フルテキストURL K000876.pdf
著者 藤原 俊義|
発行日 1990-09-30
資料タイプ 学位論文
学位授与番号 甲第876号
学位授与年月日 1990-09-30
学位・専攻分野 博士(医学)
授与大学 岡山大学
言語 Japanese
タイトル(別表記) Adenoviral p53 gene therapy for lung cancer
フルテキストURL 119_229.pdf
著者 藤原 俊義| 田中 紀章|
抄録 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.
キーワード p53 遺伝子 アデノウイルスベクター (adenovirus vector) 肺癌 (lung cancer) 臨床試験 (clinical trial)
出版物タイトル 岡山医学会雑誌
発行日 2008-01-04
119巻
3号
開始ページ 229
終了ページ 234
ISSN 00301558
言語 Japanese
著作権者 岡山医学会
論文のバージョン publisher
DOI 10.4044/joma.119.229
NAID 10020282723
著者 藤原 俊義| 田中 紀章|
発行日 2008-12-01
出版物タイトル 岡山医学会雑誌
120巻
3号
資料タイプ 学術雑誌論文
JaLCDOI 10.18926/AMO/31570
フルテキストURL fulltext.pdf
著者 Matsuoka, Junji| Sakagami, Kenichi| Fujiwara, Toshiyoshi| Onoda, Tadashi| Idani, Hitoshi| Gochi, Akira| Orita, Kunzo|
抄録 <p>A sustained release system for interleukin-2 (IL-2), and IL-2 mini-pellet (IL-2 mp), was developed by fusing IL-2 into a needle shaped collagen. Serum concentration of IL-2 after a single subcutaneous injection of the IL-2 mp into C57BL/6 mice remained elevated longer than after an injection of aqueous IL-2. IL-2 in the serum became undetectable by 6h after a subcutaneous injection of 1 x 10(6) unit of IL-2 in phosphate-buffered saline (PBS). In contrast, after a single subcutaneous injection of IL-2 mp containing the same amount of IL-2, the concentration of IL-2 increased to its maximum at 6h after injection, then began to decrease gradually. IL-2 was detected even on the third day after a single subcutaneous injection of one IL-2 mp. Augmentation of NK activity and generation of IL-2 activated killer cells were observed in the spleen from day 1--day 3 after a single subcutaneous injection of IL-2 mp into C57BL/6 mice. This activation was not observed following a single subcutaneous injection of the same amount of IL-2 in PBS. Adoptive immunotherapy by a single subcutaneous injection of IL-2 mp followed by intravenous injections of in vitro cultured IL-2 activated killer cells showed better results in decreasing the number of metastases of Lewis lung carcinoma in C57BL/6 mice than immunotherapy using IL-2 solution.(ABSTRACT TRUNCATED AT 250 WORDS)</p>
キーワード IL-2 drug delivery system immunotherapy mouse
Amo Type Article
発行日 1993-04
出版物タイトル Acta Medica Okayama
47巻
2号
出版者 Okayama University Medical School
開始ページ 79
終了ページ 84
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
論文のバージョン publisher
査読 有り
PubMed ID 8506753
Web of Science KeyUT A1993LA45200002
著者 藤原 俊義|
発行日 2010-12-01
出版物タイトル 岡山医学会雑誌
122巻
3号
資料タイプ 学術雑誌論文
著者 藤原 俊義|
発行日 2010-12-01
出版物タイトル 岡山医学会雑誌
122巻
3号
資料タイプ その他
著者 野間 和広| 田中屋 宏爾| 竹内 仁司| 小長 英二| 藤原 俊義|
発行日 2011-04-01
出版物タイトル 岡山医学会雑誌
123巻
1号
資料タイプ 学術雑誌論文
JaLCDOI 10.18926/AMO/46626
フルテキストURL 65_3_151.pdf
著者 Fujiwara, Toshiyoshi|
抄録 Replication-selective tumor-specific viruses constitute 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. Human telomerase is highly active in more than 85オ of primary cancers, regardless of their tissue origins, and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives expression of E1 genes. Since only tumor cells that express telomerase activity would activate this promoter, the hTERT proximal promoter would allow for preferential expression of viral genes in tumor cells, leading to selective viral replication and oncolytic cell death. Lymphatic invasion is a major route for cancer cell dissemination, and adequate treatment of locoregional lymph nodes is required for curative treatment in patients with gastrointestinal tumors. We demonstrated that intratumoral injection of Telomelysin mediates effective in vivo purging of metastatic tumor cells from regional lymph nodes. Moreover, using noninvasive whole-body imaging, we found that intratumoral injection of Telomelysin followed by regional irradiation induces a substantial antitumor effect, resulting from tumor cell-specific radiosensitization, in an orthotopic human esophageal cancer xenograft model. These results illustrate the potential of oncolytic virotherapy as a promising strategy in the management of human gastrointestinal cancer.
キーワード telomerase adenovirus metastasis lymph node colorectal cancer
Amo Type Review
発行日 2011-06
出版物タイトル Acta Medica Okayama
65巻
3号
出版者 Okayama University Medical School
開始ページ 151
終了ページ 162
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
著作権者 CopyrightⒸ 2011 by Okayama University Medical School
論文のバージョン publisher
査読 有り
PubMed ID 21709712
Web of Science KeyUT 000292017500001
著者 西崎 正彦| 藤原 康宏| 丁田 泰宏| 金澤 卓| 二宮 基樹| 藤原 俊義|
発行日 2012-04-01
出版物タイトル 岡山医学会雑誌
124巻
1号
資料タイプ 学術雑誌論文
JaLCDOI 10.18926/AMO/48258
フルテキストURL 66_2_83.pdf.pdf
著者 Kuroda, Shinji| Urata, Yasuo| Fujiwara, Toshiyoshi|
抄録 Radiotherapy plays a central part in cancer treatment, and use of radiosensitizing agents can greatly enhance this modality. Although studies have shown that several chemotherapeutic agents have the potential to increase the radiosensitivity of tumor cells, investigators have also studied a number of molecularly targeted agents as radiosensitizers in clinical trials based on reasonably promising preclinical data. Recent intense research into the DNA damage-signaling pathway revealed that ataxia-telangiectasia mutated (ATM) and the Mre11-Rad50-NBS1 (MRN) complex play central roles in DNA repair and cell cycle checkpoints and that these molecules are promising targets for radiosensitization. Researchers recently developed three ATM inhibitors (KU-55933, CGK733, and CP466722) and an MRN complex inhibitor (mirin) and showed that they have great potential as radiosensitizers of tumors in preclinical studies. Additionally, we showed that a telomerase-dependent oncolytic adenovirus that we developed (OBP-301 [telomelysin]) produces profound radiosensitizing effects by inhibiting the MRN complex via the adenoviral E1B55kDa protein. A recent Phase I trial in the United States determined that telomelysin was safe and well tolerated in humans, and this agent is about to be tested in combination with radiotherapy in a clinical trial based on intriguing preclinical data demonstrating that telomelysin and ionizing radiation can potentiate each other. In this review, we highlight the great potential of ATM and MRN complex inhibitors, including telomelysin, as radiosensitizing agents.
キーワード ATM (ataxia-telangiectasia mutated) MRN (Mre11-Rad50-NBS1) complex radiosensitization adenovirus E1B55kDa
Amo Type Review
発行日 2012-04
出版物タイトル Acta Medica Okayama
66巻
2号
出版者 Okayama University Medical School
開始ページ 83
終了ページ 92
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
著作権者 CopyrightⒸ 2012 by Okayama University Medical School
論文のバージョン publisher
査読 有り
PubMed ID 22525466
Web of Science KeyUT 000303175300001
著者 野口 洋文| 藤原 俊義|
発行日 2012-12-03
出版物タイトル 岡山医学会雑誌
124巻
3号
資料タイプ 学術雑誌論文
著者 宇野 太| 藤原 康宏| 藤原 俊義|
発行日 2013-04-01
出版物タイトル 岡山医学会雑誌
125巻
1号
資料タイプ 学術雑誌論文
著者 Hao, Hui-fang| Takaoka, Munenori| Bao, Xiao-hong| Wang, Zhi-gang| Tomono, Yasuko| Sakurama, Kazufumi| Ohara, Toshiaki| Fukazawa, Takuya| Yamatsuji, Tomoki| Fujiwara, Toshiyoshi| Naomoto, Yoshio|
発行日 2012-07-13
出版物タイトル Biochemical and Biophysical Research Communications
423巻
4号
資料タイプ 学術雑誌論文
著者 藤原 俊義|
発行日 2013-12-02
出版物タイトル 岡山医学会雑誌
125巻
3号
資料タイプ 一般雑誌記事
著者 藤原 俊義|
発行日 2014-07
出版物タイトル Okayama University Medical Research Updates
1巻
資料タイプ その他
著者 藤原 俊義|
発行日 2015-02
出版物タイトル Okayama University Medical Research Updates
7巻
資料タイプ その他
フルテキストURL AnnGastroenterolSurg_3_4_396.pdf
著者 Fujiwara, Toshiyoshi|
キーワード adenovirus clinical trial esophageal cancer radiotherapy telomerase
発行日 2019-07-05
出版物タイトル Annals of gastroenterological surgery
3巻
4号
出版者 John Wiley & Sons
開始ページ 396
終了ページ 404
ISSN 24750328
資料タイプ 学術雑誌論文
言語 English
OAI-PMH Set 岡山大学
著作権者 © 2019 The Authors
論文のバージョン publisher
PubMed ID 31346579
DOI 10.1002/ags3.12270
Web of Science KeyUT 000475745100009
関連URL isVersionOf https://doi.org/10.1002/ags3.12270
タイトル(別表記) The 32th Annual Meeting of the Japan Society for Biological Therapy
著者 藤原 俊義|
出版物タイトル 岡山医学会雑誌
発行日 2020-04-01
132巻
1号
開始ページ 41
終了ページ 43
ISSN 0030-1558
関連URL isVersionOf https://doi.org/10.4044/joma.132.41
言語 Japanese
著作権者 Copyright (c) 2020 岡山医学会
論文のバージョン publisher
DOI 10.4044/joma.132.41
NAID 130007840310
JaLCDOI 10.18926/AMO/53024
フルテキストURL 68_6_349.pdf
著者 Yamamoto, Tsuyoshi| Kajikawa, Yutaka| Otani, Satoru| Yamada, Yuki| Takemoto, Syunji| Hirota, Minoru| Ikeda, Masae| Iwagaki, Hiromi| Saito, Shinya| Fujiwara, Toshiyoshi|
抄録 Accumulated studies have shown that ω-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have protective roles against inflammatory responses such as hyperlipidemia, diabetes mellitus (DM) and cardiovascular diseases. Here we examined the effects of administering EPA to hyperlipidemic patients and other patients undergoing cardiac surgery to determine whether this treatment would increase plasma EPA levels and to clarify the association between EPA treatment and adiponectin production in hyperlipidemic patients. We also assessed the effect of preoperative EPA administration on postoperative adverse events such as postoperative atrial fibrillation (POAF) and postoperative infection in the cardiac surgery patients. The EPA administration significantly increased the serum EPA concentrations in both patient populations (p<0.001). In the hyperlipidemic patients, the EPA administration significantly increased plasma adiponectin levels (p<0.05), accompanied by a decrease in insulin resistance designated by the HOMA-IR (homeostasis model assessment of insulin resistance) score (p<0.05) and Hs-CRP (high sensitivity C-reactive protein) value (p<0.05). In the cardiac surgery patients, no significant effect of EPA on cardiac adverse events such as POAF was observed. However, our results clearly demonstrated that both the neutrophil-to-lymphocyte ratio and the 2nd-line antibiotic requirement in the EPA group were significantly decreased compared to the untreated control group (p<0.05). We suggest that EPA administration may exert anti-inflammatory effects in patients with hyperlipidemia and in those undergoing cardiac surgery, possibly through an increase in plasma adiponectin levels.
キーワード eicosapentaenoic acid adiponectin hyperlipidemic patients cardiac surgery atrial fibrillation
Amo Type Original Article
発行日 2014-12
出版物タイトル Acta Medica Okayama
68巻
6号
出版者 Okayama University Medical School
開始ページ 349
終了ページ 361
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
著作権者 CopyrightⒸ 2014 by Okayama University Medical School
論文のバージョン publisher
査読 有り
PubMed ID 25519029
Web of Science KeyUT 000346882200005
関連URL http://ousar.lib.okayama-u.ac.jp/metadata/53125
著者 佐藤 太祐| 八木 孝仁| 貞森 裕| 楳田 祐三| 藤原 俊義|
発行日 2011-12-01
出版物タイトル 岡山医学会雑誌
123巻
3号
資料タイプ 学術雑誌論文