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学科主题: 基础医学
题名:
The PARP1 inhibitor BMN 673 exhibits immunoregulatory effects in a Brca1(-/-) murine model of ovarian cancer
作者: Huang, Jing1,2; Wang, Lei1; Cong, Zhongyi1,3; Amoozgar, Zohreh1,4; Kiner, Evgeny1; Xing, Deyin5; Orsulic, Sandra6; Matulonis, Ursula7; Goldberg, Michael S.1
关键词: BMN 673 ; PARP1 ; Ovarian cancer ; Immune microenvironment
刊名: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
发表日期: 2015-08-07
DOI: 10.1016/j.bbrc.2015.05.083
卷: 463, 期:4, 页:551-556
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]: TUMOR-INFILTRATING LYMPHOCYTES ; CELL LUNG-CANCER ; PROGNOSTIC-SIGNIFICANCE ; INTERFERON-GAMMA ; MOUSE MODEL ; DNA-REPAIR ; CARCINOMA ; OLAPARIB ; THERAPY ; GROWTH
英文摘要:

Familial breast and ovarian cancer are often caused by inherited mutations of BRCAL While current prognoses for such patients are rather poor, inhibition of poly-ADP ribose polymerase 1 (PARPI) induces synthetic lethality in cells that are defective in homologous recombination. BMN 673 is a potent PARP1 inhibitor that is being clinically evaluated for treatment of BRCA-mutant cancers. Using the Brca1-deficient murine epithelial ovarian cancer cell line BR5FVB1-Akt, we investigated whether the antitumor effects of BMN 673 extend beyond its known pro-apoptotic function. Administration of modest amounts of BMN 673 greatly improved the survival of mice bearing subcutaneous or intraperitoneal tumors. We thus hypothesized that BMN 673 may influence the composition and function of immune cells in the tumor microenvironment. Indeed, BMN 673 significantly increases the number of peritoneal CD8(+) T cells and NK cells as well as their production of IFN-gamma and TNF-alpha. These data suggest that the cell stress caused by BMN 673 induces not only cancer cell-intrinsic apoptosis but also cancer cell-extrinsic antitumor immune effects in a syngeneic murine model of ovarian cancer. BMN 673 may therefore serve as a promising adjuvant therapy to immunotherapy to achieve durable responses among patients whose tumors harbor defects in homologous recombination. (C) 2015 Elsevier Inc. All rights reserved.

语种: 英语
项目资助者: China Scholarship Council ; Susan Smith Center for Women&prime ; s Cancer
WOS记录号: WOS:000358455300013
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54585
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA
2.Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA
3.Peking Univ, Sch Basic Med Sci, Dept Immunol, Beijing 100871, Peoples R China
4.Jilin Univ, Sch Pharmaceut Sci, Dept Regenerat Med, Changchun 130023, Peoples R China
5.Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA
6.Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA
7.Dana Farber Canc Inst, Gynecol Oncol Program, Boston, MA 02115 USA

Recommended Citation:
Huang, Jing,Wang, Lei,Cong, Zhongyi,et al. The PARP1 inhibitor BMN 673 exhibits immunoregulatory effects in a Brca1(-/-) murine model of ovarian cancer[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2015,463(4):551-556.
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