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https://www.readbyqxmd.com/read/27908594/rucaparib-in-relapsed-platinum-sensitive-high-grade-ovarian-carcinoma-ariel2-part-1-an-international-multicentre-open-label-phase-2-trial
#1
Elizabeth M Swisher, Kevin K Lin, Amit M Oza, Clare L Scott, Heidi Giordano, James Sun, Gottfried E Konecny, Robert L Coleman, Anna V Tinker, David M O'Malley, Rebecca S Kristeleit, Ling Ma, Katherine M Bell-McGuinn, James D Brenton, Janiel M Cragun, Ana Oaknin, Isabelle Ray-Coquard, Maria I Harrell, Elaina Mann, Scott H Kaufmann, Anne Floquet, Alexandra Leary, Thomas C Harding, Sandra Goble, Lara Maloney, Jeff Isaacson, Andrew R Allen, Lindsey Rolfe, Roman Yelensky, Mitch Raponi, Iain A McNeish
BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor. METHODS: ARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA...
November 28, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27903423/cytotoxicity-of-trans-chalcone-and-licochalcone-a-against-breast-cancer-cells-is-due-to-apoptosis-induction-and-cell-cycle-arrest
#2
Luis Felipe Buso Bortolotto, Flávia Regina Barbosa, Gabriel Silva, Tamires Aparecida Bitencourt, Rene Oliveira Beleboni, Seung Joon Baek, Mozart Marins, Ana Lúcia Fachin
Chalcones are precursors of flavonoids that exhibit structural heterogeneity and potential antitumor activity. The objective of this study was to characterize the cytotoxicity of trans-chalcone and licochalcone A (LicoA(1)) against a breast cancer cell line (MCF-7) and normal murine fibroblasts (3T3). Also the mechanisms of the anti-cancer activity of these two compounds were studied. The alkaline comet assay revealed dose-dependent genotoxicity, which was more responsive against the tumor cell line, compared to the 3T3 mouse fibroblast cell line...
November 27, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27901267/binge-alcohol-intake-after-hypergravity-stress-sustainably-decreases-ampk-and-transcription-factors-necessary-for-hepatocyte-survival
#3
Sang Gil Lee, Hong Min Wu, Chan Gyu Lee, Choong Sik Oh, So Won Chung, Sang Geon Kim
BACKGROUND: Binge alcohol consumption elicits mitochondrial dysfunction in hepatocytes. An understanding of the effect of ethanol (EtOH) exposure after hypergravity stress on liver function may assist in the implementation of pathophysiological countermeasures for aerospace missions. This study investigated whether a combination of hypergravity stress and binge alcohol intake has a detrimental effect on AMP-activated protein kinase (AMPK) and other molecules necessary for hepatocyte survival...
November 30, 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27898364/liquid-chromatography-tandem-mass-spectrometry-assay-for-the-quantification-of-niraparib-and-its-metabolite-m1-in-human-plasma-and-urine
#4
L van Andel, Z Zhang, S Lu, V Kansra, S Agarwal, L Hughes, M M Tibben, A Gebretensae, H Rosing, J H M Schellens, J H Beijnen
Niraparib (MK-4827) is a novel poly(ADP-Ribose) polymerase (PARP) inhibitor currently investigated in phase III clinical trials to treat cancers. The development of a new drug includes the characterisation of absorption, metabolism and excretion (AME) of the compound. AME studies are a requirement of regulatory agencies and for this purpose bioanalytical assays are essential. This article describes the development and validation of a bioanalytical assay for niraparib and its carboxylic acid metabolite M1 in human plasma and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
November 19, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27895737/high-parp-1-expression-is-associated-with-tumor-invasion-and-poor-prognosis-in-gastric-cancer
#5
Ying Liu, Yu Zhang, Ying Zhao, Dongna Gao, Jing Xing, Hui Liu
Poly (adenosine diphosphate-ribose) polymerase 1 (PARP-1) was previously demonstrated to be overexpressed in numerous malignant tumors and associated with invasiveness and poor prognosis. However, the expression of the PARP-1 protein in gastric cancer and its association with clinical outcomes requires further investigation. In the present study, the expression of PARP-1 in 564 gastric cancer tissues and 335 tumor-adjacent control tissues is investigated, using tissue microarray-based immunohistochemistry. PARP-1 expression levels were demonstrated to be significantly higher in gastric cancer tissue samples, as compared with control tissue samples...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895181/complement-protein-c1q-enhances-macrophage-foam-cell-survival-and-efferocytosis
#6
Marc C Pulanco, Jason Cosman, Minh-Minh Ho, Jessica Huynh, Karina Fing, Jacqueline Turcu, Deborah A Fraser
In the atherosclerotic lesion, macrophages ingest high levels of damaged modified low-density lipoproteins (LDLs), generating macrophage foam cells. Foam cells undergo apoptosis and, if not efficiently cleared by efferocytosis, can undergo secondary necrosis, leading to plaque instability and rupture. As a component of the innate immune complement cascade, C1q recognizes and opsonizes modified forms of LDL, such as oxidized or acetylated LDL, and promotes ingestion by macrophages in vitro. C1q was shown to be protective in an atherosclerosis model in vivo...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27887849/inhibition-of-heat-shock-protein-hsp-90-potentiates-the-antiproliferative-and-pro-apoptotic-effects-of-2-4-fluoro-phenylamino-4h-1-3-thiazine-6-5-b-indole-in-a2780cis-cells
#7
Zuzana Solárová, Martin Kello, Lenka Varinská, Mariana Budovská, Peter Solár
Ovarian carcinoma is initially sensitive to platinum-based therapy, but become resistant over time. The study of cancer sensitizing substance is therefore the major challenge for a number of scientific groups. Our experiments were carried out on human ovarian adenocarcinoma A2780cis cells resistant to cisplatin and their response to 2-(4'fluoro-phenylamino)-4H-1,3-thiazine[6,5-b]indole (thiazine[6,5-b]indole) and/or heat shock protein (Hsp) 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) using proliferation assay, cell cycle analysis and monitoring of apoptosis were examined...
November 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27880910/cdk12-inhibition-reverses-de-novo-and-acquired-parp-inhibitor-resistance-in-brca-wild-type-and-mutated-models-of-triple-negative-breast-cancer
#8
Shawn F Johnson, Cristina Cruz, Ann Katrin Greifenberg, Sofia Dust, Daniel G Stover, David Chi, Benjamin Primack, Shiliang Cao, Andrea J Bernhardy, Rhiannon Coulson, Jean-Bernard Lazaro, Bose Kochupurakkal, Heather Sun, Christine Unitt, Lisa A Moreau, Kristopher A Sarosiek, Maurizio Scaltriti, Dejan Juric, José Baselga, Andrea L Richardson, Scott J Rodig, Alan D D'Andrea, Judith Balmaña, Neil Johnson, Matthias Geyer, Violeta Serra, Elgene Lim, Geoffrey I Shapiro
Although poly(ADP-ribose) polymerase (PARP) inhibitors are active in homologous recombination (HR)-deficient cancers, their utility is limited by acquired resistance after restoration of HR. Here, we report that dinaciclib, an inhibitor of cyclin-dependent kinases (CDKs) 1, 2, 5, and 9, additionally has potent activity against CDK12, a transcriptional regulator of HR. In BRCA-mutated triple-negative breast cancer (TNBC) cells and patient-derived xenografts (PDXs), dinaciclib ablates restored HR and reverses PARP inhibitor resistance...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27878946/targeted-inhibition-of-polo-like-kinase-1-by-a-novel-small-molecule-inhibitor-induces-mitotic-catastrophe-and-apoptosis-in-human-bladder-cancer-cells
#9
Zhe Zhang, Guojun Zhang, Chuize Kong
Bladder cancer is a common cancer with particularly high recurrence after transurethral resection. Despite improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has changed very little. In this study, the anti-tumour activities of a novel Polo-like kinase 1 (PLK1) inhibitor (RO3280) was evaluated in vitro and in vivo in the bladder carcinoma cell lines 5637 and T24. MTT assays, colony-formation assays, flow cytometry, cell morphological analysis and trypan blue exclusion assays were used to examine the proliferation, cell cycle distribution and apoptosis of bladder carcinoma cells with or without RO3280 treatment...
November 23, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27878398/hsp90-is-a-promising-target-in-gemcitabine-and-5-fluorouracil-resistant-pancreatic-cancer
#10
Tarik Ghadban, Judith L Dibbern, Matthias Reeh, Jameel T Miro, Tung Y Tsui, Ulrich Wellner, Jakob R Izbicki, Cenap Güngör, Yogesh K Vashist
Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution...
November 22, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27875952/in-vitro-sensitivity-profiling-of-neuroblastoma-cells-against-a-comprehensive-small-molecule-kinase-inhibitor-library-to-identify-agents-for-future-therapeutic-studies
#11
Anjali Singh, Vanessa Meier-Stephenson, Aarthi Jayanthan, Aru Narendran
Solid tumors represent one of the most widespread causes of death in children across the world. Neuroblastoma (NB) constitutes about 8% of all childhood tumors, yet accounts for more than 15% of death, with an unacceptable overall survival rate. Despite the current multimodal therapeutic approaches involving surgery, radiation, chemotherapy with myeloablative therapy and hematopoietic stem cell rescue, there is growing realization of the limitations of conventional agents to improve the outcome in high risk metastatic disease...
November 22, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27871924/mir-335-regulates-the-chemo-radioresistance-of-small-cell-lung-cancer-cells-by-targeting-parp-1
#12
Yingshan Luo, Lihua Tong, Hui Meng, Weiliang Zhu, Linlang Guo, Ting Wei, Jian Zhang
The role of miR-335 in the regulation of chemosensitivity and radiosensitivity of small cell lung cancer (SCLC) was investigated. miR-335 was significantly downregulated in multi-drug-resistant SCLC H69AR and H446DDP cells compared with parental cells as detected by qRT-PCR. Then, we demonstrated the negative correlation between miR-335 expression and the chemo-radiosensitivity of SCLC cells, including cell proliferation, cell clonality and cell apoptosis. In addition, miR-335 overexpression inhibited cell migration in vitro and tumor growth in vivo, whereas inhibition of miR-335 promoted cell migration and tumor growth...
November 18, 2016: Gene
https://www.readbyqxmd.com/read/27869447/-testing-of-mutations-in-brca1-and-brca2-genes-in-tumor-tissues-possibilities-and-limitations
#13
Hana Vošmiková, Aleš Ryška, Kateřina Sieglová, Jan Laco
Development of targeted cancer therapy is accompanied by a search for markers allowing prediction of response to the particular treatment. Recently, the interest is focused, among other neoplasms, also on the therapy of ovarian cancer using new inhibitors of poly (ADP-ribose) polymerase (PARP) proteins, nuclear enzymes involved in the repair of single-stranded DNA breaks. The greatest benefit from the administration of PARP inhibitors have patients with a deleterious or potentially deleterious germ-line or somatic mutation of BRCA1 or BRCA2, two genes responsible for repair of double stranded DNA breaks...
2016: Ceskoslovenská Patologie
https://www.readbyqxmd.com/read/27867042/poly-adp-ribose-polymerase-1-hyperactivation-in-neurodegenerative-diseases-the-death-knell-tolls-for-neurons
#14
REVIEW
Parimala Narne, Vimal Pandey, Praveen Kumar Simhadri, Prakash Babu Phanithi
Neurodegeneration is a salient feature of chronic refractory brain disorders like Alzheimer's, Parkinson's, Huntington's, amyotropic lateral sclerosis and acute conditions like cerebral ischemia/reperfusion etc. The pathological protein aggregates, mitochondrial mutations or ischemic insults typifying these disease conditions collude with and intensify existing oxidative stress and attendant mitochondrial dysfunction. Interlocking these mechanisms is poly(ADP-ribose) polymerase (PARP-1) hyperactivation that invokes a distinct form of neuronal cell death viz...
November 17, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27865121/physiological-responses-of-a-population-of-sargassum-vulgare-phaeophyceae-to-high-pco2-low-ph-implications-for-its-long-term-distribution
#15
Lucia Porzio, Maria Cristina Buia, Maurizio Lorenti, Anna De Maio, Carmen Arena
Ocean Acidification (OA) is likely to affect macroalgal diversity in the future with species-specific responses shaping macroalgal communities. In this framework, it is important to focus research on the photosynthetic response of habitat-forming species which have an important structural and functional role in coastal ecosystems. Most of the studies on the impacts of OA involve short-term laboratory or micro/mesocosm experiments. It is more challenging to assess the adaptive responses of macroalgal community to decreasing ocean pH over long-term periods, as they represent the basis of trophic dynamics in marine environments...
November 16, 2016: Science of the Total Environment
https://www.readbyqxmd.com/read/27864909/the-mechanism-of-cirp-in-inhibition-of-keratinocytes-growth-arrest-and-apoptosis-following-low-dose-uvb-radiation
#16
Yi Liao, Jianguo Feng, Yi Zhang, Liling Tang, Shiyong Wu
UV induces CIRP expression and subsequent Stat3 activation, but the biological function and mechanism of CIRP and Stat3in mediating UVB-induced skin carcinogenesis have not been fully elucidated. In this study, we demonstrate that CIRP is elevated in all tested melanoma and non-melanoma skin cancer cell lines; and the expression of CIRP is upregulated in keratinocytes after being irradiated with relatively low dose (<5 mJ/cm(2) ), but not high dose (50 mJ/cm(2) ), UVB acutely and chronically. The increased expression of CIRP, either induced by UVB or through overexpression, leads to resistance of keratinocytes to UVB-induced growth arrest and death; and reduced expression of CIRP by RNA knockdown sensitizes keratinocyte cells to the low dose UVB radiation...
November 19, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27863838/resveratrol-enhances-the-efficacy-of-sorafenib-mediated-apoptosis-in-human-breast-cancer-mcf7-cells-through-ros-cell-cycle-inhibition-caspase-3-and-parp-cleavage
#17
Arindam Mondal, Lunawati L Bennett
Despite advances in diagnosis and treatment options, breast cancer is one of the main causes of cancer related death among women worldwide. Present study is aimed to preliminarily evaluate our hypothesis that the combination of resveratrol (RSV), a natural antioxidant, and lower dose of sorafenib (SF), a multi-kinase inhibitor and a component of ERK1/2 (extracellular signal-regulated kinase 1/2) pathway, would augment apoptosis in human breast cancer MCF7 cells. MCF7 cellexpressions s were treated with RSV, SF and their combination...
November 15, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27863407/induction-of-mitochondria-mediated-apoptosis-and-pi3k-akt-mtor-mediated-autophagy-by-aflatoxin-b2-in-hepatocytes-of-broilers
#18
Binlong Chen, Diyan Li, Miao Li, Sichen Li, Kenan Peng, Xian Shi, Lanyun Zhou, Pu Zhang, Zhongxian Xu, Huadong Yin, Yan Wang, Xiaoling Zhao
Aflatoxins have been shown to induce hepatotoxicity in animal models, but the effects of aflatoxin B2 (AFB2) on broiler hepatocytes is unclear. This study aimed to investigate the effects of AFB2 on apoptosis and autophagy to provide an experimental basis for understanding the mechanism of aflatoxin-induced hepatotoxicity. One hundred-twenty Cobb500 broilers were allocated to four groups and exposed to 0 mg/kg, 0.2 mg/kg, 0.4 mg/kg, and 0.8 mg/kg of AFB2 per day for 21 d. AFB2 exerted potent proapoptotic and proautophagic effects on hepatocytes, with increased numbers of apoptotic and autophagic hepatocytes...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27862197/gremlin1-promotes-carcinogenesis-of-glioma-in-vitro
#19
Yongchang Guan, Wen Cheng, Cunyi Zou, Tingzhong Wang, Zhi Cao, Anhua Wu
As the most prevalent and lethal type of brain tumors, gliomas, especially the malignant ones, are relatively resistant to the conventional therapies. Gremlin 1 (GREM1) is a secreted glycoprotein that is implicated in the maintenance of cancer stem cells in tumor hierarchy. In the current study, the role of GREM1 in the carcinogenesis of glioma was studied using a knockdown approach. We first examined the expression level of GREM1 in the clinical samples, and then evaluated the effect of GREM1 knockdown on the viability and colony formation capacity of U87-MG cells...
November 8, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27858200/advanced-oxidation-protein-products-induce-chondrocyte-death-through-a-redox-dependent-poly-adp-ribose-polymerase-1-mediated-pathway
#20
Wenbin Ye, Zhaoming Zhong, Siyuan Zhu, Shuai Zheng, Jun Xiao, Shaolian Song, Hui Yu, Qian Wu, Zhen Lin, Jianting Chen
This study aimed to investigate the effect of AOPPs on apoptosis in human chondrocytes. Chondrocytes were treated with AOPPs. Cell death, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, reactive oxygen species (ROS) generation, and the expression of apoptotic proteins were detected in vitro. AOPPs levels were detected by colorimetric method. The results in vitro demonstrated that AOPPs induced cell death in human chondrocyte through a redox-dependent pathway, including RAGE-mediated, NADPH oxidase-dependent ROS generation, and poly (ADP-ribose) polymerase-1 (PARP-1) activation...
November 17, 2016: Apoptosis: An International Journal on Programmed Cell Death
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