研究者詳細 - 藤原　俊義

MISC - 藤原　俊義

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特集今日の肺癌診療肺癌遺伝子治療の現状.

藤原俊義, 田中紀章

日本医師会雑誌 128,3,378 2002年

Combination of tumor necrosis factor alpha and interferon alpha induces apoptotic cell death through a c-myc-dependent pathway in p53 mutant H226br non-small-cell lung cancer cell line

Y Yasuoka, Y Naomoto, T Yamatsuji, M Takaoka, M Kimura, H Uetsuka, N Matsubara, T Fujiwara, M Gunduz, N Tanaka, M Haisa

EXPERIMENTAL CELL RESEARCH 271 ( 2 ) 214 - 222 2001年12月

記述言語：英語出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

We investigated the role of wild-type p53 and c-myc activity in apoptosis induced by a combination of natural human tumor necrosis factor alpha (TNF-alpha) and natural human interferon alpha (IFN-alpha). Studies were performed with two human non-small-cell lung cancer cell lines, H226b, which has wild-type p53, and H226br, which has a mutant p53. The combination of IFN-alpha and TNF-alpha significantly inhibited cell growth and induced apoptotic cell death of both H226b and H226br, compared with IFN-alpha or TNF-alpha alone. Treatment with one or both cytokines did not affect the expression level of p53 in both cell lines. These results suggest that the combination of IFN-alpha /TNF-alpha induces apoptotic cell death through a p53- independent pathway. The c-myc oncogene is known to be involved in apoptosis induced by TNF. Antisense c-myc oligonucleotides have been reported to modulate cell growth or apoptosis in several cell lines. Antisense oligodeoxynucleotides were added to the culture of H226br cells before the addition of IFN-alpha /TNF-alpha. Antisense c-myc inhibited IFN-alpha /TNF-alpha cytotoxicity and apoptotic cell death. In conclusion, this study provides support for the speculation that TNF-alpha /TFN-alpha induce apoptosis through a c-myc-dependent pathway rather than a p53-dependent pathway. (C) 2001 Elsevier Science.

DOI： 10.1006/excr.2001.5383

Web of Science

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Accelerated degradation of cellular FLIP protein through the ubiquitin-proteasome pathway in p53-mediated apoptosis of human cancer cells

Takuya Fukazawa, Toshiyoshi Fujiwara, Futoshi Uno, Fuminori Teraishi, Yoshihiko Kadowaki, Takahiro Itoshima, Yoshiko Takata, Shunsuke Kagawa, Jack A. Roth, Jürg Tschopp, Noriaki Tanaka

Oncogene 20 ( 37 ) 5225 - 5231 2001年8月

記述言語：英語

Apoptosis is a morphologically distinct form of programmed cell death that plays a major role in cancer treatments. This cellular suicide program is known to be regulated by many different signals from both intracellular and extracellular stimuli. Here we report that p53 suppressed expression of the cellular FLICE-inhibitory protein (FLIP) that potentially blocks apoptotic signaling in human colon cancer cell lines expressing mutated and wild-type p53. In contrast, the expression of the death receptor KILLER/DR5 (TRAIL-R2) had no effect on FLIP expression, although exogenous p53 is known to induce KILLER/DR5 expression. In line with these observations, FLIP-negative cancer cells were sensitive to both p53- and KILLER/DRS-mediated apoptosis, whereas cells containing high levels of FLIP underwent apoptotic cell death when triggered by ectopic p53 expression but not by KILLER/DR5 expression. Treating the cells with a specific inhibitor of the proteasome inhibited the decrease of FLIP by p53, suggesting that p53 enhances the degradation of FLIP via a ubiquitin-proteasome pathway. Thus, the data indicate that p53-mediated downregulation of FLIP may explain the potent sensitization of human cancer cells to the apoptotic suicide program induced by wild-type p53 gene transler.

DOI： 10.1038/sj.onc.1204673

Scopus

PubMed

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S08-03 Cre/loxP部位特異的組換え反応を用いた可逆性不死化ヒト肝臓細胞の再生医療への応用

小林直哉, 野口洋文, 松村年久, 渡辺剛正, 都津川敏範, 藤原俊義, 田中紀章

日本消化器外科学会雑誌 34 ( 7 ) 832 - 832 2001年7月

PD3-6 p53遺伝子異常を標的とした遺伝子治療:臨床試験の現況と問題点

藤原俊義, 片岡正文, 香川俊輔, 田中紀章

日本外科学会雑誌 102 51 - 51 2001年3月

SF1f-4 SV40TagとhTERTによる不死化ヒト肝類洞内皮細胞株の樹立

松村年久, 小林直哉, 野口洋文, 渡邉剛正, 都津川敏範, 藤原俊義, 田中紀章

日本外科学会雑誌 102 67 - 67 2001年3月

SF7c-2 肝細胞移植の発展に向けたテロメラーゼ遺伝子によるヒト肝細胞株の樹立

都津川敏範, 小林直哉, 野口洋文, 松村年久, 渡邉剛正, 藤原俊義, 田中紀章

日本外科学会雑誌 102 95 - 95 2001年3月

SF13a-2 高性能バイオ人工肝の実現に向けたヒト肝細胞株の樹立と至適培養担体の開発

小林直哉, 野口洋文, 松村年久, 渡邉剛正, 都津川敏範, 藤原俊義, 田中紀章

日本外科学会雑誌 102 109 - 109 2001年3月

SF13a-4 ヒト肝星様細胞へのレトロウイルスベクターによるテロメラーゼ遺伝子(hTERT)導入

渡辺剛正, 小林直哉, 野口洋文, 松村年久, 都津川敏範, 藤原俊義, 田中紀章

日本外科学会雑誌 102 110 - 110 2001年3月

p53を用いた遺伝子治療

藤原俊義, 田中紀章

「癌治療の先端に迫る！」（実験医学増刊）（黒木登志夫、編集）pp2564-2571、羊土社、東京、2001. 2001年1月

Insertion of suicide gene into an immortalized human hepatocyte cell line.

Kobayashi N, Noguchi H, Totsugawa T, Watanabe T, Matsumura T, Fujiwara T, Miyazaki M, Fukaya K, Namba M, Tanaka N

Cell Transplant 2001年

Accelerated degradation of cellular FLIP prostein through the ubiquitinproteasome pathway in p53-mediated apoptosis of human cancer cells.

Fukazawa T, Fujiwara T, Uno F, Teraishi F, Kadowaki Y, Itoshima T, Takata Y, Kagawa S, Roth JA, Tschpp J, Tanaka N

Oncogene 2001年

A tightly regulated immortalized human fetal hepatocyte cell line to develop a bioartificial liver.

Kobayashi N, Noguchi H, Watanabe T, Matsumura T, Totsugawa T, Fujiwara T, Tanaka N

Transplantation Proceedings 2001年

Role of immortalized hepatocyte transplantation in acute liver failure.

Kobayashi N, Noguchi H, Watanabe T, Matsumura T, Totsugawa T, Fujiwara T, Tanaka N

Transplantation Proceedings 2001年

Donor dendritic cells and recipient kupffer cells in the induction of donor-specific immune hyporesponsiveness.

Nakagawa K, Matsuno T, Iwagaki H, Morimoto Y, Fujiwara T, Sadamori H, Inagaki M, Urushihara N, Yagi T, Tanaka N

The Journal of International Medical Research 2001年

A family of multiple endocrine Neoplasia Type 2A with the RET proto-oncogene mutation in codon 618 (Cys→Arg).

Nakao A, Naomoto Y, Kataoka M, Haisa M, Kataoka K, Saitoh S, Fujiwara T, Yamatsuji T, Shigemitsu K, Umeoka T, Isozaki H, Futami H, Yamaguchi K, Tanaka N

Japanese Journal of Clinical Oncology 2001年

Rapidly functional immobilization of immortalized human hepatocytes using cell adhesive GRGDS peptide-carrying cellulose microspheres.

Kobayashi N, Taguchi T, Noguchi H, Okitsu T, Totsugawa T, Watanabe T, Matsumura T, Fujiwara T, Urata H, Kishimoto N, Hayashi N, Nakaji S, Murakami T, Tanaka N

Cell Transplantation 2001年

Analysis of the immune status in the recipients with long-term well-functioning kidneys allograft.

Nakagawa K, Matsuno T, Iwagaki H, Fujiwara T, Tanaka N

Acta Medica Okayama 2001年

Antisense-mediated suppression of human heparanase gene expression inhibits pleural dissemination of human cancer cells.

Uno F, Fujiwara T, Takata Y, Ohtani S, Katsuda K, Takaoka M, Ohkawa T, Naomoto Y, Nakajima M, Tanaka N

Cancer Research 2001年

Expansion of human hepatocyte populations by a retroviral gene transfer of simian virus 40 large T antigen.

Kobayashi N, Westerman KA, Taguchi T, Sakaguchi M, Fujiwara T, Urata H, Kishimoto N, Hayashi N, Nakaji S, Murakami T, Leboulch P, Tanaka N

ASAIO Journal 2001年

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