keyword
MENU ▼
Read by QxMD icon Read
search

PARP inhibitors

keyword
https://www.readbyqxmd.com/read/29684820/increased-oxidative-stress-mediates-the-antitumor-effect-of-parp-inhibition-in-ovarian-cancer
#1
Dong Hou, Zhaojian Liu, Xiuhua Xu, Qiao Liu, Xiyu Zhang, Beihua Kong, Jian-Jun Wei, Yaoqin Gong, Changshun Shao
PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful. Because PARP primarily functions in sensing and repairing DNA strand breaks, the therapeutic effect of PARP inhibition is generally believed to be attributed to impaired DNA repair. We here report that oxidative stress is also increased by PARP inhibition and mediates the antitumor effect. We showed that PARP1 is highly expressed in specimens of high grade serous ovarian carcinoma and its activity is required for unperturbed proliferation of ovarian cancer cells...
March 30, 2018: Redox Biology
https://www.readbyqxmd.com/read/29676938/the-development-of-a-biotinylated-nad-applied-human-poly-adp-ribose-polymerase-3-parp3-enzymatic-assay
#2
Ming Ji, Liyuan Wang, Nina Xue, Fangfang Lai, Sen Zhang, Jing Jin, Xiaoguang Chen
Poly(ADP-ribose) polymerase 3 (PARP3) is an important member of the PARP family and shares high structural similarities with both PARP1 and PARP2. The biological roles of PARP3 are currently under investigation; however, several key reports indicate the integral roles of PARP3 in DNA damage repair, and thus it has been investigated as a novel target in oncology. It is clear that the identification of selective PARP3 inhibitors would further advance the understanding of the biological roles of PARP3. Herein, we describe a modified PARP3 screening assay using biotinylated NAD+ as the specialized substrate...
April 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29674236/sub-lethal-ultraviolet-b-irradiation-and-poly-i-c-treatment-synergistically-induced-apoptosis-of-hacat-cells-through-nf-%C3%AE%C2%BAb-pathway
#3
Wuxiyar Otkur, Weiwei Liu, Jinda Wang, Xingfan Jia, Dianchao Huang, Fang Wang, Toshihiko Hayashi, Shin-Ichi Tashiro, Satoshi Onodera, Takashi Ikejima
Ultraviolet B (UVB) irradiation exerts multiple effects on skin cells, inducing apoptosis, senescence and carcinogenesis. Toll-like receptor 3, a member of pattern recognition receptors, is reported to initiate inflammation by recognizing double-strand RNA (dsRNA) released from UVB-irradiated cells. It has not been studied, however, whether apoptosis induction in UVB irradiation is attributed to TLR3 activation. Here, we report on the pro-apoptotic role of TLR3 in UVB-irradiated epidermal cells. Poly I:C, an analogue of dsRNA that activates TLR3, was used in combination with sub-lethal UVB (4...
April 16, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29673712/update-on-systemic-prostate-cancer-therapies-management-of-metastatic-castration-resistant-prostate-cancer-in-the-era-of-precision-oncology
#4
REVIEW
Philipp Nuhn, Johann S De Bono, Karim Fizazi, Stephen J Freedland, Maurizio Grilli, Philip W Kantoff, Guru Sonpavde, Cora N Sternberg, Srinivasan Yegnasubramanian, Emmanuel S Antonarakis
CONTEXT: Introduction of novel agents for the management of advanced prostate cancer provides a range of treatment options with notable benefits for men with metastatic castration-resistant prostate cancer (mCRPC). At the same time, understanding of optimal patient selection, effective sequential use, and development of resistance patterns remains incomplete. OBJECTIVE: To review current systemic therapies and recent advances in drug development for mCRPC and strategies to aid in patient selection and optimal sequencing...
April 16, 2018: European Urology
https://www.readbyqxmd.com/read/29672168/rucaparib-a-new-treatment-option-for-ovarian-cancer
#5
Ilaria Sabatucci, Giuseppa Maltese, Stefano Lepori, Elisa Tripodi, Giorgio Bogani, Domenica Lorusso
Approximately 50% of high-grade serous ovarian cancers present a deficiency in the pathways involved in homologous recombination (HR). PARP inhibitors prevent single-strand DNA damage repair and determine a progression of the defect towards double-strand breaks, which results in a process known as 'synthetic lethality'. Areas covered: In this review, the authors discuss the efficacy and toxicity of rucaparib either as a single agent or as a maintenance treatment for ovarian cancer. This includes the NGS Foundation Medicine evaluation of the role of this drug in the treatment algorithm of ovarian cancer...
April 19, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29671785/activation-of-er-stress-dependent-mir-216b-has-a-critical-role-in-salvia-miltiorrhiza-ethanol-extract-induced-apoptosis-in-u266-and-u937-cells
#6
Changmin Kim, Hyo-Sook Song, Hojung Park, Bonglee Kim
Although Salvia miltiorrhiza has been reported to have anti-cancer mechanisms, such as caspase activation, cell cycle arrest, an anti-angiogenesis effect, and Bcl-2 family regulation, its underlying mechanism of endoplasmic reticulum (ER) stress-mediated apoptosis has never been demonstrated. Thus, in this current study, ER stress-related apoptosis via miR-216b of the ethanol extract of Salvia miltiorrhiza (SM) is elucidated for the first time. SM treatment inhibited the viability of U266 and U937 cells in a concentration-dependent manner...
April 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29670134/detection-of-functional-protein-domains-by-unbiased-genome-wide-forward-genetic-screening
#7
Mareike Herzog, Fabio Puddu, Julia Coates, Nicola Geisler, Josep V Forment, Stephen P Jackson
Establishing genetic and chemo-genetic interactions has played key roles in elucidating mechanisms by which certain chemicals perturb cellular functions. In contrast to gene disruption/depletion strategies to identify mechanisms of drug resistance, searching for point-mutational genetic suppressors that can identify separation- or gain-of-function mutations has been limited. Here, by demonstrating its utility in identifying chemical-genetic suppressors of sensitivity to the DNA topoisomerase I poison camptothecin or the poly(ADP-ribose) polymerase inhibitor olaparib, we detail an approach allowing systematic, large-scale detection of spontaneous or chemically-induced suppressor mutations in yeast or haploid mammalian cells in a short timeframe, and with potential applications in other haploid systems...
April 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29669295/a-quantitative-chemotherapy-genetic-interaction-map-reveals-factors-associated-with-parp-inhibitor-resistance
#8
Hsien-Ming Hu, Xin Zhao, Swati Kaushik, Lilliane Robillard, Antoine Barthelet, Kevin K Lin, Khyati N Shah, Andy D Simmons, Mitch Raponi, Thomas C Harding, Sourav Bandyopadhyay
Chemotherapy is used to treat most cancer patients, yet our understanding of factors that dictate response and resistance to such drugs remains limited. We report the generation of a quantitative chemical-genetic interaction map in human mammary epithelial cells charting the impact of the knockdown of 625 genes related to cancer and DNA repair on sensitivity to 29 drugs, covering all classes of chemotherapy. This quantitative map is predictive of interactions maintained in other cell lines, identifies DNA-repair factors, predicts cancer cell line responses to therapy, and prioritizes synergistic drug combinations...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29668451/a-review-on-dna-repair-inhibition-by-parp-inhibitors-in-cancer-therapy
#9
REVIEW
Ashish P Shah, Chhagan N Patel, Dipen K Sureja, Kirtan P Sanghavi
The DNA repair process protects the cells from DNA damaging agent by multiple pathways. Majority of the cancer therapy cause DNA damage which leads to apoptosis. The cell has natural ability to repair this damage which ultimately leads to development of resistance of drugs. The key enzymes involved in DNA repair process are poly(ADP-ribose) (PAR) and poly(ADP-ribose) polymerases (PARP). Tumor cells repair their defective gene via defective homologues recombination (HR) in the presence of enzyme PARP. PARP inhibitors inhibit the enzyme poly(ADP-ribose) polymerases (PARPs) which lead to apoptosis of cancer cells...
March 1, 2018: Folia Medica
https://www.readbyqxmd.com/read/29664094/analysis-of-poly-adp-ribose-polymerase-1-by-enzyme-initiated-auto-parylation-controlled-aggregation-of-hemin-graphene-nanocomposites
#10
Yong Liu, Xiaolin Xu, Haitang Yang, Ensheng Xu, Shuangshuang Wu, Wei Wei, Jin Chen
Poly(ADP-ribose) polymerase-1 (PARP-1) is a highly conserved nuclear enzyme, which binds tightly to damaged DNA and plays a key role in DNA repair, recombination, proliferation, and genomic stability. However, due to the poor electrochemical and optical activity of PARP-1 and its product PAR, only a few studies on its activity detection method have been reported. Herein, we report a simple and sensitive colorimetric strategy to monitor PARP-1 activity based on enzyme-initiated auto-PARylation-controlled aggregation of hemin-graphene nanocomposites (H-GNs)...
April 17, 2018: Analyst
https://www.readbyqxmd.com/read/29664016/the-evolving-landscape-of-predictive-biomarkers-of-response-to-parp-inhibitors
#11
Anish Thomas, Junko Murai, Yves Pommier
Poly(ADP-ribose) polymerase inhibitors (PARPis) are DNA-damaging agents that trap PARP-DNA complexes and interfere with DNA replication. Three PARPis - olaparib, niraparib, and rucaparib - were recently approved by the FDA for the treatment of breast and ovarian cancers. These PARPis, along with 2 others (talazoparib and veliparib), are being evaluated for their potential to treat additional malignancies, including prostate cancers. While lack of PARP-1 confers high resistance to PARPis, it has not been established whether or not the levels of PARP-1 directly correlate with tumor response...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29661232/cmpd1-inhibited-human-gastric-cancer-cell-proliferation-by-inducing-apoptosis-and-g2-m-cell-cycle-arrest
#12
Yu Li, Depeng Zhang, Kaikai Yu, Yudong Hu, Qiong Wu, Feng Qian, Zishu Wang
BACKGROUND: Gastric cancer occupies the fourth highest morbidity rate of cancers worldwide. Clinical therapies of gastric cancer remain limited because of uncertainty of mechanisms and shortness of effective medicine. Thus, new drug candidates for gastric cancer treatment is urgently needed. RESULTS: In this study, CMPD1 as a wildly used MK2 phosphorylation inhibitor was employed to find its impact on gastric cancer cell proliferation, apoptosis and cell cycle using colony formation assay and flow cytometry analysis...
April 16, 2018: Biological Research
https://www.readbyqxmd.com/read/29660759/parp-inhibitors-in-breast-cancer-bringing-synthetic-lethality-to-the-bedside
#13
REVIEW
Anita A Turk, Kari B Wisinski
Individuals with breast and ovarian cancer susceptibility gene 1 (BRCA1) or BRCA2 germline mutations have a significantly increased lifetime risk for breast and ovarian cancers. BRCA-mutant cancer cells have abnormal homologous recombination (HR) repair of DNA. In these tumors, the base excision repair (BER) pathway is important for cell survival. The poly(adenosine diphosphate-ribose) polymerase (PARP) enzymes play a key role in BER, and PARP inhibitors are effective in causing cell death in BRCA-mutant cells while sparing normal cells-a concept called synthetic lethality...
April 16, 2018: Cancer
https://www.readbyqxmd.com/read/29658592/in-vitro-cytotoxic-effect-of-parp-inhibitor-alone-and-in-combination-with-nab%C3%A2-paclitaxel-on-triple%C3%A2-negative-and-luminal-a-breast-cancer-cells
#14
Mehmet Topçul, İdi L Çeti N, Suna Özbaş Turan, Melek Özlem Kolusayin Ozar
In the present study, the in vitro cytotoxic effect of poly(ADP‑ribose) polymerase (PARP) inhibitor alone and in combination with nab‑paclitaxel was evaluated on human triple‑negative breast cancer (TNBC) cell line MDA‑MB‑231 and human luminal A breast cancer cell line MCF‑7. For this purpose, cell index (CI) values obtained from xCELLigence Real‑Time Cell Analysis (RTCA) DP instrument, mitotic index (MI), labelling index (LI) and apoptotic index (AI) analysis among cell kinetic parameters were used...
April 12, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29656893/dna-repair-network-analysis-reveals-shieldin-as-a-key-regulator-of-nhej-and-parp-inhibitor-sensitivity
#15
Rajat Gupta, Kumar Somyajit, Takeo Narita, Elina Maskey, Andre Stanlie, Magdalena Kremer, Dimitris Typas, Michael Lammers, Niels Mailand, Andre Nussenzweig, Jiri Lukas, Chunaram Choudhary
Repair of damaged DNA is essential for maintaining genome integrity and for preventing genome-instability-associated diseases, such as cancer. By combining proximity labeling with quantitative mass spectrometry, we generated high-resolution interaction neighborhood maps of the endogenously expressed DNA repair factors 53BP1, BRCA1, and MDC1. Our spatially resolved interaction maps reveal rich network intricacies, identify shared and bait-specific interaction modules, and implicate previously concealed regulators in this process...
April 7, 2018: Cell
https://www.readbyqxmd.com/read/29655793/inhibition-of-nlrp9b-attenuates-acute-lung-injury-through-suppressing-inflammation-apoptosis-and-oxidative-stress-in-murine-and-cell-models
#16
Qiu Yanling, Cheng Xiaoning, Bai Fei, Fang Liyun, Hu Huizhong, Sun Daqing
Acute lung injury (ALI), known a severe disease along with high morbidity and mortality, is lacking of specific therapies. Inflammation, apoptosis and oxidative stress are critical pathologies that contribute to ALI. Recently, there is study indicated that NLRP9b, a NOD-like receptor (NLR) member, is critical in modulation of inflammatory response. However, the effects of NLRP9b on sepsis-associated ALI, and the underlying molecular mechanism have not been understood. In the present study, the wild type (WT) and NLRP9b-knockout (NLRP9b-/- ) mice with C57B/L6 background were subjected to a cecal ligation and puncture (CLP) for ALI murine model establishment...
April 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29655680/panduratin-a-induces-protective-autophagy-in-melanoma-via-the-ampk-and-mtor-pathway
#17
Siew-Li Lai, Mohd Rais Mustafa, Pooi-Fong Wong
BACKGROUND: Targeting autophagy is emerging as a promising strategy in cancer therapeutics in recent years. Autophagy can be modulated to drive cancer cell deaths that are notoriously resistant to apoptotic-inducing drugs. In addition, autophagy has been implicated as a prosurvival mechanism in mediating cancer chemoresistance. Our previous study has demonstrated that Panduratin A (PA), a plant-derived active compound exploits ER-stress-mediated apoptosis as its cytotoxic mechanism on melanoma...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29651748/improved-reperfusion-and-vasculoprotection-by-the-poly-adp-ribose-polymerase-inhibitor-pj34-after-stroke-and-thrombolysis-in-mice
#18
Mohamad El Amki, Dominique Lerouet, Marie Garraud, Fei Teng, Virginie Beray-Berthat, Bérard Coqueran, Benoît Barsacq, Charlotte Abbou, Bruno Palmier, Catherine Marchand-Leroux, Isabelle Margaill
Benefits from thrombolysis with recombinant tissue plasminogen activator (rt-PA) after ischemic stroke remain limited due to a narrow therapeutic window, low reperfusion rates, and increased risk of hemorrhagic transformations (HT). Experimental data showed that rt-PA enhances the post-ischemic activation of poly(ADP-ribose)polymerase (PARP) which in turn contributes to blood-brain barrier injury. The aim of the present study was to evaluate whether PJ34, a potent PARP inhibitor, improves poor reperfusion induced by delayed rt-PA administration, exerts vasculoprotective effects, and finally increases the therapeutic window of rt-PA...
April 12, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29651367/-lazarus-response-to-olaparib-in-a-virtually-chemonaive-breast-cancer-patient-carrying-gross-brca2-gene-deletion
#19
Vladimir M Moiseyenko, Vyacheslav A Chubenko, Fedor V Moiseyenko, Lyudmila A Zagorskaya, Yuliya A Zaytseva, Nataliya E Gesha, Evgeny N Zykov, Valeriya I Ni, Elena V Preobrazhenskaya, Anna P Sokolenko, Evgeny N Imyanitov
This report describes an estrogen receptor-positive breast cancer patient, who relapsed at two and a half years after the completion of adjuvant chemotherapy while being on the aromatase inhibition. Based on the clinical evidence for potential sensitivity of the tumor to hormone ablation, everolimus was added to continuing exemestane treatment. Oral chemotherapy was administered at further disease progression, however, it lasted only for 10 days due to rapidly deteriorating condition of the patient. BRCA test was performed just before the failure of endocrine therapy and revealed a gross deletion within BRCA2 gene...
February 4, 2018: Curēus
https://www.readbyqxmd.com/read/29650809/-molecular-targeted-therapies-for-hereditary-cancer-syndrome
#20
Hideki Shimodaira
Development of molecular targeted drugs has achieved remarkable improvement of systemic cancer therapy. Recently, the several molecular targeted drugs have become available which associated with the status of responsible genes for hereditary cancer syndrome. These drugs would allow to establish specific strategy for hereditary cancer syndrome or sporadic cancers with similar biological phenotype with hereditary cancer. Genetic tests for the diagnosis of hereditary cancer syndrome will have the meaning of biomarker for predicting the efficacy of these molecular targeted drugs...
April 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
keyword
keyword
26947
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"