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( Junko Tsuboki ),( Kiyomi Takaishi ),( Fumiko Ito ),( Ritsuo Honda ),( Hironori Tashiro ),( Hidetaka Katabuchi ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-
Objective: In epithelial ovarian cancer (EOC), M2-polarized macrophage (Mø), a component of the cancer microenvironment in ascitic fluid as well as primary tumor, is thought to play an important role in cell- proliferation via paracrine activation of the STAT3 pathway. Onionin A (ONA), a natural compound purified from onions, biologically inhibits M2 polarization, and molecularly inactivates STAT3 signaling of Mø and tumor cells. Here we elucidated the indirect and direct anti-cancer effects of ONA via the STAT3 pathway. Methods: The indirect effects of ONA on EOC cells were analyzed under the co-culture system with human monocyte- derived Mø using BrdU ELISA assay. The direct effects of ONA alone and combinations with anti-cancer drugs (PTX, CBDCA, or CDDP) on proliferation and STAT3 activation of the human EOC cell lines (SKOV3, RMG1, or ES2) were evaluated using WST assay and western blot analysis. Results: M2Mø in the co-culture system enhanced proliferation of EOC cells, whereas ONA significantly reduced the enhancement of the cell-proliferation by inhibition of M2-polarization. In addition, ONA directly inhibited STAT3-activation and proliferation of EOC cells (P value < 0.01-0.05). Moreover, the suppressive effects against EOC cell proliferation were significantly increased by the combination of ONA with anti-cancer drugs (P value < 0.01-0.05). Conclusions: ONA exhibited direct anti-cancer effects in EOC as well as indirect effects by suppression of M2-polarization in co-culture system. It was suggested that the combination of ONA and anti-cancer drugs presents a new therapeutic strategy for treatment of EOC.
High-dose oral tegafur-uracil maintenance therapy in patients with uterine cervical cancer
Isao Sakaguchi,Takeshi Motohara,Fumitaka Saito,Kiyomi Takaishi,Yukitoshi Fukumatsu,Toshimitsu Tohya,Saburo Shibata,Hiroyuki Mimori,Hironori Tashiro,Hidetaka Katabuchi 대한부인종양학회 2015 Journal of Gynecologic Oncology Vol.26 No.3
Objective: The aim of this study was to determine the efficacy and toxicity of oral administration of tegafur-uracil (UFT) at a high dose, 600 mg/day, based on the tegafur dose, against uterine cervical cancer. Methods: This study consisted of a retrospective analysis. From April 1986 to March 1997, 309 patients with uterine cervical cancer were registered. Oral UFT was administered to 162 patients for maintenance therapy after an initial treatment (the UFT group). The other 147 patients were not treated with UFT (the control group). The survival rate was calculated for both groups and statistically analyzed using the log-rank test. Adverse events were compared between the UFT and control groups. Results: In the UFT group, 103 patients (63.6%) received UFT for ≥90 days. The drug dose was 600 mg/day for 137 patients (84.6%) and 300 to 400 mg/day for the remainder. The overall survival rate was significantly higher in the UFT group than in the control group (p<0.05). The prognosis was particularly favorable in stage III cases, in cases of squamous cell carcinoma, and in cases that were treated by radiotherapy. The most frequent side effects were nausea/vomiting (12.2%), appetite loss (10.1%), and leukopenia/neutropenia (5.8%). Conclusion: High-dose oral UFT maintenance treatment prolonged the disease-free survival and overall survival of patients with uterine cervical cancer, particularly of those with advanced disease.