectinib, is dysregulated in many human cancers. However, the role of the MET signal in ALK-positive NSCLC remains unclear. In this study, we found that hepatocyte growth factor (HGF), ligand of MET, mediated the resistance to alectinib, but not to crizotinib, via the MET signal in ALK-positive NSCLC cell lines (H3122 and H2228 cell lines). In addition, alectinib activated the MET signal even in the absence of HGF and the inhibition of the MET signal enhanced the efficacy of alectinib. These findings suggest that activated MET acts as a salvage signal in ALK-positive NSCLC. This novel role of the MET signal in ALK-positive NSCLC may pave the way for further clinical trials examining MET inhibitors.
  • Yosuke Togashi; Hidetoshi Hayashi; Masato Terashima; Marco A. de Velasco; Kazuko Sakai; Yoshihiko Fujita; Shuta Tomida; Kazuhiko Nakagawa; Kazuto Nishio
    JOURNAL OF THORACIC ONCOLOGY LIPPINCOTT WILLIAMS & WILKINS 10 (1) 93 - 101 1556-0864 2015/01 [Refereed]
     
    Introduction: Patients with non-small-cell lung cancer (NSCLC) with somatic activating mutations of the epidermal growth factor receptor gene (EGFR mutations) generally respond to EGFR tyrosine kinase inhibitors (EGFR-TKIs). beta-Catenin is a key component of the Wnt/beta-Catenin signal and is an important oncogene that is involved in the pathogenesis and progression of malignant tumors, especially cancer stem cells. Methods and Results: We found that EGFR-mutated NSCLC cell lines exhibited a high expression level of beta-Catenin, compared with cell lines with the wild-type EGFR gene, and XAV939 (a beta-Catenin inhibitor) enhanced the sensitivities to EGFR-TKI in EGFR-mutated NSCLC cell lines. In EGFR-mutated NSCLC cell lines with the acquired resistance threonine-to-methionine mutation in codon 790 (T790M) mutation, XAV939 enhanced the sensitivity of the cells to an irreversible EGFR-TKI but not a reversible EGFR-TKI. The combination of XAV939 and EGFR-TKIs strongly inhibited the beta-Catenin signal and strongly decreased the phosphorylation of EGFR, compared with the use of EGFR-TKIs alone, suggesting an interaction between EGFR and the beta-Catenin signal. The stem cell-like properties of the EGFR-mutated cell line carrying the T790M mutation were inhibited by XAV939 and BIBW2992 (an irreversible EGFR-TKI). Furthermore, the stem cell-like properties were strongly inhibited by a combination of both the agents. A xenograft study demonstrated that beta-Catenin knockdown enhanced the antitumor effect of BIBW2992 in the EGFR-mutated NSCLC cell line carrying the T790M mutation. Conclusion: Our findings indicate that beta-Catenin might be a novel therapeutic target in EGFR-mutated NSCLC carrying the T790M mutation.
  • Yosuke Togashi; Akihiro Kogita; Hiroki Sakamoto; Hidetoshi Hayashi; Masato Terashima; Marco A. de Velasco; Kazuko Sakai; Yoshihiko Fujita; Shuta Tomida; Masayuki Kitano; Kiyotaka Okuno; Masatoshi Kudo; Kazuto Nishio
    CANCER LETTERS ELSEVIER IRELAND LTD 356 (2) 819 - 827 0304-3835 2015/01 [Refereed]
     
    We previously reported that activin produces a signal with a tumor suppressive role in pancreatic cancer (PC). Here, the association between plasma activin A and survival in patients with advanced PC was investigated. Contrary to our expectations, however, patients with high plasma activin A levels had a significantly shorter survival period than those with low levels (median survival, 314 days vs. 482 days, P = 0.034). The cellular growth of the MIA PaCa-2 cell line was greatly enhanced by activin A via non-SMAD pathways. The cellular growth and colony formation of an INHBA (beta subunit of inhibin)overexpressed cell line were also enhanced. In a xenograft study, INHBA-overexpressed cells tended to result in a larger tumor volume, compared with a control. The bodyweights of mice inoculated with INHBA-overexpressed cells decreased dramatically, and these mice all died at an early stage, suggesting the occurrence of activin-induced cachexia. Our findings indicated that the activin signal can promote cancer progression in a subset of PC and might be involved in cachexia. The activin signal might be a novel target for the treatment of PC. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
  • H. Hayashi; T. Arao; Y. Togashi; H. Kato; Y. Fujita; M. A. De Velasco; H. Kimura; K. Matsumoto; K. Tanaka; I. Okamoto; A. Ito; Y. Yamada; K. Nakagawa; K. Nishio
    ONCOGENE NATURE PUBLISHING GROUP 34 (2) 199 - 208 0950-9232 2015/01 [Refereed]
     
    POU5F1B (POU domain class 5 transcription factor 1B), a processed pseudogene that is highly homologous to OCT4, was recently shown to be transcribed in cancer cells, but its clinical relevance and biological function have remained unclear. We now show that POU5F1B, which is located adjacent to MYC on human chromosome 8q24, is frequently amplified in gastric cancer (GC) cell lines. POU5F1B, but not OCT4, was also found to be expressed at a high level in GC cell lines and clinical specimens. In addition, the DNA copy number and mRNA abundance for POU5F1B showed a positive correlation in both cancer cell lines and GC specimens. Overexpression of POU5F1B in GC cells promoted colony formation in vitro as well as both tumorigenicity and tumor growth in vivo, and these effects were enhanced in the additional presence of MYC overexpression. Furthermore, knockdown of POU5F1B expression with a short hairpin RNA confirmed a role for the endogenous pseudogene in the promotion of cancer cell growth in vitro and tumor growth in vivo. POU5F1B overexpression induced upregulation of various growth factors in GC cells as well as exhibited mitogenic, angiogenic and antiapoptotic effects in GC xenografts. Finally, amplification of POU5F1B was detected in 17 (12%) of 145 cases of GC and was a significant predictor of poor prognosis in patients with stage IV disease. In conclusion, we found that the POU5F1B pseudogene is amplified and expressed at a high level in, as well as confers an aggressive phenotype on, GC, and that POU5F1B amplification is associated with a poor prognosis in GC patients.
  • Hiroyuki Koike; Masahiro Nozawa; Marco A De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yutaka Yamamoto; Yuji Hatanaka; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    Asian Pacific journal of cancer prevention : APJCP 16 (5) 1827 - 31 2015 [Refereed]
     
    BACKGROUND: We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animal model was examined by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone acetate (CMA). MATERIALS AND METHODS: Six-week-old mice were treated subcutaneously with 50 μg/g of CMA three times a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary tract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation and apoptosis status in the prostate were examined by immunohistochemistry. RESULTS: CMA triggered significant shrinkage of not only the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and p=0.010, respectively), and the trend became more marked after a further five-weeks of treatment. The onset of prostate adenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggested the androgen axis is critical for cancer growth in these mice. CONCLUSIONS: Conditional PTEN-deficient mice are useful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screening of potential chemopreventive agents.
  • Kazuko Sakai; Azusa Yoneshige; Akihiko Ito; Yoji Ueda; Satoshi Kondo; Hitoshi Nobumasa; Yoshihiko Fujita; Yosuke Togashi; Masato Terashima; Marco A. De Velasco; Shuta Tomida; Kazuto Nishio
    SPRINGERPLUS SPRINGER INTERNATIONAL PUBLISHING AG 4 (1) 7  2193-1801 2015/01 [Refereed]
     
    We compared the performance of the 3D-Gene (R) mutation assay (3D-Gene (R) KRAS mutation assay kit) with the Scorpion-ARMS (therascreen (R) KRAS RGQ PCR Kit) and Luminex (MEBGEN (TM) KRAS kit) assays for the detection of KRAS mutations in formalin-fixed, paraffin-embedded tissue samples from 150 patients diagnosed with colorectal cancer. DNA was extracted from the paraffin-embedded tissue samples with or without macrodissection under hematoxylin and eosin staining and the KRAS mutation status was independently determined using these assays. Discordant results were re-analyzed by Sanger sequencing. Mutation detection analysis was successfully performed in all 150 specimens using the 3D-Gene (R) mutation assay without an invalid case. The concordance rate between the 3D-Gene (R) mutation assay and Scorpion-ARMS or Luminex was 98.7% (148/150). KRAS mutations were detected at a frequency of 35.3% (53/150) in colorectal cancer specimens. Three discrepant cases were found between the three assays. Overall, our results demonstrate a high concordance rate of between the 3D-Gene (R) mutation assay and the two existing in-vitro diagnostics kits. All three assays proved to be validated methods for detecting clinically significant KRAS mutations in paraffin-embedded tissue samples.
  • Shunsuke Sogabe; Yosuke Togashi; Hiroaki Kato; Akihiro Kogita; Takuro Mizukami; Yoichi Sakamoto; Eri Banno; Masato Terashima; Hidetoshi Hayashi; Marco A. de Velasco; Kazuko Sakai; Yoshihiko Fujita; Shuta Tomida; Takushi Yasuda; Yoshifumi Takeyama; Kiyotaka Okuno; Kazuto Nishio
    MOLECULAR CANCER THERAPEUTICS AMER ASSOC CANCER RESEARCH 13 (12) 3098 - 3106 1535-7163 2014/12 [Refereed]
     
    The prognosis for patients with unresectable advanced or recurrent gastric cancer remains poor. The identification of additional oncogenes with influences similar to those of epidermal growth factor receptor gene mutations, upon which the growth of cancer cells is dependent, is needed. In this study, we evaluated sensitivity to MEK inhibitors (GSK1120212 and PD0325901) in several gastric cancer cell lines in vitro and found three poorly differentiated gastric cancer cell lines that were hypersensitive to the inhibitors. The sequence analyses in these three cell lines revealed that one cell line had a novel MEK1 mutation, while the other two had previously reported KRAS and MEK1 mutations, respectively; the gene statuses of the other resistant cell lines were all wild-type. Experiments using MEK1 expression vectors demonstrated that the MEK1 mutations induced the phosphorylation of ERK1/2 and had a transforming potential, enhancing the tumorigenicity. The MEK inhibitor dramatically reduced the phosphorylation of ERK1/2 and induced apoptosis in the cell lines with MEK1 mutations. In vivo, tumor growth was also dramatically decreased by an inhibitor. One of the 46 gastric cancer clinical samples that were examined had a MEK1 mutation; this tumor had a poorly differentiated histology. Considering the addiction of cancer cells to active MEK1 mutations for proliferation, gastric cancer with such oncogenic MEK1 mutations might be suitable for targeted therapy with MEK inhibitors. (C)2014 AACR.
  • Marco A. De Velasco; Yuji Hatanaka; Takashi Oki; Yurie Kura; Yutaka Yamamoto; Kazuhiro Yoshimura; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 74 (19) 0008-5472 2014/10 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 74 (19) 0008-5472 2014/10 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 74 (19) 0008-5472 2014/10 [Refereed]
  • Hirotsugu Uemura; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A. De Velasco
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 74 (19) 0008-5472 2014/10 [Refereed]
  • Yurie Kura; Marco A. De Velasco; Naomi Ando; Emiko Fukushima; Yutaka Yamamoto; Yuji Hatanaka; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 74 (19) 0008-5472 2014/10 [Refereed]
  • Kazuhiro Yoshikawa; Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 74 (19) 0008-5472 2014/10 [Refereed]
  • Akihiro Kogita; Yosuke Togashi; Hidetoshi Hayashi; Shunsuke Sogabe; Masato Terashima; Marco A. De Velasco; Kazuko Sakai; Yoshihiko Fujita; Shuta Tomida; Yoshifumi Takeyama; Kiyotaka Okuno; Kazuhiko Nakagawa; Kazuto Nishio
    INTERNATIONAL JOURNAL OF ONCOLOGY SPANDIDOS PUBL LTD 45 (4) 1430 - 1436 1019-6439 2014/10 [Refereed]
     
    Patients with non-small cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements generally respond to ALK inhibitors such as crizotinib. However, some patients with EML4-ALK rearrangements respond poorly to crizotinib. Hypoxia is involved in the resistance to chemotherapeutic treatments in several cancers, and we investigated the association between the responses to ALK inhibitors and hypoxia. Sensitivity of the H3122 NSCLC cell line (EML4-ALK rearrangement) to ALK inhibitors (crizotinib or alectinib) was investigated during a normoxic or hypoxic state using an MTT assay. We found that the cell line was resistant to the inhibitors during hypoxia. Hypoxia mediated morphologic changes, including cell scattering and the elongation of the cell shape, that are characteristic of the epithelial-mesenchymal transition (EMT). A migration assay demonstrated that the number of migrating cells increased significantly during hypoxia, compared with during normoxia. Regarding EMT-related molecules, the expressions of slug, vimentin, and fibronectin were increased while that of E-cadherin was decreased by hypoxia. In addition, hypoxia inducible factor 1A-knockdown cancelled the hypoxia-induced EMT and resistance. Our findings indicate that hypoxia induces resistance to ALK inhibitors in NSCLC with an EML4-ALK rearrangement via the EMT.
  • MEK遺伝子変異を有する胃がんに対するMEK阻害剤の有効性(MEK inhibitor for gastric cancer with MEK1 gene mutations)
    冨樫 庸介; 加藤 寛章; 林 秀敏; 寺嶋 雅人; デベラスコ・マルコ; 坂井 和子; 藤田 至彦; 冨田 秀太; 安田 卓司; 西尾 和人
    日本癌学会総会記事 (一社)日本癌学会 73回 P - 2349 0546-0476 2014/09
  • Marco A De Velasco; Motoyoshi Tanaka; Yutaka Yamamoto; Yuji Hatanaka; Hiroyuki Koike; Kazuto Nishio; Kazuhiro Yoshikawa; Hirotsugu Uemura
    Carcinogenesis 35 (9) 2142 - 53 2014/09 [Refereed]
     
    Castration-resistant prostate cancer is an incurable heterogeneous disease that is characterized by a complex multistep process involving different cellular and biochemical changes brought on by genetic and epigenetic alterations. These changes lead to the activation or overexpression of key survival pathways that also serve as potential therapeutic targets. Despite promising preclinical results, molecular targeted therapies aimed at such signaling pathways have so far been dismal. In the present study, we used a PTEN-deficient mouse model of prostate cancer to show that plasticity in castration-resistant tumors promotes therapeutic escape. Unlike castration-naïve tumors which depend on androgen receptor and PI3K/AKT signal activation for growth and survival, castration-resistant tumors undergo phenotypic plasticity leading to increased intratumoral heterogeneity. These tumors attain highly heterogeneous phenotypes that are characterized by cancer cells relying on alternate signal transduction pathways for growth and survival, such as mitogen-activated protein kinase and janus kinase/signal transducer and activator of transcription, and losing their dependence on PI3K signaling. These features thus enabled castration-resistant tumors to become insensitive to the therapeutic effects of PI3K/AKT targeted therapy. Overall, our findings provide evidence that androgen deprivation drives phenotypic plasticity in prostate cancer cells and implicate it as a crucial contributor to therapeutic resistance in castration-resistant prostate cancer. Therefore, incorporating intratumoral heterogeneity in a dynamic tumor model as a part of preclinical efficacy determination could improve prediction for response and provide better rationale for the development of more effective therapies.
  • Masato Terashima; Yoshihiko Fujita; Yosuke Togashi; Kazuko Sakai; Marco A. De Velasco; Shuta Tomida; Kazuto Nishio
    ONCOTARGET IMPACT JOURNALS LLC 5 (16) 7040 - 7050 1949-2553 2014/08 [Refereed]
     
    The KIAA1199 gene was first discovered to be associated with non-syndromic hearing loss. Recently, several reports have shown that the up-regulation of KIAA1199 is associated with cancer cell migration or invasion and a poor prognosis. These findings indicate that KIAA1199 may be a novel target for cancer therapy. Therefore, we explored in detail the function of KIAA1199 in cancer cells. In this study, we investigated the interaction of KIAA1199 protein with intracellular proteins in cancer cells. To this end, we expressed KIAA1199-MBP fusion protein and performed a pull-down assay. In addition, KIAA1199-overexpressing cancer cell lines were constructed using a retroviral vector and were used for further experiments. A pull-down analysis showed that the glycogen phosphorylase kinase beta-subunit (PHKB) interacted with the C-terminal region of KIAA1199 protein. Furthermore, we observed the interaction of KIAA1199 with glycogen phosphorylase brain form (PYGB) under serum-free conditions. The interaction promoted glycogen breakdown and cancer cell survival. Our findings indicate that KIAA1199 plays an important role in glycogen breakdown and cancer cell survival and that it may represent a novel target for cancer therapy.
  • Masato Terashima; Kazuko Sakai; Yosuke Togashi; Hidetoshi Hayashi; Marco A. De Velasco; Junji Tsurutani; Kazuto Nishio
    SPRINGERPLUS SPRINGER INTERNATIONAL PUBLISHING AG 3 (1) 417  2193-1801 2014/08 [Refereed]
     
    Triple-negative breast cancer (TNBC) is associated with a higher incidence of recurrence and distant metastasis and a poor prognosis, whereas effective treatment strategies remain to be established. Finding an effective treatment for TNBC has become imperative. We examined the effect of the combination of S-1 (or 5-FU in an in vitro study) and eribulin in TNBC cell lines. The in vitro effect of the combination was examined in four TNBC cell lines (MDA-MB-231, MDA-MB-468, BT-549 and MX-1) using a combination index and isobolograms. In addition, we assessed the effect of the combination in an MDA-MB-231 tumor xenograft model. A synergistic effect was observed in three TNBC cell lines (MDA-MB-231, MDA-MB-468, and MX-1), and in an in vivo study, the combination of S-1 and eribulin resulted in significantly higher antitumor effects compared with S-1 or eribulin alone. 5-FU induced epithelial-mesenchymal transition (EMT) change in the TNCB cell line, as supported by the decreased expression of epithelial marker and the increased expression of mesenchymal markers. Meanwhile, TGF-beta induced EMT changes in a TNBC cell line and decreased the sensitivity to 5-FU. This result suggests that 5-FU-induced EMT changes reduce the sensitivity to 5-FU. In contrast, eribulin induced a mesenchymal-epithelial transition (MET) in a TNBC cell line. The EMT phenotype induced by 5-FU was also canceled by eribulin. We demonstrate that the combination of S-1 (5-FU) and eribulin exerts a synergistic effect for TNBC cell lines through MET-induction by eribulin. Therefore, this combination therapy may be a potential treatment option for TNBC.
  • Hidenori Tsuji; Nobutaka Shimizu; Masahiro Nozawa; Tohru Umekawa; Kazuhiro Yoshimura; Marco A De Velasco; Hirotsugu Uemura; Saeed R Khan
    Urolithiasis 42 (3) 195 - 202 2014/06 [Refereed]
     
    Osteopontin (OPN) expression is increased in kidneys of rats with ethylene glycol (EG) induced hyperoxaluria and calcium oxalate (CaOx) nephrolithiasis. The aim of this study is to clarify the effect of OPN knockdown by in vivo transfection of OPN siRNA on deposition of CaOx crystals in the kidneys. Hyperoxaluria was induced in 6-week-old male Sprague-Dawley rats by administering 1.5% EG in drinking water for 2 weeks. Four groups of six rats each were studied: Group A, untreated animals (tap water); Group B, administering 1.5% EG; Group C, 1.5% EG with in vivo transfection of OPN siRNA; Group D, 1.5% EG with in vivo transfection of negative control siRNA. OPN siRNA transfections were performed on day 1 and 8 by renal sub-capsular injection. Rats were killed at day 15 and kidneys were removed. Extent of crystal deposition was determined by measuring renal calcium concentrations and counting renal crystal deposits. OPN siRNA transfection resulted in significant reduction in expression of OPN mRNA as well as protein in group C compared to group B. Reduction in OPN expression was associated with significant decrease in crystal deposition in group C compared to group B. Specific suppression of OPN mRNA expression in kidneys of hyperoxaluric rats leads to a decrease in OPN production and simultaneously inhibits renal crystal deposition.
  • Minami, Takafumi; Minami, Tomoko; Shimizu, Nobutaka; Yamamoto, Yutaka; De Velasco, Marco; Nozawa, Masahiro; Yoshimura, Kazuhiro; Harashima, Nanae; Harada, Mamoru; Uemura, Hirotsugu
    INTERNATIONAL IMMUNOPHARMACOLOGY ELSEVIER SCIENCE BV 20 (1) 59 - 65 1567-5769 2014/05 [Refereed]
     
    Molecular targeting therapy with anti-angiogenic agents, including sunitinib and sorafenib, has been proven to be the first- and second-line standard treatments for metastatic renal cell carcinoma (mRCC) worldwide. Despite their significant antitumor effects, most of the patients with mRCC have not been cured. Under such circumstances, anti-cancer immunotherapy has been considered as a promising treatment modality for mRCC, and cytotoxic T lymphocytes (CTLs) are the most powerful effectors among several immune cells and molecules. Therefore, we previously conducted anti-cancer vaccine therapy with peptides derived from carbonic anhydrase-9 and vascular endothelial growth factor receptor-1 as phase-I/II trials for mRCC patients and reported their clinical benefits. Alternatively, up-regulated expression of erythropoietin (Epo) and its receptor (EpoR) in RCC has been reported, and their co-expression is involved in tumorigenesis. In order to increase options for peptide-based vaccination therapy, we searched for novel EpoR-peptides for HLA-A24(+) RCC patients. Among 5 peptides derived from EpoR, which were prepared based on the binding motif to the HLA-A24 allele, EpoR(52-60) peptide had the potential to induce peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24(+) RCC patients. Cytotoxicity toward HLA-A24 and EpoR-expressing RCC cells was ascribed to peptide-specific CD8(+) T cells. These results indicate that the EpoR(52-60) peptide could be a promising candidate for a peptide-based anti-cancer vaccine for HLA-A24(+) mRCC patients. (C) 2014 Elsevier B.V. All rights reserved.
  • Yosuke Togashi; Hiroki Sakamoto; Hidetoshi Hayashi; Masato Terashima; Marco A. de Velasco; Yoshihiko Fujita; Yasuo Kodera; Kazuko Sakai; Shuta Tomida; Masayuki Kitano; Akihiko Ito; Masatoshi Kudo; Kazuto Nishio
    MOLECULAR CANCER BIOMED CENTRAL LTD 13 (1) 126  1476-4598 2014/05 [Refereed]
     
    Background: Transforming growth factor, beta (TGFB) signal is considered to be a tumor suppressive pathway based on the frequent genomic deletion of the SMAD4 gene in pancreatic cancer (PC); however; the role of the activin signal, which also belongs to the TGFB superfamily, remains largely unclear. Methods and results: We found a homozygous deletion of the activin A receptor, type IB (ACVR1B) gene in 2 out of 8 PC cell lines using array-comparative genomic hybridization, and the absence of ACVR1B mRNA and protein expression was confirmed in these 2 cell lines. Activin A stimulation inhibited cellular growth and increased the phosphorylation level of SMAD2 and the expression level of p21(CIP1/WAF1) in the Sui66 cell line (wild-type ACVR1B and SMAD4 genes) but not in the Sui68 cell line (homozygous deletion of ACVR1B gene). Stable ACVR1B-knockdown using short hairpin RNA cancelled the effects of activin A on the cellular growth of the PC cell lines. In addition, ACVR1B-knockdown significantly enhanced the cellular growth and colony formation abilities, compared with controls. In a xenograft study, ACVR1B-knockdown resulted in a significantly elevated level of tumorigenesis and a larger tumor volume, compared with the control. Furthermore, in clinical samples, 6 of the 29 PC samples (20.7%) carried a deletion of the ACVR1B gene, while 10 of the 29 samples (34.5%) carried a deletion of the SMAD4 gene. Of note, 5 of the 6 samples with a deletion of the ACVR1B gene also had a deletion of the SMAD4 gene. Conclusion: We identified a homozygous deletion of the ACVR1B gene in PC cell lines and clinical samples and proposed that the deletion of the ACVR1B gene may mediate an aggressive cancer phenotype in PC. Our findings provide novel insight into the role of the activin signal in PC.
  • Yosuke Togashi; Tokuzo Arao; Hiroaki Kato; Kazuko Matsumoto; Masato Terashima; Hidetoshi Hayashi; Marco A. de Velasco; Yoshihiko Fujita; Hideharu Kimura; Takushi Yasuda; Hitoshi Shiozaki; Kazuto Nishio
    ONCOTARGET IMPACT JOURNALS LLC 5 (10) 2962 - 2973 1949-2553 2014/05 [Refereed]
     
    Chromosomal band 11q13 seems to be one of the most frequently amplified lesions in human cancer, including esophageal squamous cell cancer (ESCC). The oral cancer overexpressed 1 (ORAOV1) gene has been identified within this region, but its detailed biological function in human ESCC remains largely unclear. In our clinical samples of stage III ESCC, ORAOV1 amplification was observed in 49 of 94 cases (53%). ORAOV1 amplification was significantly associated with a poorly differentiated histology and tumors located in the upper or middle esophagus. Patients with ORAOV1 amplification tended to have a shorter survival period, although the difference was not significant. To investigate the function of ORAOV1, we created ORAOV1-overexpressed ESCC cell lines that exhibited increased cellular proliferation and colony formation, compared with in vitro controls. In vivo, ORAOV1-overexpressed cells exhibited a significantly increased tumorigenicity and a significantly larger tumor volume and poorer differentiation than controls. The peptide mass fingerprinting technique demonstrated that ORAOV1 bound to pyrroline-5-carboxylate reductase (PYCR), which is associated with proline metabolism and reactive oxygen species (ROS) production. Then, ORAOV1-overexpressed cell lines were resistant to stress treatment, which was cancelled by PYCR-knockdown. In addition, the ORAOV1-overexpressed cell line had a higher intracellular proline concentration and a lower ROS level. Our findings indicate that the ORAOV1 gene is frequently amplified in ESCC, enhances tumorigenicity and tumor growth, and is associated with a poorly differentiated tumor histology via proline metabolism and ROS production. ORAOV1 could be a novel target for the treatment of ESCC.
  • Yoshihiko Fujita; Satoshi Koinuma; Marco A. De Velasco; Jan Bolz; Yosuke Togashi; Masato Terashima; Hidetoshi Hayashi; Takuya Matsuo; Kazuto Nishio
    PLOS ONE PUBLIC LIBRARY SCIENCE 9 (4) e94772  1932-6203 2014/04 [Refereed]
     
    The tissue distribution and function of hemoglobin or myoglobin are well known; however, a newly found cytoglobin (CYGB), which also belongs to the globin family, remains to be characterized. To assess its expression in human malignancies, we sought to screen a number of cell lines originated from many tissues using northern blotting and real time PCR techniques. Unexpectedly, we found that several, but not all, melanoma cell lines expressed CYGB mRNA and protein at much higher levels than cells of other origins. Melanocytes, the primary origin of melanoma, also expressed CYGB at a high level. To verify these observations, immunostaining and immunoblotting using anti-CYGB antibody were also performed. Bisulfite-modified genomic sequencing revealed that several melanoma cell lines that abrogated CYGB expression were found to be epigenetically regulated by hypermethylation in the promoter region of CYGB gene. The RNA interference-mediated knockdown of the CYGB transcript in CYGB expression-positive melanoma cell lines resulted in increased proliferation in vitro and in vivo. Flow cytometric analysis using 2'-, 7'-dichlorofluorescein diacetate (DCFH-DA), an indicator of reactive oxygen species (ROS), revealed that the cellular ROS level may be involved in the proliferative effect of CYGB. Thus, CYGB appears to play a tumor suppressive role as a ROS regulator, and its epigenetic silencing, as observed in CYGB expression-negative melanoma cell lines, might function as an alternative pathway in the melanocyte-to-melanoma transition.
  • Nobutaka Shimizu; Marco A De Velasco; Tohru Umekawa; Hirotsugu Uemura; Kazuhiro Yoshikawa
    International journal of urology : official journal of the Japanese Urological Association 20 (11) 1136 - 43 2013/11 [Refereed]
     
    OBJECTIVE: To evaluate the effect of the Rho kinase inhibitor, hydroxyfasudil, on bladder function in a rat model of HCl-induced chemical cystitis, and to elucidate the possible mechanisms associated with its therapeutic effect. METHODS: Female Sprague-Dawley rats with HCl-induced cystitis were given hydroxyfasudil (10 mg/kg, i.p.) for 7 days. Treatment efficacy was determined by comparing bladder function and histopathology to sham and untreated control rats. Bladder function was determined by cystometric analysis. Rho kinase activity was determined by quantitative reverse transcription polymerase chain reaction and signal inhibition of downstream Ras homolog member A/Rho kinase signaling molecules by western blot and immunohistochemistry. RESULTS: Treatment with hydroxyfasudil significantly improved bladder intercontraction intervals. Rats treated with hydroxyfasudil also showed a significant reduction of histopathological features associated with cystitis. Western blot and immunohistochemistry findings showed that hydroxyfasudil inhibited downstream molecules of Rho kinase that ameliorated changes associated with HCl-induced chemical cystitis, such as inflammatory cell recruitment and smooth muscle cell proliferation. CONCLUSION: The findings from the present study suggest a promising therapeutic role for hydroxyfasudil in bladder inflammation associated with cystitis.
  • Shigeru Hatabe; Hideharu Kimura; Tokuzo Arao; Hiroaki Kato; Hidetoshi Hayashi; Tomoyuki Nagai; Kazuko Matsumoto; Marco DE Velasco; Yoshihiko Fujita; Go Yamanouchi; Masao Fukushima; Yasuhide Yamada; Akihiko Ito; Kiyotaka Okuno; Kazuto Nishio
    Molecular and clinical oncology 1 (5) 845 - 850 2049-9450 2013/09 [Refereed]
     
    The heparan sulfate sulfotransferase gene family catalyzes the transfer of sulfate groups to heparan sulfate and regulates various growth factor-receptor signaling pathways. However, the involvement of this gene family in cancer biology has not been elucidated. It was demonstrated that the heparan sulfate D-glucosaminyl 6-O-sulfotransferase-2 (HS6ST2) gene is overexpressed in colorectal cancer (CRC) and its clinical significance in patients with CRC was investigated. The mRNA levels of HS6ST2 in clinical CRC samples and various cancer cell lines were assessed using a microarray analysis and quantitative RT-PCR, respectively. An immunohistochemical (IHC) analysis of the HS6ST2 protein was performed using 102 surgical specimens of CRC. The correlations between the HS6ST2 expression status and clinicopathological characteristics were then evaluated. HS6ST2 mRNA was significantly overexpressed by 37-fold in CRC samples compared to paired colonic mucosa. High levels of HS6ST2 mRNA expression were also observed in colorectal, esophageal and lung cancer cell lines. The IHC analysis demonstrated that HS6ST2 was expressed in the cytoplasmic region of CRC cells, but not in normal colonic mucosal cells. Positive staining for HS6ST2 was detected in 40 patients (39.2%). There was no significant association between the clinicopathological characteristics and HS6ST2 expression. However, positive staining for HS6ST2 was associated with a poor survival (P=0.074, log-rank test). In conclusion, HS6ST2 was found to be overexpressed in CRC and its expression tended to be a poor prognostic factor, although the correlation was not significant. These findings indicate that HS6ST2 may be a novel cancer-related marker that may provide insight into the glycobiology of CRC.
  • Marco A. De Velasco; Yutaka Yamamoto; Yuji Hatanaka; Yurie Kura; Naomi Ando; Emiko Fukushima; Masahiro Nozawa; Nobutaka Shimizu; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 73 (8) 0008-5472 2013/04 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 73 (8) 0008-5472 2013/04 [Refereed]
  • Daisuke Tamura; Tokuzo Arao; Tomoyuki Nagai; Hiroyasu Kaneda; Keiichi Aomatsu; Yoshihiko Fujita; Kazuko Matsumoto; Marco A. De Velasco; Hiroaki Kato; Hidetoshi Hayashi; Shuhei Yoshida; Hideharu Kimura; Yoshimasa Maniwa; Wataru Nishio; Yasuhiro Sakai; Chiho Ohbayashi; Yoshikazu Kotani; Yoshihiro Nishimura; Kazuto Nishio
    CANCER MEDICINE WILEY-BLACKWELL 2 (2) 144 - 154 2045-7634 2013/04 [Refereed]
     
    Transcription factor Slug/SNAI2 (snail homolog 2) plays a key role in the induction of the epithelial mesenchymal transition in cancer cells; however, whether the overexpression of Slug mediates the malignant phenotype and alters drug sensitivity in lung cancer cells remains largely unclear. We investigated Slug focusing on its biological function and involvement in drug sensitivity in lung cancer cells. Stable Slug transfectants showed typical morphological changes compared with control cells. Slug overexpression did not change the cellular proliferations; however, migration activity and anchorage-independent growth activity with an antiapoptotic effect were increased. Interestingly, stable Slug overexpression increased drug sensitivity to tubulin-binding agents including vinorelbine, vincristine, and paclitaxel (5.8- to 8.9-fold increase) in several lung cancer cell lines but did not increase sensitivity to agents other than tubulin-binding agents. Real-time RT-PCR (polymerase chain reaction) and western blotting revealed that Slug overexpression downregulated the expression of beta III and beta IVa-tubulin, which is considered to be a major factor determining sensitivity to tubulin-binding agents. A luciferase reporter assay confirmed that Slug suppressed the promoter activity of beta IVa-tubulin at a transcriptional level. Slug overexpression enhanced tumor growth, whereas Slug overexpression increased drug sensitivity to vinorelbine with the downregulation of beta III and beta IV-tubulin in vivo. Immunohistochemistry of Slug with clinical lung cancer samples showed that Slug overexpression tended to be involved in response to tubulin-binding agents. In conclusion, our data indicate that Slug mediates an aggressive phenotype including enhanced migration activity, anoikis suppression, and tumor growth, but increases sensitivity to tubulin-binding agents via the downregulation of beta III and beta IVa-tubulin in lung cancer cells.
  • Yoshihiko Fujita; Rafiqul Islam; Kazuko Sakai; Hiroyasu Kaneda; Kanae Kudo; Daisuke Tamura; Keiichi Aomatsu; Tomoyuki Nagai; Hidekazu Kimura; Kazuko Matsumoto; Marco A. de Velasco; Tokuzo Arao; Tadashi Okawara; Kazuto Nishio
    INVESTIGATIONAL NEW DRUGS SPRINGER 30 (5) 1878 - 1886 0167-6997 2012/10 [Refereed]
     
    Resveratrol (3, 4', 5-trihydroxy-trans-stilbene), a natural phytoalexin found in grapes and wine, has anti-proliferative activity on human-derived cancer cells. In our study, we used a conventional condensation reaction between aldehydes and amines to provide a number of aza-resveratrol (3, 4', 5-trihydroxy-trans- aza-stilbene) derivatives in an attempt to screen for compounds with resveratrol's action but with increased potency. Aza-resveratrol and its hydroxylated derivative (3, 4, 4', 5-tetrahydroxy-trans- aza-stilbene) showed a more enhanced anti-proliferative effect than resveratrol in an MCF-7 breast carcinoma cell line. To identify the cellular targets of the aza derivatives of resveratrol, we conjugated the latter aza-stilbene compound with epoxy-activated agarose and performed affinity purification. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, was identified as a major target protein in MCF-7 cell lysates using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS). The aza-resveratrol and its hydroxylated derivative, but not resveratrol, were also found to be potent inhibitors of MIF tautomerase activity, which may be associated with their inhibitory effects on MIF bioactivity for cell growth.
  • 食事誘導性レプチンは前立腺癌の進行に寄与する(Diet-induced leptin contributes to prostate cancer progression)
    De Velasco Marco A.; Hatanaka Yuji; Yamamoto Yutaka; Yoshimura Kazuhiro; Shimizu Nobutaka; Nozawa Masahiro; Yoshikawa Kazuhiro; Nishio Kazuto; Uemura Hirotsugu
    日本癌学会総会記事 日本癌学会 71回 430 - 430 0546-0476 2012/08 [Refereed]
  • Mitsuyama Kodama; Marco A. De Velasco; Yutaka Yamamoto; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 72 0008-5472 2012/04 [Refereed]
  • Yutaka Yamamoto; Marco A. De Velasco; Yuji Hatanaka; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Mitsumasa Kodama; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 72 0008-5472 2012/04 [Refereed]
  • Yasuyuki Kobayashi; Marco A. De Velasco; Yuji Hatanaka; Yutaka Yamamoto; Motoyoshi Tanaka; Nozawa Masahiro; Nobutaka Shimizu; Kazuhiro Yoshimura; Mitsuyama Kodama; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 72 0008-5472 2012/04 [Refereed]
  • Kazuhiro Yoshimura; Marco A. De Velasco; Yuji Hatanaka; Yutaka Yamamoto; Mitsumasa Kodama; Motoyoshi Tanaka; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 72 0008-5472 2012/04 [Refereed]
  • Yuji Hatanaka; Marco A. De Velasco; Yurie Kura; Yuji Yamamoto; Mitsumasa Kodama; Masahiro Nozawa; Nobutaka Shimizu; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 72 0008-5472 2012/04 [Refereed]
  • Marco A De Velasco; Hirotsugu Uemura
    Advances in urology 2012 419348 - 419348 2012 [Refereed][Invited]
     
    Knowledge gained from the identification of genetic and epigenetic alterations that contribute to the progression of prostate cancer in humans is now being implemented in the development of functionally relevant translational models. GEM (genetically modified mouse) models are being developed to incorporate the same molecular defects associated with human prostate cancer. Haploinsufficiency is common in prostate cancer and homozygous loss of PTEN is strongly correlated with advanced disease. In this paper, we discuss the evolution of the PTEN knockout mouse and the cooperation between PTEN and other genetic alterations in tumor development and progression. Additionally, we will outline key points that make these models key players in the development of personalized medicine, as potential tools for target and biomarker development and validation as well as models for drug discovery.
  • H. Kaneda; T. Arao; K. Matsumoto; M. A. De Velasco; D. Tamura; K. Aomatsu; K. Kudo; K. Sakai; T. Nagai; Y. Fujita; K. Tanaka; K. Yanagihara; Y. Yamada; I. Okamoto; K. Nakagawa; K. Nishio
    BRITISH JOURNAL OF CANCER NATURE PUBLISHING GROUP 105 (8) 1210 - 1217 0007-0920 2011/10 [Refereed]
     
    BACKGROUND: Activin A is a multi-functional cytokine belonging to the transforming growth factor-beta (TGF-beta) superfamily; however, the effect of activin A on angiogenesis remains largely unclear. We found that inhibin beta A subunit (INHBA) mRNA is overexpressed in gastric cancer (GC) specimens and investigated the effect of activin A, a homodimer of INHBA, on angiogenesis in GC. METHODS: Anti-angiogenic effects of activin A via p21 induction were evaluated using human umbilical vein endothelial cells (HUVECs) in vitro and a stable INHBA-introduced GC cell line in vivo. RESULTS: Compared with TGF-beta, activin A potently inhibited the cellular proliferation and tube formation of HUVECs with induction of p21. A promoter assay and a chromatin immunoprecipitation assay revealed that activin A directly regulates p21 transcriptional activity through Smads. Stable p21-knockdown significantly enhanced the cellular proliferation of HUVECs. Notably, stable p21-knockdown exhibited a resistance to activin-mediated growth inhibition in HUVECs, indicating that p21 induction has a key role on activin A-mediated growth inhibition in vascular endothelial cells. Finally, a stable INHBA-introduced GC cell line exhibited a decrease in tumour growth and angiogenesis in vivo. CONCLUSION: Our findings highlight the suppressive role of activin A, unlike TGF-beta, on tumour growth and angiogenesis in GC. British Journal of Cancer (2011) 105, 1210-1217. doi:10.1038/bjc.2011.348 www.bjcancer.com Published online 6 September 2011 (C) 2011 Cancer Research UK
  • Kenji Zennami; Kazuhiro Yoshikawa; Eisaku Kondo; Kogenta Nakamura; Yoshiaki Upsilonamada; Marco A De Velasco; Motoyoshi Tanaka; Hirotsugu Uemura; Toru Shimazui; Hideyuki Akaza; Shinsuke Saga; Ryuzo Ueda; Nobuaki Honda
    Oncology reports 26 (2) 327 - 33 2011/08 [Refereed]
     
    Molecular targeting agents have become formidable anticancer weapons showing much promise against refractory tumors and functional peptides and are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms the basis for a potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. We examine the growth suppression efficiency of human renal cell carcinoma (RCC) by single-peptide targeting. We simultaneously introduced p16INK4a tumor suppressor peptides by Wr-T-mediated peptide delivery. Wr-T-mediated transport of p16INK4a functional peptide into 10 RCC lines, lacking expression of the p16INK4a molecule, reversed the specific loss of p16 function, thereby drastically inhibiting tumor growth in all but 3 lines by >95% within the first 96 h. In vivo analysis using SK-RC-7 RCC xenografts in nude mice demonstrated tumor growth inhibition by the p16INK4a peptide alone, however, inoculation of Wr-T and the p16INK4a functional peptide mixture, via the heart resulted in complete tumor regression. Thus, restoration of tumor suppressor function with Wr-T peptide delivery represents a powerful approach, with mechanistic implications for the development of efficacious molecular targeting therapeutics against intractable RCC.
  • Keiji Shimada; Satoshi Anai; Develasco A Marco; Kiyohide Fujimoto; Noboru Konishi
    BMC urology BIOMED CENTRAL LTD 11 (1) 8 - 8 1471-2490 2011/05 [Refereed]
     
    BACKGROUND: Survival rate for patients presenting muscle invasive bladder cancer is very low, and useful therapeutic target has not been identified yet. In the present study, new COX2 downstream signals involved in urothelial carcinoma cell survival were investigated in vitro and in vivo. METHODS: COX2 gene was silenced by siRNA transfection. Orthotopic implantation animal model and transurethral instillation of siRNA with atelocollagen was constructed to examine the effects of COX2 knockdown in vivo. Cell cycle was examined by flowcytoketry. Surgical specimens derived from patients with urinary bladder cancer (all were initially diagnosed cases) were used for immunohistochemical analysis of the indicated protein expression in urothelial carcinoma cells. RESULTS: Treatment with the COX2 inhibitor or knockdown of COX2 reduced expression of casein kinase (CK) 2 α, a phophorylated Akt and urokinase type plasminogen activator (uPA), resulting in p27 induction, cell cycle arrest at G1 phase and cell growth suppression in human urothelial carcinoma cell lines expressing COX2. Silencing of CK2α exhibited the similar effects. Even in UMUC3 cells lacking the COX2 gene, COX2 inhibition also inhibited cell growth through down-regulation of the CK2α-Akt/uPA axis. The mouse orthotropic bladder cancer model demonstrated that the COX2 inhibitor, meloxicam significantly reduced CK2α, phosphorylated Akt and uPA expression, whereas induced p27 by which growth and invasiveness of bladder cancer cells were strongly inhibited. Immunohistochemically, high expression of COX2, CK2α and phosphorylated form of Akt was found in high-grade, invasive carcinomas as well as carcinoma in situ, but not in low-grade and noninvasive phenotypes. CONCLUSIONS: COX2-dependent and independent activation of CK2α-Akt/uPA signal is mainly involved in urothelial carcinoma cell survival, moreover, not only COX2 but also CK2α could be direct targets of COX2 inhibitors.
  • Hirotsugu Uemura; Yuji Hatanaka; Ayaka Izumi; Erina Okazaki; Makiko Doi; Motoyoshi Tanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A. De Velasco
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 71 0008-5472 2011/04 [Refereed]
  • Yutaka Yamamoto; Marco A. De Velasco; Yi Wang; Ayaka Izumi; Erina Okazaki; Makiko Doi; Yuji Hatanaka; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Hirotugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 71 0008-5472 2011/04 [Refereed]
  • Yuji Hatanaka; Marco A. De Velasco; Motoyoshi Tanaka; Makiko Doi; Erina Okazaki; Ayaka Izumi; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 71 0008-5472 2011/04 [Refereed]
  • Marco A. De Velasco; Erina Okazaki; Yi Wang; Ayaka Izumi; Yuji Hatanaka; Motoyoshi Tanaka; Charles Rosser; Steve Goodison; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 71 0008-5472 2011/04 [Refereed]
  • Yi Wang; Marco A. De Velasco; Erina Okazaki; Ayaka Izumi; Motoyoshi Tanka; Yutaka Yamamoto; Yuji Hatanaka; Kazuhiro Yoshimura; Masahiro Nozawa; Charles Rosser; Steve Goodison; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 71 0008-5472 2011/04 [Refereed]
  • Uemura, Hirotsugu; De Velasco, Marco; Yoshimura, Kazuhiro; Nozawa, Masahiro; Minami, Takafumi
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 185 (4) E710 - E710 0022-5347 2011/04 [Refereed]
  • Koichi Sugimoto; Hiroyuki Koike; Kiyoshi Hashimoto; Atsunobu Esa; Yoshitaka Saitou; Yuji Hatanaka; Masaaki Imanishi; Nobutaka Shimizu; Hideo Taharac; Marco De Velasco; Hirotsugu Uemura
    Current Urology 5 (1) 41 - 45 1661-7649 2011/04 [Refereed]
     
    Background: Bacillus Calmette-Guerin (BCG) instillation has been considered to be the most effective method of treatment for non-muscle invasive bladder cancer. The objective of the study was to evaluate the efficacy of between 6 and 8 intravesical BCG instillations after transurethral resection of bladder tumor (TUR-Bt) for Grade 3 nonmuscle invasive bladder cancer. Methods: Between January 2000 and December 2007, a total of 68 cases (58 males and 10 females) with nonmuscle invasive bladder cancer (pTa-1 G3, without carcinoma in situ) were used in the study. After TUR-Bt, patients were divided into a non-infusion group (group A) and BCG (Tokyo 172 strain BCG, 80 mg in 40 ml saline or Connaught BCG, 81 mg in 40 ml saline) infusion groups administered weekly for 6 (group B) and 8 weeks (group C). Recurrence rates were used as endpoints for this study. Also, a single variable and multivariable analysis in a T classification (Ta or T1), tumor multiplicity, tumor size (diameter) and presence or absence of concomitant carcinoma in situ was conducted. Results: In group A, one-year recurrence free survival was 59.1%, and three-year recurrence free survival was 45.2%. In group B, one-year recurrence free survival was 63.6%, and three-year recurrence free survival was 53%. In group C, one-year recurrence free survival was 81%, and three-year recurrence free survival was 72%. Conclusion: This study showed that there may be an increased advantage from adjuvant treatment therapy consisting of 8 weekly intravesical administrations of BCG following TUR-Bt for patients suffering from grade 3 non-muscle invasive bladder cancer. © 2011 S. Karger AG, Basel.
  • Kanae Kudo; Tokuzo Arao; Kaoru Tanaka; Tomoyuki Nagai; Kazuyuki Furuta; Kazuko Sakai; Hiroyasu Kaneda; Kazuko Matsumoto; Daisuke Tamura; Keiichi Aomatsu; Marco A. De Velasco; Yoshihiko Fujita; Nagahiro Saijo; Masatoshi Kudo; Kazuto Nishio
    CLINICAL CANCER RESEARCH AMER ASSOC CANCER RESEARCH 17 (6) 1373 - 1381 1078-0432 2011/03 [Refereed]
     
    Purpose: BIBF 1120 is a potent, orally available triple angiokinase inhibitor that inhibits VEGF receptors (VEGFR) 1, 2, and 3, fibroblast growth factor receptors, and platelet-derived growth factor receptors. This study examined the antitumor effects of BIBF 1120 on hepatocellular carcinoma (HCC) and attempted to identify a pharmacodynamic biomarker for use in early clinical trials. Experimental Design: We evaluated the antitumor and antiangiogenic effects of BIBF 1120 against HCC cell line both in vitro and in vivo. For the pharmacodynamic study, the phosphorylation levels of VEGFR2 in VEGF-stimulated peripheral blood leukocytes (PBL) were evaluated in mice inoculated with HCC cells and treated with BIBF 1120. Results: BIBF 1120 (0.01 mu mol/L) clearly inhibited the VEGFR2 signaling in vitro. The direct growth inhibitory effects of BIBF 1120 on four HCC cell lines were relatively mild in vitro (IC50 values: 2-5 mu mol/L); however, the oral administration of BIBF 1120 (50 or 100 mg/kg/d) significantly inhibited the tumor growth and angiogenesis in a HepG2 xenograft model. A flow cytometric analysis revealed that BIBF 1120 significantly decreased the phosphotyrosine (pTyr) levels of VEGFR2(+)CD45(dim) PBLs and the percentage of VEGFR2(+)pTyr(+) PBLs in vivo; the latter parameter seemed to be a more feasible pharmacodynamic biomarker. Conclusions: We found that BIBF 1120 exhibited potent antitumor and antiangiogenic activity against HCC and identified VEGFR2(+)pTyr(+) PBLs as a feasible and noninvasive pharmacodynamic biomarker in vivo. Clin Cancer Res; 17(6); 1373-81. (C)2010 AACR.
  • Taiji Hayashi; Marco Antonio De Velasco; Yoshitaka Saitou; Kazuhiro Nose; Tsukasa Nishioka; Tokumi Ishii; Hirotsugu Uemura
    International journal of urology : official journal of the Japanese Urological Association 17 (12) 989 - 95 2010/12 [Refereed]
     
    OBJECTIVES: Renal ischemia-reperfusion injury (IRI), leading to acute kidney injury, is a frequent complication with renal transplantation and it is associated with graft function. Its pathogenesis involves ischemia, vascular congestion and reactive oxygen metabolites. Carvedilol is an antihypertensive drug with potent anti-oxidant properties. In this study we investigated the protective effects of carvedilol in a rat renal IRI model. METHODS: Twenty-four rats were randomized into sham, untreated control and carvedilol (2 mg/kg 30 min before surgery and 12 hr after reperfusion) treatment groups and were subjected to 60 min of left renal ischemia followed by reperfusion at 24, 48, 96 and 168 hr. RESULTS: Treatment with carvedilol significantly decreased plasma creatinine levels after IRI (up to 168 hr) compared to controls (P < 0.001), suggesting an improvement in renal function. Histopathological analysis revealed decreased IRI-induced damage in kidneys from carvedilol-treated rats. A significant increase in the expression levels of Cu/Zn superoxide dismutase and reduction of 8-hydroxydeoxyguanosine and apoptosis levels (P < 0.005) suggested a protective effect after treatment with carvedilol. CONCLUSIONS: Our findings suggest that carvedilol ameliorates IRI resulting in improved renal function.
  • 大腸がん高発現遺伝子FOXQ1の機能解析(FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth)
    金田 裕靖; 荒尾 徳三; 松本 和子; 田中 薫; 田村 大介; 青松 圭一; デベラスコ・マルコ; 山田 康秀; 西條 長宏; 鶴谷 純司; 岡本 勇; 中川 和彦; 西尾 和人
    日本癌学会総会記事 日本癌学会 69回 314 - 315 0546-0476 2010/08 [Refereed]
  • がんの予防・化学予防 前立腺癌に対する酢酸クロルマジノンの術前化学予防効果(Cancer prevention and chemoprevention Pre-clinical chemopreventive efficacy of chlormadinone acetate against prostate cancer)
    Koike Hiroyuki; De Velasco Marco A.; Shimada Keiji; Yoshikawa Kazuhiro; Arao Tokuzu; Nishio Kazuto; Konishi Noboru; Uemura Hirotsugu
    日本癌学会総会記事 日本癌学会 69回 234 - 234 0546-0476 2010/08 [Refereed]
  • ドラッグデリバリーシステム、その他 前臨床マウスモデル系における前立腺癌に対するeverolimusと酢酸クロルマジノンの抗腫瘍作用(Drug delivery system, others Anti-tumor effects of everolimus and chlormadinone acetate against prostate cancer in a pre-clinical mouse model)
    De Velasco Marco A.; Koike Hiroyuki; Shimada Keiji; Yoshikawa Kazuhiro; Konishi Noboru; Arao Tokuzu; Nishio Kazuto; Uemura Hirotsugu
    日本癌学会総会記事 日本癌学会 69回 424 - 424 0546-0476 2010/08 [Refereed]
  • 膀胱癌におけるシクロオキシゲナーゼ2依存、非依存性シグナルの分子病理学的意義(Cyclooxygenase 2-dependent and independent casein kinase2/Akt signal contributes to human bladder cancer progression)
    浅井 修; 島田 啓司; 平尾 和也; De Velasco Marco A; 小西 登
    日本癌学会総会記事 日本癌学会 69回 470 - 470 0546-0476 2010/08 [Refereed]
  • Hiroyasu Kaneda; Tokuzo Arao; Kaoru Tanaka; Daisuke Tamura; Keiichi Aomatsu; Kanae Kudo; Kazuko Sakai; Marco Antonio De Velasco; Kazuko Matsumoto; Fujita Yoshihiko; Yasuhide Yamada; Junji Tsurutani; Isamu Okamoto; Kazuhiko Nakagawa; Kazuto Nishio; Tomoyuki Nagai; Kazuyuki Furuta
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 70 0008-5472 2010/04 [Refereed]
  • Hirotsugu Uemura; Kiyohide Fujimoto; Takashi Mine; Shigeya Uejima; Marco A de Velasco; Yoshihiko Hirao; Nobukazu Komatsu; Akira Yamada; Kyogo Itoh
    Cancer science 101 (3) 601 - 8 2010/03 [Refereed]
     
    We previously reported that personalized peptide vaccine (PPV) therapy in combination with leutenizing hormone-releasing hormone (LH-RH) analog and estramustine phosphate in certain cases is safe and capable of inducing both immune responses and clinical responses for metastatic castration-resistant prostate cancer (CRPC) patients. In the present study, PPV monotherapy was given to CRPC patients. Twenty-three patients with metastatic CRPC were treated with PPV without any additional treatment modalities, including LH-RH analogs. Samples were analyzed for peptide-specific cytotoxic T-lymphocyte (CTL) precursor analysis and peptide-reactive IgG. Toxicity and immunological and clinical responses were assessed on a three-monthly basis. Seventeen patients were available for immunological and clinical evaluation. The vaccines were well tolerated, with grade 3 erythema at injection sites in only one patient. Augmentation of CTL or IgG responses to at least one of the peptides was observed in six of 17 (35%) and 15 of 17 (88%) patients tested, respectively. Among 57 peptides used, 9 and 36 peptides induced CTL and IgG responses, respectively. Delayed-type hypersensitivity reaction was observed in eight of 17 patients. More than 30% prostate-specific antigen (PSA) decline was observed in four of 17 patients. Of these, one patient achieved a complete PSA response and another patient showed a partial PSA response with profound shrinking of lymph node metastases and prostate. The overall median survival time was 24 months (range, 5-37 months). These results suggest that PPV monotherapy appears to be safe and capable of inducing peptide-specific immune responses and clinical responses in CRPC patients. This trial was registered with University Hospital Medical Information Network (UMIN) number R000003339.
  • Hiroyasu Kaneda; Tokuzo Arao; Kaoru Tanaka; Daisuke Tamura; Keiichi Aomatsu; Kanae Kudo; Kazuko Sakai; Marco A. De Velasco; Kazuko Matsumoto; Yoshihiko Fujita; Yasuhide Yamada; Junji Tsurutani; Isamu Okamoto; Kazuhiko Nakagawa; Kazuto Nishio
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 70 (5) 2053 - 2063 0008-5472 2010/03 [Refereed]
     
    Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family, and it has recently been proposed to participate in gastric acid secretion and mucin gene expression in mice. However, the role of FOXQ1 in humans and especially in cancer cells remains unknown. We found that FOXQ1 mRNA is overexpressed in clinical specimens of colorectal cancer (CRC; 28-fold/colonic mucosa). A microarray analysis revealed that the knockdown of FOXQ1 using small interfering RNA resulted in a decrease in p21(CIP1/WAF1) expression, and a reporter assay and a chromatin immunoprecipitation assay showed that p21 was one of the target genes of FOXQ1. Stable FOXQ1-overexpressing cells (H1299/FOXQ1) exhibited elevated levels of p21 expression and inhibition of apoptosis induced by doxorubicin or camptothecin. Although cellular proliferation was decreased in H1299/FOXQ1 cells in vitro, H1299/FOXQ1 cells significantly increased tumorigenicity [ enhanced green fluorescent protein (EGFP): 2/15, FOXQ1: 7/15] and enhanced tumor growth (437 +/- 301 versus 1735 +/- 769 mm(3), P < 0.001) in vivo. Meanwhile, stable p21 knockdown of H1299/FOXQ1 cells increased tumor growth, suggesting that FOXQ1 promotes tumor growth independent of p21. Microarray analysis of H1299/EGFP and H1299/FOXQ1 revealed that FOXQ1 overexpression upregulated several genes that have positive roles for tumor growth, including VEGFA, WNT3A, RSPO2, and BCL11A. CD31 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining of the tumor specimens showed that FOXQ1 overexpression mediated the angiogenic and antiapoptotic effect in vivo. In conclusion, FOXQ1 is overexpressed in CRC and enhances tumorigenicity and tumor growth presumably through its angiogenic and antiapoptotic effects. Our findings show that FOXQ1 is a new member of the cancer-related FOX family. Cancer Res; 70(5); 2053-63. (C) 2010 AACR.
  • Keiji Shimada; Mitsutoshi Nakamura; Marco A. De Velasco; Motoyoshi Tanaka; Yukiteru Ouji; Makito Miyake; Kiyohide Fujimoto; Kazuya Hirao; Noboru Konishi
    CANCER SCIENCE WILEY-BLACKWELL PUBLISHING, INC 101 (1) 155 - 160 1347-9032 2010/01 [Refereed]
     
    Heparan sulfate proteoglycan syndecan-1, CD138, is well known to be associated with cell proliferation, adhesion, and migration in various types of malignancies. In the present study, we focused on the role of syndecan-1 in human urothelial carcinoma of the urinary bladder. Silencing of syndecan-1 by siRNA transfection down-regulated transcriptional factor junB and the long isoform of FLICE-inhibitory protein (FLIP long), resulting in the induction of apoptosis in the urothelial carcinoma cell lines UMUC2 and UMUC3. Knockdown of junB and FLIP long as well as syndecan-1 silencing mediated apoptosis that was inhibited by pan-caspase inhibitors. Transurethral injection of syndecan-1 siRNA into the urinary bladder significantly reduced syndecan-1 gene expression and growth of red fluorescent-labeled KU-7/RFP bladder cancer cells in the mouse orthotopic bladder cancer model. Immunohistochemical examination showed high syndecan-1 protein expression in high-grade, superficial, and deep invasive carcinomas (pT1 and >= pT2) as well as carcinoma in situ, but not in low-grade and noninvasive phenotypes (pTa). In addition, the percentage of cancer cells positive for syndecan-1 at initial diagnosis was statistically associated with the frequency of bladder cancer recurrence after transurethral resection. In conclusion, syndecan-1 might contribute to urothelial carcinoma cell survival and progression; therefore, this molecule could be a new therapeutic target in human urinary bladder cancer. (Cancer Sci 2009).
  • 個別化治療マウスモデルにおける抗腫瘍薬の薬効測定におけるヒト腫瘍移植片の利用(Use of human tumor explants for the determination of anti-tumor drug efficacy in a personalized medicine mouse model)
    Yoshimura Kazuhiro; De Velasco Marco A.; Tanaka Motoyoshi; Nishio Kazuto; Uemura Hirotsugu
    日本癌学会総会記事 日本癌学会 68回 188 - 188 0546-0476 2009/08 [Refereed]
  • syndecan-1(CD138)を介した膀胱癌の新規進展メカニズムの解析(The role of syndecan-1 (CD138) in progression of human urinary bladder cancer)
    島田 啓司; 中村 光利; De Velasco Marco A.; 田中 基幹; 小西 登
    日本癌学会総会記事 日本癌学会 68回 227 - 227 0546-0476 2009/08 [Refereed]
  • 遺伝子改変マウスにおける近赤外蛍光画像による腫瘍量の測定(Use of near infrared fluorescence imaging to determine tumor burden in genetically engineered mice)
    Uemura Hirotsugu; Yoshikawa Kazuhiro; Tanaka Motoyoshi; Nishio Kazuto; De Velasco Marco A.
    日本癌学会総会記事 日本癌学会 68回 457 - 457 0546-0476 2009/08 [Refereed]
  • Keiji Shimada; Mitsutoshi Nakamura; Marco A. De Velasco; Motoyoshi Tanaka; Yukiteru Ouji; Noboru Konishi
    CANCER SCIENCE WILEY-BLACKWELL PUBLISHING, INC 100 (7) 1248 - 1254 1347-9032 2009/07 [Refereed]
     
    Heparan sulfate proteoglycan syndecan-1 (CD138) is well known to be associated with cell proliferation, adhesion and migration in various types of malignancies. In the present study, we focused on the role of syndecan-1 in human prostate cancer. Immunohistochemical analysis revealed either no or rare expression of syndecan-1 in normal secretory glands and prostate cancer cells at hormone naive status, whereas the expression was significantly increased in viable cancer cells following neo-adjuvant hormonal therapy. Syndecan-1 expression was much higher in the androgen independent prostate cancer cell lines DU145 and PC3, rather than the androgen-dependent LNCaP, but the level in LNCaP was up-regulated in response to long-term culture under androgen deprivation. Silencing of syndecan-1 by siRNA transfection reduced endogenous production of reactive oxygen species through down-regulating NADPH oxidase 2 and induced apoptosis in DU145 and PC3 cells. Consistently, NADPH oxidase 2 knockdown induced apoptosis to a similar extent. Subcutaneous inoculation of PC3 cells in nude mice demonstrated the reduction of tumor size by localized injection of syndecan-1 siRNA in the presence of atelocollagen. Moreover, the mouse model and chorioallantoic membrane assay demonstrated significant inhibition of vascular endothelial growth factor and tumor angiogenesis by silencing of syndecan-1. In conclusion, syndecan-1 might participate in the process of androgen-dependent to -independent conversion, and be a new target molecule for hormone resistant prostate cancer therapy. (Cancer Sci 2009; 100: 1248-1254)
  • Yoshihiko Fujita; Kazuko Matsumoto; Kaoru Tanaka; Hiroyasu Kaneda; Kanae Kudo; Mari Maegawa; Daisuke Tamura; Keiichi Aomatsu; Marco DeVelasco; Tokuzo Arao; Kazuto Nishio
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 69 0008-5472 2009/05 [Refereed]
  • Keiji Shimada; Mitsutoshi Nakamura; Satoshi Anai; Marco De Velasco; Motoyoshi Tanaka; Kazutake Tsujikawa; Yukiteru Ouji; Noboru Konishi
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 69 (7) 3157 - 3164 0008-5472 2009/04 [Refereed]
     
    We recently identified a novel human AlkB homologue, ALKBH8, which is expressed in various types of human cancers including human urothelial carcinomas. In examining the role and function of ALKBH8 in human bladder cancer development in vitro, we found that silencing of ALKBH8 through small interfering RNA transfection reduced reactive oxygen species (ROS) production via down-regulation of NAD(P)H oxidase-1 (NOX-1) and induced apoptosis through subsequent activation of c-jun NH2-terminal kinase (JNK) and p38. However, we also found that JNK and p38 activation resulted in phosphorylation of H2AX (gamma H2AX), a variant of mammalian histone H2A, which contributes to the apoptosis induced by silencing ALKBH8 and NOX-1. Silencing of ALKBH8 significantly suppressed invasion, angiogenesis, and growth of bladder cancers in vivo as assessed both in the chorioallantoic membrane assay and in an orthotopic mouse model using green fluorescent protein-labeled KU7 human urothelial carcinoma cells. Immunohistochemical examination showed high expression of ALKBH8 and NOX-1 proteins in high-grade, superficially and deeply invasive carcinomas (pT(1) and >pT(2)) as well as in carcinoma in situ, but not in low-grade and noninvasive phenotypes (pT(a)). These findings indicate an essential role for ALKBH8 in urothelial carcinoma cell survival mediated by NOX-1-dependent ROS signals, further suggesting new therapeutic strategies in human bladder cancer by inducing JNK/p38/gamma H2AX-mediated cell death by silencing of ALKBH8. [Cancer Res 2009;69(7):3157-64]
  • Marcela A. Avila; Stacy L. Sell; Yuji Kadoi; Donald S. Prough; Helen L. Hellmich; Marco Velasco; Douglas S. Dewitt
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM NATURE PUBLISHING GROUP 28 (10) 1733 - 1741 0271-678X 2008/10 [Refereed]
     
    Peroxynitrite is a powerful oxidant capable of nitrating phenolic moieties, such as tyrosine or tyrosine residues in proteins and increases after traumatic brain injury (TBI). First, we tested the hypothesis that TBI increases nitrotyrosine (NT) immunoreactivity in the brain by measuring the number of NT-immunoreactive neurons in the cerebral cortex and hippocampus of rats subjected to parasagittal fluid-percussion TBI. Second, we tested the hypothesis that treatment with L-arginine, a substrate for nitric oxide synthase, further increases NT immunoreactivity over TBI alone. Rats were anesthetized with isoflurane and subjected to TBI, sham TBI, or TBI followed by treatment with L-arginine (100 mg/kg). Twelve, 24, or 72 h after TBI, brains were harvested. Coronal sections (10 mu m) were incubated overnight with rabbit polyclonal anti-NT antibody, rinsed, and incubated with a biotinylated secondary antibody. The antigen-antibody complex was visualized using a peroxidase-conjugated system with diaminobenzidine as the chromagen. The number of NT-positive cortical and hippocampal neurons increased significantly in both ipsilateral and contralateral hemispheres up to 72 h after TBI compared with the sham-injured group. Remarkably, treatment with L-arginine reduced the number of NT-positive neurons after TBI in both cortex and hippocampus. Our results indicate that L-arginine actually prevents TBI-induced increases in NT immunoreactivity.
  • Marco A De Velasco; Motoyoshi Tanaka; Satoshi Anai; Atsushi Tomioka; Kazuto Nishio; Hirotsugu Uemura
    Oncology reports 20 (3) 543 - 7 1021-335X 2008/09 [Refereed]
     
    Precise and objective measurements of tumor response have yet to be standardized in the mouse orthotopic bladder cancer model. In this study, we used image analysis and green fluorescent protein (GFP) to objectively measure tumor size in response to chemotherapy. KU-7 human bladder cancer cells transfected with GFP were intravesically inoculated into 8-week-old female nude mice. Fourteen days after tumor cell inoculation, the mice were assigned into a control (PBS) group or a doxorubicin (conc. 1.0 mg/ml) treatment group and received a single instillation of treatment. Fourteen days after treatment, the bladders were surgically exposed and fluorescent images were captured and later analyzed using image analysis. Bladders were processed for histological examination. Tumor incidence determined by GFP expression and histology was 100 and 80%, respectively, in the doxorubicin treatment group. A 9-fold (histology) vs. 12-fold (GFP expression) difference in tumor regression measured by tumor area (P<0.05) and a 5-fold (histology) vs. 9-fold (GFP expression) difference in tumor regression measured by the percent of tumor area in the bladder (P<0.001) were observed in the doxorubicin treatment group. Our findings suggest that using image analysis provides a precise, sensitive and objective means to measure tumor growth and treatment response in the mouse orthotopic bladder cancer model in lieu of histological methods. Consequently, the number of mice required in an experiment can be reduced since tissue samples are not needed for histology, thus making tissue samples readily available for additional assays in both a labor-effective and cost-effective manner.
  • Atsushi Tomioka; Motoyoshi Tanaka; Marco A De Velasco; Satoshi Anai; Satoshi Takada; Toshihiro Kushibiki; Yasuhiko Tabata; Charles J Rosser; Hirotsugu Uemura; Yoshihiko Hirao
    Molecular cancer therapeutics 7 (7) 1864 - 70 2008/07 [Refereed]
     
    The tumor suppressor gene MMAC/PTEN located on chromosome10q23.3 has dual phosphatase activity in the phosphoinositide-3-kinase signaling pathway and inhibits Akt activation, a serine-threonine kinase, which is involved in proliferative and antiapoptotic pathways. Furthermore, MMAC/PTEN is frequently inactivated in a variety of tumors including prostate cancer. In this study, we generated a new type of gene transfer drug, GelaTen, which is a microsphere of cationized gelatin hydrogels incorporating PTEN plasmid DNA. Using our previously reported radiation-resistant PC3-Bcl-2 human prostate cancer cells (PTEN deleted), we examined the efficacy of GelaTen to force the expression of PTEN in vivo to inhibit tumor growth after intratumoral injection alone or with irradiation. Combinational therapy with GelaTen and irradiation improved both the in vitro and in vivo efficacy of growth inhibition compared with GelaTen or irradiation alone. These data show that GelaTen gene therapy, enabling radiosensitization, can potentially treat prostate cancers that have MMAC/PTEN gene alterations associated with radioresistance.
  • Argun Akcakanat; Aysegul Sahin; Alexandra N. Shaye; Marco A. Velasco; Funda Meric-Bernstam
    CANCER JOHN WILEY & SONS INC 112 (11) 2352 - 2358 0008-543X 2008/06 [Refereed]
     
    BACKGROUND. The Akt/mammalian target of the rapamycin (mTOR) signaling pathway represents a promising target for cancer therapy. The phosphorylation status of Akt and of mTOR's phosphorylation target eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) is often used to assess the activity of Akt and mTOR signaling. The purpose of this study was to determine whether primary tumors differ from their metastasis in their expression of pAkt and p4E-BP1. METHODS. Primary breast tumors and their distant metastases surgically resected from the same patients were evaluated with immunohistochemical analysis (IHC) for pAkt (Ser473) and p4E-BP1 (Ser65). The agreement between the IHC results for the primary tumor and metastases was evaluated with Cohen kappa (kappa) RESULTS. Most primary breast tumors and metastatic tumors expressed pAkt (76% of each). Of the 23 matched evaluable pairs, however, 11 (47.8%) had discordant IHC results (kappa -0.31; 95% confidence interval [CI], -0.49 to -0.13). Similarly, although most of the primary and metastatic tumors were positive for p4E-BP1 (75% and 74%), of the 23 matched evaluable pairs, 8 (47.8%) were discordant (kappa 0.10; 95% CI, -0.33-0.52). CONCLUSIONS. in this series, most primary breast tumors and metastases expressed pAkt and p4E-BP1 by IHC. Concordance between IHC findings in primary tumors and metastases was poor, however. Further work is needed to determine whether this reflects true biological heterogeneity or poor reproducibility of IHC with phosphospecific antibodies, and to identify which biornarkers can be assessed most reproducibly in primary tumors to predict activity of Akt/mTOR signaling and sensitivity to pathway inhibitors.
  • Hirotsugu Uemura; Marco A De Velasco
    World journal of urology 26 (2) 147 - 54 2008/04 [Refereed][Invited]
     
    INTRODUCTION: Although most vaccines target foreign infectious agents, therapeutic cancer vaccines target both well-established and metastatic tumor cells expressing tumor antigens. Active immunotherapy is intended to enhance or activate the immunosurveillance of an individual through a therapeutic vaccine. Renal cell carcinoma (RCC) is one of the most immunoresponsive cancers in humans, which in turn makes it an ideal candidate for immune based therapies. METHOD: Several types of therapeutic vaccines have been tested and applied in the clinical setting and can be divided into cell-based vaccines including direct application of inactivated autologous tumor cells, gene modified tumor cell-based, dendritic cell-based (expressing RCC derived tumor antigens), and non-cell-based vaccines. This review will examine the current status of cell-based vaccine immunotherapy and focuses on non-cell-based vaccine strategies. CONCLUSION: Recent advances in molecular targeting therapy have introduced a battery receptor tyrosine kinase (RTK) and mTOR inhibitors that provide promising treatment options, however, the tolerability of tumor vaccines and the success of clinical effectiveness in selected populations combined with recent advances in cellular therapies warrant the continued exploration of novel methods of tumor vaccine therapies in the clinical setting.
  • Tomioka Atsushi; Tanaka Motoyoshi; Anai Satoshi; Ikeda Tomohiro; Shimada Keiji; Velasco Marco; Saito Keigo; Hirao Yoshihiko; Uemura Hirotsugu
    日本泌尿器科学会雑誌 (一社)日本泌尿器科学会 99 (2) 149 - 149 0021-5287 2008/02 [Refereed]
  • 混合PEG修飾Doxorubicin含有リポソームの有用性とヒト膀胱腫瘍への適用
    杉山 育美; 神山 晋太郎; De Velasco Marco; 穴井 智; 富岡 厚志; 田中 基幹; 佐塚 泰之
    Drug Delivery System 日本DDS学会 22 (3) 327 - 327 0913-5006 2007/05 [Refereed]
  • Satoshi Anai; Atsushi Tomioka; Yoshihiko Hirao; Ikumi Sugiyama; Yasuyuki Sadzuka; Motoyoshi Tanaka; Marco DeVelasco; Hirotsugu Uemura
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 177 (4) 293 - 293 0022-5347 2007/04 [Refereed]
  • MJ Wargovich; P Chang; M Velasco; F Sinicrope; E Eisenbrodt; J Sellin
    APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LIPPINCOTT WILLIAMS & WILKINS 12 (4) 350 - 355 1062-3345 2004/12 [Refereed]
     
    Aberrant crypt foci (ACFs) may be the earliest recognizable histologic precursor lesion for colon cancer. ACF may develop from a complex of events, including the development of cryptal hyperproliferation, defects in the rate of apoptosis, and abnormalities in cellular adhesion. In this study, we hypothesized that human ACF would exhibit discrete differences in cell adhesion proteins compared with normal mucosa of biologic markers associated with colon cancer. ACFs were isolated from resected colon mucosa from 45 patients undergoing surgery for colon cancer. We evaluated the protein expression of 3 biologic markers that may be related to the progression of aberrant crypt foci to tumors: care inoembryonic antigen, E-cadherin, and sialyl Tn antigen. In general, ACFs located near cancers in the right colon were more often hyperplastic than dysplastic; this was more noticeable in the left colon. Carcinoembryonic antigen expression was found to be more intense in apical portions of ACF crypts, with sialyl Tn antigen moderately increased, whereas E-cadherin diffusely stained throughout crypts within ACFs. There are significant biologic changes in potential tumor markers that accompany the early transformation of the normal glandular epithelium, some of which are expressed very early in the colon at the stage of appearance of ACF.
  • LL Chen; JC Trent; EF Wu; GN Fuller; L Ramdas; W Zhang; AK Raymond; VG Prieto; CO Oyedeji; KK Hunt; RE Pollock; BW Feig; KJ Hayes; H Choi; HA Macapinlac; W Hittelman; MA Velasco; S Patel; MA Burgess; RS Benjamin; ML Frazier
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 64 (17) 5913 - 5919 0008-5472 2004/09 [Refereed]
     
    KIT gain of function mutations play an important role in the pathogenesis of gastrointestinal stromal tumors (GISTs). Imatinib is a selective tyrosine kinase inhibitor of ABL, platelet-derived growth factor receptor (PDGFR), and KIT and represents a new paradigm of targeted therapy against GISTs. Here we report for the first time that, after imatinib treatment, an additional specific and novel KIT mutation occurs in GISTs as they develop resistance to the drug. We studied 12 GIST patients with initial near-complete response to imatinib. Seven harbored mutations in KIT exon 11, and 5 harbored mutations in exon 9. Within 31 months, six imatinib-resistant rapidly progressive peritoneal implants (metastatic foci) developed in five patients. Quiescent residual GISTs persisted in seven patients. All six rapidly progressive imatinib-resistant implants from five patients show an identical novel KIT missense mutation, 1982T --> C, that resulted in Val654Ala in KIT tyrosine kinase domain 1. This novel mutation has never been reported before, is not present in pre-imatinib or post-imatinib residual quiescent GISTs, and is strongly correlated with imatinib resistance. Allelic-specific sequencing data show that this new mutation occurs in the allele that harbors original activation mutation of KIT.
  • S Cobb; T Wood; J Ceci; A Varro; M Velasco; P Singh
    CANCER JOHN WILEY & SONS INC 100 (6) 1311 - 1323 0008-543X 2004/03 [Refereed]
     
    BACKGROUND. The authors recently reported that transgenic mice (h GAS) expressing pharmacologic levels of progastrin (PG) (> 10 nM to 100 nM) exhibited increased susceptibility to colon carcinogenesis in response to azoxymethane (AOM). It is not known whether PG functions as a cocarcinogen at the concentrations observed in patients with hypergastrinemia (similar to1.0 nM). METHODS, The authors generated transgenic mice that overexpressed either wildtype (wtPG) or mutant (mtPG) human PG in the intestinal mucosa using the murine fatty acid binding protein (Fabp) promoter. Fabp-PG mice and their wildtype littermates were treated with AOM, and their colons were examined for preneoplastic (aberrant crypt foci [ACF]) and neoplastic (adenomas [Ads] and adenocarcinomas [AdCas]) lesions after 2 weeks and 6 months of treatment. RESULTS. ACF and tumors were significantly more common (by a factor of similar to2) in colon specimens from both Fabp-wtPG mice and Fabp-mtPG mice relative to wild-type mice. It is noteworthy that the multiplicity of ACF and the total number of small and large Ads and AdCas were significantly greater in colon specimens from Fabp-PG mice compared with colon specimens from wild-type mice, irrespective of gender. CONCLUSIONS. The results of the current study suggest that at concentrations (similar to1.0 nM) far lower than the ones observed in hGAS mice, PG functions as an equally potent cocarcinogen and significantly increases the risk of colon carcinogenesis in response to AOM. Thus, PG may represent a clinically relevant target molecule in patients with hypergastrinemia or colon carcinoma. (C) 2004 American Cancer Society.
  • HL Hellmich; CJ Frederickson; DS DeWitt; R Saban; MO Parsley; R Stephenson; M Velasco; T Uchida; M Shimamura; DS Prough
    NEUROSCIENCE LETTERS ELSEVIER SCI IRELAND LTD 355 (3) 221 - 225 0304-3940 2004/01 [Refereed]
     
    Chelation of excessive neuronal zinc ameliorates zinc neurotoxicity and reduces subsequent neuronal injury. To clarify the molecular mechanisms of this neuroprotective effect, we used a focused cDNA array of stress-response genes with zinc chelation (calcium EDTA) in our rat model of fluid percussion brain injury at 2 h, 24 h, and 7 days after injury. In parallel experiments, we compared neuronal cell death in TUNEL-stained brain sections in traumatized rats with and without calcium EDTA treatment. Zinc chelation induced the expression of several neuroprotective genes; neuroprotective gene expression correlated with substantially decreased numbers of TUNEL-positive cells. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
  • S Cobb; T Wood; L Tessarollo; M Velasco; R Given; A Varro; N Tarasova; P Singh
    GASTROENTEROLOGY W B SAUNDERS CO 123 (2) 516 - 530 0016-5085 2002/08 [Refereed]
     
    Background & Aims: We recently reported that transgenic mice overexpressing progastrin were at a higher risk for developing colon cancers in response to azoxymethane (AOM), whereas mice overexpressing gastrin-17 were at a reduced risk. To examine further the role of gastrins in colon carcinogenesis, we generated gastrin gene knockout mice (GAS-KO). Methods: The height and proliferative index (PI) of colonic crypts were similar in GAS-KO and wild-type (WT) mice, suggesting that the absence of gastrins in GAS-KO mice did not significantly affect the growth of colonic mucosa. GAS-KO and WT mice were treated with AOM for 3-4 weeks; control mice received saline. Results: Colonic proliferation in response to AOM was significantly increased in GAS-KO vs. WT mice. Aberrant crypt foci (ACFs) were similarly increased significantly by similar to2-5-fold in GAS-KO vs. WT mice after 2 weeks of AOM treatment. Female GAS-KO mice developed adenomas (Ads) and adenocarcinomas (AdCAs) at earlier times (similar to10 months) than the male GAS-KO mice and the male and female WT mice (similar to12 months). The total numbers of Ads and AdCAs were significantly higher in GAS-KO than in WT mice. Conclusions: These results suggest the novel possibility that loss of gastrin expression (and hence amidated gastrins) significantly increases susceptibility to colon carcinogenesis in response to AM Previous studies with FVB/N transgenic mice similarly suggested a protective role of amidated gastrins against colon carcinogenesis, which supports the present findings of an increase in colon carcinogenesis in GAS-KO mice lacking normal physiological levels of amidated gastrins.
  • Y Gokmen-Polar; NR Murray; MA Velasco; Z Gatalica; AP Fields
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 61 (4) 1375 - 1381 0008-5472 2001/02 [Refereed]
     
    Protein kinase C (PKC) has been implicated in colon carcinogenesis in humans and in rodent models. However, little is known about the specific role of individual PKC isozymes in this process. We recently demonstrated that elevated expression of PKC PII in the coIonic epithelium induces hyperproliferation in vivo (N. R, Murray ef at, J, Cell Biol,, 145: 699-711, 1999), Because hyperproliferation is a major risk factor for colon cancer, we assessed whether specific alterations in PKC pn expression occur during azoxymethane-induced colon carcinogenesis in mice. An increase in PKC PII expression was observed in preneoplastic lesions (aberrant crypt foci, 3.7-fold) compared with saline-treated animals, and in colon tumors (7.8-fold; P = 0.011) compared with uninvolved colonic epithelium, In contrast, PKC cu and PKC PI (a splicing variant of PKC PII) expression was slightly decreased in aberrant crypt foci and dramatically reduced in colon tumors. Quantitative reverse transcription-PCR analysis revealed that PRC mRNA levels do not directly correlate with PKC protein levels, indicating that PKC isozyme expression is likely regulated at the posttranstriptional/translational level. Finally, transgenic mice expressing elevated PKC PII in the colonic epithelium exhibit a trend toward increased colon tumor formation after exposure to azoxymethane. Taken together, our results demonstrate that elevated expression of PKC beta II is an important early, promotive event that plays a role in colon cancer development.
  • P Singh; M Velasco; R Given; A Varro; TC Wang
    GASTROENTEROLOGY W B SAUNDERS CO 119 (1) 162 - 171 0016-5085 2000/07 [Refereed]
     
    Background & Aims: Processing intermediates of preprogastrin (gly-gastrin and progastrin), termed nonamidated gastrins, are mitogenic for several cell types including colonic epithelial cells. However, presently it is not known if nonamidated gastrins play a role in colon carcinogenesis and if the effects are similar to those of amidated gastrins, Methods: Colon carcinogenesis in response to azoxymethane (AOM) was examined in transgenic mice overexpressing either progastrin (hGAS) or amidated gastrin (INS-GAS), compared with that in wild-type (WT) mice. Results: In AOM-treated groups, the total number of tumors per colon was significantly higher in hGAS (4.8 +/- 0.34) than INS-GAS (3.0 +/- 0.16) and WT (2.7 +/- 0.35) mice. Total numbers of adenocarcinomas and adenomas per animal colon were also significantly higher in hGAS than INS-GAS and WT mice. The size of the tumors was greater in hGAS mice, resulting in a significantly higher tumor burden per mouse in the hGAS mice than INS-GAS and WT mice. Although >90% of the tumors were located in the distal half of the colon in INS-GAS and WT mice, a significant number (42%) were present at the proximal end of the colon in hGAS mice. Conclusions: The results suggest that the risk for developing colon carcinomas and adenomas in response to AOM is significantly increased in mice expressing high levels of progastrin, but not amidated gastrins.
  • MJ Wargovich; A Jimenez; K McKee; VE Steele; M Velasco; J Woods; R Price; K Gray; GJ Kelloff
    CARCINOGENESIS OXFORD UNIV PRESS 21 (6) 1149 - 1155 0143-3334 2000/06 [Refereed]
     
    We assessed the effects of 78 potential chemopreventive agents in the F344 rat using two assays in which the inhibition of carcinogen-induced aberrant crypt foci (ACF) in the colon was the measure of efficacy. In both assays ACF were induced by the carcinogen azoxymethane (AOM) in F344 rats by two sequential weekly injections at a dose of 15 mg/kg. Two weeks after the last AOM injection, animals were evaluated for the number of aberrant crypts detected in methylene blue stained whole mounts of rat colon. In the initiation phase protocol agents were given during the period of AOM administration, whereas in the post-initiation assay the chemopreventive agent was introduced during the last 4 weeks of an 8 week assay, a time when ACF had progressed to multiple crypt clusters. The agents were derived from a priority listing based on reports of chemopreventive activity in the literature and/ or efficacy data from in vitro models of carcinogenesis. During the initiation phase carboxyl amidoimidazole, p-chlorphenylacetate, chlorpheniramine maleate, D609, diclofenac, etoperidone, eicosatetraynoic acid, farnesol, ferulic acid, lycopene, meclizine, methionine, phenylhexylisothiocyanate, phenylbutyrate, piroxicam, 9-cis-retinoic acid, S-allylcysteine, taurine, tetracycline and verapamil were strong inhibitors of ACF. During the post-initiation phase aspirin, calcium glucarate, ketoprofen, piroxicam, 9-cis-retinoic acid, retinol and rutin inhibited the outgrowth of ACF into multiple crypt clusters. Based on these data, certain phytochemicals, antihistamines, non-steroidal antiinflammatory drugs and retinoids show unique preclinical promise for chemoprevention of colon cancer, with the latter two drug classes particularly effective in the post-initiation phase of carcinogenesis.
  • M Purewal; M Velasco; AJ Fretland; DW Hein; MJ Wargovich
    CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION AMER ASSOC CANCER RESEARCH 9 (5) 529 - 532 1055-9965 2000/05 [Refereed]
     
    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine carcinogen in the human diet and is a colon carcinogen in the rat. N-Acetyltransferase-2 (NAT2) catalyzes the conversion of PhIP and other heterocyclic amines to a DNA-reactive form. NAT2 has a polymorphic distribution in humans and other mammals, including rats. The rapid NAT2 genotype has been shown to be associated with increased colorectal cancer risk in some, but not all, human epidemiological studies. This investigation was designed to study the role of acetylator genotype in PhIP-induced colon carcinogenesis using aberrant crypt foci (ACF) as an intermediate biomarker, Five-week-old male, rapid-acetylator Fischer 344 (F344) rats and slow-acetylator Wistar-Kyoto (WKY) rats were fed the semipurified AIN76A diet with 0.01% PhIP, 0.04% PhIP, or no PhIP (control) for 8 weeks. PhIP induced ACF in both rapid-and slow-acetylator rats; 0.04% PhIP induced more ACF than 0.01% PhIP, There was no difference in the number of ACF between rapid- and slow-acetylator rats that were fed 0.01% PhIP, However, 0.04% PhIP induced 2-fold higher ACF and a greater dose-dependent increase in PhIP-induced ACF in the rapid-acetylator F344 rats compared with the slow-acetylator WKY rats. The results support human epidemiological studies showing higher risk for colorectal cancer in rapid acetylators who frequently consume meat that is very well done.
  • P Singh; M Velasco; R Given; M Wargovich; A Varro; TC Wang
    AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY AMER PHYSIOLOGICAL SOC 278 (3) G390 - G399 0193-1857 2000/03 [Refereed]
     
    Recent studies show that nonamidated gastrins (Gly-gastrin and progastrin) stimulate colonic proliferation. However, the role of nonamidated vs. amidated gastrins in colon carcinogenesis has not been defined. We measured intermediate markers of carcinogenesis in transgenic mice overexpressing either progastrin (hGAS) or amidated gastrin (INS-GAS) in response to azoxymethane (AOM). The hGAS mice showed significantly higher numbers of aberrant crypt foci (140-200% increase) compared with that in wild-type (WT) and INS-GAS mice (P < 0.05) after AOM treatment. The bromode-oxyuridine-labeling index of colonic crypts also was significantly elevated in hGAS mice vs; that in WT and INS-GAS mice. The results therefore provide evidence for a mitogenic and cocarcinogenic role of nonamidated gastrins (progastrin), which is apparently not shared by the amidated gastrins. Although nonamidated gastrins are now believed to mediate mitogenic effects via novel receptors, amidated gastrins mediate biological effects via different receptor subtypes, which may explain the difference in the cocarcinogenic potential of nonamidated vs, amidated gastrins. In conclusion, our results provide strong support for a cocarcinogenic role for nonamidated gastrins in colon carcinogenesis.
  • MJ Wargovich; N Uda; C Woods; M Velasco; K McKee
    BIOCHEMICAL SOCIETY TRANSACTIONS PORTLAND PRESS 24 (3) 811 - 814 0300-5127 1996/08 [Refereed]
  • MJ Wargovich; CD Chen; A Jimenez; VE Steele; M Velasco; LC Stephens; R Price; K Gray; GJ Kelloff
    CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION AMER ASSOC CANCER RESEARCH 5 (5) 355 - 360 1055-9965 1996/05 [Refereed]
     
    We assessed the effects of 41 potential chemopreventive agents in the F344 rat using the inhibition of carcinogen-induced aberrant crypt foci (ACF) in the colon as the measure of efficacy. ACF were induced by the carcinogen azoxymethane in F344 rats by two sequential weekly injections at a dose of 15 mg/kg. Two weeks after the last azoxymethane injection, animals were evaluated for the number of aberrant crypts detected in methylene blue-stained whole mounts of rat colon. The 41 agents were derived from a priority listing that was based on reports of chemopreventive activity in the literature and/or efficacy data from in vitro models of carcinogenesis. The list of agents included representative examples of phytochemicals, vitamins, minerals, inhibitors of proliferation, inducers of Phase 1 and Phase 2 metabolism systems, nonsteroidal anti-inflammatory agents, and differentiation agents. Eighteen agents were positive in the assay, significantly reducing the incidence of ACF at least in one of two doses tested. As a chemical class, the nonsteroidal anti-inflammatory drugs, which included ibuprofen, ketoprofen, piroxicam, and indomethacin, were most active; other less potent agents were arginine, butylated hydroxyanisole, curcumin, diallyl sulfide, difluoromethylornithine, 18 beta-glycyrrhetinic acid, indole-3-carbinol, oltipraz, purpurin, rutin, and the sodium salts of butyrate, selenite, and thiosulfate. Twenty-three agents did not inhibit ACF; included among these were several agents that promoted the development of ACF at one or both doses tested: benzyl isothiocyanate, calcium glucarate, catechin, dihydroepiandosterone, fluocinolone acetonide, folic acid, levamisole, 2-mercaptoethanesulfonic acid, nordihydroguiaretic acid, potassium glucarate, propyl gallate, beta-sitosterol, sodium cromolyn, sodium molybdate, and sulfasalazine. The aberrant crypt assay demonstrates reasonable specificity and sensitivity in predicting which agents are likely to prevent colon cancer.
  • MJ WARGOVICH; CD CHEN; C HARRIS; E YANG; M VELASCO
    INTERNATIONAL JOURNAL OF CANCER WILEY-LISS 60 (4) 515 - 519 0020-7136 1995/02 [Refereed]
     
    Aberrant crypts are aggregates of single to multiple colonic crypts evidencing hallmarks of dysplasia and may be the earliest detectable pathological lesions for colon cancer. The aberrant crypt assay has been developed in 2 protocols. In one, putative chemoprevention agents are tested for inhibitory effects when administered concomitantly with a carcinogen. In the other, the objective of this study, aberrant crypts were induced in F344 rats by parenteral injection of the colon carcinogen azoxymethane (AOM) and allowed to develop for 4 weeks, when an average of 90-100 aberrant crypt foci per colon were found in the methylene blue-stained colon. Then, during the second 4 weeks of the experiment, aberrant crypts were allowed to further develop to a frequency of > 150 foci per colon, a time when multi-crypt foci were observed. During this time we tested the inhibitory effects of 4 analgesic drugs and 2 differentiation agents for effects of aberrant crypt growth and development. We found the non-steroidal anti-inflammatory drugs piroxicam, aspirin and ibuprofen, but not acetaminophen, to be effective in suppressing aberrant crypt formation or the progression to foci of multiple aberrant crypts. Treatment with chemo-suppressing agents 13-cis-retinoic acid (13-cRA) and 4-hydroxy-phenretinamide (4-HPR), known differentiating agents, however, did suppress expansion of aberrant crypt foci, with 13-cRA being the much more potent agent. (C) 1995 Wiley-Liss, Inc.
  • SE BENNER; SM LIPPMAN; MJ WARGOVICH; JJ LEE; M VELASCO; JW MARTIN; BB TOTH; WK HONG
    INTERNATIONAL JOURNAL OF CANCER WILEY-LISS 59 (4) 457 - 459 0020-7136 1994/11 [Refereed]
     
    Biomarkers are being sought that could serve as surrogate end points for chemoprevention trials. Micronuclei, cytoplasmic fragments of DNA, have been proposed as a biomarker and studied in oral pre-malignancy. This study evaluated micronuclei frequency in a randomized chemoprevention trial of oral pre-malignancy. A recent clinical trial evaluated the responses of pre-malignant oral lesions to 3 months of therapy with isotretinoin followed by 9 months of either low-dose isotretinoin or beta-carotene. For 57 study participants, micronuclei were counted in mucosal scrapings of the lesion and in normal-appearing mucosa at baseline and following 3 months and 12 months of therapy. Micronuclei counts were higher in scrapings from the lesion than in the normal-appearing mucosa. Following 3 months of isotretinoin, the micronuclei counts in scrapings of the lesion were significantly reduced. With treatment, the mean micronuclei count declined at 3 months. In a randomized comparison, both isotretinoin and beta-carotene maintained the suppression of micronuclei. The change in micronuclei count was not associated with the clinical or histological response to treatment. Chemoprevention treatment with isotretinoin led to a reduction in frequency of micronuclei, a marker of recent DNA injury, which was then maintained by both isotretinoin and beta-carotene. (C) 1994 Wiley-Liss, Inc.
  • SE BENNER; ML WARGOVICH; SM LIPPMAN; R FISHER; M VELASCO; RJ WINN; WK HONG
    CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION AMER ASSOC CANCER RESEARCH 3 (1) 73 - 76 1055-9965 1994/01 [Refereed]
     
    Micronuclei frequency, a marker of genotoxicity, was studied within a trial of alpha-tocopherol for chemoprevention of oral leukoplakia. Oral swabs were obtained from two sites, the leukoplakia lesion and normal-appearing mucosa, at baseline and following 24 weeks of therapy with 400 international units of alpha-tocopherol twice daily. These specimens were analyzed for micronuclei frequency. The major risk factors for oral carcinogenesis in the group studied were cigarette smoking and alcohol consumption. alpha-tocopherol therapy produced a significant reduction in micronuclei frequencies in specimens from both the visible lesions (P < 0.01) and the normal-appearing mucosa (P < 0.01). The micronuclei frequencies, both at baseline and following therapy, were greater in specimens taken from the lesion than in those from the normal-appearing mucosa. Although these results indicate that alpha-tocopherol has a beneficial effect in oral carcinogenesis, there was no significant clinical or histological response associated with the change in micronuclei frequency. Micronuclei frequency has not yet been validated as a biomarker for cancer incidence, and consequently, its utility as an intermediate end point for chemoprevention trials is not known. Determining clinical significance of micronuclei frequency patterns in oral carcinogenesis and chemoprevention will require further study.
  • SE BENNER; SM LIPPMAN; MJ WARGOVICH; M VELASCO; EJ PETERS; RC MORICE; WK HONG
    INTERNATIONAL JOURNAL OF CANCER WILEY-LISS 52 (1) 44 - 47 0020-7136 1992/08 [Refereed]
     
    Bronchial micronuclei, small fragments of extra-nuclear DNA formed during cell division, provide a non-specific but quantifiable marker of DNA damage. Micronuclei have been used to assess carcinogen exposure and as an intermediate endpoint in chemoprevention trials. As part of an ongoing chemoprevention trial, heavy smokers underwent screening bronchoscopy, with biopsies taken at 6 standardized sites. Micronuclei counts were obtained for each site in each of the 40 volunteers found to have squamous metaplasia. Unlike squamous metaplasia, the average micronuclei counts among these heavy smokers were not associated with smoking history. Micronuclei counts were also not associated with the presence or extent of metaplasia. A striking degree of intra-individual variability was observed by comparing the micronuclei counts from different biopsy sites within individuals. The findings suggest that use of micronuclei from single sites may be misleading as a marker of carcinogen exposure or as an estimate of cancer risk. Serial measurements in individuals may provide the most useful information concerning carcinogenic exposure and the impact of chemopreventive agents.

MISC

  • ヒトおよびマウスの前立腺癌腸内細菌叢の包括的解析について(Integrative gut microbiome analysis of human and mouse prostate cancer)
    若森 千怜; デベラスコ・マルコ; 倉 由吏恵; 藤田 和利; 坂井 和子; 松下 慎; 森 康範; 野澤 昌弘; 西本 光寿; 吉村 一宏; 野々村 祝夫; 西尾 和人; 植村 天受  日本癌学会総会記事  82回-  71  -71  2023/09
  • 前立腺癌マウスにおける腫瘍浸潤ミエロイド細胞について(Targeting tumor immunosuppressive myeloid cells in mouse Pten-null prostate cancer)
    植村 天受; 倉 由吏恵; 藤田 和利; 坂井 和子; シュラー・アルウイン; サッハセンマイヤー・クリス; 野澤 昌弘; 吉村 一宏; 西尾 和人; デベラスコ・マルコ  日本癌学会総会記事  82回-  408  -408  2023/09
  • 前臨床癌マウスモデルにおけるPD-L1に対する抗薬物抗体の制御について(Preclinical model to counter antidrug antibodies to programmed cell death-1 blockade)
    デベラスコ・マルコ; 倉 由吏恵; 藤田 和利; 西本 光寿; 坂井 和子; 吉村 一宏; 野澤 昌弘; ハモンド・スコット; ドベディ・シモン; デービス・バリー; 西尾 和人; 植村 天受  日本癌学会総会記事  82回-  1019  -1019  2023/09
  • 前立腺癌Ptenノックアウトマウスを用いたCD73とA2aR阻害の効果について(Efficacy of combined CD73 and A2aR blockade in mouse Pten-deficient prostate cancer)
    デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 藤田 和利; 橋本 士; 坂野 恵里; 西本 光寿; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受  日本泌尿器科学会総会  110回-  OP76  -02  2023/04
  • アンドロゲン受容体シグナル阻害を標的とした分子および免疫応答を評価可能とする前臨床前立腺癌マウスモデルの活用について(Use of a preclinical prostate cancer model to assess molecular and immune responses to androgen receptor signaling axis blockade)
    植村 天受; 倉 由吏恵; 藤田 和利; 坂井 和子; 橋本 士; 西本 光寿; 吉村 一宏; 野澤 昌弘; 西尾 和人; デベラスコ・マルコ  日本泌尿器科学会総会  110回-  OP76  -03  2023/04
  • アンドロゲン除去療法とJAK1/2およびPD-L1阻害による前立腺特異的Ptenノックアウトマウスモデルにおける抗腫瘍効果の改善について
    倉 由吏恵; 西本 光寿; 清水 信貴; 南 高文; 坂井 和子; 藤田 和利; 野澤 昌弘; 吉村 一宏; デベラスコ・マルコ; 西尾 和人; 植村 天受  日本泌尿器科学会総会  109回-  OP71  -01  2021/12
  • A2aRの阻害はPten欠損前立腺癌マウスにおいてCTLA4抗体の抗腫瘍活性を高める
    デベラスコ・マルコ; 倉 由吏恵; 西本 光寿; 坂井 和子; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受  日本泌尿器科学会総会  109回-  OP71  -02  2021/12
  • 前立腺特異的Ptenノックアウトマウスにおけるアパルタミドの短期免疫反応について
    植村 天受; 倉 由吏恵; 西本 光寿; 南 高文; 坂井 和子; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; デベラスコ・マルコ  日本泌尿器科学会総会  109回-  OP71  -03  2021/12
  • マウスPTEN欠失前立腺癌に対するJAK1/2標的療法が腸内細菌叢に与える影響について
    橋本 士; De Velasco Marco; 坂野 恵里; 清水 信貴; 森 康範; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 植村 天受  日本泌尿器科学会総会  109回-  PP12  -01  2021/12
  • 異種間遺伝子発現解析から免疫療法のための免疫表現型解析への応用
    坂野 恵里; 橋本 士; 安富 正悟; 西本 光寿; 倉 由吏恵; 藤田 和利; 野澤 昌弘; 吉村 一宏; De Velasco Marco; 植村 天受  日本泌尿器科学会総会  109回-  PP12  -07  2021/12
  • Apalutamide induces acute immune responses in mouse Pten-deficient prostate cancer(和訳中)
    倉 由吏恵; デベラスコ マルコ; 坂井 和子; 橋本 士; 藤田 和利; 野澤 昌弘; 吉村 一宏; 植村 天受; 西尾 和人  近畿大学医学雑誌  46-  (3-4)  19A  -19A  2021/12
  • Pten欠損前立腺癌マウスにおける糞便中の微生物とアンドロゲン除去の関係について
    若森 千怜; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 橋本 士; 坂野 恵里; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受  日本癌学会総会記事  80回-  [E3  -4]  2021/09
  • A2aR阻害はPten欠損前立腺癌マウスモデルにおいてCTLA4阻害薬の抗腫瘍活性を増強する
    デベラスコ・マルコ; 倉 由吏恵; 坂野 恵里; 坂井 和子; 清水 信貴; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受  日本癌学会総会記事  80回-  [E12  -1]  2021/09
  • 前立腺癌マウスにおける抗PD-L1免疫療法およびJAK1/2阻害と糞便中の細菌について
    坂野 恵里; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 橋本 士; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受  日本癌学会総会記事  80回-  [E14  -4]  2021/09
  • クルクミンモノグルクロニドはPten欠損前立腺癌の腫瘍微小環境を調節し抗腫瘍活性を示す
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 藤田 至彦; 橋本 士; 森 康範; 南 高文; 藤田 和利; 掛谷 秀昭; 植村 天受; 西尾 和人  日本癌学会総会記事  80回-  [E17  -3]  2021/09
  • アパルタミドが惹起する短期免疫反応の前臨床評価について
    植村 天受; 倉 由吏恵; 坂野 恵里; 橋本 士; 坂井 和子; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; デベラスコ・マルコ  日本癌学会総会記事  80回-  [J14  -3]  2021/09
  • Yurie Kura; Develasco Marco; Naomi Ando; Noriko Sako; Kazuko Sakai; Kazuto Nishio; Hirotsugu Uemura  ANNALS OF ONCOLOGY  32-  S295  -S295  2021/07
  • Develasco Marco; Yurie Kura; Kazuko Sakai; Hideki Nakagaki; Kazuto Nishio; Hirotsugu Uemura  ANNALS OF ONCOLOGY  32-  S305  -S305  2021/07
  • Yurie Kura; Kazuko Sakai; Yoshihiko Fujita; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A. De Velasco; Hirotsugu Uemura  CANCER SCIENCE  112-  261  -261  2021/02
  • Kazuto Nishio; Kazuko Sakai; Yurie Kura; Kyoshiro Takegahara; Marco A. De Velasco  CANCER SCIENCE  112-  261  -261  2021/02
  • Hirotsugu Uemura; Yurie Kura; Kazuko Sakai; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A. De Velasco  CANCER SCIENCE  112-  398  -398  2021/02
  • アンドロゲン受容体標的治療による前立腺癌の腫瘍微小環境の変化
    デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 清水 信貴; 森 康範; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会総会  108回-  1162  -1162  2020/12
  • 遺伝子改変前立腺癌マウスモデルにおける食餌性イソフラボンの化学予防効果
    森 康範; デベラスコ・マルコ; 倉 由吏恵; 清水 信貴; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会総会  108回-  1162  -1162  2020/12
  • 腫瘍免疫環境プロファイルと抗腫瘍免疫反応(Profiling the tumor immune milieu to assess and predict immune responses)
    デベラスコ・マルコ; 倉 由吏恵; 森 康範; 清水 信貴; 大關 孝之; 坂井 和子; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  78回-  E  -2067  2019/09
  • アパルタミドによる前立腺腫瘍内の免疫環境の変化(Apalutamide reworks the tumor immune microenvironment of prostate tumors)
    清水 信貴; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  78回-  P  -2267  2019/09
  • TAS-115マルチキナーゼ阻害薬のマウス前立腺癌モデルにおける免疫調整について(Immunomodulation of the multi-tyrosine kinase inhibitor TAS-115 in a mouse Pten-deficient prostate cancer)
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  78回-  P  -2360  2019/09
  • イソフラボン摂取はマウス前立腺癌転移モデルにおいて癌の進行を抑制し生存期間を延長させる(Chemopreventive effects of dietary isoflavone in conditional Pten/Trp53-deficient mouse model of prostate cancer)
    森 康範; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  78回-  J  -3030  2019/09
  • リアルタイムPCRを用いた腫瘍免疫プロファイルと免疫反応性の評価について(A real-time PCR-based approach to quantitatively assess tumor immune profiles and immune responses)
    野澤 昌弘; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  78回-  J  -3035  2019/09
  • アンドロゲン受容体標的治療は前立腺癌の腫瘍微小免疫環境を変化させる(Targeting the androgen receptor to remodel the tumor immune microenvironment of prostate cancers)
    植村 天受; デベラスコ・マルコ  日本癌学会総会記事  78回-  P  -3272  2019/09
  • 坂井和子; 藤田至彦; デベラスコ マルコ; 西尾和人  日本臨床プロテオゲノミクス研究会要旨集(Web)  2019-  2019
  • 坂井和子; 藤田至彦; デベラスコ マルコ; 西尾和人  日本臨床プロテオゲノミクス研究会要旨集(Web)  2019-  2019
  • 西尾和人; 坂井和子; DE VELASCO Marco; 藤田至彦  日本がん分子標的治療学会学術集会プログラム・抄録集  23rd-  2019
  • 倉由吏恵; 坂井和子; 野澤昌弘; 藤田至彦; DE VELASCO Marco A.; DE VELASCO Marco A.; 西尾和人; 植村天受  日本がん分子標的治療学会学術集会プログラム・抄録集  23rd-  2019
  • Hirotsugu Uemura; Marco A. De Velasco  CANCER SCIENCE  109-  682  -682  2018/12
  • 前立腺癌における遺伝子改変マウスモデル ヒトからマウスへ マウスからヒトへ(Genetically engineered mouse models of prostate cancer: from man to mouse and back)
    植村 天受; デベラスコ・マルコ  日本癌学会総会記事  77回-  1150  -1150  2018/09
  • 遺伝子改変Ptenノックアウトマウス前立腺癌モデルにおけるApalutamideの有効性についての検討(Preclinical activity of apalutamide (ARN-509) in genetically engineered mouse models of Pten-deficient prostate cancer)
    森 康範; デベラスコ・マルコ; 倉 由吏恵; 大關 孝之; 清水 信貴; 野澤 昌弘; 吉村 一宏; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  77回-  179  -179  2018/09
  • Pimキナーゼ阻害薬は去勢抵抗性マウス前立腺癌モデルにおいて腫瘍増殖を抑制し生存期間を延長する(PIM inhibition reduces tumor growth and improves survival in mouse advanced castration-resistant prostate cancer)
    倉 由吏恵; デベラスコ・マルコ; 森 康範; 清水 信貴; 大關 孝之; 坂井 和子; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  77回-  264  -264  2018/09
  • Ptenノックアウトマウス前立腺癌モデルにおけるマルチキナーゼ阻害薬TAS-115の有効性についての検討(Preclinical evaluation of the multi tyrosine kinase inhibitor TAS-115 in mouse Pten-deficient prostate cancer)
    野澤 昌弘; デベラスコ・マルコ; 倉 由吏恵; 清水 信貴; 森 康範; 吉村 一宏; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  77回-  265  -265  2018/09
  • 免疫療法開発における遺伝子改変マウス前立腺癌モデルの有用性について(Interrogating genetically engineered mouse models of prostate cancer to aid in immunotherapy development)
    デベラスコ・マルコ; 倉 由吏恵; 森 康範; 清水 信貴; 大關 孝之; 坂井 和子; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  77回-  414  -414  2018/09
  • 前立腺癌患者の予後不良に関わる遺伝子群の同定(Identification of a gene set associated with poor clinical outcomes in prostate cancer patients)
    橋本 士; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 清水 信貴; 森 康範; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  77回-  792  -792  2018/09
  • Ptenノックアウトマウス前立腺癌モデルを用いたアビラテロンによる抗腫瘍免疫効果に関する検討(Effect of abiraterone therapy on anti-tumor immunity in a mouse Pten-deficient prostate cancer model)
    清水 信貴; デベラスコ・マルコ; 倉 由吏恵; 大關 孝之; 森 康範; 野澤 昌弘; 吉村 一宏; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  77回-  1792  -1792  2018/09
  • 遺伝子改変前立腺癌マウスモデルを用いた新規化合物の包括的前臨床評価について
    植村 天受; 倉 由吏恵; 杉本 公一; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 西尾 和人; デベラスコ・マルコ  日本泌尿器科学会総会  106回-  OP  -004  2018/04
  • PTENノックアウト前立腺癌マウスモデルにおける腫瘍免疫の包括的分析
    デベラスコ・マルコ; 倉 由吏恵; 杉本 公一; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 西尾 和人; 植村 天受  日本泌尿器科学会総会  106回-  OP  -005  2018/04
  • 遺伝子改変前立腺癌マウスモデルにおけるPD-L1免疫チェックポイント阻害薬について
    清水 信貴; 倉 由吏恵; 杉本 公一; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 西尾 和人; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会総会  106回-  OP  -006  2018/04
  • 前立腺特異的PTENノックアウトマウスモデルを用いたAKTおよびPim阻害薬の併用による抗腫瘍効果の検討
    倉 由吏恵; 杉本 公一; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 西尾 和人; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会総会  106回-  OP  -007  2018/04
  • ヒト前立腺癌におけるSTAT3について
    森 康範; デベラスコ・マルコ; 倉 由吏恵; 杉本 公一; 畑中 祐二; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会総会  106回-  PP3  -058  2018/04
  • アンドロゲンレセプターを標的とした次世代アンチセンスオリゴヌクレオチドとAKT阻害薬併用療法の治療効果の検討
    杉本 公一; 吉村 一宏; 野澤 昌弘; 南 高文; 森 康範; 倉 由吏恵; 吉川 和宏; 坂井 和子; 西尾 和人; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会総会  106回-  PP3  -066  2018/04
  • 遺伝子改変前立腺癌マウスモデルを用いた新規化合物の包括的前臨床評価について
    植村 天受; 倉 由吏恵; 杉本 公一; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 西尾 和人; デベラスコ・マルコ  日本泌尿器科学会総会  106回-  OP  -004  2018/04
  • PTENノックアウト前立腺癌マウスモデルにおける腫瘍免疫の包括的分析
    デベラスコ・マルコ; 倉 由吏恵; 杉本 公一; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 西尾 和人; 植村 天受  日本泌尿器科学会総会  106回-  OP  -005  2018/04
  • 遺伝子改変前立腺癌マウスモデルにおけるPD-L1免疫チェックポイント阻害薬について
    清水 信貴; 倉 由吏恵; 杉本 公一; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 西尾 和人; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会総会  106回-  OP  -006  2018/04
  • 前立腺特異的PTENノックアウトマウスモデルを用いたAKTおよびPim阻害薬の併用による抗腫瘍効果の検討
    倉 由吏恵; 杉本 公一; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 西尾 和人; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会総会  106回-  OP  -007  2018/04
  • ヒト前立腺癌におけるSTAT3について
    森 康範; デベラスコ・マルコ; 倉 由吏恵; 杉本 公一; 畑中 祐二; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会総会  106回-  PP3  -058  2018/04
  • アンドロゲンレセプターを標的とした次世代アンチセンスオリゴヌクレオチドとAKT阻害薬併用療法の治療効果の検討
    杉本 公一; 吉村 一宏; 野澤 昌弘; 南 高文; 森 康範; 倉 由吏恵; 吉川 和宏; 坂井 和子; 西尾 和人; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会総会  106回-  PP3  -066  2018/04
  • PTENノックアウト前立腺癌マウスモデルにおける腫瘍免疫の包括的分析
    De Velasco Marco A; 倉 由吏恵; 坂井 和子; 杉本 公一; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  76回-  P  -1222  2017/09
  • 遺伝子改変前立腺癌マウスモデルにおけるPD-L1免疫チェックポイント阻害薬について
    清水 信貴; De Velasco Marco A; 倉 由吏恵; 坂井 和子; 杉本 公一; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  76回-  P  -1246  2017/09
  • アンドレゲンレセプターを標的とした次世代アンチセンスオリゴヌクレオチドとAKT阻害薬併用療法の治療効果について
    杉本 公一; De Velasco Marco A; 倉 由吏恵; 坂井 和子; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  76回-  P  -1376  2017/09
  • AKTおよびPimキナーゼをターゲットにした治療戦略はPTEN欠出前立腺癌前臨床動物モデルにおいて治療効果改善を示す
    倉 由吏恵; De Velasco Marco A; 杉本 公一; 坂井 和子; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  76回-  J  -2099  2017/09
  • 遺伝子改変マウス前立腺癌モデルを用いた新規化合物の包括的前臨床評価について
    植村 天受; 倉 由吏恵; 杉本 公一; 森 康範; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; De Velasco Marco A  日本癌学会総会記事  76回-  J  -3121  2017/09
  • ヒト前立腺癌におけるSTAT3について
    森 康範; De Velasco Marco A; 畑中 祐二; 倉 由吏恵; 杉本 公一; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  76回-  P  -3215  2017/09
  • PTENノックアウト前立腺癌マウスモデルにおける腫瘍免疫の包括的分析
    De Velasco Marco A.; 倉 由吏恵; 坂井 和子; 杉本 公一; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  76回-  P  -1222  2017/09  [Refereed]
  • 遺伝子改変前立腺癌マウスモデルにおけるPD-L1免疫チェックポイント阻害薬について
    清水 信貴; De Velasco Marco A.; 倉 由吏恵; 坂井 和子; 杉本 公一; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  76回-  P  -1246  2017/09  [Refereed]
  • アンドレゲンレセプターを標的とした次世代アンチセンスオリゴヌクレオチドとAKT阻害薬併用療法の治療効果について
    杉本 公一; De Velasco Marco A.; 倉 由吏恵; 坂井 和子; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  76回-  P  -1376  2017/09  [Refereed]
  • AKTおよびPimキナーゼをターゲットにした治療戦略はPTEN欠失前立腺癌前臨床動物モデルにおいて治療効果改善を示す
    倉 由吏恵; De Velasco Marco A.; 杉本 公一; 坂井 和子; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  76回-  J  -2099  2017/09  [Refereed]
  • 遺伝子改変マウス前立腺癌モデルを用いた新規化合物の包括的前臨床評価について
    植村 天受; 倉 由吏恵; 杉本 公一; 森 康範; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; De Velasco Marco A.  日本癌学会総会記事  76回-  J  -3121  2017/09  [Refereed]
  • ヒト前立腺癌におけるSTAT3について
    森 康範; De Velasco Marco A.; 畑中 祐二; 倉 由吏恵; 杉本 公一; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  76回-  P  -3215  2017/09  [Refereed]
  • HLA-A24陽性腎細胞癌患者におけるcancer-reactive cytotoxic T lymphocytesを誘導しうるHIF-1α由来ペプチドの同定
    南 高文; 杉本 公一; 清水 信貴; デベラスコ・マルコ; 野澤 昌弘; 吉村 一宏; 原嶋 奈々江; 原田 守; 植村 天受  日本癌学会総会記事  76回-  P  -1325  2017/09
  • Rich Woessner; Vasu Sah; Patricia McCoon; Shaun Grosskurth; Nanhua Deng; Rachel DuPont; Deborah Lawson; Lourdes Pablo; Corinne Reimer; Marco A. De Velasco; Hirotsugu Uemura; Juliana Candido; Paul Lyne  CANCER RESEARCH  77-  2017/07
  • De Velasco, Marco A.; Kura, Yurie; Ando, Naomi; Sugimoto, Koichi; Sakai, Kazuko; Davies, Barry R.; Kim, Youngsoo; MacLeod, A. Robert; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu  CANCER RESEARCH  77-  2017/07
  • De Velasco, Marco A.; Hatanaka, Yuji; Kura, Yurie; Ando, Naomi; Sakai, Kazuko; Sugimoto, Koichi; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu  CANCER RESEARCH  77-  2017/07
  • De Velasco, Marco A.; Sugimoto, Koichi; Kura, Yurie; Ando, Naomi; Sato, Noriko; Sakai, Kazuko; Davies, Barry R.; Huszar, Dennis; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu  CANCER RESEARCH  77-  2017/07
  • De Velasco, Marco A.; Kura, Yurie; Ando, Naomi; Sato, Noriko; Sakai, Kazuko; Davies, Barry R.; Sugimoto, Koichi; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu  CANCER RESEARCH  77-  2017/07
  • FGFR遺伝子異常を有する肺扁平上皮癌の術後再発生存期間に対する影響とマルチキナーゼ阻害薬に対する感受性
    西尾 和人; 金田 裕靖; 谷崎 潤子; 坂井 和子; 冨樫 庸介; 寺嶋 雅人; デベラスコ・マルコ; 藤田 至彦; 坂野 恵里; 中村 雄; 武田 真幸; 伊藤 彰彦; 光冨 徹哉; 中川 和彦; 岡本 勇  肺癌  57-  (3)  253  -253  2017/06
  • 前立腺特異的PTENノックアウトマウスを用いたJak1/2阻害薬であるAZD1480による抗腫瘍効果および転移抑制についての検討
    倉 由吏恵; 吉村 一宏; 野澤 昌弘; 南 高文; 杉本 公一; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受  105th Annual Meeting of the Japan Urological Association  105回-  OP42  -6  2017/04
  • PTEN/p53ダブルノックアウト前立腺癌マウスモデルにおけるAutophagy阻害薬クロロキンの治療効果について
    杉本 公一; 吉村 一宏; 野澤 昌弘; 南 高文; 清水 信貴; 倉 由吏恵; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受  105th Annual Meeting of the Japan Urological Association  105回-  PP16  -07  2017/04
  • 遺伝子改変前立腺癌マウスモデルにおける高脂肪食摂取による腫瘍増殖について
    森 康範; デベラスコ・マルコ; 倉 由吏恵; 沖 貴士; 杉本 公一; 畑中 祐二; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  105th Annual Meeting of the Japan Urological Association  105回-  PP16  -10  2017/04
  • 西尾和人; 金田裕靖; 谷崎潤子; 坂井和子; 冨樫庸介; 寺嶋雅人; デベラスコ マルコ; 藤田至彦; 坂野恵里; 中村雄; 武田真幸; 伊藤彰彦; 光冨徹哉; 中川和彦; 岡本勇  肺癌(Web)  57-  (3)  2017
  • 非小細胞肺がんにおける受容体型チロシンキナーゼ遺伝子変異の機能解析
    寺嶋 雅人; 冨樫 庸介; 佐藤 克明; 水内 寛; 坂井 和子; 須田 健一; 中村 雄; 坂野 恵里; 林 秀敏; デベラス・マルコ; 藤田 至彦; 冨田 秀太; 光冨 徹哉; 西尾 和人  近畿大学医学雑誌  41-  (3-4)  20A  -20A  2016/12
  • PTENノックアウトマウス前立腺癌におけるノンコーディングRNAの検討
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 藤田 至彦; 冨樫 庸介; 寺嶋 雅人; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  75回-  E  -1029  2016/10
  • PTENノックアウトマウス前立腺癌において選択的スプライシングは頻繁に認められる
    デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 藤田 至彦; 冨樫 庸介; 寺嶋 雅人; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  75回-  E  -1073  2016/10
  • PTENノックアウト前立腺癌マウスモデルにおけるJAK1/2阻害による腫瘍増殖及び転移抑制効果の検討
    植村 天受; 倉 由吏恵; 森 康範; 畑中 祐二; 沖 貴士; 杉本 公一; 吉村 一宏; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ  日本癌学会総会記事  75回-  E  -2085  2016/10
  • PTEN/p53ダブルノックアウト前立腺癌マウスモデルにおけるクロロキン経口による治療効果
    杉本 公一; デベラスコ・マルコ; 倉 由吏恵; 森 康範; 畑中 祐二; 沖 貴士; 吉村 一宏; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  75回-  E  -3065  2016/10
  • 頭頸部または食道扁平上皮癌に対するアファチニブの効果 頭頸部扁平上皮癌における活性型発癌性HER4遺伝子変異
    中村 雄; 冨樫 庸介; 寺嶋 雅人; デベラスコ・マルコ; 坂井 和子; 藤田 至彦; 桶川 隆嗣; 濱田 傑; 西尾 和人  75th Annual Meeting of Japan Cancer Association  75回-  P  -2296  2016/10
  • DDR2 E655K変異タンパク質はユビキチン-プロテアソーム系による分解を受け機能が喪失する
    寺嶋 雅人; 冨樫 庸介; 坂井 和子; 中村 雄; 坂野 恵里; デベラスコ・マルコ; 藤田 至彦; 西尾 和人  75th Annual Meeting of Japan Cancer Association  75回-  P  -3047  2016/10
  • 腫瘍内クローン数定量化プログラムによる卵巣がんのクローン数と遺伝子変異の関連解析
    坂井 和子; 浮田 真沙世; 高矢 寿光; 藤田 至彦; 寺嶋 雅人; デベラスコ・マルコ; 万代 昌紀; 西尾 和人  75th Annual Meeting of Japan Cancer Association  75回-  P  -3191  2016/10
  • 遺伝子改変と前立腺癌マウスモデルにおける高脂肪食摂取による腫瘍増殖について
    森 康範; デベラスコ・マルコ; 倉 由吏恵; 畑中 祐二; 沖 貴士; 杉本 公一; 吉村 一宏; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  75回-  P  -3348  2016/10
  • Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Yuji Hatanaka; Yoshihiko Fujita; Yosuke Togashi; Masato Terashima; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura  CANCER RESEARCH  76-  2016/07
  • Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Yoshihiko Fujita; Yosuke Togashi; Masato Terashima; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura  CANCER RESEARCH  76-  2016/07
  • HLA-A24陽性腎細胞癌症例においてCancer-reactive cytotoxic T lymphocytesを誘導しうるEpoR、PD-L1ペプチドの同定
    南 高文; 南 知子; 清水 信貴; 山本 豊; デベラスコ・マルコ; 野澤 昌弘; 吉村 一宏; 原嶋 奈々江; 原田 守; 植村 天受  日本泌尿器科学会総会  104回-  PP1  -015  2016/04
  • 前立腺癌マウスモデルを用いたAKT阻害薬AZD5363の抗腫瘍効果の検討
    植村 天受; 吉村 一宏; 野澤 昌弘; 南 高文; 杉本 公一; 倉 由吏恵; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会総会  104回-  OP  -228  2016/04
  • 前立腺癌におけるAKT/PI3KおよびMAPK経路阻害による治療相互作用について
    山本 豊; 吉村 一宏; 野澤 昌弘; 南 高文; 杉本 公一; 倉 由吏恵; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会総会  104回-  PP3  -265  2016/04
  • 去勢抵抗性前立腺癌におけるPim-1キナーゼ阻害薬AZD1208の治療効果
    杉本 公一; 吉村 一宏; 野澤 昌弘; 南 高文; 倉 由吏恵; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会総会  104回-  PP3  -266  2016/04
  • 前立腺癌マウスモデルを用いたAKT阻害薬AZD5363の抗腫瘍効果の検討
    植村 天受; 吉村 一宏; 野澤 昌弘; 南 高文; 杉本 公一; 倉 由吏恵; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会総会  104回-  OP  -228  2016/04
  • 前立腺癌におけるAKT/PI3KおよびMAPK経路阻害による治療相互作用について
    山本 豊; 吉村 一宏; 野澤 昌弘; 南 高文; 杉本 公一; 倉 由吏恵; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会総会  104回-  PP3  -265  2016/04
  • 去勢抵抗性前立腺癌におけるPim-1キナーゼ阻害薬AZD1208の治療効果
    杉本 公一; 吉村 一宏; 野澤 昌弘; 南 高文; 倉 由吏恵; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会総会  104回-  PP3  -266  2016/04
  • Y. Togashi; Y. Nakamura; S. Tomida; H. Hayashi; M. A. de Velasco; K. Sakai; Y. Fujita; S. Hamada; K. Nishio  ANNALS OF ONCOLOGY  26-  97  -97  2015/12
  • Yosuke Togashi; Hiroshi Mizuuchi; Kazuko Sakai; Eri Banno; Hidetoshi Hayashi; Marco de Velasco; Yoshihiko Fujita; Shuta Tomida; Tetsuya Mitsudomi; Kazuto Nishio  ANNALS OF ONCOLOGY  26-  73  -73  2015/11
  • Takuro Mizukami; Yosuke Togashi; Shunsuke Sogabe; Marco A. de Velasco; Kazuko Sakai; Yoshihiro Fujita; Shuta Tomida; Takako Eguchi Nakajima; Narikazu Boku; Kazuto Nishio  ANNALS OF ONCOLOGY  26-  129  -129  2015/11
  • 非小細胞肺がんにおけるDDR2変異の機能解析
    寺嶋 雅人; 冨樫 庸介; 坂井 和子; 佐藤 克明; 須田 健一; 水上 拓郎; 坂野 恵里; 中村 雄; De Velasco Marco; 藤田 至彦; 冨田 秀太; 光冨 徹哉; 西尾 和人  日本癌学会総会記事  74回-  P  -2223  2015/10
  • マウス前立腺癌モデルを用いたAKT阻害薬AZD5356の抗腫瘍効果
    植村 天受; 倉 由吏恵; 清水 信貴; 吉村 一宏; 野澤 昌弘; 吉川 和宏; 西尾 和人; De Velasco Marco A.  日本癌学会総会記事  74回-  E  -1099  2015/10  [Refereed]
  • 去勢抵抗性前立腺癌に対するPim-1キナーゼ阻害薬AZD1208の治療効果
    倉 由吏恵; De Velasco Marco A.; 沖 貴士; 山本 豊; 畑中 祐二; 清水 信貴; 吉村 一宏; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  74回-  E  -1100  2015/10  [Refereed]
  • PTEN欠損前立腺癌マウスモデルにおけるオートファジー阻害薬CQによる長期治療効果について
    杉本 公一; De Velasco Marco A.; 倉 由吏恵; 山本 豊; 畑中 祐二; 沖 貴士; 清水 信貴; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  74回-  P  -1039  2015/10  [Refereed]
  • 前立腺癌におけるAkt/P13KおよびMAPK経路阻害の治療相乗効果について
    山本 豊; De Velasco Marco A.; 倉 由吏恵; 畑中 祐二; 沖 貴士; 清水 信貴; 野澤 昌弘; 吉川 和宏; 吉村 一宏; 西尾 和人; 植村 天受  日本癌学会総会記事  74回-  E  -1340  2015/10  [Refereed]
  • 前立腺癌に対するオートファジー阻害薬CQと分子標的薬の併用療法について
    畑中 祐二; De Velasco Marco A.; 倉 由吏恵; 山本 豊; 沖 貴士; 清水 信貴; 吉村 一宏; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  74回-  E  -1341  2015/10  [Refereed]
  • アンドロゲン受容体に対する次世代アンチセンスオリゴヌクレオチドを用いた前立腺癌治療
    De Velasco Marco A.; 倉 由吏恵; 畑中 祐二; 山本 豊; 吉川 和宏; 清水 信貴; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受  日本癌学会総会記事  74回-  P  -3355  2015/10  [Refereed]
  • 非小細胞肺がんにおけるDDR2変異の機能解析
    寺嶋 雅人; 冨樫 庸介; 坂井 和子; 佐藤 克明; 須田 健一; 水上 拓郎; 坂野 恵里; 中村 雄; De Velasco Marco; 藤田 至彦; 冨田 秀太; 光冨 徹哉; 西尾 和人  日本癌学会総会記事  74回-  P  -2223  2015/10  [Refereed]
  • T. Mizukami; Y. Togashi; E. Banno; M. Terashima; M. A. De Velasco; K. Sakai; H. Hayashi; Y. Fujita; S. Tomida; T. Eguchi Nakajima; N. Boku; A. Ito; K. Nakagawa; K. Nishio  EUROPEAN JOURNAL OF CANCER  51-  S46  -S46  2015/09
  • Yosuke Togashi; Akihiro Kogita; Hiroki Sakamoto; Hidetoshi Hayashi; Masato Terashima; Marco A. de Velasco; Kazuko Sakai; Yoshihiko Fujita; Shuta Tomida; Masayuki Kitano; Masatoshi Kudo; Kazuto Nishio  CANCER RESEARCH  75-  2015/08
  • Kazuhiro Yoshikawa; Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yutaka Yamamoto; Yuji Hatanaka; Takashi Oki; Nobutaka Shimizu; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura  CANCER RESEARCH  75-  2015/08
  • Yoshihiko Fujita; Satoshi Koinuma; Marco De Velasco; Bolz Jan; Yosuke Togashi; Masato Terashima; Hidetoshi Hayashi; Takuya Matsuo; Kazuto Nishio  CANCER RESEARCH  75-  2015/08
  • Takuro Mizukami; Yosuke Togashi; Eri Banno; Masato Terashima; Marco A. de Velasco; Kazuko Sakai; Yoshihiko Fujita; Shuta Tomida; Takako Eguchi Nakajima; Narikazu Boku; Kazuto Nishio  CANCER RESEARCH  75-  2015/08
  • 沖 貴士; デベラスコ・マルコ; 倉 由吏恵; 畑中 祐二; 山本 豊; 吉村 一宏; 清水 信貴; 野澤 昌弘; 小池 浩之; 吉川 和弘; 西尾 和人; 植村 天受  日本泌尿器科学会総会  103回-  710  -710  2015/04
  • 畑中 祐二; デベラスコ・マルコ; 沖 貴士; 倉 由吏恵; 安藤 直美; 福島 恵美子; 山本 豊; 清水 信貴; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会総会  103回-  710  -710  2015/04
  • Yosuke Togashi; Hiroki Sakamoto; Hidetoshi Hayashi; Masato Terashima; Marco A. de Velasco; Yoshihiko Fujita; Yasuo Kodera; Kazuko Sakai; Shuta Tomida; Masayuki Kitano; Masatoshi Kudo; Kazuto Nishio  CANCER RESEARCH  74-  (19)  2014/10
  • 林 秀敏; 冨樫 庸介; 岡本 邦男; 田中 妙; 文田 壮一; 新谷 亮多; 清川 寛文; 坂本 洋一; 寺嶋 雅人; de Velasco Marco A; 坂井 和子; 藤田 至彦; 冨田 秀太; 加藤 元一; 中川 和彦; 西尾 和人  肺癌  54-  (5)  626  -626  2014/10  [Refereed]
  • オートファジーと前立腺癌発生-進展に関する関係について、PTEN/Atg-7ダブルKO前立腺癌マウスを作製し、検討した(Autophagy in Prostate Tumorigenesis and Its Clinical Implications)
    デベラスコ・マルコ; 倉 由吏恵; 畑中 祐二; 山本 豊; 清水 信貴; 吉村 一宏; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  73回-  J  -2002  2014/09
  • 去勢抵抗性前立腺癌においてアンドロゲン受容体およびmTORの抑制によって、抗腫瘍効果は増強する(Improved antitumor effects of androgen receptor and mTOR inhibition in castration resistant prostate cancer)
    倉 由吏恵; デベラスコ・マルコ; 畑中 祐二; 山本 豊; 清水 信貴; 吉村 一宏; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  73回-  E  -3064  2014/09
  • 前立腺癌自然発生マウスモデルPTEN KOマウスより、PTEN/p53ダブルKOマウスを確立し、その有用性について報告する(Development of a Lethal Genetically Engineered Mouse Model of Prostate Cancer for Survival Studies and End-stage Cancer)
    植村 天受; 倉 由吏恵; 畑中 祐二; 山本 豊; 清水 信貴; 吉村 一宏; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ  日本癌学会総会記事  73回-  P  -2023  2014/09
  • メラノサイトからメラノーマへの移行は、しばしばがん抑制因子であるサイトグロビンの発現低下を伴う(Cytoglobin, a putative tumor suppressor, is frequently lost in melanocyte during melanoma transition)
    藤田 至彦; 鯉沼 聡; デベラスコ・マルコ; ボルツ・ヤン; 富樫 庸介; 寺嶋 雅人; 林 秀敏; 松尾 拓哉; 西尾 和人  日本癌学会総会記事  73回-  P  -3066  2014/09
  • PTEN欠損マウス前立腺がん由来細胞株の樹立(Establishment and characterization of cell lines derived from mouse PTEN-deficient prostate cancer)
    吉川 和宏; デベラスコ・マルコ; 倉 由吏恵; 畑中 祐二; 山本 豊; 清水 信貴; 吉村 一宏; 野澤 昌弘; 西尾 和人; 植村 天受  日本癌学会総会記事  73回-  P  -3172  2014/09
  • HOXA10の発現異常が前立腺全摘出術後の再発を予測する可能性の検討(Aberrantly Expressed HOXA10 Could Possibly Predict Recurrence after Radical Prostatectomy)
    畑中 祐二; マルコ・デベラスコ; 沖 貴士; 倉 由吏恵; 山本 豊; 吉村 一宏; 清水 信貴; 野沢 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  73回-  P  -1303  2014/09
  • ヒト前立腺癌におけるLumicanの発現についての検討(Expression of Lumican in Human Prostate Cancer)
    沖 貴士; デベラスコ・マルコ; 畑中 祐二; 倉 由吏恵; 山本 豊; 吉村 一宏; 清水 信貴; 野澤 昌弘; 吉川 和弘; 西尾 和人; 植村 天受  日本癌学会総会記事  73回-  P  -1313  2014/09
  • 山本 豊; デベラスコ・マルコ; 倉 由吏恵; 安藤 直美; 福島 恵美子; 畑中 祐二; 清水 信貴; 野沢 昌弘; 吉村 一宏; 吉川 和弘; 西尾 和人; 植村 天受  日本泌尿器科学会総会  102回-  514  -514  2014/04
  • 倉 由吏恵; デベラスコ・マルコ; 安藤 直美; 福島 恵美子; 畑中 祐二; 山本 豊; 清水 信貴; 野沢 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会総会  102回-  566  -566  2014/04
  • 植村 天受; 倉 由吏恵; 安藤 直美; 福島 恵美子; 畑中 祐二; 山本 豊; 清水 信貴; 野沢 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; デベラスコ・マルコ  日本泌尿器科学会総会  102回-  566  -566  2014/04
  • デベラスコ・マルコ; 倉 由吏恵; 安藤 直美; 福島 恵美子; 畑中 祐二; 山本 豊; 清水 信貴; 吉村 一宏; 野澤 昌弘; 吉川 和弘; 西尾 和人; 植村 天受  日本泌尿器科学会総会  102回-  566  -566  2014/04
  • 畑中 祐二; デベラスコ・マルコ; 山本 豊; 沖 貴士; 倉 由吏恵; 清水 信貴; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会総会  102回-  662  -662  2014/04
  • 沖 貴士; デベラスコ・マルコ; 畑中 祐二; 倉 由吏恵; 山本 豊; 吉村 一宏; 清水 信貴; 野澤 昌弘; 吉川 和弘; 西尾 和人; 江左 篤宣; 植村 天受  日本泌尿器科学会総会  102回-  666  -666  2014/04
  • M. Terashima; K. Sakai; Y. Fujita; M. A. De Velasco; K. Nishio  ANNALS OF ONCOLOGY  24-  2013/11
  • PTENノックアウト前立腺癌マウスにおけるMAPKシグナル抑制と抗腫瘍効果(Tumor responses to MAPK signal inhibition in a preclinical model of PTEN deficient prostate cancer)
    山本 豊; デベラスコ・マルコ; 倉 由吏恵; 安藤 直美; 福島 恵美子; 畑中 祐二; 清水 信貴; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  72回-  197  -197  2013/10
  • STAT3転写活性の抑制による前立腺癌治療(Targeting Prostate Cancer Through Inhibition of STAT3 Transcriptional Activation)
    倉 由吏恵; デベラスコ・マルコ; 安藤 直美; 福島 恵美子; 畑中 祐二; 山本 豊; 清水 信貴; 吉村 一宏; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  72回-  197  -197  2013/10
  • オートファジーと前立腺癌(Autophagy and prostate cancer)
    デベラスコ・マルコ; 倉 由吏恵; 安藤 直美; 福島 恵美子; 畑中 祐二; 山本 豊; 清水 信貴; 吉村 一宏; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  72回-  227  -227  2013/10
  • 前立腺癌のPTEN・P53ダブルノックアウトによる相乗効果(Synchronous inactivation of PTEN and P53 accelerates prostate cancer)
    植村 天受; 倉 由吏恵; 安藤 直美; 福島 恵美子; 畑中 祐二; 山本 豊; 清水 信貴; 吉村 一宏; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ  日本癌学会総会記事  72回-  232  -232  2013/10
  • 前立腺癌におけるHOXA10の発現異常について(HOXA10 is aberrantly expressed in prostate cancer)
    畑中 祐二; デベラスコ・マルコ; 倉 由吏恵; 清水 信貴; 山本 豊; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  72回-  308  -308  2013/10
  • NGSによる極微量検体を用いたmultiplex mutation analysisの最適化(Optimization of multiplex mutation analysis based on minimum amount of lung cancer specimen)
    冨田 秀太; 坂井 和子; 藤田 至彦; 寺嶋 雅人; 富樫 庸介; デベラスコ・マルコ; 光冨 徹哉; 中川 和彦; 西尾 和人  日本癌学会総会記事  72回-  458  -458  2013/10
  • 前立腺特異的PTENノックアウト前立腺癌マウスを用いた抗腫瘍メカニズムの検討
    山本 豊; デベラスコ・マルコ; 小林 泰之; 清水 信貴; 南 高文; 林 泰司; 辻 秀憲; 野澤 昌弘; 吉村 一宏; 石井 徳味; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会雑誌  104-  (2)  221  -221  2013/03
  • 前立腺癌のバイオマーカーを発見するためのマウスモデルの作製
    畑中 祐二; デベラスコ・マルコ; 清水 信貴; 山本 豊; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会雑誌  104-  (2)  410  -410  2013/03
  • 前立腺がんに対するStat3を標的とした阻害の治療の有効性(The potential of targeted Stat3 inhibition for prostate cancer)
    デ・ベラスコ・マルコ; 倉 由吏恵; 小林 泰之; 畑中 祐二; 山本 豊; 吉村 一宏; 清水 信貴; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会雑誌  104-  (2)  412  -412  2013/03
  • ヒト前立腺がんにおけるルミカンの発現(Expression of lumican in human prostate adenocarcinoma)
    倉 由吏恵; デベラスコ・マルコ; 畑中 祐二; 山本 豊; 吉村 一弘; 清水 信貴; 野澤 昌弘; 吉川 和弘; 西尾 和人; 植村 天受  日本泌尿器科学会雑誌  104-  (2)  416  -416  2013/03
  • レプチンは前立腺がんの進行に寄与する(Leptin contributes to drive prostate cancer progression)
    吉村 一宏; デベラスコ・マルコ; 倉 由吏恵; 畑中 祐二; 山本 豊; 清水 信貴; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会雑誌  104-  (2)  416  -416  2013/03
  • H. Hayashi; T. Arao; K. Matsumoto; T. Nagai; H. Kimura; M. A. De Velasco; Y. Fujita; Y. Yamada; K. Nakagawa; K. Nishio  ANNALS OF ONCOLOGY  23-  112  -112  2012/10
  • H. Kaneda; T. Arao; K. Tanaka; K. Matsumoto; H. Kimura; T. Nagai; K. Sakai; Y. Fujita; M. A. De Velasco; Y. Yamada; J. Tsurutani; I. Okamoto; K. Nakagawa; K. Nishio  ANNALS OF ONCOLOGY  23-  112  -112  2012/10
  • H. Kaneda; T. Arao; K. Tanaka; K. Matsumoto; H. Kimura; T. Nagai; Y. Fujita; M. A. De Velasco; Y. Yamada; I. Okamoto; K. Nakagawa; K. Nishio  ANNALS OF ONCOLOGY  23-  134  -134  2012/10
  • 転移性腎がんに対するMHCクラスIペプチドワクチン療法の役割(Clinical role of MHC-class I peptide vaccines for metastatic renal cell carcinoma)
    植村 天受; 吉村 一宏; 南 高文; デベラスコ・マルコ  日本癌学会総会記事  71回-  146  -146  2012/08
  • HLA-A24陽性腎細胞癌患者におけるcancer-reactive CTLsを誘導し得るEpoR抗原由来ペプチドの同定(Identification of EpoR-derived peptides having the potential to induce cancer-reactive CTLs from HLA-A24+RCC patients)
    南 高文; 南 知子; 大関 孝之; デベラスコ・マルコ; 清水 信貴; 山本 豊; 辻 秀憲; 野澤 昌弘; 吉村 一宏; 植村 天受  日本癌学会総会記事  71回-  151  -151  2012/08
  • OCT4偽遺伝子であるPOU5F1Bの増殖は胃がんにおいて予後不良因子である(Amplification of OCT4-pseudogene POU5F1B is a poor prognostic factor in gastric cancer)
    林 秀敏; 荒尾 徳三; 松本 和子; 永井 知行; 木村 英晴; デベラスコ・マルコ; 藤田 至彦; 山田 康秀; 中川 和彦; 西尾 和人  日本癌学会総会記事  71回-  186  -186  2012/08
  • ヒト前立腺癌におけるルミカンの発現について(Expression of Lumican in Human Prostate Adenocarcinoma)
    吉村 一宏; デベラスコ・マルコ; 畑中 祐二; 倉 由吏恵; 山本 豊; 清水 信貴; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  71回-  293  -293  2012/08
  • 前立腺特異的PTENノックアウトマウスにおけるSTAT3の転写活性に関する検討(Stat3 Transcriptional Activation in a Pten-mutant Mouse Model of Prostate Cancer)
    小林 泰之; デベラスコ・マルコ; 倉 由吏恵; 畑中 祐二; 山本 豊; 吉村 一宏; 清水 信貴; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  71回-  437  -437  2012/08
  • 前立腺癌マウスモデルに対する分子標的治療薬の抗腫瘍効果の検討(Preclinical evaluation of combined targeted therapy for the treatment of prostate cancer)
    山本 豊; デベラスコ・マルコ; 倉 由吏恵; 畑中 祐二; 吉村 一宏; 清水 信貴; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  71回-  437  -437  2012/08
  • ヒト前立腺癌の進展におけるHOXA10の発現異常について(Deregulation of HOXA10 is Associated with Progression of Human Prostate Cancer)
    畑中 祐二; デベラスコ・マルコ; 倉 由吏恵; 山本 豊; 吉村 一宏; 清水 信貴; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  71回-  519  -519  2012/08
  • Marco A. De Velasco; Motoyoshi Tanaka; Kaori Fujimoto-Ouchi; Yoichiro Moriya; Yurie Kura; Yasuki Kobayashi; Yutaka Yamamoto; Yuji Hatanaka; Hiroyuki Kato; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura  CANCER RESEARCH  72-  2012/04
  • Hidetoshi Hayashi; Tokuzo Arao; Kazuko Matsumoto; Tomoyuki Nagai; Hideharu Kimura; Marco A. De Velasco; Yoshihiko Fujita; Yasuhide Yamada; Isamu Okamoto; Kazuhiko Nakagawa; Kazuto Nishio  CANCER RESEARCH  72-  2012/04
  • 高脂肪摂取と前立腺癌の進展について マウス前立腺癌モデルを用いた検討
    辻 秀憲; 植村 天受; 畑中 祐二; 山本 豊; 清水 信貴; 児玉 光正; 田中 基幹; 野澤 昌弘; 吉村 一宏; De Velasco Marco  日本泌尿器科学会雑誌  103-  (2)  278  -278  2012/03  [Refereed]
  • 前立腺癌増殖進展におけるSTAT3活性化の役割について マウス前立腺癌モデルによる検討
    De Velasco Marco; 田中 基幹; 加藤 博之; 大内 香; 守屋 陽一郎; 小林 泰之; 山本 豊; 野澤 昌弘; 植村 天受  日本泌尿器科学会雑誌  103-  (2)  455  -455  2012/03  [Refereed]
  • 前立腺癌におけるLumicanの発現異常について
    吉村 一宏; De Velasco Marco; 畑中 祐二; 山本 豊; 田中 基幹; 清水 信貴; 野澤 昌弘; 植村 天受  日本泌尿器科学会雑誌  103-  (2)  462  -462  2012/03  [Refereed]
  • Ptenノックアウト前立腺癌モデルにおけるsorafenibの治療効果
    山本 豊; De Velasco Marco; 南 高文; 畑中 祐二; 小池 浩之; 田中 基幹; 野澤 昌弘; 吉村 一宏; 児玉 光正; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会雑誌  103-  (2)  372  -372  2012/03  [Refereed]
  • 前立腺癌におけるHOXA-10の発現意義
    畑中 祐二; De Velasco Marco; 山本 豊; 清水 信貴; 小林 泰之; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会雑誌  103-  (2)  462  -462  2012/03  [Refereed]
  • 前立腺癌におけるルミカン発現(Lumican expression in prostate cancer)
    王 一; デベラスコ・マルコ; 畑中 祐二; 山本 豊; 田中 基幹; 清水 信貴; 児玉 光正; 吉川 和宏; 荒尾 徳三; 西尾 和人; 植村 天受  日本癌学会総会記事  70回-  69  -69  2011/09
  • PTENコンディショナルノックアウト前立腺癌マウスモデルを用いた新規バイオマーカの同定(Use of the prostate-specific PTEN conditional knockout mouse model to Identify prognostic biomarkers in prostate cancer)
    デベラスコ・マルコ; 田中 基幹; 畑中 祐二; 山本 豊; 清水 信貴; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 荒尾 徳三; 植村 天受; 西尾 和人  日本癌学会総会記事  70回-  69  -70  2011/09
  • Ptenノックアウト前立腺癌モデルにおけるsorafenibの治療効果(Pre-clinical efficacy of sorafenib on a Pten knockout mouse prostate cancer model)
    山本 豊; デベラスコ・マルコ; 王 一; 畑中 祐二; 田中 基幹; 清水 信貴; 児玉 光正; 吉川 和宏; 荒尾 徳三; 西尾 和人; 植村 天受  日本癌学会総会記事  70回-  70  -70  2011/09
  • 高脂肪食摂取量の増大と前立腺癌の進行の関係に関するリスク評価のための臨床前モデル(A preclinical model to evaluate the risk of increased dietary fat consumption and prostate cancer progression)
    吉村 一宏; デベラスコ・マルコ; 畑中 祐二; 田中 基幹; 山本 豊; 王 一; 清水 信貴; 野澤 昌弘; 荒尾 徳三; 西尾 和人; 植村 天受  日本癌学会総会記事  70回-  101  -101  2011/09
  • 前立腺特異的PTENノックアウトマウスモデルを用いた前立腺癌におけるChemopreventionおよびInterventionに関する研究(Use of prostate-specific PTEN conditional knockout mice in prostate cancer prevention and intervention research)
    植村 天受; 田中 基幹; 小池 浩之; 山本 豊; 畑中 祐二; 王 一; 清水 信貴; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; デベラスコ・マルコ  日本癌学会総会記事  70回-  161  -161  2011/09
  • HOXA10 expression in prostate cancer(HOXA10 is aberrantly expressed in prostate cancer)
    畑中 祐二; デベラスコ・マルコ; 王 一; 山本 豊; 田中 基幹; 清水 信貴; 児玉 光正; 吉川 和宏; 荒尾 徳三; 西尾 和人; 植村 天受  日本癌学会総会記事  70回-  439  -439  2011/09
  • Kazuko Sakai; Tokuzo Arao; Kazuko Matsumoto; Hideharu Kimura; Yoshihiko Fujita; Hiroyasu Kaneda; Daisuke Tamura; Keiichi Aomatsu; Kanae Kudo; Tomoyuki Nagai; Marco A. De Velasco; Isamu Okamoto; Kazuhiko Nakagawa; Kazuto Nishio  CANCER RESEARCH  71-  2011/04
  • 山本 豊; マルコ デ ベラスコ; 宮崎 友香; 朝日 千織; 牛田 博; 吉川 和宏; 酒井 和子; 西尾 和人; 植村 天受  日本泌尿器科學會雜誌  102-  (2)  409  -409  2011/03
  • 清水 信貴; De Velasco Marco A.; 梅川 徹; 植村 天受; 吉川 和宏  日本泌尿器科学会雑誌  102-  (2)  351  -351  2011/03  [Refereed]
  • 小池 浩之; デベラスコ・マルコ; 山本 豊; 畑中 祐二; ワン・イー; 島田 啓司; 吉川 和宏; 荒尾 徳三; 西尾 和人; 小西 登; 植村 天受  日本泌尿器科学会雑誌  102-  (2)  489  -489  2011/03
  • デベラスコ・マルコ; 田中 基幹; 島田 健二; 小池 浩之; 宮崎 友佳; 朝日 千織; 牛田 博; 西尾 和人; 植村 天受  日本泌尿器科学会雑誌  102-  (2)  489  -489  2011/03
  • 畑中 祐二; デベラスコ・マルコ; 清水 信貴; 山本 豊; 田中 基幹; 宮崎 友佳; 朝日 千織; 牛田 博; 冨岡 厚志; 吉川 和宏; 西尾 和人; 植村 天受  日本泌尿器科学会雑誌  102-  (2)  539  -539  2011/03
  • 前立腺がんの基礎・臨床研究の最前線 前立腺特異的PTENコンディショナルノックアウトマウスモデルによるヒト前立腺癌への応用(Front line of basic and clinical researches of prostate cancer The prostate-specific PTEN conditional knockout mouse as a model for human prostate cancer)
    デベラスコ・マルコ; 小池 浩之; 吉川 和宏; 荒尾 徳三; 西尾 和人; 植村 天受  日本癌学会総会記事  69回-  363  -363  2010/08
  • Hiroyuki Koike; Marco A. De Velasco; Yuka Miyazaki; Chiori Asahi; Hiroshi Ushida; Keiji Shimada; Kazuhiro Yoshikawa; Kazuto Nishio; Noboru Konishi; Hirotsugu Uemura  CANCER RESEARCH  70-  2010/04
  • CD138を介したホルモン不応性前立腺癌進展メカニズムの解析と病理学的意義について
    島田 啓司; De Velasco Marco A.; 植村 天受; 田崎 正人; 小西 登  日本病理学会会誌  99-  (1)  203  -203  2010/03  [Refereed]
  • 高悪性度膀胱癌におけるCyclooxygenase2(COX2)を介したakt活性化の病理学的意義について
    大嶋 正人; 島田 啓司; De Velasco Marco A.; 田崎 正人; 植村 天受; 小西 登  日本病理学会会誌  99-  (1)  344  -344  2010/03  [Refereed]
  • 全並 賢二; 吉川 和宏; 中村 小源太; 山田 芳彰; 本多 靖明; デベラスコ マルコ; 植村 天授; 島居 徹; 赤座 英之; 近藤 栄作; 上田 龍三  日本泌尿器科學會雜誌  101-  (2)  211  -211  2010/02
  • Marco DeVelasco; Motoyoshi Tanaka; Atsushi Tomioka; Satoshi Anai; Hirotsugu Uemura  JOURNAL OF GENE MEDICINE  11-  (12)  1182  -1182  2009/12
  • Motoyoshi Tanaka; Satoshi Anai; Marco DeVelasco; Keigo Saito; Atsushi Tomioka; Kazuhiro Yoshikawa; Hirotsugu Uemura  JOURNAL OF GENE MEDICINE  11-  (12)  1183  -1183  2009/12
  • Satoshi Anai; Motoyoshi Tanaka; Marco De Velasco; Keigo Saito; Atsushi Tomioka; Kazuhiro Yoshikawa; Toru Shimazhui; Eisaku Kondo; Yoshihiko Hirao; Hirotsugu Uemura  JOURNAL OF GENE MEDICINE  11-  (12)  1181  -1181  2009/12
  • エクソンアレイとSNPアレイによるがん細胞株のエクソン異常の探索(Whole genome exon array and SNP array detected alternative splicing in gastrointestinal cancer cell lines)
    古田 一行; 荒尾 徳三; 坂井 和子; 永井 知行; 田村 大介; 青松 圭一; 工藤 可苗; デベラスコ・マルコ; 金田 裕靖; 藤田 至彦; 松本 和子; 関島 勝; 西尾 和人  日本癌学会総会記事  68回-  165  -165  2009/08
  • mTORシグナルとHIF-1 alphaは癌細胞のCD133の発現を制御する(mTOR signal and HIF-1 alpha regulate CD133 expression in cancer cells)
    松本 和子; 荒尾 徳三; 坂井 和子; 永井 知行; 田村 大介; 青松 圭一; 工藤 可苗; デベラスコ・マルコ; 金田 裕靖; 藤田 至彦; 山田 康秀; 西尾 和人  日本癌学会総会記事  68回-  276  -276  2009/08
  • 血液標本における新規薬物動態バイオマーカーの血管新生阻害剤BIBF1120の抗腫瘍活性(Antitumor activity of a novel angiogenesis inhibitor BIBF1120 a new pharamacodynamic biomarker in blood samples)
    工藤 可苗; 荒尾 徳三; 坂井 和子; 永井 知行; 田村 大介; 青松 圭一; デベラスコ・マルコ; 金田 裕靖; 藤田 至彦; 松本 和子; 工藤 正俊; 西尾 和人  日本癌学会総会記事  68回-  484  -484  2009/08
  • Motoyoshi Tanaka; Marco De Velasco; Keiji Shimada; Hirotsugu Uemura  CANCER RESEARCH  69-  2009/05
  • Kazuhiro Yoshikawa; Kenji Zennami; Kogenta Nakamura; Nobuaki Honda; Eisaku Kondo; Toru Shimazui; Motoyoshi Tanaka; Marco De Velasco; Horotsugu Uemura; Hideyuki Akaza; Ryuzo Ueda  CANCER RESEARCH  69-  2009/05
  • Marco De Velasco; Motoyoshi Tanaka; Kazuto Nishio; Hirotsugu Uemura  CANCER RESEARCH  69-  2009/05
  • 田中 基幹; デベラスコ マルコ; 島田 啓司; 植村 天受  日本泌尿器科學會雜誌  100-  (2)  147  -147  2009/02
  • マルコ・デベラスコ; 田中 基幹; 植村 天受  日本泌尿器科学会雑誌  100-  (2)  341  -341  2009/02
  • 吉川 元清; デベラスコ・マルコ; 大関 孝之; 田中 基幹; 植村 天受  日本泌尿器科学会雑誌  100-  (2)  380  -380  2009/02
  • 全並 賢二; 吉川 和宏; 中村 小源太; 山田 芳彰; 本多 靖明; マルコ・デベラスコ; 田中 基幹; 植村 天受; 島居 徹; 赤座 英之; 近藤 英作; 上田 龍三  日本泌尿器科学会雑誌  100-  (2)  126  -126  2009/02
  • Motoyoshi Tanaka; Marco de Velasco; Hirotsugu Uemura  UroToday International Journal  1-  (3)  2008/09
  • リポソーム化ドキソルビシン膀胱内注入によるマウス膀胱癌モデルでの検討(Intravesical administration of liposomal doxorubicin in mouse orthotopic bladder cancer model)
    吉川 元清; デベラスコ・マルコ; 田中 基幹; 佐塚 泰之; 穴井 智; 植村 天受  日本癌学会総会記事  67回-  356  -356  2008/09
  • Pten機能性ペプチドによる前立腺癌治療の試み(Pten functional peptide therapy in prostate cancer)
    田中 基幹; 穴井 智; デベラスコ・マルコ; 吉川 和宏; 植村 天受  日本癌学会総会記事  67回-  370  -370  2008/09
  • 腎細胞癌における、テーラーメイド医療に向けた動物モデル(Tumor explant animal model: aiming towards tailor-made therapy of renal cell carcinoma)
    デベラスコ・マルコ; 田中 基幹; 吉川 元清; 穴井 智; 西尾 和人; 植村 天受  日本癌学会総会記事  67回-  183  -183  2008/09
  • ユニークなインターロック分子 ロタキサンの抗がん物質としての有用性(Rotaxane, a unique interlocked molecule, as a potential antitumor agent)
    藤田 至彦; 小野 信文; 高田 十志和; パトラ・ラジャシュリー; デベラスコ・マルコ; 横手 秀行; 荒尾 徳三; 松本 和子; 前川 麻里; 田中 薫; 金田 裕靖; 工藤 可苗; 西尾 和人  日本癌学会総会記事  67回-  391  -391  2008/09
  • Satoshi Anai; Motoyoshi Tanaka; Marco De Velasco; Keigo Saito; Atsushi Tomioka; Tomohiro Ikeda; Kazuhiro Yoshikawa; Toru Shimazui; Eisaku Kondo; Yoshihiko Hirao; Hirotsugu Uemura  JOURNAL OF UROLOGY  179-  (4)  228  -229  2008/04
  • Motoyoshi Tanaka; Satoshi Anai; Keigo Saito; Marco De Velasco; Atsushi Tomioka; Kazuhiro Yoshikawa; Hirotsugu Uemura  JOURNAL OF UROLOGY  179-  (4)  224  -224  2008/04
  • 田中 基幹; 野澤 昌弘; マルコ デベラスコ; 植村 天受  日本泌尿器科學會雜誌  99-  (2)  2008/02
  • 田中 基幹; 穴井 智; 冨岡 厚志; デベラスコ マルコ; 齋藤 桂吾; 吉川 和宏; 植村 天受  日本泌尿器科學會雜誌  99-  (2)  232  -232  2008/02
  • 穴井 智; 田中 基幹; デベラスコ・マルコ; 池田 朋博; 冨岡 厚志; 島居 徹; 近藤 英作; 吉川 和宏; 平尾 佳彦; 植村 天授  日本泌尿器科学会雑誌  99-  (2)  229  -229  2008/02
  • 田中 基幹; 野澤 昌弘; デベラスコ・マルコ; 植村 天受  日本泌尿器科学会雑誌  99-  (2)  162  -162  2008/02
  • Tomioka Atsushi; Tanaka Motoyoshi; Anai Satoshi; Ikeda Tomohiro; Shimada Keiji; Velasco Marco; Saito Keigo; Hirao Yoshihiko; Uemura Hirotsugu  The Japanese Journal of Urology  99-  (2)  149  -149  2008
  • 前立腺癌に対する新しいPTENペプチド療法(The novel PTEN peptide therapy for prostate cancer)
    穴井 智; 田中 基幹; De Velasco Marco; 冨岡 篤志; 池田 朋博; 吉川 和宏; 藤本 清秀; 平尾 佳彦; 植村 天授  日本癌学会総会記事  66回-  384  -384  2007/08  [Refereed]
  • 前立腺特異的PTEN欠損マウスにおける前立腺発癌(Cancer development in the mouse by prostate specific deletion of PTEN)
    冨岡 厚志; 田中 基幹; 穴井 智; De Velasco Marco; 植村 天受; 平尾 佳彦  日本癌学会総会記事  66回-  117  -117  2007/08  [Refereed]
  • マウス同所性膀胱癌モデルにおける画像解析を用いた評価法(Use of Image Analysis of Treatment Response in Mouse Orthotopic Bladder Cancer Model)
    デベラスコ・マルコ; 田中 基幹; 穴井 智; 冨岡 厚志; 杉山 育美; 佐塚 泰之; 西尾 和人; 植村 天受  日本癌学会総会記事  66回-  121  -121  2007/08
  • 新規連結分子ロタキサンの抗腫瘍活性と作用様式(Antitumor activitiy and mode of action of a unique interlocked molecule rotaxane)
    藤田 至彦; 小野 信文; 高田 十志和; デベラスコ・マルコ; 横手 秀行; 荒尾 徳三; 松本 和子; 前川 麻里; 田中 薫; 金田 裕靖; 阿部 譲; 西尾 和人  日本癌学会総会記事  66回-  205  -205  2007/08
  • 変異型EGFRのシグナル伝達経路(A novel signaling pathway of deletional mutant EGFR)
    前川 麻里; 横手 秀行; 松本 和子; 田中 薫; 金田 裕靖; 藤田 至彦; デベラスコ・マルコ; 荒尾 徳三; 小泉 史明; 伊藤 文昭; 西尾 和人  日本癌学会総会記事  66回-  501  -501  2007/08
  • フコシル化によるEGFレセプター活性化の制御とEGFR-TKIの感受性の検討(Regulation of EGFR activity through N-glycan fucosylation and effect on the sensitivity of EGFR-TKI)
    松本 和子; 横手 秀行; 前川 麻里; 田中 薫; 金田 裕靖; デベラスコ・マルコ; 藤田 至彦; 荒尾 徳三; 西尾 和人  日本癌学会総会記事  66回-  501  -501  2007/08
  • 佐塚 泰之; 杉山 育美; De Velasco Marco; 穴井 智; 富岡 厚志; 田中 基幹  薬剤学: 生命とくすり  67-  (Suppl.)  356  -356  2007/05  [Refereed]
  • Atsushi Tomioka; Satoshi Anai; Yoshihiko Hirao; Keiji Shimada; Marco DeVelasco; Motoyoshi Tanaka; Hirotsugu Uemura  JOURNAL OF UROLOGY  177-  (4)  218  -219  2007/04
  • R. Molina; J. M. Auge; M. Munoz; J. Pahisa; A. Torne; M. Velasco; B. Farrus; X. Filella  TUMOR BIOLOGY  28-  21  -21  2007
  • S Cobb; M Velasco; P Singh  GASTROENTEROLOGY  124-  (4)  A461  -A462  2003/04
  • M Velasco; TC Wang; R Given; M Wargovich; P Singh  GASTROENTEROLOGY  116-  (4)  A524  -A524  1999/04
  • P Singh; M Velasco; R Given; A Owlia; M Wargovich; TC Wang  GASTROENTEROLOGY  114-  (4)  A680  -A680  1998/04
  • MM Morse; LM Lichtenberger; EJ Dial; JJ Romero; MJ Wargovich; M Velasco  GASTROENTEROLOGY  112-  (4)  A620  -A620  1997/04
  • PC Chang; MA Velasco; JJ Lee; JH Sellin; MJ Wargovich  GASTROENTEROLOGY  110-  (4)  A502  -A502  1996/04
  • MJ WARGOVICH; A JIMENEZ; VE STEELE; M VELASCO; GJ KELLOFF  GASTROENTEROLOGY  108-  (4)  A551  -A551  1995/04

Lectures, oral presentations, etc.

  • Marco A De Velasco; Yurie Kura; Noriko Sako; Naomi Ando; Kazuko Sakai; Eri Banno; Shogo Adomi; Mitsuhisa Nishimoto; Takafumi Minami; Yasunori Mori; Kazutoshi Fujita; Masahiro Nozawa Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    American Association for Cancer Research Annual Meeting 2023  2023/04
  • Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Cancer Research  2021/07  American Association for Cancer Research
  • Marco A. De Velasco; Kazuko Sakai; Yurie Kura; Naomi Ando; Noriko Sako; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Cancer Research  2021/07  American Association for Cancer Research
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Kazuko Sakai; Nobutaka Shimizu; Eri Banno; Masahiro Nozawa; Kazuhiro Fujita; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Cancer Research  2021/07  American Association for Cancer Research
  • Marco A. De Velasco; Yurie Kura; Noriko Sako; Naomi Ando; Kazuko Sakai; Alwin Schuller; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Cancer Research  2021/07  American Association for Cancer Research
  • Marco A. De Velasco; Kazuko Sakai; Yurie Kura; Eri Banno; Naomi Ando; Noriko Sako; Nobutaka Shimizu; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Cancer Research  2021/07  American Association for Cancer Research
  • Preclinical Study of JAK1/2 Inhibitors and PD-L1 Inhibitors with Androgen Deprivation Therapy in a Mouse Model of Prostate Cancer
    Yurie Kura; De Velasco Marco; Kazuko Sakai; Kazuto Nishio; Hirotsugu Uemura
    The 25th Annual Meeting of the Japanese Association for Molecular Target Therapy of Cancer  2021/05
  • Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    American Association for Cancer Research Annual Meeting 2021  2021/05  AACR
  • From mouse to human: Focused gene panel immunoprofiling
    Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Hideki Nakagaki; Kazuto Nishio; Hirotsugu Uemura
    2021 the Japanease Society of Medical Oncology Annual Meeting  2021/02
  • Preclinical evaluation of androgen deprivation with JAK1/2 and PD-L1 inhibition in mouse Pten-deficient prostate cancer
    Yurie Kura; Marco A. De Velasco; Naomi Ando; Noriko Sako; Kazuko Sakai; Kazuto Nishio; Hirotsugu Uemura
    2021 the Japanease Society of Medical Oncology Annual Meeting  2021/02
  • Targeting extracellular adenosine in mouse Pten-deficient prostate cancer
    Marco A. De Velasco; Yurie Kura; Noriko Sako; Naomi Ando; Kazuko Sakai; Alwin Schuller; Kazuto Nishio; Hirotsugu Uemura
    2021 the Japanease Society of Medical Oncology Annual Meeting  2021/02
  • A real-time PCR-based approach to quantitatively assess tumor immune profiles and immune responses
    Hirotsugu Uemura; Yurie Kura; Kazuko Sakai; Nobutaka Shimizu; Yasunori Mori; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A. De Velasco
    The 108th Annual Meating of the Japanease Urological Association  2020/12
  • Immunomodulation of TAS-115, a Multi-Tyrosine Kinase Inhibitor, in a Prostate Cancer Specific Pten Knockout Mouse Model
    Yurie Kura; Marco A. De Velasco; Kazuko Sakai; Nobutaka Shimizu; Yasunori Mori; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    The 108th Annual Meating of the Japanease Urological Association  2020/12
  • Targeting the androgen receptor to remodel the tumor microenvironment of prostate cancers
    Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Nobutaka Shimizu; Yasunori Mori; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    The 108th Annual Meating of the Japanease Urological Association  2020/12
  • Profiling the fecal microbiome of mouse Pten-deficient prostate cancer
    Yurie Kura; Kazuko Sakai; Yoshihiko Fujita; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A De Velasco; Hirotsugu Uemura
    The 79th Annual Meeting of the Japanese Cancer Association  2020/10
  • Sequencing androgen deprivation augments the antitumor efficacy of immunotherapy in mouse Pten-null prostate cancer
    Hirotsugu Uemura; Yurie Kura; Kazuko Sakai; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A De Velasco
    The 79th Annual Meeting of the Japanese Cancer Association  2020/10
  • Effects of JAK1/2 targeted therapy for Pten-deficient prostate cancer on the fecal microbiome
    Marco A De Velasco; Yurie Kura; Kazuko Sakai; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    The 79th Annual Meeting of the Japanese Cancer Association  2020/10
  • Interactome analysis of colitis-induced colorectal cancer and microbiota diversity
    Kazuto Nishio; Kazuko Sakai; Yurie Kura; Kyoshiro Takegahara; Marco A De Velasco
    The 79th Annual Meeting of the Japanese Cancer Association  2020/10
  • Cross-species gene expression analysis for gene-based immunoprofiling
    Eri Banno; Yurie Kura; Kazuko Sakai; Yoshihiko Fujita; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A De Velasco; Hirotsugu Uemura
    The 79th Annual Meeting of the Japanese Cancer Association  2020/10
  • Androgen deprivation following JAK1/2 and PD-L1 inhibition improves antitumor efficacy in mouse models of Pten-deficient prostate cancer
    Marco A De Velasco; Yurie Kura; Naomi Ando; Noriko Sako; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    Annual Meeting of the American Association for Cancer Research 2020  2020/06
  • Systemic targeted JAK1/2 therapy for mouse Pten-deficient prostate cancer model influences the diversity and composition of the gut microbiome
    A. De Velasco; Kazuko Sakai; Yurie Kura; Naomi Ando; Noriko Sako; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    Annual Meeting of the American Association for Cancer Research 2020  2020/06
  • Prostate cancer alters gut microbiota in mice
    Marco A De Velasco; Kazuko Sakai; Yurie Kura; Eri Banno; Naomi Ando; Noriko Sako; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    American Association for Cancer Research 2020  2020/06
  • The multi tyrosine kinase inhibitor TAS-115 promotes innate and adaptive immune responses of androgen deprivation therapy in mouse prostate cancer  [Not invited]
    Marco A De Velasco; Yurie Kura; Naomi Ando; Noriko Sako; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    Annual Meeting of the American Association for Cancer Research 2020  2020/06
  • Cross-species analysis and immunophenotyping using of a focused panel of immune-responsive genes
    Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Hideki Nakagaki; Kazuto Nishio; Hirotsugu Uemura
    Annual Meeting of the American Association for Cancer Research 2020  2020/06
  • Targeting A2aR in mouse Pten-deficient prostate cancer
    Marco A De Velasco; Yurie Kura; Noriko Sako; Naomi Ando; Kazuko Sakai; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Alwin Schuller; Kazuto Nishio; Hirotsugu Uemura
    Annual Meeting of the American Association for Cancer Research 2020  2020/06
  • De Velasco, Marco A.; Kura, Yurie; Sato, Noriko; Ando, Naomi; Sakai, Kazuko; Yoshimura, Kazuhiro; Nozawa, Masahiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER RESEARCH  2019/07  AMER ASSOC CANCER RESEARCH
  • Mon, Yasunori; De Velasco, Marco A.; Kura, Yurie; Benno, Eh; Ando, Naomi; Sato, Noriko; Nozawa, Masahiro; Yoshimura, Kazuhiro; Sakai, Kazuko; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER RESEARCH  2019/07  AMER ASSOC CANCER RESEARCH
  • De Velasco, Marco A.; Kura, Yurie; Sato, Noriko; Ando, Naomi; Sakai, Kazuko; Mori, Yasunori; Davies, Barry R.; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER RESEARCH  2019/07  AMER ASSOC CANCER RESEARCH
  • De Velasco, Marco A.; Kura, Yurie; Ando, Naomi; Sato, Noriko; Nozawa, Masahiro; Yoshimura, Kazuhiro; Sakai, Kazuko; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER RESEARCH  2019/07  AMER ASSOC CANCER RESEARCH
  • Effect of abiraterone therapy on anti-tumor immunity in a mouse Pten-deficient prostate cancer model  [Not invited]
    Shimizu, Nobutaka; De Velasco, Marco A.; Kura, Yurie; Ozeki, Takayuki; Mori, Yasunori; Nozawa, Masahiro; Yoshimura, Kazuhiro; Sakai, Kazuko; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER SCIENCE  2018/12  WILEY
  • Preclinical evaluation of the multi tyrosine kinase inhibitor TAS-115 in mouse Pten-deficient prostate cancer  [Not invited]
    Nozawa, Masahiro; De Velasco, Marco A.; Kura, Yurie; Shimizu, Nobutaka; Mori, Yasunori; Yoshimura, Kazuhiro; Sakai, Kazuko; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER SCIENCE  2018/12  WILEY
  • PIM inhibition reduces tumor growth and improves survival in mouse advanced castration-resistant prostate cancer  [Not invited]
    Kura, Yurie; De Velasco, Marco A.; Mori, Yasunori; Shimizu, Nobutaka; Ozeki, Takayuki; Sakai, Kazuko; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER SCIENCE  2018/12  WILEY
  • Preclinical activity of apalutamide (ARN-509) in genetically engineered mouse models of Pten-deficient prostate cancer  [Not invited]
    Mori, Yasunori; De Velasco, Marco A.; Kura, Yurie; Ozeki, Takayuki; Shimizu, Nobutaka; Nozawa, Masahiro; Yoshimura, Kazuhiro; Sakai, Kazuko; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER SCIENCE  2018/12  WILEY
  • Identification of a gene set associated with poor clinical outcomes in prostate cancer patients  [Not invited]
    Hashimoto, Mamoru; De Velasco, Marco A.; Kura, Yurie; Sakai, Kazuko; Shimizu, Nobutaka; Mori, Yasunori; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER SCIENCE  2018/12  WILEY
  • Interrogating genetically engineered mouse models of prostate cancer to aid in immunotherapy development  [Not invited]
    De Velasco, Marco A.; Kura, Yurie; Mori, Yasunori; Shimizu, Nobutaka; Ozeki, Takayuki; Sakai, Kazuko; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER SCIENCE  2018/12  WILEY
  • De Velasco, Marco A.; Kura, Yurie; Ando, Naomi Ando; Sato, Noriko; Davies, Barry R.; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER RESEARCH  2018/07  AMER ASSOC CANCER RESEARCH
  • De Velasco, Marco A.; Nozawa, Masahiro; Kura, Yurie; Ando, Naomi; Sato, Noriko; Yoshimura, Kazuhiro; Sakai, Kazuko; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER RESEARCH  2018/07  AMER ASSOC CANCER RESEARCH
  • De Velasco, Marco A.; Kura, Yurie; Ando, Naomi; Sato, Noriko; Nozawa, Masahiro; Yoshimura, Kazuhiro; Sakai, Kazuko; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER RESEARCH  2018/07  AMER ASSOC CANCER RESEARCH
  • De Velasco, Marco A.; Kura, Yurie; Ando, Naomi; Sakai, Kazuko; Davies, Barry R.; Kim, Youngsoo; MacLeod, A. Robert; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER RESEARCH  2018/07  AMER ASSOC CANCER RESEARCH
  • Banno, Eri; De Velasco, Marco A.; Kura, Yurie; Ando, Naomi; Sato, Noriko; Nozawa, Masahiro; Yoshimura, Kazuhiro; Sakai, Kazuko; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER RESEARCH  2018/07  AMER ASSOC CANCER RESEARCH
  • Marco A De Velasco; Yurie Kura; Naomi Ando; Kazuko Sakai; Barry R Davies; Youngsoo Kim; A Robert MacLeod; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    2018/04
  • Eri Banno; Marco A. De Velasco; Yurie Kura; Naomi Ando; Noriko Sato; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    AACR Annual Meeting 2018  2018/04
  • HIF-1 alpha-derived peptide capable of inducing cancer-reactive cytotoxic T lymphocytes from HLA-A24+patients with RCC  [Not invited]
    Minami, Takafumi; Sugimoto, Koichi; Shimizu, Nobutaka; De Velasco, Marco; Nozawa, Masahiro; Yoshimura, Kazuhiro; Harashima, Nanae; Harada, Mamoru; Uemura, Hirotsugu
    CANCER SCIENCE  2018/01  WILEY
  • Comprehensive preclinical assessment of novel compounds using genetically engineered mouse models of prostate cancer  [Not invited]
    Uemura, Hirotsugu; Kura, Yurie; Sugimoto, Kouichi; Mori, Yasunori; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; De Velasco, Marco A.
    CANCER SCIENCE  2018/01  WILEY
  • Targeting prostate cancer with next generation antisense oligonucleotide against androgen receptor and AKT inhibition  [Not invited]
    Sugimoto, Kouichi; De Velasco, Marco A.; Kura, Yurie; Sakai, Kazuko; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER SCIENCE  2018/01  WILEY
  • PD-L1 immune checkpoint blockade in genetically engineered mouse models of prostate cancer  [Not invited]
    Shimizu, Nobutaka; De Velasco, Marco A.; Kura, Yurie; Sakai, Kazuko; Sugimoto, Kouichi; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER SCIENCE  2018/01  WILEY
  • Targeting AKT and Pim kinases improves treatment responses in preclinical models of PTEN-deficient prostate cancer  [Not invited]
    Kura, Yurie; De Velasco, Marco A.; Sugimoto, Kouichi; Sakai, Kazuko; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER SCIENCE  2018/01  WILEY
  • STAT3 activity in human prostate cancer  [Not invited]
    Mori, Yasunori; De Velasco, Marco A.; Hatanaka, Yuji; Kura, Yurie; Sugimoto, Kouichi; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER SCIENCE  2018/01  WILEY
  • Comprehensive analyses of tumor immunity in PTEN-deficient mouse models of prostate cancer  [Not invited]
    De Velasco, Marco A.; Kura, Yurie; Sakai, Kazuko; Sugimoto, Kouichi; Nozawa, Masahiro; Yoshimura, Kazuhiro; Yoshikawa, Kazuhiro; Nishio, Kazuto; Uemura, Hirotsugu
    CANCER SCIENCE  2018/01  WILEY
  • Comprehensive preclinical assessment of novel compounds using genetically engineered mouse models of prostate cancer  [Not invited]
    Hirotsugu Uemura; Yurie Kura; Kouichi Sugimoto; Yasunori Mori; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A De Velasco
    The 76th Annual Meeting of the Japanese Cancer Association  2017/09
  • Targeting AKT and Pim kinases improves treatment responses in preclinical models of PTEN-deficient prostate cancer  [Not invited]
    Yurie Kura; Marco A De Velasco; Kouichi Sugimoto; Kazuko Sakai; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    The 76th Annual Scientific Meeting of the Japanese Cancer Association  2017/09
  • PD-L1 immune checkpoint blockade in genetically engineered mouse models of prostate cancer  [Not invited]
    Nobutaka Shimizu; Marco A De Velasco; Yurie Kura; Kazuko Sakai; Kouichi Sugimoto; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    The 76th Annual Scientific Meeting of the Japanese Cancer Association  2017/09
  • Targeting prostate cancer with next generation antisense oligonucleotide against androgen receptor and AKT inhibition  [Not invited]
    Kouichi Sugimoto; Marco A De Velasco; Yurie Kura; Kazuko Sakai; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    The 76th Annual Scientific Meeting of the Japanese Cancer Association  2017/09
  • HIF-1 alpha-derived peptide capable of inducing cancer-reactive cytotoxic T lymphocytes from HLA-A24+ patients with RCC  [Not invited]
    Takafumi Minami; Koichi Sugimoto; Nobutaka Shimizu; Marco De Velasco; Masahiro Nozawa; Kazuhiro Yoshimura; Nanae Harashima; Mamoru Harada; Hirotsugu Uemura
    The 76th Annual Scientific Meeting of the Japanese Cancer Association  2017/09
  • STAT3 activity in human prostate cancer  [Not invited]
    Yasunori Mori; Marco A De Velasco; Yuji Hatanaka; Yurie Kura; Kouichi Sugimoto; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    The 76th Annual Scientific Meeting of the Japanese Cancer Association  2017/09
  • Comprehensive analyses of tumor immunity in PTEN-deficient mouse models of prostate cancer  [Not invited]
    Marco A De Velasco; Yurie Kura; Kazuko Sakai; Kouichi Sugimoto; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    The 76th Annual Scientific Meeting of the Japanese Cancer Association  2017/09
  • Marco A De Velasco; Koichi Sugimoto; Yurie Kura; Naomi Ando; Noriko Sato; Kazuko Sakai; Barry R Davies; Dennis Huszar; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC  2017/04
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Koichi Sugimoto; Kazuko Sakai; Barry R. Davies; Youngsoo Kim; A. Robert MacLeod; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC  2017/04
  • Marco A De Velasco; Yurie Kura; Naomi Ando; Noriko Sato; Kazuko Sakai; Barry R Davies; Koichi Sugimoto; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC  2017/04
  • Marco A De Velasco; Yuji Hatanaka; Yurie Kura; Naomi Ando; Kazuko Sakai; Koichi Sugimoto; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC  2017/04
  • Rich Woessner; Vasu Sah; Patricia McCoon; Shaun Grosskurth; Nanhua Deng; Rachel DuPont; Deborah Lawson; Lourdes Pablo; Corinne Reimer; Marco A. De Velasco; Hirotsugu Uemura; Juliana Candido; Paul Lyne
    AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC  2017/04
  • FGFR gene alterations in lung squamous cell carcinoma are potential targets for the multikinase inhibitor nintedanib.  [Not invited]
    Sakai K; Hibi M; Kaneda H; Tanizaki J; Togashi Y; Terashima M; Velasco MA; Fujita Y; Banno E; Nakamura Y; Takeda M; Ito A; Mitsudomi T; Nakagawa K; Nishio K
    The 12th International Conference on Protein Phosphatase  2016/10
  • Marco A De Velasco; Koichi Sugimoto; Yurie Kura; Yuji Hatanaka; Yutaka Yamamoto; Takashi Oki; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    107th Annual Meeting of the American Association for Cancer Research  2016
  • Marco A De Velasco; Yurie Kura; Kazuko Sakai; Yoshihiko Fujita; Yosuke Togashi; Masato Terashima; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    107th Annual Meeting of the American Association for Cancer Research  2016
  • Marco A De Velasco; Yurie Kura; Kazuko Sakai; Yuji Hatanaka; Yoshihiko Fujita; Yosuke Togashi; Masato Terashima; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    107th Annual Meeting of the American Association for Cancer Research  2016
  • Marco A De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Takashi Oki; Kazuhiro Yoshimura; Masahiro Nozawa; Barry R Davies; Dennis Huszdar; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    107th Annual Meeting of the American Association for Cancer Research  2016
  • Marco A De Velasco; Yurie Kura; Yuji Hatanaka; Takashi Oki; Yutaka Yamamoto; Koichi Sugimoto; Yasunori Mori; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    107th Annual Meeting of the American Association for Cancer Research  2016
  • Y Togashi; Y Nakamura; S Tomida; H Hayashi; MA de Velasco; K Sakai; Y Fujita; S Hamada; K Nishio
    European Society for Medical Oncology  2015
  • Yosuke Togashi; Hiroshi Mizuuchi; Kazuko Sakai; Eri Banno; Hidetoshi Hayashi; Marco de Velasco; Yoshihiko Fujita; Shuta Tomida; Tetsuya Mitsudomi; Kazuto Nishio
    European Society for Medical Oncology  2015
  • Takuro Mizukami; Yosuke Togashi; Shunsuke Sogabe; Marco A de Velasco; Kazuko Sakai; Yoshihiro Fujita; Shuta Tomida; Takako Eguchi Nakajima; Narikazu Boku; Kazuto Nishio
    European Society for Medical Oncology  2015
  • Clinicopathological and genetic differences between low-grade and high-grade colorectal mucinous adenocarcinoma  [Not invited]
    Y Togashi; Y Yoshioka; T Chikugo; M Terashima; T Mizukami; H Hayashi; K Sakai; M De Velasco; S Tomida; Y Fujita; K Okuno; K Nishio
    European Cancer Congress  2015
  • T Mizukami; Y Togashi; E Banno; M Terashima; MA De Velasco; K Sakai; H Hayashi; Y Fujita; S Tomida; T Eguchi Nakajima; N Boku; A Ito; K Nakagawa; K Nishio
    European Cancer Congress  2015
  • Marco A De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Barry R Davies; Hayley Campbell; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    106th Annual Meeting of the American Association for Cancer Research  2015
  • Marco A De Velasco; Yutaka Yamamoto; Yurie Kura; Emiko Fukushima; Naomi Ando; Barry Davies; Yuji Hatanaka; Takashi Oki; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    106th Annual Meeting of the American Association for Cancer Research  2015
  • Marco A De Velasco; Yuji Hatanaka; Yurie Kura; Emiko Fukushima; Naomi Ando; Barry R Davies; Yutaka Yamamoto; Takashi Oki; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    106th Annual Meeting of the American Association for Cancer Research  2015
  • Kazuhiro Yoshikawa; Marco A De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yutaka Yamamoto; Yuji Hatanaka; Takashi Oki; Nobutaka Shimizu; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    106th Annual Meeting of the American Association for Cancer Research  2015
  • Marco A De Velasco; Takashi Oki; Yurie Kura; Naomi Ando; Emiko Fukushima; Barry R Davies; Dennis Huszar; Yutaka Yamamoto; Yuji Hatanaka; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    106th Annual Meeting of the American Association for Cancer Research  2015
  • Yoshihiko Fujita; Satoshi Koinuma; Marco De Velasco; Bolz Jan; Yosuke Togashi; Masato Terashima; Hidetoshi Hayashi; Takuya Matsuo; Kazuto Nishio
    106th Annual Meeting of the American Association for Cancer Research  2015
  • Kazuhiro Yoshikawa; Marco A De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuto Nishio; Hirotsugu Uemura
    105th Annual Meeting of the American Association for Cancer Research  2014
  • Hirotsugu Uemura; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A De Velasco
    105th Annual Meeting of the American Association for Cancer Research  2014
  • Marco A De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    105th Annual Meeting of the American Association for Cancer Research  2014
  • Yurie Kura; Marco A De Velasco; Naomi Ando; Emiko Fukushima; Yutaka Yamamoto; Yuji Hatanaka; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    105th Annual Meeting of the American Association for Cancer Research  2014
  • Marco A De Velasco; Yuji Hatanaka; Takashi Oki; Yurie Kura; Yutaka Yamamoto; Kazuhiro Yoshimura; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    105th Annual Meeting of the American Association for Cancer Research  2014
  • Marco A De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    105th Annual Meeting of the American Association for Cancer Research  2014
  • M Terashima; K Sakai; Y Fujita; MA De Velasco; K Nishio
    11th Annual Meeting of the Japanese Society of Medical Oncology  2013
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    104th Annual Meeting of the American Association for Cancer Research  2013
  • Marco A De Velasco; Yutaka Yamamoto; Yuji Hatanaka; Yurie Kura; Naomi Ando; Emiko Fukushima; Masahiro Nozawa; Nobutaka Shimizu; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    104th Annual Meeting of the American Association for Cancer Research  2013
  • Hirotsugu Uemura; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A De Velasco
    104th Annual Meeting of the American Association for Cancer Research  2013
  • Yurie Kura; Marco A De Velasco; Yasuyuki Kobayashi; Naomi Ando; Emiko Fukushima; Yutaka Yamamoto; Yuji Hatanaka; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    104th Annual Meeting of the American Association for Cancer Research  2013
  • Marco A De Velasco; Yuji Hatanaka; Yurie Kura; Naomi Ando; Emiko Fukushima; Yutaka Yamamoto; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    104th Annual Meeting of the American Association for Cancer Research  2013
  • Marco A De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    104th Annual Meeting of the American Association for Cancer Research  2013
  • H Kaneda; T Arao; K Tanaka; K Matsumoto; H Kimura; T Nagai; K Sakai; Y Fujita; MA De Velasco; Y Yamada; J Tsurutani; I Okamoto; K Nakagawa; K Nishio
    10th Annual Meeting of JSMO  2012
  • Yasuyuki Kobayashi; Marco A De Velasco; Yuji Hatanaka; Yutaka Yamamoto; Motoyoshi Tanaka; Nozawa Masahiro; Nobutaka Shimizu; Kazuhiro Yoshimura; Mitsuyama Kodama; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    103rd Annual Meeting of the American Association for Cancer Research  2012
  • Yuji Hatanaka; Marco A De Velasco; Yurie Kura; Yuji Yamamoto; Mitsumasa Kodama; Masahiro Nozawa; Nobutaka Shimizu; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    103rd Annual Meeting of the American Association for Cancer Research  2012
  • Kazuhiro Yoshimura; Marco A De Velasco; Yuji Hatanaka; Yutaka Yamamoto; Mitsumasa Kodama; Motoyoshi Tanaka; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    103rd Annual Meeting of the American Association for Cancer Research  2012
  • Marco A De Velasco; Motoyoshi Tanaka; Kaori Fujimoto-Ouchi; Yoichiro Moriya; Yurie Kura; Yasuki Kobayashi; Yutaka Yamamoto; Yuji Hatanaka; Hiroyuki Kato; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    103rd Annual Meeting of the American Association for Cancer Research  2012
  • Hidetoshi Hayashi; Tokuzo Arao; Kazuko Matsumoto; Tomoyuki Nagai; Hideharu Kimura; Marco A De Velasco; Yoshihiko Fujita; Yasuhide Yamada; Isamu Okamoto; Kazuhiko Nakagawa; Kazuto Nishio
    103rd Annual Meeting of the American Association for Cancer Research  2012
  • H Kaneda; T Arao; K Tanaka; K Matsumoto; H Kimura; T Nagai; Y Fujita; MA De Velasco; Y Yamada; I Okamoto; K Nakagawa; K Nishio
    10th Annual Meeting of JSMO  2012
  • Yutaka Yamamoto; Marco A De Velasco; Yuji Hatanaka; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Mitsumasa Kodama; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    103rd Annual Meeting of the American Association for Cancer Research  2012
  • Yutaka Yamamoto; Marco A De Velasco; Yi Wang; Ayaka Izumi; Erina Okazaki; Makiko Doi; Yuji Hatanaka; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Hirotugu Uemura
    102nd Annual Meeting of the American Association for Cancer Research  2011
  • Yuji Hatanaka; Marco A De Velasco; Motoyoshi Tanaka; Makiko Doi; Erina Okazaki; Ayaka Izumi; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    102nd Annual Meeting of the American Association for Cancer Research  2011
  • Hirotsugu Uemura; Yuji Hatanaka; Ayaka Izumi; Erina Okazaki; Makiko Doi; Motoyoshi Tanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A De Velasco
    102nd Annual Meeting of the American Association for Cancer Research  2011
  • Hirotsugu Uemura; Marco De Velasco; Kazuhiro Yoshimura; Masahiro Nozawa; Takafumi Minami
    2011 AUA Annual Meeting  2011
  • Marco A De Velasco; Erina Okazaki; Yi Wang; Ayaka Izumi; Yuji Hatanaka; Motoyoshi Tanaka; Charles Rosser; Steve Goodison; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotugu Uemura
    102nd Annual Meeting of the American Association for Cancer Research  2011
  • Yi Wang; Marco A De Velasco; Erina Okazaki; Ayaka Izumi; Motoyoshi Tanka; Yutaka Yamamoto; Yuji Hatanaka; Kazuhiro Yoshimura; Masahiro Nozawa; Charles Rosser; Steve Goodison; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotugu Uemura
    102nd Annual Meeting of the American Association for Cancer Research  2011
  • Kazuko Sakai; Tokuzo Arao; Kazuko Matsumoto; Hideharu Kimura; Yoshihiko Fujita; Hiroyasu Kaneda; Daisuke Tamura; Keiichi Aomatsu; Kanae Kudo; Tomoyuki Nagai; Marco A De Velasco; Isamu Okamoto; Kazuhiko Nakagawa; Kazuto Nishio
    102nd Annual Meeting of the American Association for Cancer Research  2011
  • Hirotsugu Uemura; Hiroshi Ushida; Chiori Asahi; Yuka Miyazaki; Kazuhiro Yoshikawa; Marco A De Velasco
    101st Annual Meeting of the American Association for Cancer Research  2010
  • Kazuhiro Yoshikawa; Marco A De Velasco; Motoyoshi Tanaka; Yuka Miyazaki; Hiroshi Ushida; Chiori Asahi; Kazuto Nishio; Hirotsugu Uemura
    101st Annual Meeting of the American Association for Cancer Research  2010
  • Marco A De Velasco; Chiori Asahi; Yuka Miyazaki; Hiroshi Ushida; Keiji Shimada; Kazuhiro Yoshikawa; Kazuto Nishio; Noboru Konishi; Hirotsugu Uemura
    101st Annual Meeting of the American Association for Cancer Research  2010
  • Hiroyasu Kaneda; Tokuzo Arao; Kaoru Tanaka; Daisuke Tamura; Keiichi Aomatsu; Kanae Kudo; Kazuko Sakai; Marco Antonio De Velasco; Kazuko Matsumoto; Fujita Yoshihiko; Yasuhide Yamada; Junji Tsurutani; Isamu Okamoto; Kazuhiko Nakagawa; Kazuto Nishio; Tomoyuki Nagai; Kazuyuki Furuta
    101st Annual Meeting of the American Association for Cancer Research  2010
  • Marco A De Velasco; Motoyoshi Tanaka; Keiji Shimada; Kazuto Nishio; Hirotsugu Uemura
    AACR International Conference on Frontiers in Cancer Prevention Research  2010
  • Hiroyuki Koike; Marco A De Velasco; Yuka Miyazaki; Chiori Asahi; Hiroshi Ushida; Keiji Shimada; Kazuhiro Yoshikawa; Kazuto Nishio; Noboru Konishi; Hirotsugu Uemura
    101st Annual Meeting of the American Association for Cancer Research  2010
  • デベラスコ マルコ; 田中 基幹; 植村 天受
    The Japanese Journal of Urology  2009/02
  • Kazuhiro Yoshikawa; Kenji Zennami; Kogenta Nakamura; Nobuaki Honda; Eisaku Kondo; Toru Shimazui; Motoyoshi Tanaka; Marco De Velasco; Hirotsugu Uemura; Hideyuki Akaza; Ryuzo Ueda
    AACR Annual Meeting  2009
  • Motoyoshi Tanaka; Marco De Velasco; Keiji Shimada; Hirotsugu Uemura
    AACR Annual Meeting  2009
  • Marco De Velasco; Motoyoshi Tanaka; Kazuto Nishio; Hirotsugu Uemura
    100th American Association for Cancer Research Annual Meeting  2009
  • Satoshi Anai; Motoyoshi Tanaka; Marco De Velasco; Keigo Saito; Atsushi Tomioka; Tomohiro Ikeda; Kazuhiro Yoshikawa; Toru Shimazui; Eisaku Kondo; Yoshihiko Hirao; Hirotsugu Uemura
    2008 AUA Annual Meeting  2008
  • Satoshi Anai; Motoyoshi Tanaka; Marco De Velasco; Keigo Saito; Atsushi Tomioka; Tomohiro Ikeda; Kazuhiro Yoshikawa; Toru Shimazui; Eisaku Kondo; Yoshihiko Hirao; Hirotsugu Uemura
    AACR Annual Meeting  2008
  • Satoshi Anai; Motoyoshi Tanaka; Marco De Velasco; Keigo Saito; Atsushi Tomioka; Kazuhiro Yoshikawa; Toru Shimazhui; Eisaku Kondo; Yoshihiko Hirao; Hirotsugu Uemura
    The 14th Annual Meeting 2008 Japan Society of Gene Therapy  2008
  • Motoyoshi Tanaka; Satoshi Anai; Keigo Saito; Marco De Velasco; Atsushi Tomioka; Kazuhiro Yoshikawa; Hirotsugu Uemura
    2008 AUA Annual Meeting  2008
  • Marco De Velasco; Motoyoshi Tanaka; Keigo Saito; Satoshi Anai; Kazuto Nishio; Hirotsugu Uemura
    American Association for Cancer Research  2008
  • Atsushi Tomioka; Satoshi Anai; Yoshihiko Hirao; Keiji Shimada; Marco De Velasco; Motoyoshi Tanaka; Hirotsugu Uemura
    AACR Annual Meeting  2007
  • Marco De Velasco; Motoyoshi Tanaka; Satoshi Anai; Atsushi Tomioka; Sayaka Yoshiba; Kazuto Nishio; Hirotsugu Uemura
    American Association for Cancer Research Annual Meeting  2007
  • Motoyoshi Tanaka; Satoshi Anai; Marco De Velasco; Atsushi Tomioka; Ikumi Sugiyama; Yasuyuki Sadzuka; Hirotsugu Uemura
    American Association for Cancer Research  2007
  • MA Avila; LA Vergara; GX Yu; KA Eidson; BA Capra; MA Parsley; JC Cowart; M Velasco; DS Prough; DS DeWitt
    The 23rd Annual National Neurotrauma Society Symposium  2005
  • Marco Develasco
    Annual Meeting of the American Gastroenterological Association and Digestive Disease Week  2003
  • Full-length, unprocessed, progastrin peptide (PG) exerts proliferative effects on colonic mucosa of mice via high affinity binding sites, that are specific for gastrin-like peptides with negligible affinity for cholecystokinin  [Not invited]
    Stephanie Cobb; Azar Owlia; Xian B Lu; Randall Given; Marco Velasco; Brian Miller; Andrea Varro; Pomila Singh
    Annual Meeting of the American Gastroenterological Association and Digestive Disease Week  2001
  • Loss of functional gastrin gene results in significantly increasing the incidence of pre-neoplastic and neoplastic changes in the colonic mucosa of mice in response to azoxymethane (AOM)  [Not invited]
    Stephanie Cobb; Randall Given; Marco Velasco; Thomas Wood; Lino Tessarollo; Andrea Varro; Pomila Singh
    Annual Meeting of the American Gastroenterological Association and Digestive Disease Week  2001
  • Mammary and salivary epidermal growth factor in altered gravity  [Not invited]
    MA Velasco; E Durban; EM Durban
    MOLECULAR BIOLOGY OF THE CELL  2000
  • Non-amidated gastrins, but not amidated gastrins function as co-carcinogens in an azoxymethane (AOM) induced colon cancer model  [Not invited]
    M Velasco; TC Wang; R Given; M Wargovich; P Singh
    Annual Meeting of the American Gastroenterological Association and Digestive Disease Week  1999
  • P Singh; M Velasco; R Given; A Owlia; M Wargovich; TC Wang
    Annual Meeting of the American Gastroenterological Association and Digestive Disease Week  1998
  • Chemoprevention of aberrant crypt foci in the rat colon with aspirin (ASA), phosphatidylcholine (PC) and ASA-PC complex  [Not invited]
    MM Morse; LM Lichtenberger; EJ Dial; JJ Romero; MJ Wargovich; M Velasco
    Annual Meeting of the American Gastroenterological Association and Digestive Disease Week  1997
  • Altered expression of adhesion molecules in human aberrant crypt foci  [Not invited]
    PC Chang; MA Velasco; JJ Lee; JH Sellin; MJ Wargovich
    Annual Meeting of the American Gastroenterological Association and Digestive Disease Week  1996
  • Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression  [Not invited]
    MJ Wargovich; A Jimenez; VE Steele; M VELASCO; GJ KELLOFF
    Annual Meeting of the American Gastroenterological Association and Digestive Disease Week  1995

Affiliated academic society

  • THE JAPANESE UROLOGICAL ASSOCIATION   THE JAPANESE CANCER ASSOCIATION   American Association for Cancer Research   

Research Themes

  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2023/04 -2026/03 
    Author : 西尾 和人; 林 秀敏; デベラスコ マルコ; 坂井 和子
  • 日本学術振興会:科学研究費助成事業
    Date (from‐to) : 2023/04 -2026/03 
    Author : 藤田 和利; デベラスコ マルコ; 野々村 祝夫; 波多野 浩士; 植村 天受; 中村 昇太
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2023/04 -2026/03 
    Author : 西尾 和人; 林 秀敏; デベラスコ マルコ; 坂井 和子
  • 日本学術振興会:科学研究費助成事業 基盤研究(B)
    Date (from‐to) : 2022/04 -2025/03 
    Author : 植村 天受; デベラスコ マルコ; 原田 守; 南 高文
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2020/04 -2023/03 
    Author : 坂本 信一; 西尾 和人; 金田 篤志; 今村 有佑; デベラスコ マルコ; 坂井 和子; 川上 英良; 落谷 孝広; 安西 尚彦; 植村 天受
     
    1.前立腺癌細胞において、L型アミノ酸トランスポーター1(LAT1)とヘテロダイマーを構成するSLC3A2/4F2hcの解析を行った。C4-2細胞をsi4F2hcで処理すると、細胞の成長、移動性、浸潤性の能力が抑制される。また、4F2hcの下流分子がSKP2であることがRNA seqによって証明された。4F2hcの高発現は無増悪生存率の独立した予後因子であった。Sci Rep. 2021 Jun 1;11(1):11478.2.AR-V7を発現するCRPC細胞であるLNCaP95を比較して、エピゲノムとトランスクリプトームの解析を行った。ChIP-seq解析で同定された399個のAR-V7標的領域のうち、377個はホルモン刺激を受けたARが共通して標的となりうる領域であり、22個はAR-V7が特異的に標的とする領域であった。AR-V7ノックダウンによって最も抑制された遺伝子としてSLC3A2/4F2hcを同定した。Transl Oncol. 2021 Jan;14(1):100915. 3.L型アミノ酸トランスポーター3(LAT3、SLC43A1)は去勢感受性前立腺癌(PC)で豊富に発現。AR のクロマチン免疫沈降法シークエンスにおいて、SLC43A1 領域への AR の結合は、ジヒドロテストステロン刺激により増加した。LAT3 をノックダウンすると、細胞増殖、遊走、浸潤が抑制され、p70S6K と 4EBP-1 のリン酸化が抑制された。多変量解析では、LAT3の高発現は無再発生存の独立した予後因子であった(ハザード比:3.24;P = 0.0018)。Cancer Sci. 2021 Sep;112(9):3871-3883.
  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    Date (from‐to) : 2020/04 -2023/03 
    Author : デベラスコ マルコ; 植村 天受
     
    我々のトランスジェニックマウス前立腺癌モデル(去勢感受性癌および去勢抵抗性癌モデル)を用いて、内分泌治療(ADT)やアンドロゲンレセプターARをターゲットにした治療(ART)および他の増殖シグナルpathway分子(Jack1/2、PI3K/AKT、Parpなど)を標的とした治療に加え、抗PDL1抗体や抗CTLA4抗体を用いて免疫チェックポイント分子阻害による免疫治療による腫瘍微小免疫環境の変化などについて、これまでのpreclinical研究から得られた結果を参考に昨年度同様に基礎的検討行った。研究結果として、ADTにより腫瘍の微小免疫環境は炎症性分子をエンハンスすること、Jac1/2阻害と抗PDL1やA2aR阻害と抗CTLA4の併用により、ADTによる免疫抑制効果を抑制すること、樹状細胞の再活性化と抑制性T細胞の不活性化による抗腫瘍効果のUpdateについて、2021年の日本癌学会(JCA)で報告し、前立腺癌マウスモデルを用いた他の研究成果として、①ADTと腸内細菌プロファイルについて、②抗PDL1治療やJAK1/2阻害治療と腸内細菌プロファイルの関連について、③ADT+ART治療と腫瘍内の免疫環境の変化のUpdateについても、2021年9月のJCAで報告している(以下)。また、2022年4月開催のAACRにはこれらのUpdate結果がAcceptされ、報告する予定である。 演題番号:J14-9-3、演題番号:E12-4-1、演題番号:E14-8-4、演題番号:E17-1-3、演題番号:E3-4。(学会発表欄参照。)
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2019/04 -2022/03 
    Author : Uemura Hirotsugu
     
    We have been working on the development of new MHC Class-I restricted peptide vaccines for five independent therapeutic targets (CA9, VEGFR1, EPOR, PDL1, HIF1) and our studies have successfully resulted in two Japanese patents (#6900610, #6918333) in 2021. We are currently investigating immunological evaluations of our peptide vaccines with immune check point therapies using PBMCs from advanced RCC patients receiving IO-drugs. Most of the data such as ability of specific CTL induction are not reported in public due to patent.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2017/04 -2020/03 
    Author : DE VELASCO Marco
     
    We previously showed that androgen withdrawal led to increased alternatively spliced products in our originally established mouse prostate tumors. Here, we perform gene expression analysis this mouse prostate cancer model to identify candidate mRNA processing genes implicated in the progression to castration-resistant disease. Affymetrix GeneChip mouse transcriptome assay to perform comparative analysis of the transcriptomes of normal prostate tissue and PTEN-deficient castration-naïve, castration-sensitive prostate cancers. Clustering analysis revealed genes enriched with the functions involved in mRNA splicing and processing in mice with prostate tumors. Of these. We focused on NEAT1(encoding nuclear paraspeckle assembly transcript 1)and investigated anti-tumor effects using our mouse prostate cancer model. A part of the date was reported at JCA and AACR meetings.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2016/04 -2019/03 
    Author : UEMURA Hirotsugu
     
    We have been working on the development of new MHC-class-I restricted peptide vaccines for five independent therapeutic targets (CA9、VEGFR1、EPOR、PDL1、HIF1)and have identified a significant candidate a part of HLA-A2 restricted peptide vaccines (EPOR, PDL1 and HIF1). We are currently investigating their clinical relevance. Together with CA9 and VEGFR1 previously developed peptide vaccines, we will establish multi-peptide vaccination system using these five peptide vaccines.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2014/04 -2017/03 
    Author : DE VELASCO Marco
     
    We have previously developed a PTEN flox/PSA-Cre transgenic mouse prostate cancer model. In the current research, we focused on p53 (Trp53) to establish a more aggressive metastatic prostate cancer model. Using the same gene engineering method, we established a PSA-conditional PTEN/p53 double knockout (PTEN/p53 DKO) mouse prostate cancer model. Mice with DKO homo-deletion develop an aggressive phenotype characterized by a higher incidence of metastasis, including multiple metastases to lungs, liver, lymph nodes and other distant organs, and decreased survival (median overall survival, 55 weeks of the age), enabling us to use the PTEN/p53 DKO mouse model to evaluate the therapeutic efficacy in a ramdomised controlled studies with similar end points of PFS and OS to a human phase-3 trial. These findings demonstrate the usefulness of the PTEN/p53 DKO mouse prostate cancer model for the preclinical development of novel treatment strategies for prostate cancer.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2013/04 -2016/03 
    Author : UEMURA Hirotsugu; DEVELASCO Marco; MINAMI Takafumi; HARADA Mamoru; YOSHIMURA Kazuhiro
     
    We have been working on the development of new MHC-class-I restricted peptide vaccines for five independent therapeutic targets and have identified a significant candidate EPOR, PDL1 and HIF1. We made the application of patents for EPOR and PDL1 peptide vaccine and are preparing the application for HIF1. Together with CA9 and VEGFR1 previously developed peptide vaccines, we established multi-peptide vaccination system using these five peptide vaccines.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    Date (from‐to) : 2011 -2012 
    Author : NOZAWA Masahiro; YOSHIDA Munehiro; DEVELASCO Marco
     
    e conducted this study to research the effect of selenium intake on prevention of the prostate cancer using a mouse model. As a result, no significant difference was detected in the occurrence of prostate cancer among three groups of mice that had been fed with the control or low- or high-concentration selenium-containing feeds.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2010 -2012 
    Author : UEMURA Hirotsugu; MINAMI Takafumi; DE VELASCO Marco; HARADA Mamoru; YOSHIMURA Kazuhiro
     
    e have been working on the development of new MHC-class-I restricted peptide vaccines for five independent therapeutic targets and have identified a significant candidate EPORxx. We are preparing the application of a patent for this particular peptide vaccine. We also carried out phase-I/II clinical study with VEGFR1 peptide vaccines for 18 patients with disseminated renal cell carcinoma, and showed the safty and efficacy of the vaccination treatment.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2010 -2012 
    Author : DE VELASCO Marco; UEMURA Hirotsugu
     
    To better understand the disease process of prostate cancer, we have developed a prostate-specific conditional knockout mouse model that targets the PTEN tumor suppressor gene. Our model is based on PSA-Cre recombinase driven inactivation of Pten to alter PI3K/Akt/mTOR signaling specific to the prostate, resulting in a stage-specific development and progression of cancer that mimics humans recapitulating various stages of disease progression ranging from precancerous PIN lesions to castration resistant prostate cancer. We performed several experiments that demonstrate the versatility and usefulness of this model for validation of preclinical targeted intervention, biomarker discovery (leptin, lumican and HOXA10) and characterizing lifestyle behavior effects on cancer progression.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    Date (from‐to) : 2009 -2010 
    Author : SHIMADA Keiji; KONISHI Noboru; TSUJIKAWA Kazutake; OUJI Yukiteru; DEVELASCO Marco; TANAKA Motoyoshi; FUJIMOTO Kiyohide; HIRAO Yoshihiko
     
    We found for the first time that a novel DNA repair protein, hABH-8 promotes survival of human urothelial carcinoma cells through up-regulating generation of reactive oxygen species, moreover, the expression of hABH-8 is a useful marker to predict clinical development of urinary bladder cancer.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2007 -2008 
    Author : TANAKA Motoyoshi; UEMURA Hirotsugu; NOZAWA Masahiro; DEVELASCO Marco; YOSHIKAWA Kazuhiro; SHIMADA Keiji
     
    我々はPTENという癌抑制伝子を中心に前立腺癌の研究を重ねてきた。今回樹立したPTEN遺伝子改変マウスは、前立腺における多段階発癌と徐睾術によりホルモン抵抗性前立腺癌-移行する前立腺癌発症モデルである。このモデルを中心に前立腺癌の発癌機序解明およびホルモン抵抗性獲得の分子機構の網羅的な解析を行った。また、選択的Cox2阻害薬(Meloxicam)による癌予防研究、さらに新規合成したペプチドによる創薬の有用性をこのモデルを用いて検証した。