IR@PKUHSC  > 北京大学基础医学院  > 免疫学系
学科主题基础医学
The PARP1 inhibitor BMN 673 exhibits immunoregulatory effects in a Brca1(-/-) murine model of ovarian cancer
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
2015-08-07
DOI10.1016/j.bbrc.2015.05.083
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
WOS记录号WOS:000358455300013
资助机构China Scholarship Council ; Susan Smith Center for Women&prime ; s Cancer
引用统计
被引频次:25[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54585
专题北京大学基础医学院_免疫学系
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
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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.
APA Huang, Jing.,Wang, Lei.,Cong, Zhongyi.,Amoozgar, Zohreh.,Kiner, Evgeny.,...&Goldberg, Michael S..(2015).The PARP1 inhibitor BMN 673 exhibits immunoregulatory effects in a Brca1(-/-) murine model of ovarian cancer.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,463(4),551-556.
MLA Huang, Jing,et al."The PARP1 inhibitor BMN 673 exhibits immunoregulatory effects in a Brca1(-/-) murine model of ovarian cancer".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 463.4(2015):551-556.
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