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poly ADP-ribose polymerase

Fatima Karzai, David VanderWeele, Ravi A Madan, Helen Owens, Lisa M Cordes, Amy Hankin, Anna Couvillon, Erin Nichols, Marijo Bilusic, Michael L Beshiri, Kathleen Kelly, Venkatesh Krishnasamy, Sunmin Lee, Min-Jung Lee, Akira Yuno, Jane B Trepel, Maria J Merino, Ryan Dittamore, Jennifer Marté, Renee N Donahue, Jeffrey Schlom, Keith J Killian, Paul S Meltzer, Seth M Steinberg, James L Gulley, Jung-Min Lee, William L Dahut
BACKGROUND: Checkpoint inhibitors have not been effective for prostate cancer as single agents. Durvalumab is a human IgG1-K monoclonal antibody that targets programmed death ligand 1 and is approved by the U.S. Food and Drug Administration for locally advanced or metastatic urothelial cancer and locally advanced, unresectable stage 3 non-small cell lung cancer. Olaparib, a poly (ADP-ribose) polymerase inhibitor, has demonstrated an improvement in median progression-free survival (PFS) in select patients with metastatic castration-resistant prostate cancer (mCRPC)...
December 4, 2018: Journal for Immunotherapy of Cancer
Giovanna Sociali, Alessia Grozio, Irene Caffa, Susanne Schuster, Pamela Becherini, Patrizia Damonte, Laura Sturla, Chiara Fresia, Mario Passalacqua, Francesca Mazzola, Nadia Raffaelli, Antje Garten, Wieland Kiess, Michele Cea, Alessio Nencioni, Santina Bruzzone
Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD+ salvage pathway from nicotinamide. By controlling the biosynthesis of NAD+ , NAMPT regulates the activity of NAD+ -converting enzymes, such as CD38, poly-ADP-ribose polymerases, and sirtuins (SIRTs). SIRT6 is involved in the regulation of a wide number of metabolic processes. In this study, we investigated the ability of SIRT6 to regulate intracellular NAMPT activity and NAD(P)(H) levels. BxPC-3 cells and MCF-7 cells were engineered to overexpress a catalytically active or a catalytically inactive SIRT6 form or were engineered to silence endogenous SIRT6 expression...
December 4, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Shimei Qi, Zunyong Feng, Qiang Li, Zhilin Qi, Yao Zhang
Purpose: Reactive oxygen species (ROS) are considered a direct cause of neurodegenerative diseases (NDDs). Drugs developed to target ROS are effective for the treatment of NDDs. Orientin is a pyrone glucoside extracted from Polygonum orientale , and it exhibits many pharmacological activities. In this study, we aimed to determine whether orientin could relieve hydrogen peroxide (H2 O2 )-induced neuronal apoptosis and to investigate the specific target of orientin. Materials and methods: In this study, the neuroprotective effect and its possible mechanisms of orientin in mouse pheochromocytoma cell line (PC12) cells stimulated by H2 O2 , establishing an oxidative stress model, were investigated...
2018: Drug Design, Development and Therapy
Tatiana V Gorodnova, Anna P Sokolenko, Ekatherina Kuligina, Igor V Berlev, Evgeny N Imyanitov
Epithelial ovarian cancer (EOC) is a common malignant disease, which remains asymptomatic for a prolonged period of time and is usually diagnosed at advanced stages. Cytoreductive surgery is a backbone of EOC treatment. Wherever possible, EOC patients are subjected to primary debulking surgery (PDS) with the aim to remove all visible tumor lumps. Some patients cannot undergo PDS due to extensive disease spread and/or high risk of perioperative morbidity, therefore they are subjected to neoadjuvant chemotherapy (NACT) before the surgery...
December 2018: Chinese Clinical Oncology
Ji Young Hwang, Jung Hwa Park, Min Jae Kim, Woo Jean Kim, Ki-Tae Ha, Byung Tae Choi, Seo-Yeon Lee, Hwa Kyoung Shin
Glioblastoma multiforme (GBM) is the most common malignant brain tumor, which remains incurable. Plant extracts are a potential source of potent anticancer medicines. In this study, we investigated the effect of isolinderalactone from Lindera aggregata on tumor growth using U-87 human glioblastoma cells. Treatment with isolinderalactone inhibited cell viability and promoted apoptotic cell death. In addition, intraperitoneal injection of isolinderalactone significantly inhibited tumor growth in a human GBM xenograft mouse model...
November 29, 2018: Cancer Letters
An Wang, Yanqin Zhang, Peilong Cao
Cervical cancer is reported as one of the most lethal types of cancer among female. However, extensive studies of the molecular mechanisms that regulate the progression of cervical cancer are still required. B-cell associated protein (BAP)-31 is a 28-kDa integral membrane protein in the endoplasmic reticulum (ER), playing essential role in modulating various physiological processes. The present study indicated that BAP31 was a novel gene associated with cervical cancer development. Here, we demonstrated that BAP31 was significantly increased in human cervical cancer specimens, which was positively correlated to histological grade of the cancer...
November 29, 2018: Biochemical and Biophysical Research Communications
Zsolt Regdon, Agnieszka Robaszkiewicz, Katalin Kovács, Żaneta Rygielska, Csaba Hegedűs, Khaldon Bodoor, Éva Szabó, László Virág
In inflamed tissues or during ischemia-reperfusion episodes, activated macrophages produce large amounts of reactive species and are, thus, exposed to the damaging effects of reactive species. Here, our goal was to investigate the mechanism whereby activated macrophages protect themselves from oxidant stress-induced cell death. Hydrogen peroxide-treated mouse bone marrow-derived macrophages (BMDM) and THP-1 human monocyte-derived cells were chosen as models. We found a gradual development of resistance: first in monocyte-to-macrophage differentiation, and subsequently after lipopolysaccharide (LPS) exposure...
November 28, 2018: Free Radical Biology & Medicine
Raedeh Saraei, Faroogh Marofi, Adel Naimi, Mehdi Talebi, Mahnaz Ghaebi, Naser Javan, Omid Salimi, Ali Hassanzadeh
Flavonoids are a varied family of phytonutrients (plant chemicals) usually are detected in fruits and vegetables. In this big family, there exist more than 10,000 members that is separated into six chief subtypes: isoflavonols, flavonoenes, flavones, flavonols, anthocyanins, and chalcones. The natural compounds, such as fruits, have visible positive effects in regulating of survival involved signaling pathways that performance as the regulator of cell survival, growth, and proliferation. Researchers have established that commonly consumption up flavonoids decreases incidence and development risk of certain cancers, especially leukemia...
November 30, 2018: Journal of Cellular Physiology
Valentina Vio, Ana L Riveros, Andrea Tapia-Bustos, Carolyne Lespay-Rebolledo, Ronald Perez-Lobos, Luis Muñoz, Paola Pismante, Paola Morales, Eyleen Araya, Natalia Hassan, Mario Herrera-Marschitz, Marcelo J Kogan
Background: Perinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated with systemic and neurological diseases. Despite the important role of poly (ADP-ribose) polymerase 1 (PARP-1) in the regulation of gene expression and DNA repair, overactivation of PARP-1 in asphyxia-exposed animals worsens the ATP-dependent energetic crisis. Inhibition of PARP-1 offers a therapeutic strategy for diminishing the effects of perinatal asphyxia. Methods: We designed a nanosystem that incorporates a specific siRNA for PARP-1 knockdown...
2018: International Journal of Nanomedicine
Mona Dehhaghi, Vanessa Tan, Benjamin Heng, Fatemeh Mohammadipanah, Gilles J Guillemin
Astrocytes, the main non-neuronal cells in the brain, have significant roles in the maintenance and survival of neurons. Oxidative stress has been implicated in various neurodegenerative disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Myxobacteria produce a wide range of bioactive metabolites with notable structures and modes of action, which introduce them as potent natural product producers. In the present study, we evaluated the effects of myxobacterial extracts on hydrogen peroxide (H2 O2 ) mediated toxicity on primary human astrocytes...
November 26, 2018: Neuroscience
Fei Liang
No abstract text is available yet for this article.
November 29, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Poonam Giri, Lakshmikant Gupta, Sanjay Singh, Nirmal Patel, Nuggehally R Srinivas, Brijeshkumar Srivastva, Ranjit C Desai, Pankaj R Patel
1. ZYTP1 is a novel Poly (ADP-ribose) polymerase protein inhibitor being developed for cancer indications. 2. The focus of the work was to determine if ZYTP1 had a perpetrator role in the in vitro inhibition of cytochrome P450 (CYP) enzymes to aid dosing decisions during the clinical development of ZYTP1. 3. ZYTP1 IC50 for CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4/5 was determined using human liver microsomes and LC-MS/MS detection. CYP3A4/5 IC50 of depropylated metabolite of ZYTP1 was also determined. Time dependent inhibition of CYP3A4/5 by ZYTP1 was also assessed using substrates, testosterone and midazolam...
November 29, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Mathieu Césaire, Juliette Thariat, Serge M Candéias, Dinu Stefan, Yannick Saintigny, François Chevalier
Immunotherapy has revolutionized the practice of oncology, improving survival in certain groups of patients with cancer. Immunotherapy can synergize with radiation therapy, increase locoregional control, and have abscopal effects. Combining it with other treatments, such as targeted therapies, is a promising means of improving the efficacy of immunotherapy. Because the value of immunotherapy is amplified with the expression of tumor antigens, coupling poly(ADP-ribose) polymerase (PARP) inhibitors and immunotherapy might be a promising treatment for cancer...
November 28, 2018: International Journal of Molecular Sciences
Kathleen E Fenerty, Michelle Padget, Benjamin Wolfson, Sofia R Gameiro, Zhen Su, John H Lee, Shahrooz Rabizadeh, Patrick Soon-Shiong, James W Hodge
BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) prevent single-stranded DNA repair. Olaparib is a PARPi approved for the treatment of BRCA mutant ovarian and breast carcinoma. Emerging clinical data suggest a benefit of combining olaparib with immunotherapy in prostate cancer patients both with and without somatic BRCA mutations. METHODS: We examined if olaparib, when combined with IgG1 antibody-dependent cellular cytotoxicity (ADCC)-mediating monoclonal antibodies (mAbs) cetuximab (anti-EGFR), or avelumab (anti-PD-L1), would increase tumor cell sensitivity to killing by natural killer (NK) cells independently of BRCA status or mAb target upregulation...
November 29, 2018: Journal for Immunotherapy of Cancer
Eugene Roscioli, Rhys Hamon, Susan E Lester, Hubertus P A Jersmann, Paul N Reynolds, Sandra Hodge
BACKGROUND: Individuals with respiratory disease are being increasingly exposed to wildfire smoke as populations encroach further into forested regions and climate change continues to bring higher temperatures with lower rainfall. Frequent exposures have significant potential to accelerate conditions such as chronic obstructive pulmonary disease (COPD) which is characterised by an exaggerated inflammatory response to environmental stimuli. Here we employ models of human airway epithelium exposed to wildfire smoke-extract (WFSE) to examine modulation in airway epithelial cell (AEC) survival, fragility and barrier function...
November 28, 2018: Respiratory Research
Dinh-Chuong Pham, Yu-Chuan Chang, Shian-Ren Lin, Yuh-Ming Fuh, May-Jywan Tsai, Ching-Feng Weng
Human neuroblastoma cancer is the most typical extracranial solid tumor. Yet, new remedial treatment therapies are demanded to overcome its sluggish survival rate. Neferine, isolated from the lotus embryos, inhibits the proliferation of various cancer cells. This study aimed to evaluate the anti-cancer activity of neferine in IMR32 human neuroblastoma cells and to expose the concealable molecular mechanisms. IMR32 cells were treated with different concentrations of neferine, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability...
November 28, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jeong Yong Moon, Le Van Manh Hung, Tatsuya Unno, Somi Kim Cho
Drug resistance is a major problem in the treatment of non-small-cell lung cancer (NSCLC). In this study, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to identify the differentially expressed genes in Adriamycin (ADR)-resistant NSCLC A549/ADR cells compared with parental A549 cells. Among the tested phytochemicals, nobiletin (NBT) is able to overcome the ADR resistance of A549/ADR cells. NBT treatment decreased the expression of a neuroblastoma-derived MYC (MYCN) and multidrug resistance-associated protein 1 (MRP1) as well as downregulating Akt, GSK3β, and β-catenin...
November 26, 2018: Nutrients
Sithuraj Saranya, Rathinasamy Baskaran, Paramasivan Poornima, Viswanadha Vijaya Padma
Berbamine (BBM), a bisbenzylisoquinoline alkaloid from roots, bark, and stem of Berberis plant such as Berberis aristata has a wide range of pharmacological activities. However, the evidence for the cardioprotective effect of BBM is inadequate and the molecular mechanism of BBM remains unclear. This study investigated the underlying molecular mechanism of BBM-mediated cardioprotection on isoproterenol (ISO)-induced mitochondrial dysfunction and apoptosis in rats. The assays of mitochondria antioxidant status, mitochondrial marker enzymes, and electron microscopic analysis of mitochondria revealed BBM significantly prevented the mitochondrial dysfunction induced by ISO...
November 28, 2018: Journal of Cellular Biochemistry
Min-Gu Lee, Kyu-Shik Lee, Kyung-Soo Nam
Fewer than 20% of patients diagnosed with pancreatic cancer can be treated with surgical resection. The effects of proton beam irradiation were evaluated on the cell viabilities in Panc‑1 and Capan‑1 pancreatic cancer cells. The cells were irradiated with proton beams at the center of Bragg peaks with a 6‑cm width using a proton accelerator. Cell proliferation was assessed with the MTT assay, gene expression was analyzed with semi‑quantitative or quantitative reverse transcription‑polymerase chain reaction analyses and protein expression was evaluated by western blotting...
November 22, 2018: International Journal of Oncology
Jianfeng Shen, Wei Zhao, Zhenlin Ju, Lulu Wang, Yang Peng, Marilyne Labrie, Timothy A Yap, Gordon B Mills, Guang Peng
Poly-(ADP-ribose) polymerase (PARP) inhibitors (PARPi) have shown remarkable therapeutic efficacy against BRCA1/2 mutant cancers through a synthetic lethal interaction. PARPi exert their therapeutic effects mainly through the blockade of single-stranded DNA damage repair, which leads to the accumulation of toxic DNA double-strand breaks specifically in cancer cells with DNA repair deficiency (BCRAness), including those harboring BRCA1/2 mutations. Here we show that PARPi-mediated modulation of the immune response contributes to their therapeutic effects independently of BRCA1/2 mutations...
November 27, 2018: Cancer Research
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