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肿瘤靶向性鼠伤寒沙门氏菌A1-R对转移性和播散性人卵巢癌裸鼠模型的疗效

Efficacy of tumor-targeting Salmonella typhimurium A1-R on nude mouse models of metastatic and disseminated human ovarian cancer.

作者信息

Matsumoto Yasunori, Miwa Shinji, Zhang Yong, Hiroshima Yukihiko, Yano Shuya, Uehara Fuminari, Yamamoto Mako, Toneri Makoto, Bouvet Michael, Matsubara Hisahiro, Hoffman Robert M, Zhao Ming

机构信息

AntiCancer, Inc., San Diego, California; Department of Surgery, University of California San Diego, San Diego, California; Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.

出版信息

J Cell Biochem. 2014 Nov;115(11):1996-2003. doi: 10.1002/jcb.24871.

Abstract

We report here the efficacy of tumor-targeting Salmonella typhimurium A1-R (A1-R) on mouse models of disseminated and metastatic ovarian cancer. The proliferation-inhibitory efficacy of A1-R on human ovarian cancer cell lines (SKOV-3-GFP, OVCAR-3-RFP) was initially demonstrated in vitro. Orthotopic and dissemination mouse models of ovarian cancer were made with the human ovarian cancer cell line SKOV-3-GFP. After tumor implantation, the mice were treated with A1-R (5 × 10(7)  colony-forming units [CFU], i.v.), and there were no severe adverse events observed. In the orthotopic model, tumor volume after treatment was 276 ± 60.8 mm(3), compared to 930 ± 342 mm(3) in the untreated control group (P = 0.022). There was also a significant difference in survival between treated mice and untreated mice in a peritoneal dissemination model (P = 0.005). The results of this report demonstrate that A1-R is effective for highly aggressive human ovarian cancer in metastatic and dissemination mouse models and suggest its clinical potential for this highly treatment-resistant disease.

摘要

我们在此报告肿瘤靶向性鼠伤寒沙门氏菌A1-R(A1-R)对播散性和转移性卵巢癌小鼠模型的疗效。A1-R对人卵巢癌细胞系(SKOV-3-GFP、OVCAR-3-RFP)的增殖抑制疗效最初在体外得到证实。用人卵巢癌细胞系SKOV-3-GFP构建卵巢癌原位和播散小鼠模型。肿瘤植入后,用A1-R(5×10⁷集落形成单位[CFU],静脉注射)治疗小鼠,未观察到严重不良事件。在原位模型中,治疗后肿瘤体积为276±60.8 mm³,而未治疗的对照组为930±342 mm³(P = 0.022)。在腹膜播散模型中,治疗小鼠和未治疗小鼠的生存率也有显著差异(P = 0.005)。本报告结果表明,A1-R对转移性和播散性小鼠模型中的高侵袭性人卵巢癌有效,并提示其对这种高度耐药疾病的临床应用潜力。

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