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Author: Shimada, Sawako ; Asada, Shin ; Sakai, Ayako ; Tsuchiya, Toshiyuki ; Araki, Harumi ; Washizuka, Masataka ; Umeda, Makoto ; Nakamura, Yoshiyuki ; Takagi, Hiroki ; Kitou, Nobuko ; Yatsushiro, Tomoko ; Fushiwaki, Yuichi ; Yamamura, Eiji ; Yoshimura, Isao ; Oishi, Hidetoshi ; Hamada, Shuichi ; Tanaka, Noriho ; Sasaki, Satoshi ; Nakamura, Tetsu ; Sasaki, Kiyoshi ; Asakura, Masumi ; Yajima, Satoshi ; Baba, Hiroshi ; Ohmori, Kiyomi ; Uno, Yoshifumi ; Yamamoto, Yasuhito

The Bhas promotion assay is a cell culture transformation assay designed as a sensitive and economical method for detecting the tumour-promoting activities of chemicals. In order to validate the transferability and applicability of this assay, an inter-laboratory collaborative study was conducted with the participation of 14 laboratories. After confirmation that these laboratories could obtain positive results with two tumour promoters, 12- O-tetradecanoylphorbol-13-acetate (TPA) and lithocholic acid (LCA), 12 coded chemicals were assayed. Each chemical was tested in four laboratories. For eight chemicals, all four laboratories obtained consistent results, and for two of the other four chemicals, only one of the four laboratories showed inconsistent results. Thus, the rate of consistency was high. During the study, several issues were raised, each of which were analysed step-by-step, leading to revision of the protocol of the original assay. Among these issues were the importance of careful maintenance of mother cultures and the adoption of test concentrations for toxic chemicals. In addition, it is suggested that three different types of chemicals show positive promoting activity in the assay. Those designated as T-type induced extreme growth enhancement, and included TPA, mezerein, PDD and insulin. LCA and okadaic acid belonged to the L-type category, in which transformed foci were induced at concentrations showing growth-inhibition. In contrast, M-type chemicals, progesterone, catechol and sodium saccharin, induced foci at concentrations with little or slight growth inhibition. The fact that different types of chemicals similarly induce transformed foci in the Bhas promotion assay may provide clues for elucidating mechanisms of tumour promotion.

01 Oct 2005·Gan to kagaku ryoho. Cancer & chemotherapy

[Antitumor effect of docetaxel against human endometrial tumor cell lines].

Article

Author: Noguchi, Keiko ; Shakuto, Shuji ; Bissery, Marie-Christine

The antitumor effect of docetaxel against human endometrial tumor cell lines was investigated in vitro and in vivo. In the in vitro study,docetaxel showed concentration-dependent inhibition of the growth of 4 tumor cell lines having different degrees of differentiation (AN3 CA, KLE, HEC-1-A and HEC-1-B), with IC(50) values ranging from 2.48 to 82.40 ng/ml. These values represent ca. 1/900-1/30 of the mean maximum plasma concentration of 2.27 microg/ml attained when the recommended dose of 70 mg/m(2) for patients with endometrial cancer was administered to patients with various types of cancer in phase I trial. In addition, the activity was nearly equal to paclitaxel, and much more potent than fluorouracil, cisplatin and doxorubicin. Docetaxel also showed strong antitumor activity against xenografts of the AN3 CA human endometrial adenocarcinoma cell line in nude mice. In the docetaxel treated group at its MTD (33 mg/kg/dose, q 6 d x 3, iv), all of the animals were tumor-free survivors on Day 62 after xenografting. The antitumor effect in the MTD-administered group was the strongest of all of the tested anticancer drug groups (cyclophosphamide, mitomycin C, fluorouracil, cisplatin, doxorubicin). Even at two docetaxel dosages below its MTD (20.5 and 12.5 mg/kg/day), the drug showed a marked cytotoxic activity. These results demonstrated that docetaxel shows potent antitumor efficacy against human endometrial tumor cell lines, leading to the expectation that it will be useful as a therapeutic agent for endometrial cancer.

01 Feb 2005·Clinical and Vaccine Immunology

Long-Term Infection of Mongolian Gerbils withHelicobacter pylori:Microbiological, Histopathological, and Serological Analyses

Article

Author: Nakagawa, Shigehito ; Fujioka, Yasunori ; Kamiya, Shigeru ; Yamaguchi, Hiroyuki ; Osaki, Takako

ABSTRACTThe effects of long-term infection withHelicobacter pylorion the gastric mucosa of Mongolian gerbils were examined. Colonization byH. pyloriwas evaluated by both microaerobic cultivation and real-time reverse transcriptase PCR (RT-PCR). Persistent infection withH. pyloriin gastric mucosa was detected by real-time RT-PCR during 6 months after infection, but noH. pyloriwas isolated 4 months after infection by cultivation. Infiltration with neutrophils and mononuclear cells was observed from 2 months after infection. Both intestinal metaplasia and gastric atrophy were also detected from 2 months after infection. The results by enzyme-linked immunosorbent assay indicated that antibody titers against wholeH. pyloriantigens,H. pyloriheat shock protein 60 (HSP60), andEscherichia coliGroEL were significantly higher in the infected gerbils than in noninfected gerbils. After long-term infection withH. pylorifor 18 months, marked atrophy of gastric mucosa and multiple cysts in the submucosa were observed in the glandular stomach of the infected gerbils. In addition, squamous cell papilloma with hyperkeratosis was observed in cardia of all the infected gerbils. These results indicate that evaluation of bacterial colonization during long-term infection can be done by real-time RT-PCR and that mucosal damage might be induced by host immune response against wholeH. pyloriantigen.

100 Deals associated with Aventis Pharma Ltd.

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100 Translational Medicine associated with Aventis Pharma Ltd.

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Pipeline

Pipeline Snapshot as of 22 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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1

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Fexofenadine Hydrochloride ( H1 receptor )	Rhinitis, Allergic, Seasonal More	Approved
Caplacizumab-YHDP ( vWF )	Thrombotic Thrombocytopenic Purpura, Acquired More	Approved
RPR-201985	Asthma More	Pending