Faculty Profiles - FUJIWARA Toshiyoshi

MISC - FUJIWARA Toshiyoshi

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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 2013.1

Language：English Publisher：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 2013.1

Language：English Publisher：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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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

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

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

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

A case of metastatic cecal cancer with mutation in the BRAF oncogene and poor survival

125 ( 1 ) 47 - 50 2013

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

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

Language：English

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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Kinetics of high-mobility group box 1 after living donor liver transplantation

Hiroshi Sadamori, Yasuharu Sato, Masahiro Nishibori, Daisuke Sato, Daisuke Nobuoka, Masahiro Sugihara, Takahito Yagi, Toshiyoshi Fujiwara

Japanese Journal of Gastroenterological Surgery 46 ( 3 ) 232 - 235 2013

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

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

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

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

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

Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis

125 ( 3 ) 195 - 199 2013

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

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

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

TWO CASES OF DIAPHRAGMATIC HERNIA FOLLOWING PERCUTANEOUS RADIOFREQUENCY ABLATION FOR HEPATOCELLULAR CARCINOMA

WATANABE Megumi, HAYASHI Dofu, MATSUMURA Toshihisa, NONAKA Yasuyuki, FUJIMARA Toshiyoshi

The journal of the Japanese Practical Surgeon Society 74 ( 8 ) 2128 - 2133 2013

Language：Japanese Publisher：Japan Surgical Association

Reports of diaphragmatic hernia associated with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) are rare. We report 2 cases of diaphragmatic hernia that developed after RFA for HCC. Case 1 involved a 65-year-old man who had undergone percutaneous RFA for HCC located in the S5 and S7 areas. Three years later, he underwent surgery from the abdominal cavity side based on the diagnosis of right diaphragmatic hernia made by another hospital. One year later, the right diaphragmatic hernia recurred, necessitating the performance of video-assisted thoracic surgery at our hospital. The defect of the diaphragm was covered with mesh. Case 2 involved a 73-year-old woman who had undergone percutaneous RFA for HCC located in the S7 area. Subsequently, she underwent 3 sessions of RFA for HCC localized in the S3, S1, and S4 areas. Seven years after the first RFA, right diaphragmatic hernia occurred, and we performed surgery via thoracotomy. The defect of the diaphragm was repaired by direct suture. The thoracotomic approach may be a safe and useful option for the treatment of diaphragmatic hernia after RFA.

DOI： 10.3919/jjsa.74.2128

CiNii Article

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2014115098

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