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Your search keyword '"Yoshitaka Sekido"' showing total 3 results
Start Over Author "Yoshitaka Sekido" Topic mesothelioma Topic therapeutics
3 results on '"Yoshitaka Sekido"'

1. Therapeutic activity of glycoengineered anti-GM2 antibodies against malignant pleural mesothelioma

Author

Seiji Yano, Shotaro Iwakiri, Shigeru Iida, Ken-ichiro Nan-ya, Wei Wang, Masanobu Oshima, Yusuke Machino, Yui Suzuki, Kenji Kita, Kazumi Itoi, Tadaaki Yamada, Kazuyasu Nakamura, Qi Li, Mami Tsuchiya, and Yoshitaka Sekido

Subjects
Male, Mesothelioma, Cancer Research, Pathology, medicine.medical_specialty, endocrine system, Lung Neoplasms, Pleural Neoplasms, medicine.medical_treatment, Antineoplastic Agents, G(M2) Ganglioside, Mice, SCID, Therapeutics, Antibodies, Monoclonal, Humanized, Protein Engineering, Antibodies, Flow cytometry, Antibody-dependent cell cytotoxicity, In vivo, Cell Line, Tumor, medicine, Animals, Humans, Neoplasm, Pleural Neoplasm, Aged, Aged, 80 and over, Chemotherapy, medicine.diagnostic_test, Ganglioside GM2, business.industry, Mesothelioma, Malignant, Cancer, Original Articles, General Medicine, Middle Aged, medicine.disease, Xenograft Model Antitumor Assays, Radiation therapy, carbohydrates (lipids), Oncology, Female, lipids (amino acids, peptides, and proteins), business
Abstract

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive neoplasm that arises from the pleural, pericardial, or peritoneal lining. Although surgery, chemotherapy, radiotherapy, and combinations of these therapies are used to treat MPM, the median survival of such patients is dismal. Therefore, there is a compelling need to develop novel therapeutics with different modes of action. Ganglioside GM2 is a glycolipid that has been shown to be overexpressed in various types of cancer. However, there are no published reports regarding the use of GM2 as a potential therapeutic target in cases of MPM. In this study, we evaluated the efficacy of the anti-GM2 antibody BIW-8962 as an anti-MPM therapeutic using in vitro and in vivo assays. Consequently, the GM2 expression in the MPM cell lines was confirmed using flow cytometry. In addition, eight of 11 cell lines were GM2-positive (73%), although the GM2 expression was variable. BIW-8962 showed a significant antibody-dependent cellular cytotoxicity activity against the GM2-expressing MPM cell line MSTO-211H, the effect of which depended on the antibody concentration and effector/target ratio. In an in vivo orthotropic mouse model using MSTO-211H cells, BIW-8962 significantly decreased the incidence and size of tumors. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. Fifty-eight percent of the MPM tumors were positive for GM2, with individual variation in the intensity and frequency of staining. These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients. In this study, the anti-GM2 antibody BIW-8962 first showed a significant ADCC activity against malignant pleural mesothelioma (MPM) cell line and therapeutic activity in an in vivo orthotropic mouse model using the cell line. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Published
2015

2. JBIR-23 and -24, Novel Anticancer Agents from Streptomycessp. AK-AB27.

Author

Keiichiro Motohashi, Ji-Hwan Hwang, Yoshitaka Sekido, Motoki Takagi, and Kazuo Shin-ya

Subjects
*ANTINEOPLASTIC agents, *STREPTOMYCES, *MESOTHELIOMA, *FURANS, *CHEMICAL structure, *NUCLEAR magnetic resonance, *MASS spectrometry, *THERAPEUTICS
Abstract

The screening for active compounds against malignant pleural mesothelioma (MPM) cells produced by Streptomycessp. AK-AB27 resulted in the isolation of two compounds with a dodecahydrodibenzo[b,d]furan skeleton named JBIR-23 (1) and -24 (2). Their structures were established on the basis of extensive NMR and MS analyses. Compounds 1and 2exhibited cytotoxic effects against several MPM cell lines. [ABSTRACT FROM AUTHOR]

Published
2009
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3. A Novel Targeting Therapy of Malignant Mesothelioma Using Anti-Podoplanin Antibody.

Author

Shinji Abe, Yuki Morita, Mika Kato Kaneko, Masaki Hanibuchi, Yuta Tsujimoto, Hisatsugu Goto, Soji Kakiuchi, Yoshinori Aono, Jun Huang, Seidai Sato, Masatoshi Kishuku, Yuki Taniguchi, Mami Azuma, Kazuyoshi Kawazoe, Yoshitaka Sekido, Seiji Yano, Shin-ichi Akiyama, Saburo Sone, Kazuo Minakuchi, and Yukinari Kato

Subjects
*MESOTHELIOMA, *GLYCOPROTEINS, *BLOOD platelet aggregation, *CELL-mediated cytotoxicity, *KILLER cells, *LABORATORY rats, *THERAPEUTICS
Abstract

Podoplanin (Aggrus), which is a type I transmembrane sialomucin-like glycoprotein, is highly expressed in malignant pleural mesothelioma (MPM). We previously reported the generation of a rat anti-human podoplanin Ab, NZ-1, which inhibited podoplanin-induced platelet aggregation and hematogenous metastasis. In this study, we examined the antitumor effector functions of NZ-1 and NZ-8, a novel rat-human chimeric Ab generated from NZ-1 including Ab-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against MPM in vitro and in vivo. Immunostaining with NZ-1 showed the expression of podoplanin in 73% (11 out of 15) of MPM cell lines and 92% (33 out of 36) of malignant mesothelioma tissues. NZ-1 could induce potent ADCC against podoplanin-positive MPM cells mediated by rat NK (CD161a+) cells, but not murine splenocytes or human mononuclear cells. Treatment with NZ-1 significantly reduced the growth of s.c. established tumors of MPM cells (ACC-MESO-4 or podoplanin-transfected MSTO-211H) in SCID mice, only when NZ-1 was administered with rat NK cells. In in vivo imaging, NZ-1 efficiently accumulated to xenograft of MPM, and its accumulation continued for 3 wk after systemic administration. Furthermore, NZ-8 preferentially recognized podoplanin expressing in MPM, but not in normal tissues. NZ-8 could induce higher ADCC mediated by human NK cells and complement-dependent cytotoxicity as compared with NZ-1. Treatment with NZ-8 and human NK cells significantly inhibited the growth of MPM cells in vivo. These results strongly suggest that targeting therapy to podoplanin with therapeutic Abs (i.e., NZ-8) derived from NZ-1 might be useful as a novel immunotherapy against MPM. [ABSTRACT FROM AUTHOR]

Published
2013
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