研究者詳細 - 藤原　俊義

MISC - 藤原　俊義

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Antiproliferative effect of the HSP90 inhibitor NVP-AUY922 is determined by the expression of PTEN in esophageal cancer

Xiao-Hong Bao, Munenori Takaoka, Hui-Fang Hao, Takuya Fukazawa, Tomoki Yamatsuji, Kazufumi Sakurama, Nagio Takigawa, Motowo Nakajima, Toshiyoshi Fujiwara, Yoshio Naomoto

ONCOLOGY REPORTS 29 ( 1 ) 45 - 50 2013年1月

記述言語：英語出版者・発行元：SPANDIDOS PUBL LTD

Heat shock protein 90 (HSP90), a molecular chaperone, has provoked great interest as a promising molecular target for cancer treatment, due to its involvement in regulating the conformation, stability and functions of key oncogenic proteins. At present, a variety of chemical compounds targeting HSP90 have been developed and have shown convincing anti-neoplastic activity in various preclinical tumor models. The aim of our study was to evaluate the antitumor effects of a novel HSP90 inhibitor, NVP-AUY922, in esophageal squamous cancer cells (ESCC). Four ESCC cell lines (TE-1, TE-4, TE-8, TE-10) were examined. NVP-AUY922 potently inhibited the proliferation of ESCC, particularly in PTEN-null TE-4 cells with a 2-3 times lower IC50 than the other three cell lines. Western blot analysis showed that PTEN-null TE-4 cells exhibited higher AKT and ERK activity, which contribute to cell proliferation and survival. NVP-AUY922 significantly suppressed the activity of AKT and ERK in TE-4 but not in PTEN-proficient TE-10 cells. Genetic modification experiments demonstrated that the sensitivity to NVP-AUY922 was decreased by exogenous transduction of PTEN in TE-4 and increased by silencing PTEN expression in intact PTEN-expressing TE-10, suggesting that the expression of PTEN may be associated with cell sensitivity in HSP90 inhibition. Furthermore, the enhanced activity of AKT in PTEN-silenced TE-10 was more easily suppressed by NVP-AUY922. Collectively, NVP-AUY922 exhibits a strong antiproliferative effect, revealing its potential as a novel therapeutic alternative to current ESCC treatment. The effect may be improved further by impeding PTEN expression.

DOI： 10.3892/or.2012.2074

Web of Science

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Peptide vaccines for hepatocellular carcinoma

Daisuke Nobuoka, Toshiaki Yoshikawa, Yu Sawada, Toshiyoshi Fujiwara, Tetsuya Nakatsura

HUMAN VACCINES & IMMUNOTHERAPEUTICS 9 ( 1 ) 210 - 212 2013年1月

記述言語：英語出版者・発行元：TAYLOR & FRANCIS INC

Immunotherapy is a potentially attractive treatment option for patients with hepatocellular carcinoma (HCC). We have reported that glypican-3 (GPC3) is an ideal target for anticancer immunotherapy against HCC because its expression is specifically detected in > 80% of HCCs, even during the early stages. Further, increased GPC3 expression is correlated with a poor prognosis. Based on results obtained from a preclinical study using mice, we conducted a phase I clinical trial using a GPC3-derived peptide vaccine. Phase I results showed that the GPC3-derived peptide vaccine was well tolerated. Furthermore, this was the first study to show that the frequency of peptide-specific cytotoxic T lymphocytes was correlated with overall survival in patients with HCC receiving a peptide vaccine. Next, we conducted a phase II clinical trial using the GPC3-derived peptide vaccine in patients with HCC after surgery or radiofrequency ablation (adjuvant setting). We are currently evaluating a third trial involving liver biopsies removed from patients with advanced HCC before and after GPC3-derived peptide vaccination. We expect that the results of these trials will result in future drug development.

DOI： 10.4161/hv.22473

Web of Science

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Isolation Efficiency of Mouse Pancreatic Stem Cells Is Age Dependent

Kuise T, Noguchi H, Saitoh I, Kataoka H, Watanabe M, Noguchi Y, Fujiwara T

Cell Medicine 2013年

遺伝子情報を用いた多臓器転移大腸癌の検討および治療戦略の構築.

稲田涼, 永坂岳司, 母里淑子, 楳田祐三, 森川達也, 久保田暢人, 竹原裕子, 河合毅, 宇野太, 八木孝仁, 藤原俊義

癌の臨床 2013年

直腸癌術後10年を経て発症した局所再発に対して治癒切除を施行した1例.

西江尚貴, 稲田涼, 母里淑子, 近藤喜太, 宇野太, 永坂岳司, 藤原俊義

癌と化学療法 2013年

術後5年を経て発症した肛門管粘液癌局所再発に対し治癒切除を施行した1例.

濱田侑紀, 稲田涼, 母里淑子, 近藤喜太, 永坂岳司, 藤原俊義

日本外科系連合学会誌 38 ( 5 ) 1086 - 1090 2013年

記述言語：日本語出版者・発行元：Japanese College of Surgeons

症例は60代男性．2005年肛門管癌に対して腹会陰式直腸切断術を施行．病理組織は粘液癌，pA，pN0，pH0，pP0，pM0，pStageⅡ，curAであった．術後観察していたが，2010年会陰部痛出現し，CTで骨盤内に長径90mmの多房性の充実性腫瘍を指摘され，局所再発と診断．再発病変に対して骨盤内臓全摘術を施行．術後大きな合併症なく第25病日に退院となった．病理診断にて粘液癌で初回手術後の再発を示唆，切除断端は陰性であった．再発手術後２年４カ月現在も無再発生存中である．大腸癌の組織型は多くが，高分化ないし中分化の腺癌であり，粘液癌の頻度は低い．粘液癌は分化度の高い癌に比べ，進行が早く，化学療法に抵抗性で，予後不良とされている．今回われわれは初回手術から５年を経て局所再発した粘液癌に対して骨盤内臓全摘術による治癒切除を行い，長期の無再発生存を得た症例を経験したので報告する．

DOI： 10.4030/jjcs.38.1086

CiNii Article

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術後感染予防のための抗菌薬使用ガイドライン.

篠浦先, 藤原俊義

岡山医学会雑誌 2013年

予後不良な経過をたどったBRAF遺伝子変異を伴うStage IV 大腸癌の１例.

稲田涼, 永坂岳司, 竹原清人, 杉原正大, 母里淑子, 楳田祐三, 久保田暢人, 森川達也, 近藤喜太, 宇野太, 貞森裕, 八木孝仁, 藤原俊義

岡山医学会雑誌 125 ( 1 ) 47 - 50 2013年

記述言語：日本語出版者・発行元：岡山医学会

A 79-year-old woman visited a previous hospital with a complaint of general fatigue. The patient was diagnosed with cecal cancer with multiple liver metastases and lymph node metastases on colonoscopy, abdominal ultrasonography and CT scan, and was referred to our division for treatment. Based on the diagnosis of non-curative colonic cancer, we planned to perform systematic chemotherapy after local surgical treatment. We performed an ileocecal resection, and the specimen showed poorly differentiated adenocarcinoma with mutation in the BRAF oncogene. After the surgical treatment, the tumor grew rapidly and the patient died from cancer on the 19th postoperative day without having the opportunity to undergo chemotherapy. Multiple genetic and epigenetic alterations in oncogenes and tumor suppressor genes are involved in the process of colorectal carcinogenesis. Some of the alterations have been identified as predictive and prognostic biomarkers. A mutation in the BRAF oncogene was reported to be associated with a very unfavorable prognosis in colorectal cancers. Some of the cases with rapid progression are suggested to have the BRAF oncogene mutation. According to our experience, chemotherapy before surgical treatment might improve the prognosis of cases with the BRAF mutation.

DOI： 10.4044/joma.125.47

CiNii Article

CiNii Books

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その他リンク： http://ousar.lib.okayama-u.ac.jp/49384

癌微小リンパ節転移を標的とするテロメラーゼ特異的制限増殖型ウイルス製剤の開発.

児島亨, 渡邉雄一, 橋本悠里, 黒田新士, 山崎泰源, 矢野修也, 田澤大, 宇野太, 香川俊輔, 田中紀章, 浦田泰生, 藤原俊義

岡山医学会雑誌 2013年

New Surgical Approach to Large Splenorenal Shunt in Living Donor Liver Transplantation: Diversion of SMV and SPV Blood Flow

Hiroshi Sadamori, Takahito Yagi, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Satoh, Daisuke Nobuoka, Masashi Utsumi, Toshiyoshi Fujiwara

Journal of Gastrointestinal Surgery 17 ( 2 ) 403 - 407 2013年

記述言語：英語

Introduction: The management of a large splenorenal shunt is important because it affects recipient outcome, particularly in living donor liver transplantation. Methods: To manage large splenorenal shunts in living donor liver transplantation, we diverted superior mesenteric vein and splenic portal vein blood flow by ligation at the root of the splenic portal vein. Result: This procedure was applied for five patients in whom superior mesenteric vein blood flow had been completely stolen by a splenorenal shunt preoperatively. Postoperative course was excellent in all cases. Conclusion: This technique completely prevents morbidity related to large splenorenal shunts after living donor liver transplantation. © 2012 The Society for Surgery of the Alimentary Tract.

DOI： 10.1007/s11605-012-2006-3

Scopus

PubMed

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生体肝移植におけるhigh mobility group box-1の動態解析．

貞森裕, 佐藤康晴, 西堀正洋, 佐藤太祐, 信岡大輔, 杉原正大, 八木孝仁, 藤原俊義

日本消化器外科学会雑誌 46 ( 3 ) 232 - 235 2013年

The Maximum standardized uptake value is more reliable than size measurement in early follow-up to evaluate potential pulmonary malignancies following radiofrequency ablation.

Alafate A, Shinya T, Okumura Y, Sato S, Hiraki T, Ishii H, Gobara H, Kato K, Fujiwara T, Miyoshi S, Kaji M, Kanazawa S

Acta Med Okayama 2013年

Successfully treated pneumatosis cystoides intestinalis with pneumoperitoneum onset in a patient administered α-glucosidase inhibitor.

Tanabe S, Shirakawa Y, Takehara Y, Maeda N, Katsube R, Ohara T, Sakurama K, Noma K, Fujiwara T

Acta Med Okayama 2013年

Living donor liver transplantation to a survivor of liver resection for hepatocellular carcinoma with major portal vein invasion.

Sadamori H, Yagi T, Shinoura S, Umeda Y, Yoshida R, Sato D, Nobuoka D, Utsumi M, Fujiwara T

Acta Med Okayama 2013年

進行食道癌における術前化学療法の現況.

田辺俊介, 白川靖博, 前田直見, 勝部亮一, 大原利章, 櫻間教文, 野間和広, 藤原俊義

癌と化学療法 2013年

遠隔転帰・再発を伴う進行S状結腸癌に対して集学的治療を行い長期生存を得た1例.

西江尚貴, 稲田涼, 母里淑子, 近藤喜太, 宇野太, 永坂岳司, 内海方嗣, 楳田祐三, 貞森裕, 八木孝仁, 藤原俊義

癌と化学療法 2013年

腫瘍融解アデノウイルスによるE2F1-マイクロRNA-7-EGFR経路を介したオートファジー細胞死の誘導分子機構.

田澤大, 矢野修也, 吉田亮介, 山崎泰源, 佐々木剛, 橋本悠里, 黒田新士, 大内正明, 大西哲平, 宇野太, 香川俊輔, 浦田泰生, 藤原俊義

岡山医学会雑誌 125 ( 3 ) 195 - 199 2013年

一次治療でセツキシマブ不耐となった後，三次治療での再使用により奏功した進行大腸癌の一例.

稲田涼, 永坂岳司, 母里淑子, 楳田祐三, 久保田暢人, 森川達也, 近藤喜太, 宇野太, 貞森裕, 八木孝仁, 藤原俊義

岡山医学会雑誌 2013年

イマチニブが長期に奏効している同時性肝転移を伴う消化管間質腫瘍の１例.

宇野太, 藤原康宏, 藤原俊義

岡山医学会雑誌 2013年

Occult Bleedingの検出により診断に至った, Hemosuccus Pancreaticusの1例.

杭瀬崇, 楳田祐三, 三村卓司, 金田道弘, 八木孝仁, 藤原俊義

胆と膵 2013年

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