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https://www.readbyqxmd.com/read/29044520/quercetin-protects-against-radiocontrast-medium-toxicity-in-human-renal-proximal-tubular-cells
#1
Michele Andreucci, Teresa Faga, Antonio Pisani, Raffele Serra, Domenico Russo, GIovambattista De Sarro, Ashour Michael
Radiocontrast media (RCM)-induced acute kidney injury (CI-AKI) is a major clinical problem whose, pathophysiology is not well understood. Direct toxic effects on renal cells, possibly mediated by reactive oxygen species, have been postulated as contributing to CI-AKI. We investigated the effect of quercetin on human renal proximal tubular (HK-2) cells treated with the radiocontrast medium (RCM) sodium diatrizoate. Quercetin is the most widely studied flavonoid, and the most abundant flavonol present in foods...
October 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29044514/ccdc6-the-identity-of-a-protein-known-to-be-partner-in-fusion
#2
REVIEW
Aniello Cerrato, Francesco Merolla, Francesco Morra, Angela Celetti
Coiled Coil Domain Containing 6 gene, CCDC6, was initially isolated as part of a tumorigenic DNA originated by the fusion of CCDC6 with the tyrosine kinase of RET receptor, following a paracentric inversion of chromosome 10. For a long time CCDC6 has been considered as an accidental partner of the RET protooncogene, providing the promoter and the first 101 aa necessary for the constitutive activation of the oncogenic Tyrosine Kinase (TK) RET in thyroid cells. With the advent of more refined diagnostic tools and bioinformatic algorithms, an exponential growth in fusion genes discoveries has allowed the identification of CCDC6 as partner of genes other than RET in different tumor types...
October 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29043098/spermidine-is-protective-against-kidney-ischemia-and-reperfusion-injury-through-inhibiting-dna-nitration-and-parp1-activation
#3
Jinu Kim
Kidney ischemia and reperfusion injury (IRI) is associated with a high mortality rate, which is attributed to tubular oxidative and nitrative stresses; however, an effective approach to limit IRI remains elusive. Spermidine, a naturally occurring polyamine, protects yeast cells against aging through the inhibition of oxidative stress and necrosis. In the present study, spermidine supplementation markedly attenuated histological damage and kidney dysfunction during IRI. In addition, exogenous spermidine potently inhibited poly(ADP-ribose) polymerase 1 (PARP1) activation and DNA nitrative/oxidative stress following IRI...
September 2017: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/29029467/nherf1-together-with-parp1-and-brca1-expression-as-a-new-potential-biomarker-to-stratify-breast-cancer-patients
#4
Anita Mangia, Emanuela Scarpi, Giulia Partipilo, Laura Schirosi, Giuseppina Opinto, Francesco Giotta, Giovanni Simone
It has been recognized that Na(+)/H(+) Exchanger Regulatory Factor 1 (NHERF1) in breast cancer (BC) acts as a tumor suppressor or as an oncogenic protein, depending on its subcellular localization. This study aims to correlate NHERF1 expression to BRCA1 and PARP1 proteins, to investigate their relationship, and their biological and clinical significance. Using immunohistochemistry on tissue microarrays, we evaluated subcellular NHERF1, BRCA1 and PARP1 expression in 308 BCs including a subgroup (n=80) of triple negative BCs (TNBCs)...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29021870/the-potential-role-of-mirnas-in-therapy-of-breast-and-ovarian-cancers-associated-with-brca1-mutation
#5
REVIEW
Agnieszka Strumidło, Sylwia Skiba, Rodney J Scott, Jan Lubiński
Germline variants within BRCA1 or BRCA2 genes account for approximately 25% of familial aggregations of breast-ovarian cancers. Low or no expression of BRCA1 in breast and ovarian cancers is associated with a good clinical response to treatment with platinum therapies and PARP1 inhibitors. Recent studies demonstrated that microRNAs - small non-coding RNAs, involved in the control of gene expression, can decrease BRCA1 expression by targeting the 3'UTR region of the gene. This article reviews reported relationships between various miRNAs, such as miRNA-9, miRNA-146a, miRNA-182 miRNA-218, miRNA-638 and the response to cytostatic drugs, mainly to platins and PARP1 inhbitors, for the treatment of breast and ovarian cancer associated with BRCA1 mutations...
2017: Hereditary Cancer in Clinical Practice
https://www.readbyqxmd.com/read/28993682/olaparib-modulates-dna-repair-efficiency-sensitizes-cervical-cancer-cells-to-cisplatin-and-exhibits-anti-metastatic-property
#6
Chandra Bhushan Prasad, Shyam Babu Prasad, Suresh Singh Yadav, Laxmi Kant Pandey, Sunita Singh, Satyajit Pradhan, Gopeshwar Narayan
PARP1 trapping at DNA lesion by pharmacological inhibitors has been exploited in several cancers exhibiting defects in DNA repair mechanisms. PARP1 hyperactivation is involved in therapeutic resistance in multiple cancers. The role of PARP1 in cervical cancer (CC) resistance and implication of PARP inhibitor is yet to be elucidated. Our data demonstrates significantly higher expression of PARP1 in primary cervical tumors and CC cell lines SiHa and ME180. Upon cisplatin treatment CC cells display significant overexpression of PARP1 and its hyperactivation...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28993289/sirt1-and-parp1-as-epigenome-safeguards-and-micrornas-as-sasp-associated-signals-in-cellular-senescence-and-aging
#7
REVIEW
Seyedhossein Hekmatimoghaddam, Ali Dehghani Firoozabadi, Mohamad Reza Zare-Khormizi, Fatemeh Pourrajab
Cellular senescence (CS) is underlying mechanism of organism aging and is closely interconnected with age-related diseases (ARDs). Thus, any attempt that influences CS, may be undertaken to reverse or inhibit senescence, whereby could prolong healthy life span. Until now, two main proposes are epigenetic and genetic modifications of cell fate. The first one concerns rejuvenation through effective reprogramming in cells undergoing senescence, or derived from very old or progeroid patients, by which is effective in vitro in induced pluripotent stem cells (iPSCs)...
October 6, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28993228/kinase-independent-role-of-nuclear-ripk1-in-regulating-parthanatos-through-physical-interaction-with-parp1-upon-oxidative-stress
#8
Ki-Hong Jang, Taeik Jang, Eunji Son, Soonjin Choi, Eunhee Kim
Regulated necrosis occurs in various pathophysiological conditions under oxidative stress. Here, we report that receptor-interacting protein kinase 1 (RIPK1), a key player in one type of regulated necrosis (necroptosis), also participates in another type of poly (ADP-ribose) polymerase 1 (PARP1)-dependent regulated necrosis (parthanatos). Various biological signatures of parthanatos were significantly attenuated in Ripk1(-/-) mouse embryonic fibroblasts, including PARylation, nuclear translocation of apoptosis-inducing factor, and PARP1-dependent cell death under H2O2 exposure...
October 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28991194/parp1-in-carcinomas-and-parp1-inhibitors-as-antineoplastic-drugs
#9
REVIEW
Luyao Wang, Chao Liang, Fangfei Li, Daogang Guan, Xiaoqiu Wu, Xuekun Fu, Aiping Lu, Ge Zhang
Poly (ADP-ribose) polymerase 1 (PARP1), the best-studied isoform of the nuclear enzyme PARP family, plays a pivotal role in cellular biological processes, such as DNA repair, gene transcription, and so on. PARP1 has been found to be overexpressed in various carcinomas. These all indicate the clinical potential of PARP1 as a therapeutic target of human malignancies. Additionally, multiple preclinical research studies and clinical trials demonstrate that inhibition of PARP1 can repress tumor growth and metastasis...
October 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28985359/parp1-controls-klf4-mediated-telomerase-expression-in-stem-cells-and-cancer-cells
#10
Meng-Hsun Hsieh, Yi-Ting Chen, You-Tzung Chen, Yi-Hsuan Lee, Jean Lu, Chung-Liang Chien, Hsin-Fu Chen, Hong-Nerng Ho, Chia-Jung Yu, Zhao-Qi Wang, Shu-Chun Teng
Telomerase is highly expressed in cancer and embryonic stem cells (ESCs) and implicated in controlling genome integrity, cancer formation and stemness. Previous studies identified that Krüppel-like transcription factor 4 (KLF4) activates telomerase reverse transcriptase (TERT) expression and contributes to the maintenance of self-renewal in ESCs. However, little is known about how KLF4 regulates TERT expression. Here, we discover poly(ADP-ribose) polymerase 1 (PARP1) as a novel KLF4-interacting partner. Knockdown of PARP1 reduces TERT expression and telomerase activity not only in cancer cells, but also in human and mouse ESCs...
August 1, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28981112/berberine-induces-oxidative-dna-damage-and-impairs-homologous-recombination-repair-in-ovarian-cancer-cells-to-confer-increased-sensitivity-to-parp-inhibition
#11
Dong Hou, Guangwei Xu, Caibo Zhang, Boxuan Li, Junchao Qin, Xiaohe Hao, Qiao Liu, Xiyu Zhang, Jinsong Liu, Jianjun Wei, Yaoqin Gong, Zhaojian Liu, Changshun Shao
Many cancer drugs exert their therapeutic effect by inducing oxidative stress in the cancer cells. Oxidative stress compromises cell survival by inflicting lesions in macromolecules like DNA. Cancer cells rely on enhanced antioxidant metabolism and increased DNA repair function to survive oxidative assault. PARP1, a protein that senses DNA-strand breaks and orchestrates their repair, has an important role in the repair of oxidative DNA damage. Berberine, an alkaloid compound present in many herbal plants, is capable of inducing oxidative DNA damage and downregulating homologous recombination repair (HRR) in cancer cells...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28978150/parp-inhibitors-protect-against-sex-and-aag-dependent-alkylation-induced-neural-degeneration
#12
Mariacarmela Allocca, Joshua J Corrigan, Kimberly R Fake, Jennifer A Calvo, Leona D Samson
Alkylating agents are commonly used to treat cancer. Although base excision repair (BER) is a major pathway for repairing DNA alkylation damage, under certain conditions, the initiation of BER produces toxic repair intermediates that damage healthy tissues. The initiation of BER by the alkyladenine DNA glycosylase (AAG, a.k.a. MPG) can mediate alkylation-induced cytotoxicity in specific cells in the retina and cerebellum of male mice. Cytotoxicity in both wild-type and Aag-transgenic (AagTg) mice is abrogated in the absence of Poly(ADP-ribose) polymerase-1 (PARP1)...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977823/intraductal-cisplatin-treatment-in-a-brca-associated-breast-cancer-mouse-model-attenuates-tumor-development-but-leads-to-systemic-tumors-in-aged-female-mice
#13
Jolien S de Groot, Paul J van Diest, Miranda van Amersfoort, Eva J Vlug, Xiaojuan Pan, Natalie D Ter Hoeve, Hilde Rosing, Jos H Beijnen, Sameh A Youssef, Alain de Bruin, Jos Jonkers, Elsken van der Wall, Patrick W B Derksen
BRCA deficiency predisposes to the development of invasive breast cancer. In BRCA mutation carriers this risk can increase up to 80%. Currently, bilateral prophylactic mastectomy and prophylactic bilateral salpingo-oophorectomy are the only preventive, albeit radical invasive strategies to prevent breast cancer in BRCA mutation carriers. An alternative non-invasive way to prevent BRCA1-associated breast cancer may be local prophylactic treatment via the nipple. Using a non-invasive intraductal (ID) preclinical intervention strategy, we explored the use of combined cisplatin and poly (ADP)-ribose polymerase 1 (PARP1) inhibition to prevent the development of hereditary breast cancer...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977496/kinetics-of-poly-adp-ribosyl-ation-but-not-parp1-itself-determines-the-cell-fate-in-response-to-dna-damage-in-vitro-and-in-vivo
#14
Harald Schuhwerk, Christopher Bruhn, Kanstantsin Siniuk, Wookee Min, Suheda Erener, Paulius Grigaravicius, Annika Krüger, Elena Ferrari, Tabea Zubel, David Lazaro, Shamci Monajembashi, Kirstin Kiesow, Torsten Kroll, Alexander Bürkle, Aswin Mangerich, Michael Hottiger, Zhao-Qi Wang
One of the fastest cellular responses to genotoxic stress is the formation of poly(ADP-ribose) polymers (PAR) by poly(ADP-ribose)polymerase 1 (PARP1, or ARTD1). PARP1 and its enzymatic product PAR regulate diverse biological processes, such as DNA repair, chromatin remodeling, transcription and cell death. However, the inter-dependent function of the PARP1 protein and its enzymatic activity clouds the mechanism underlying the biological response. We generated a PARP1 knock-in mouse model carrying a point mutation in the catalytic domain of PARP1 (D993A), which impairs the kinetics of the PARP1 activity and the PAR chain complexity in vitro and in vivo, designated as hypo-PARylation...
August 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28976888/modifications-of-expression-of-genes-and-proteins-involved-in-dna-repair-and-nitric-oxide-metabolism-by-carbatonides-disodium-2-6-dimethyl-1-4-dihydropyridine-3-5-bis-carbonyloxyacetate-derivatives-in-intact-and-diabetic-rats
#15
Kristīne Ošiņa, Elina Leonova, Sergejs Isajevs, Larisa Baumane, Evita Rostoka, Tatjana Sjakste, Egils Bisenieks, Gunars Duburs, Brigita Vīgante, Nikolajs Sjakste
Studies on the pathogenesis of diabetes mellitus complications indicate that the compounds reducing free radicals and enhancing DNA repair could be prospective as possible remedies. Carbatonides, the disodium-2,6-dimethyl-1,4- dihydropyridine-3,5-bis(carbonyloxyacetate) derivatives, were tested for these properties. EPR spectroscopy showed that metcarbatone was an effective scavenger of hydroxyl radicals produced in the Fenton reaction, etcarbatone, and propcarbatone were less effective, styrylcarbatone was ineffective...
September 26, 2017: Arhiv za Higijenu Rada i Toksikologiju
https://www.readbyqxmd.com/read/28970491/rev1-contributes-to-proper-mitochondrial-function-via-the-parp-nad-sirt1-pgc1%C3%AE-axis
#16
Nima Borhan Fakouri, Jon Ambæk Durhuus, Christine Elisabeth Regnell, Maria Angleys, Claus Desler, Mahdi Hasan- Olive, Ana Martín-Pardillos, Anastasia Tsaalbi-Shtylik, Kirsten Thomsen, Martin Lauritzen, Vilhelm A Bohr, Niels de Wind, Linda Hildegard Bergersen, Lene Juel Rasmussen
Nucleic acids, which constitute the genetic material of all organisms, are continuously exposed to endogenous and exogenous damaging agents, representing a significant challenge to genome stability and genome integrity over the life of a cell or organism. Unrepaired DNA lesions, such as single- and double-stranded DNA breaks (SSBs and DSBs), and single-stranded gaps can block progression of the DNA replication fork, causing replicative stress and/or cell cycle arrest. However, translesion synthesis (TLS) DNA polymerases, such as Rev1, have the ability to bypass some DNA lesions, which can circumvent the process leading to replication fork arrest and minimize replicative stress...
October 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28964869/anti-proliferative-and-pro-apoptotic-effects-of-uncaria-tomentosa-aqueous-extract-in-squamous-carcinoma-cells
#17
Francesca Ciani, Simona Tafuri, Annaelena Troiano, Alessio Cimmino, Bianca Saveria Fioretto, Andrea Maria Guarino, Alessandra Pollice, Maria Vivo, Antonio Evidente, Domenico Carotenuto, Viola Calabrò
Uncaria tomentosa (Willd.) DC. (Rubiacee), also known as uña de gato, is a plant that grows wild in the upper Amazon region of Peru and has been widely used in folk medicine to treat several health conditions including cancer. We have produced an aqueous extract from Uncaria tomentosa (UT-ex) and analyzed its effects on squamous carcinoma cells and immortalized HaCaT keratinocytes. Squamous cell carcinoma (SCC) is an uncontrolled growth of abnormal cells arising in the skin's squamous layer of epidermis. When detected at an early stage, SCCs are almost curable, however, if left untreated, they can penetrate the underlying tissue and become disfiguring...
September 28, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28956326/erratum-to-methodology-to-identify-poly-adp-ribose-polymerase-1-parp1-mrna-targets-by-par-clip
#18
Manana Melikishvili, Elena Matveeva, Yvonne Fondufe-Mittendorf
No abstract text is available yet for this article.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28948212/dna-repair-deficiency-biomarkers-and-the-70-gene-ultra-high-risk-signature-as-predictors-of-veliparib-carboplatin-response-in-the-i-spy-2-breast-cancer-trial
#19
Denise M Wolf, Christina Yau, Ashish Sanil, Annuska Glas, Emanuel Petricoin, Julia Wulfkuhle, Tesa M Severson, Sabine Linn, Lamorna Brown-Swigart, Gillian Hirst, Meredith Buxton, Angela DeMichele, Nola Hylton, Fraser Symmans, Doug Yee, Melissa Paoloni, Laura Esserman, Don Berry, Hope Rugo, Olufunmilayo Olopade, Laura van 't Veer
Veliparib combined with carboplatin (VC) was an experimental regimen evaluated in the biomarker-rich neoadjuvant I-SPY 2 trial for breast cancer. VC showed improved efficacy in the triple negative signature. However, not all triple negative patients achieved pathologic complete response and some HR+HER2- patients responded. Pre-specified analysis of five DNA repair deficiency biomarkers (BRCA1/2 germline mutation; PARPi-7, BRCA1ness, and CIN70 expression signatures; and PARP1 protein) was performed on 116 HER2- patients (VC: 72 and concurrent controls: 44)...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28940655/classification-of-in-vitro-genotoxicants-using-a-novel-multiplexed-biomarker-assay-compared-to-the-flow-cytometric-micronucleus-test
#20
Sabrina Wilde, Miriam Dambowsky, Claudia Hempt, Andreas Sutter, Nina Queisser
Regulatory in vitro genotoxicity testing exhibits shortcomings in specificity and mode of action (MoA) information. Thus, the aim of this work was to evaluate the performance of the novel MultiFlow(®) assay composed of mechanistic biomarkers quantified in TK6 cells after treatment (4 and 24 hr): γH2AX (DNA double strand breaks), phosphorylated H3 (mitotic cells), translocated p53 (genotoxicity), and cleaved PARP1 (apoptosis). A reference dataset of 31 compounds with well-established MoA was studied using the MicroFlow(®) micronucleus assay...
September 21, 2017: Environmental and Molecular Mutagenesis
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