Faculty Profiles - FUJIWARA Toshiyoshi

MISC - FUJIWARA Toshiyoshi

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Effects of a novel palatinose based enteral formula (MHN-01) carbohydrate-adjusted fluid diet in improving the metabolism of carbohydrates and lipids in patients with esophageal cancer complicated by diabetes mellitus

Toshiya Fujiwara, Yoshio Naomoto, Takayuki Motoki, Kaori Shigemitsu, Yasuhiro Shirakawa, Tomoki Yamatsuji, Masafumi Kataoka, Minoru Haisa, Toshiyoshi Fujiwara, Maritoki Egi, Hiroshi Morimatsu, Motohiko Hanazaki, Hiroshi Katayama, Kiyoshi Morita, Kenji Mizumoto, Takanobu Asou, Hirofumi Arima, Hajime Sasaki, Motoi Matsuura, Mehmet Gunduz, Noriaki Tanaka

JOURNAL OF SURGICAL RESEARCH 138 ( 2 ) 231 - 240 2007.4

Language：English Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

Background. During perioperative management of patients with gastrointestinal cancer complicated by diabetes mellitus, adequate alimentation is required, but we often face difficulties associated with hyperglycemia and other accompanying complications. Recently, we investigated the effects of a novel palatinose based enteral formula (MHN-01) in suppressing post-prandial hyperglycemia and improving lipid metabolism in experimental animals and perioperative management of patients with esophageal cancer complicated by diabetes mellitus.
Materials and methods. We gave normal rats and rats with type 2 diabetes mellitus a single oral dose of fluid diet, and analyzed comparatively the time course of blood glucose level in each group until 3 h after the dose. In both the normal rat group and the type 2 diabetes group, peak blood glucose level after the MHN-01 dose was significantly lower than after a dose of ordinary fluid diet and was comparable to the peak level after a dose of a fluid diet rich in MUFA (monounsaturated fatty acid). We allowed normal mice free access to fluid diet for 43 days, and measured their body fat levels. Fat accumulation was significantly lower in mice given MHN-01 than in mice given ordinary fluid diet. We also analyzed the respiratory quotient and resting energy expenditure of normal Sprague-Dawley rats fed by MHN-01 or an ordinary fluid diet. The respiratory quotient of the MHN-01 group was significantly lower than the ordinary fluid group, although the resting energy expenditure of both groups was almost the same level. The effect of MHN-01 was estimated to be based on improvement of lipid metabolism.
Results. Between 2003 and 2005, among 164 patients who underwent radical thoracic esophagectomy and/or reconstruction for esophageal carcinoma at Okayama University Hospital, nine patients (5.5%) were diagnosed with diabetes mellitus in preoperative screening and were treated with MHN-01. Clinical courses of two cases with severe status of diabetes mellitus were presented as successful case reports of MHN-01.
Conclusion. MHN-01 was very useful in perioperative management of patients complicated by diabetes mellitus, unable to ingest food p.o. such as esophageal cancer or other diseases. (c) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jss.2006.06.025

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DP-139-6 切除不能gastrointestinalstromaltumor(GIST)に対する制限増殖型アデノウイルス(Telome-lysin)を用いた新規癌ウイルス療法の確立(第107回日本外科学会定期学術集会)

寺石文則, 橋本悠里, 児島亨, 宇野太, 香川俊輔, 合地明, 田中紀章, 藤原俊義

日本外科学会雑誌 108 ( 2 ) 598 - 598 2007.3

DP-190-6 食道癌周術期管理におけるCTの有用性の検討(第107回日本外科学会定期学術集会)

藤原康宏, 猶本良夫, 田辺俊介, 櫻間一史, 高岡宗徳, 白川靖博, 山辻知樹, 小林直哉, 藤原俊義, 松原長秀, 羽井佐実, 岩垣博巳, 松岡順治, 田中紀章

日本外科学会雑誌 108 ( 2 ) 700 - 700 2007.3

胃癌腹膜播種に対するTRAIL発現 oncolytic adenovirus の抗腫瘍効果

香川俊輔, 日置勝義, 池田義博, 児島亨, 酒井亮, 宇野太, 寺石文則, 橋本悠里, 浦田泰生, 田中紀章, 藤原俊義

日本外科学会雑誌 108 310 - 310 2007.3

DP-190-1 パラチノースを主糖質源とした調整流動食MHN-01(Inslow)の糖質脂質代謝改善効果 : 糖尿病合併食道癌周術期栄養管理への応用(第107回日本外科学会定期学術集会)

山辻知樹, 猶本良夫, 藤原俊哉, 田辺俊介, 藤原康宏, 元木崇之, 渡辺信之, 櫻間一史, 田淵陽子, 大多和泰幸, 鴨宣之, 西川敏雄, 高岡宗徳, 伊藤充矢, 白川靖博, 藤原俊義, 松原長秀, 岩垣博巳, 松剛順治, 羽井佐実, 田中紀章

日本外科学会雑誌 108 ( 2 ) 699 - 699 2007.3

DP-180-4 食道癌放射線化学療法施行後に発症した骨髄異形成症候群の検討(第107回日本外科学会定期学術集会)

田辺俊介, 猶本良夫, 藤原康宏, 櫻間一史, 高岡宗徳, 白川靖博, 山辻知樹, 小林直哉, 藤原俊義, 松原長秀, 羽井佐実, 岩垣博巳, 松岡順治, 田中紀章

日本外科学会雑誌 108 ( 2 ) 679 - 679 2007.3

消化器癌の微小リンパ節転移を標的とする新規ウイルス製剤OBP-301による治療法の開発

児島亨, 藤原俊義, 渡辺雄一, 橋本悠里, 酒井亮, 黒田新士, 浦田泰生, 宇野太, 香川俊輔, 田中紀章

日本外科学会雑誌 108 77 - 77 2007.3

Telomerase-specific oncolytic virotherapy for human cancer with the hTERT promoter

Toshiyoshi Fujiwara, Yasuo Urata, Noriaki Tanaka

CURRENT CANCER DRUG TARGETS 7 ( 2 ) 191 - 201 2007.3

Language：English Publishing type：Book review, literature introduction, etc. Publisher：BENTHAM SCIENCE PUBL LTD

Replication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. For targeting cancer cells, there is a need for tissue- or cell-specific promoters that can express in diverse tumor types and are silent in normal cells. Recent advances in molecular biology have fostered remarkable insights into the molecular basis of neoplasm. Telomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. Since only tumor cells that express telomerase activity would activate this promoter, the hTERT proximal promoter allows for preferential expression of viral genes in tumor cells, leading to selective viral replication. We constructed an attenuated adenovirus 5 vector (Telotnelysin, OBP-301), in which the hTERT promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site (IRES). Telomelysin replicated efficiently and induced marked cell killing in a panel of human cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal human cells lacking telomerase activity. Thus, the hTERT promoter confers competence for selective replication of Telomelysin in human cancer cells, an outcome that has important implications for the treatment of human cancers. This article reviews recent findings in this rapidly evolving field: cancer therapeutic and cancer diagnostic approaches using the hTERT promoter.

DOI： 10.2174/156800907780058835

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Telomerase-specific oncolytic virotherapy for human cancer with the hTERT promoter

Toshiyoshi Fujiwara, Yasuo Urata, Noriaki Tanaka

Current Cancer Drug Targets 7 ( 2 ) 191 - 201 2007.3

Language：English Publishing type：Book review, literature introduction, etc.

Replication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. For targeting cancer cells, there is a need for tissue- or cell-specific promoters that can express in diverse tumor types and are silent in normal cells. Recent advances in molecular biology have fostered remarkable insights into the molecular basis of neoplasm. Telomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. Since only tumor cells that express telomerase activity would activate this promoter, the hTERT proximal promoter allows for preferential expression of viral genes in tumor cells, leading to selective viral replication. We constructed an attenuated adenovirus 5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site (IRES). Telomelysin replicated efficiently and induced marked cell killing in a panel of human cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal human cells lacking telomerase activity. Thus, the hTERT promoter confers competence for selective replication of Telomelysin in human cancer cells, an outcome that has important implications for the treatment of human cancers. This article reviews recent findings in this rapidly evolving field: cancer therapeutic and cancer diagnostic approaches using the hTERT promoter. © 2007 Bentham Science Publishers Ltd.

DOI： 10.2174/156800907780058835

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PubMed

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Clonal and parallel evolution of primary lung cancers and their metastases revealed by molecular dissection of cancer cells

Kenji Takahashi, Takashi Kohno, Shingo Matsumoto, Yukihiro Nakanishi, Yasuhito Arai, Seiichiro Yamamoto, Toshiyoshi Fujiwara, Noriaki Tanaka, Jun Yokota

CLINICAL CANCER RESEARCH 13 ( 1 ) 111 - 120 2007.1

Language：English Publisher：AMER ASSOC CANCER RESEARCH

Purpose: Several models of cancer progression, including clonal evolution, parallel evolution, and same-gene models, have been proposed to date. The purpose of this study is to investigate the authenticity of these models by comparison of accumulated genetic alterations between primary and corresponding metastatic lung cancers.
Experimental Design: A whole-genome allelic imbalance scanning using a high-resolution single nucleotide polymorphism array and mutational analysis of the p53, EGFR, and KRAS genes were done on eight sets of primary and metastatic lung cancers. Based on the genotype data, the natural history of each case was deduced, and candidate metastasis suppressor loci were determined.
Results: Five to 20 chromosomal regions showed allelic imbalance in each tumor. Accumulated genetic alterations were similar between primary and corresponding metastatic tumors, and the majority (>67%) of genetic alterations detected in metastatic tumors was also detected in the corresponding primary tumors. On the other hand, in seven of the eight cases, there were genetic alterations accumulated only in metastatic tumors. Among these alterations, allelic imbalances at chromosome 11p15 and 11p11-p13 regions were the most frequent ones (4 of 8, 50%). Likewise, four cases showed genetic alterations detected only In primary tumors.
Conclusions: The natural history of each case indicated that the process of metastasis varies among cases, and that all three models are applicable to lung cancer progression. According to the clonal and parallel evolution models, it is possible that a metastasis suppressor gene(s) for lung cancer is present on chromosome 11p.

DOI： 10.1158/1078-0432.CCR-06-0659

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Cisplatin/Docetaxel+同時性放射線照射が奏効し根治手術を施行し得たstage IIIA非小細胞肺癌の1例

寺石文則, 香川俊輔, 宇野太, 武田洋正, 瀧川奈義夫, 藤原俊義, 田中紀章

癌と化学療法 34 ( 9 ) 1493 - 1495 2007

A case of nodular silicosis mimicking metastatic lung tumors

62 ( 9 ) 1269 - 1271 2007

Focal GGO病変に対するCTガイド下肺生検についての検討

井上大作, 郷原英夫, 三村秀文, 加藤勝也, 平木隆夫, 藤原寛康, 田尻展久, 金澤右, 藤原俊義, 佐野由文, 伊達洋至

肺癌 47 ( 5 ) 2007

テロメラーゼ特異的ウイルス製剤の癌診断・治療への応用.

藤原俊義, 田中紀章

ゲノム医学 7 ( 2 ) 129 - 134 2007

GFP発現ウイルス製剤を用いた消化器癌微小転移のin vivoイメージングシステム.

藤原俊義, 田中紀章

医学のあゆみ 220 ( 8 ) 659 - 661 2007

Theranostic application of telomerase-specific oncolytic adenovirus for human cancer

Japanese journal of clinical medicine 65 ( 10 ) 1913 - 1922 2007

「腫瘍外科治療の最前線」癌のウイルス療法.

藤原俊義, 田中紀章

外科治療 96 ( Suppl ) 368 - 373 2007

Adenoviral p53 Gene Therapy for Lung Cancer

Fujiwara Toshiyoshi, Tanaka Noriaki

Okayama Igakkai Zasshi (Journal of Okayama Medical Association) 119 ( 3 ) 229?234 - 234 2007

Language：Japanese Publisher：Okayama Medical Association

To determine the feasibility, safety, humoral immune response, and biological activity of multiple intratumoral injections of Ad5CMV-p53, and to characterize the pharmacokinetics of Ad5CMV-p53 in patients with advanced non-small cell lung cancer (NSCLC). Fifteen patients with histologically confirmed NSCLC and p53 mutations were enrolled into this phase I trial. Nine patients received escalating dose levels of Ad5CMV-p53 (1 × 10⁹ to 1 × 10¹¹ plaque-forming units[PFU]) as monotherapy once every 4 weeks. Six patients were treated on a 28-day schedule with Ad5CMV-p53 in combination with intravenous administration of cisplatin (80 mg/m²). Patients were monitored for toxicity, vector distribution, antibody formation, and tumor response. Fifteen patients received a total of 63 intratumoral injections of Ad5CMV-p53 without dose-limiting toxicity. The most common treatment-related toxicity was a transient fever. Specific p53 transgene expression was detected using reverse-transcriptase polymerase chain reaction in biopsied tumor tissues throughout the period of treatment despite of the presence of neutralizing anti-adenovirus antibody. Distribution studies revealed that the vector was detected in the gargle and plasma, but rarely in the urine. Thirteen of 15 patients were assessable for efficacy; one patient had a partial response (squamous cell carcinoma at the carina), 10 patients had stable disease, with three lasting ≥9 months, and 2 patients had progressive disease. Multiple courses of intratumoral Ad5CMV-p53 injection alone or in combination with intravenous administration of cisplatin were feasible and well tolerated in advanced NSCLC patients, and appeared to provide clinical benefit.

DOI： 10.4044/joma.119.229

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Other Link： http://ousar.lib.okayama-u.ac.jp/13215

ナノバイオ・ウイルス製剤のがん診断への応用.

藤原俊義

Medical Bio 4 ( 7 ) 39 - 43 2007

O-8 テロメラーゼ活性を標的とした新規腫瘍融解ウイルスによる悪性胸膜中皮腫の診断と治療(中皮腫, 第47回日本肺癌学会総会)

藤原俊義, 渡辺雄一, 橋本悠里, 香川俊輔, 宇野太, 寺石文則, 浦田泰生, 田中紀章

肺癌 46 ( 5 ) 488 - 488 2006.11

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