scholarly journals Synergistic effects of a novel lipid-soluble extract from Pinellia pedatisecta Schott and cisplatin on human cervical carcinoma cell lines through the regulation of DNA damage response signaling pathway

2017 ◽  
Vol 13 (4) ◽  
pp. 2121-2128 ◽  
Author(s):  
Mingxing Zhang ◽  
Hongwei Zhang ◽  
Yi Yu ◽  
Haixia Huang ◽  
Guiling Li ◽  
...  
Keyword(s):  
Dna Damage ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Dna Damage Response ◽  
Cervical Carcinoma ◽  
Carcinoma Cell ◽  
Synergistic Effects ◽  
Soluble Extract ◽  
Carcinoma Cell Lines ◽  
Damage Response

scholarly journals Synergistic effects of mifepristone on the cytotoxicity of cisplatin in cervical carcinoma cell lines and tumors grown in athymic mice

BMC Cancer ◽  
2007 ◽  
Vol 7 (S1) ◽  
Author(s):  
Rafael Jurado ◽  
Angélica López-Flores ◽  
Aarón Álvarez-Figueroa ◽  
Patricia García-López
Keyword(s):  
Cell Lines ◽  
Cervical Carcinoma ◽  
Carcinoma Cell ◽  
Synergistic Effects ◽  
Athymic Mice ◽  
Carcinoma Cell Lines

Synergistic effects of ICI 182,780 on the cytotoxicity of cisplatin in cervical carcinoma cell lines

2004 ◽  
Vol 53 (6) ◽  
pp. 533-540 ◽  
Author(s):  
Patricia Garc�a-L�pez ◽  
Mauricio Rodr�guez-Dorantes ◽  
Enrique P�rez-C�rdenas ◽  
Marco Cerb�n ◽  
Alejandro Mohar-Betancourt
Keyword(s):  
Cell Lines ◽  
Cervical Carcinoma ◽  
Carcinoma Cell ◽  
Synergistic Effects ◽  
Ici 182,780 ◽  
Carcinoma Cell Lines

The status of the p53 gene in human papilloma virus positive or negative cervical carcinoma cell lines

1992 ◽  
Vol 13 (7) ◽  
pp. 1273-1275 ◽  
Author(s):  
Shiv Srivastava ◽  
Yue A. Tong ◽  
Krishnakumar Devadas ◽  
Zhi-Qiang Zou ◽  
Yawen Chen ◽  
...  
Keyword(s):  
Human Papilloma Virus ◽  
Cell Lines ◽  
Cervical Carcinoma ◽  
Carcinoma Cell ◽  
P53 Gene ◽  
Papilloma Virus ◽  
Carcinoma Cell Lines ◽  
The Status

scholarly journals HPV16-E2 induces prophase arrest and activates the cellular DNA damage response in vitro and in precursor lesions of cervical carcinoma

Oncotarget ◽  
2015 ◽  
Vol 6 (33) ◽  
pp. 34979-34991 ◽  
Author(s):  
Yuezhen Xue ◽  
Shen Yon Toh ◽  
Pingping He ◽  
Thimothy Lim ◽  
Diana Lim ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Cervical Carcinoma ◽  
Precursor Lesions ◽  
Damage Response ◽  
Cellular Dna

scholarly journals NKX3.1 contributes to S phase entry and regulates DNA damage response (DDR) in prostate cancer cell lines

2011 ◽  
Vol 414 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Burcu Erbaykent-Tepedelen ◽  
Besra Özmen ◽  
Lokman Varisli ◽  
Ceren Gonen-Korkmaz ◽  
Bilge Debelec-Butuner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Cell Lines ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Prostate Cancer Cell ◽  
S Phase ◽  
Prostate Cancer Cell Lines ◽  
Damage Response ◽  
Phase Entry

scholarly journals 900 Depleting non-canonical, cell-intrinsic PD-L1 signals induces synthetic lethality to small molecule DNA damage response inhibitors in an immune independent and dependent manner

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A944-A944
Author(s):  
Anand Kornepati ◽  
Clare Murray ◽  
Barbara Avalos ◽  
Cody Rogers ◽  
Kavya Ramkumar ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Cell Lines ◽  
Dna Damage Response ◽  
Small Molecule ◽  
Treatment Resistance ◽  
Programmed Death ◽  
Damage Response ◽  
Response Biomarker

BackgroundTumor surface-expressed programmed death-ligand 1 (PD-L1) suppresses immunity when it engages programmed death-1 (PD-1) on anti-tumor immune cells in canonical PD-L1/PD-1.1 Non-canonical, tumour-intrinsic PD-L1 signals can mediate treatment resistance2–6 but mechanisms remain incompletely understood. Targeting non-canonical, cell-intrinsic PD-L1 signals, especially modulation of the DNA damage response (DDR), remains largely untapped.MethodsWe made PD-L1 knockout (PD-L1 KO) murine transplantable and human cell lines representing melanoma, bladder, and breast histologies. We used biochemical, genetic, and cell-biology techniques for mechanistic insights into tumor-intrinsic PD-L1 control of specific DDR and DNA repair pathways. We generated a novel inducible melanoma GEMM lacking PD-L1 only in melanocytes to corroborate DDR alterations observed in PD-L1 KO of established tumors.ResultsGenetic tumor PD-L1 depletion destabilized Chk2 and impaired ATM/Chk2, but not ATR/Chk1 DDR. PD-L1KO increased DNA damage (γH2AX) and impaired homologous recombination DNA repair (p-RPA32, BRCA1, RAD51 nuclear foci) and function (DR-GFP reporter). PD-L1 KO cells were significantly more sensitive versus controls to DDR inhibitors (DDRi) against ATR, Chk1, and PARP but not ATM in multiple human and mouse tumor models in vitro and in vivo in NSG mice. PD-1 independent, intracellular, not surface PD-L1 stabilized Chk2 protein with minimal Chek2 mRNA effect. Mechanistically, PD-L1 could directly complex with Chk2, protecting it from PIRH2-mediated polyubiquitination. PD-L1 N-terminal domains Ig-V and Ig-C but not the PD-L1 C-terminal tail co-IP’d with Chk2 and restored Chk1 inhibitor (Chk1i) treatment resistance. Tumor PD-L1 expression correlated with Chk1i sensitivity in 44 primary human small cell lung cancer cell lines, implicating tumor-intrinsic PD-L1 as a DDRi response biomarker. In WT mice, genetic PD-L1 depletion but not surface PD-L1 blockade with αPD-L1, sensitized immunotherapy-resistant, BRCA1-WT 4T1 tumors to PARP inhibitor (PARPi). PARPi effects were reduced on PD-L1 KO tumors in RAG2KO mice indicating immune-dependent DDRi efficacy. Tumor PD-L1 depletion, likely due to impaired DDR, enhanced PARPi induced tumor-intrinsic STING activation (e.g., p-TBK1, CCL5) suggesting potential to augment immunotherapies.ConclusionsWe challenge the prevailing surface PD-L1 paradigm and establish a novel mechanism for cell-intrinsic PD-L1 control of the DDR and gene product expression. We identify therapeutic vulnerabilities from tumor PD-L1 depletion utilizing small molecule DDRi currently being tested in clinical trials. Data could explain αPD-L1/DDRi treatment resistance. Intracellular PD-L1 could be a pharmacologically targetable treatment target and/or response biomarker for selective DDRi alone plus other immunotherapies.ReferencesTopalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer 16:275–287, doi:10.1038/nrc.2016.36 (2016).Clark CA, et al. Tumor-intrinsic PD-L1 signals regulate cell growth, pathogenesis and autophagy in ovarian cancer and melanoma. Canres 0258.2016 (2016).Gupta HB et al. Tumor cell-intrinsic PD-L1 promotes tumor-initiating cell generation and functions in melanoma and ovarian cancer. 1, 16030 (2016).Zhu H, et al. BET bromodomain inhibition promotes anti-tumor immunity by suppressing PD-L1 expression. Cell Rep 16:2829–2837, doi:10.1016/j.celrep.2016.08.032 (2016)Wu B, et al. Adipose PD-L1 modulates PD-1/PD-L1 checkpoint blockade immunotherapy efficacy in breast cancer. Oncoimmunology 7:e1500107, doi:10.1080/2162402X.2018.1500107 (2018)Liang J, et al. Verteporfin inhibits PD-L1 through autophagy and the STAT1-IRF1-TRIM28 signaling axis, exerting antitumor efficacy. Cancer Immunol Res 8:952–965, doi:10.1158/2326-6066.CIR-19-0159 (2020)

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