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Articles by H Yasui
Total Records ( 2 ) for H Yasui
  H Ikeda , T Hideshima , M Fulciniti , R. J Lutz , H Yasui , Y Okawa , T Kiziltepe , S Vallet , S Pozzi , L Santo , G Perrone , Y. T Tai , D Cirstea , N. S Raje , C Uherek , B Dalken , S Aigner , F Osterroth , N Munshi , P Richardson and K. C. Anderson
 

Purpose: We investigated the antitumor effect of murine/human chimeric CD138-specific monoclonal antibody nBT062 conjugated with highly cytotoxic maytansinoid derivatives against multiple myeloma (MM) cells in vitro and in vivo.

Experimental Design: We examined the growth inhibitory effect of BT062-SPDB-DM4, BT062-SMCC-DM1, and BT062-SPP-DM1 against MM cell lines and primary tumor cells from MM patients. We also examined in vivo activity of these agents in murine MM cell xenograft model of human and severe combined immunodeficient (SCID) mice bearing implant bone chips injected with human MM cells (SCID-hu model).

Results: Anti-CD138 immunoconjugates significantly inhibited growth of MM cell lines and primary tumor cells from MM patients without cytotoxicity against peripheral blood mononuclear cells from healthy volunteers. In MM cells, they induced G2-M cell cycle arrest, followed by apoptosis associated with cleavage of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase. Nonconjugated nBT062 completely blocked cytotoxicity induced by nBT062-maytansinoid conjugate, confirming that specific binding is required for inducing cytotoxicity. Moreover, nBT062-maytansinoid conjugates blocked adhesion of MM cells to bone marrow stromal cells. The coculture of MM cells with bone marrow stromal cells protects against dexamethasone-induced death but had no effect on the cytotoxicity of immunoconjugates. Importantly, nBT062-SPDB-DM4 and nBT062-SPP-DM1 significantly inhibited MM tumor growth in vivo and prolonged host survival in both the xenograft mouse models of human MM and SCID-hu mouse model.

Conclusion: These results provide the preclinical framework supporting evaluation of nBT062-maytansinoid derivatives in clinical trials to improve patient outcome in MM.

  T Shukuya , H Yasui , N Boku , Y Onozawa , A Fukutomi , K Yamazaki , K Taku , T Kojima and N. Machida
  Objectives

Peritoneal metastasis is one of the major sites of disease progression of pancreatic cancer. There have been few trials in the second-line setting after gemcitabine failure because patients can hardly be candidates for chemotherapy after failure in the first-line chemotherapy, especially those with malignant ascites. The safety and efficacy of weekly paclitaxel therapy was evaluated for pancreatic cancer patients with malignant ascites in this retrospective study.

Methods

The subjects of this retrospective study were 23 advanced pancreatic cancer patients with malignant ascites who received weekly paclitaxel therapy after gemcitabine failure. Paclitaxel (80 mg/m2, div. for 1 h) was administered on Days 1, 8 and 15, every 4 weeks.

Results

While the disease control rate was 35%, decrease of ascites was obtained in 30% of the patients and ascites control rate was 61%. The median survival time was 101 days. Toxicities were mild, although one treatment-related death occurred.

Conclusions

Weekly paclitaxel therapy may be useful treatment option for pancreatic cancer patients with malignant ascites after gemcitabine failure.

 
 
 
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