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NAD+ AND cancer

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https://www.readbyqxmd.com/read/29160590/corrigendum-expression-of-nad-p-h-quinone-dehydrogenase-1-nqo1-is-increased-in-the-endometrium-of-women-with-endometrial-cancer-and-women-with-polycystic-ovary-syndrome
#1
William Atiomo, Mohamad Nasir Shafiee, Caroline Chapman, Veronika M Metzler, Jad Abouzeid, Ayşe Latif, Amy Chadwick, Sarah Kitson, Vanitha N Sivalingam, Ian J Stratford, Catrin S Rutland, Jenny L Persson, Niels Ødum, Pablo Fuentes-Utrilla, Jennie N Jeyapalan, David M Heery, Emma J Crosbie, Nigel P Mongan
No abstract text is available yet for this article.
December 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/29156703/preclinical-efficacy-of-the-novel-competitive-nampt-inhibitor-stf-118804-in-pancreatic-cancer
#2
Jair Machado Espindola-Netto, Claudia C S Chini, Mariana Tarragó, Enfeng Wang, Shamit Dutta, Krishnendu Pal, Debabrata Mukhopadhyay, Mauro Sola-Penna, Eduardo N Chini
NAD salvage is one of the pathways used to generate NAD in mammals. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this pathway, uses nicotinamide (NAM) to generate nicotinamide mononucleotide (NMN). NMN is one of the main precursors of NAD synthesis in cells. Our previous study showed the importance of NAMPT in maintaining NAD levels in pancreatic ductal adenocarcinoma cells (PDAC), and that the NAMPT inhibitor FK866 decreased pancreatic cancer growth. We now tested the effect of STF-118804, a new highly specific NAMPT inhibitor, in models of pancreatic ductal adenocarcinoma...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151986/pyrrolyl-pyrazoline-carbaldehydes-as-enoyl-acp-reductase-inhibitors-design-synthesis-and-antitubercular-activity
#3
Sheshagiri R Dixit, Shrinivas D Joshi, Venkatarao H Kulkarni, Sunil S Jalalpure, Vijay M Kumbar, Tulasigiriyappa Y Mudaraddi, Mallikarjuna N Nadagouda, Tejraj M Aminabhavi
Introduction: In efforts to develop new antitubercular (anti-TB) compounds, herein we describe cytotoxic evaluation of 15 newly synthesized pyrrolyl pyrazoline carbaldehydes. Method & Materials: Surflex-Docking method was used to study binding modes of the compounds at the active site of the enzyme enoyl ACP reductase from Mycobacterium tuberculosis (M. tuberculosis), which plays an important role in FAS-II biosynthetic pathway of M. tuberculosis and also it is an important target for designing novel anti-TB agents...
2017: Open Medicinal Chemistry Journal
https://www.readbyqxmd.com/read/29144773/cancer-chemopreventive-antiproliferative-and-superoxide-anion-scavenging-properties-of-kluyveromyces-marxianus-and-saccharomyces-cerevisiae-var-boulardii-cell-wall-components
#4
Olivier Fortin, Blanca Aguilar-Uscanga, Khanh Dang Vu, Stephane Salmieri, Monique Lacroix
This study investigated the cancer chemopreventive, the antiradical, and the antiproliferative properties of polysaccharides extracts from cell wall of Saccharomyces boulardii and Kluyveromyces marxianus. β-glucan, mannan, and chitin were also quantified to identify the most important extract responsible for these biological properties. Soluble and insoluble glucans as well as mannoprotein were extracted from cell wall using single hot-alkaline method. Superoxide anion scavenging (antiradical capacity), NAD(P)H: quinone reductase (QR) (EC 1...
November 16, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/29125463/pharmacological-augmentation-of-nicotinamide-phosphoribosyltransferase-nampt-protects-against-paclitaxel-induced-peripheral-neuropathy
#5
Peter M LoCoco, April L Risinger, Hudson R Smith, Teresa S Chavera, Kelly A Berg, William P Clarke
Chemotherapy-induced peripheral neuropathy (CIPN) arises from collateral damage to peripheral afferent sensory neurons by anticancer pharmacotherapy, leading to debilitating neuropathic pain. No effective treatment for CIPN exists, short of dose-reduction which worsens cancer prognosis. Here we report that stimulation of nicotinamide phosphoribosyltransferase (NAMPT) produced robust neuroprotection in an aggressive CIPN model utilizing the frontline anticancer drug, paclitaxel (PTX). Daily treatment of rats with the first-in-class NAMPT stimulator, P7C3-A20, prevented behavioral and histologic indicators of peripheral neuropathy, stimulated tissue NAD recovery, improved general health, and abolished attrition produced by a near maximum-tolerated dose of PTX...
November 10, 2017: ELife
https://www.readbyqxmd.com/read/29123410/long-noncoding-rna-and-mrna-profiling-in-mda-mb-231-cells-following-rnai-mediated-knockdown-of-sirt7
#6
Kun-Lin Chen, Lian Li, Yi-Ru Wang, Cheng-Min Li, Tarig Mohammed Badri, Gen-Lin Wang
Breast cancer is one of the most common malignant cancers among women and a major clinical obstacle. Although studies have reported the abnormal expression of SIRT7 in breast cancer, whether the function of SIRT7 regulates the expression of long noncoding RNAs (lncRNAs) in breast cancer remains unknown. We aimed to determine the differential expressions of mRNAs and lncRNAs associated with SIRT7 and understand the regulatory mechanism of SIRT7 in breast cancer. RNA sequencing was performed to explore the transcriptome in MDA-MB-231 cells after SIRT7 depletion, and a total of 50,634 different transcripts were identified...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29108235/regulation-of-sirt3-signal-related-metabolic-reprogramming-in-gastric-cancer-by-helicobacter-pylori-oncoprotein-caga
#7
Do Yeon Lee, Dawoon E Jung, Sung Sook Yu, Yeo Song Lee, Beom Ku Choi, Yong Chan Lee
Injection of the Helicobacter pylori cytotoxin-associated gene A (CagA) is closely associated with the development of chronic gastritis and gastric cancer. Individuals infected with H. pylori possessing the CagA protein produce more reactive oxygen species (ROS) and show an increased risk of developing gastric cancer. Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases and mitochondrial SIRT3 is known to be a tumor suppressor via its ability to suppress ROS and hypoxia inducible factor 1α (HIF-1α)...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100982/thermodynamics-of-cooperative-binding-of-fad-to-human-nqo1-implications-to-understanding-cofactor-dependent-function-and-stability-of-the-flavoproteome
#8
Rafael Clavería-Gimeno, Adrian Velazquez-Campoy, Angel Luis Pey
The stability of human flavoproteins strongly depends on flavin levels, although the structural and energetic basis of this relationship is poorly understood. Here, we report an in-depth analysis on the thermodynamics of FAD binding to one of the most representative examples of such relationship, NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 is a dimeric enzyme that tightly binds FAD, which triggers large structural changes upon binding. A common cancer-associated polymorphism (P187S) severely compromises FAD binding...
October 31, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29100430/novel-naprt-specific-antibody-identifies-small-cell-lung-cancer-and-neuronal-cancers-as-promising-clinical-indications-for-a-nampt-inhibitor-niacin-co-administration-strategy
#9
Jonathan Cole, Marie-Christine Guiot, Michel Gravel, Cynthia Bernier, Gordon C Shore, Anne Roulston
Tumor cells are particularly dependent on NAD(+) due to higher rates of metabolism, DNA synthesis and repair. Nicotinamide phosphoribosyltransferase inhibitors (NAMPTis) inhibit NAD(+) biosynthesis and represent promising new anti-cancer agents. However, clinical efficacy has been limited by toxicities demonstrating the need for drug combinations to broaden the therapeutic index. One potential combination involves niacin/NAMPTi co-administration. Niacin can rescue NAD(+) biosynthesis through a parallel pathway that depends on nicotinic acid phosphoribosyltransferase (NAPRT) expression...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29095437/metformin-ameliorates-arsenic-trioxide-hepatotoxicity-via-inhibiting-mitochondrial-complex-i
#10
Sunbin Ling, Qiaonan Shan, Peng Liu, Tingting Feng, Xuanyu Zhang, Penghui Xiang, Kangchen Chen, Haiyang Xie, Penghong Song, Lin Zhou, Jimin Liu, Shusen Zheng, Xiao Xu
Arsenic trioxide (ATO) is a well-accepted chemotherapy agent in managing promyelocytic leukemia. ATO often causes severe health hazards such as hepatotoxicity, dermatosis, neurotoxicity, nephrotoxicity and cardiotoxicity. The production of reactive oxygen species, (ROS) play a significant role in ATO-induced hepatotoxicity. The oral hypoglycemic drug, metformin, is considered to be a potential novel agent for chemoprevention in the treatment of cancer. Moreover, metformin has also been shown to have hepatoprotective effects...
November 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29090698/novel-half-sandwich-iridium-iii-imino-pyridyl-complexes-showing-remarkable-in-vitro-anticancer-activity
#11
JuanJuan Li, Lihua Guo, Zhenzhen Tian, Meng Tian, Shumiao Zhang, Ke Xu, Yuchuan Qian, Zhe Liu
Seven novel half-sandwich Ir(III) cyclopentadienyl complexes, [(η(5)-Cp(x))Ir(N^N)Cl]PF6, have been prepared and characterized, where Cp(x) is Cp* or the biphenyl derivative Cp(xbiph) (C5Me4C6H4C6H5), and the N^N-chelating ligands are imino-pyridyl Schiff-bases. The X-ray crystal structures of complexes 2A, 2B, and 3A have been determined. Excitingly, most of the complexes show potent antiproliferative activity towards A549 and HeLa cancer cells, except for Cp* complex 1A towards HeLa cells. Cp(xbiph) complex 2B displayed the highest potency, about 19 and 6 times more active than the clinically used drug cisplatin toward A549 and HeLa cells, respectively...
November 14, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29089150/hemin-reduces-hmgb1-release-by-uvb-in-an-ampk-ho-1-dependent-pathway-in-human-keratinocytes-hacat-cells
#12
Eun Jung Park, Young Min Kim, Ki Churl Chang
BACKGROUND AND AIMS: High mobility group box 1 (HMGB1) plays an important role as a pro-inflammatory cytokine that regulates inflammation in various diseases. We hypothesized that hemin might reduce HMGB1 release through the induction of HO-1 in UVB-induced HaCaTs. METHODS: The effects of hemin on the release of HMGB1 in UVB exposure were evaluated. The mechanisms were investigated using various signal inhibitors and small interfering RNA techniques. RESULTS: Treatment with hemin inhibited reactive oxygen species (ROS) in UVB-induced HaCaTs in a dose-dependent manner...
October 28, 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/29069770/genome-wide-functional-analysis-on-the-molecular-mechanism-of-specifically-biosynthesized-fluorescence-eu-complex
#13
Jing Ye, Xiawei Dong, Xuerui Jiang, Hui Jiang, Chen-Zhong Li, Xuemei Wang
Fluorescence imaging as an attractive diagnostic technique is widely employed for early diagnosis of cancer. Self-biosynthesized fluorescent Eu complex in situ in Hela cells have realized specifically and accurately fluorescence imaging for cancer cells. But the molecular mechanism of the in situ biosynthesized process is still unclear. In order to reveal this mechanism, we have investigated whole-genome expression profiles with cDNA microarray, incubated with Eu solution in Hela cells for 24 h. Methylthiazoltetrazolium (MTT) assay and laser confocal fluorescence microscopy study showed the low cytotoxicity and specifically fluorescence imaging of Eu complex in Hela cells...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29065820/recent-advances-in-antabuse-disulfiram-the-importance-of-its-metal-binding-ability-to-its-anticancer-activity
#14
Maricela Viola-Rhenals, Kush Rohit Patel, Laura Jaimes-Santamaria, Guojun Wu, Jinbao Liu, Q Ping Dou
Disulfiram (DSF, also called tetraethylthiuram disulphide), a disulfide derivative of N,N-diethyldithiocarbamate (DEDTC), is an antialcoholism drug that is currently being repurposed as a promising anticancer drug. DSF has been investigated in many studies, including in vitro, in vivo, preclinical and clinical. Various mechanisms have been proposed to be responsible for the cytotoxic effect of DSF on cancer cells. DSF is a pro-drug which is converted to its metabolite DEDTC in human body. A complex of DEDTC with a metal ion [usually Cu(II) or Zn(II)] could be responsible for the anticancer activity of DSF in breast, prostate, glioblastoma, lung, melanoma, cervical, colorectal cancers as well as myeloma and leukemia...
October 23, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29065631/association-patterns-of-ontological-features-signify-electronic-health-records-in-liver-cancer
#15
Lawrence W C Chan, S C Cesar Wong, Choo Chiap Chiau, Tak-Ming Chan, Liang Tao, Jinghan Feng, Keith W H Chiu
Electronic Health Record (EHR) system enables clinical decision support. In this study, a set of 112 abdominal computed tomography imaging examination reports, consisting of 59 cases of hepatocellular carcinoma (HCC) or liver metastases (so-called HCC group for simplicity) and 53 cases with no abnormality detected (NAD group), were collected from four hospitals in Hong Kong. We extracted terms related to liver cancer from the reports and mapped them to ontological features using Systematized Nomenclature of Medicine (SNOMED) Clinical Terms (CT)...
2017: Journal of Healthcare Engineering
https://www.readbyqxmd.com/read/29061583/bioengineered-nrf2-sirna-is-effective-to-interfere-with-nrf2-pathways-and-improve-chemosensitivity-of-human-cancer-cells
#16
Peng-Cheng Li, Mei-Juan Tu, Pui Yan Ho, Joseph L Jilek, Zhijiang Duan, Qian-Yu Zhang, Ai-Xi Yu, Ai-Ming Yu
The nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a transcription factor in the regulation of many oxidative enzymes and efflux transporters critical for oxidative stress and cellular defense against xenobiotics. NRF2 is dysregulated in patient osteosarcoma (OS) tissues and correlates with therapeutic outcomes. Nevertheless, research on the NRF2 regulatory pathways and its potential as a therapeutic target is limited to the use of synthetic small interfering RNA (siRNA) carrying extensive artificial modifications...
October 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29054982/discovery-of-a-highly-selective-nampt-inhibitor-that-demonstrates-robust-efficacy-and-improved-retinal-toxicity-with-nicotinic-acid-co-administration
#17
Genshi Zhao, Colin F Green, Yu-Hua Hui, Lourdes Prieto, Robert Shepard, Sucai Dong, Tao Wang, Bo Tan, Xueqian Gong, Lisa Kays, Robert L Johnson, Wenjuan Wu, Shobha Bhattachar, Miriam Del Prado, James R Gillig, Maria-Carmen Fernandez, Ken D Roth, Sean Buchanan, Ming-Shang Kuo, Sandaruwan Geeganage, Timothy P Burkholder
NAMPT, an enzyme essential for NAD+ biosynthesis, has been extensively studied as an anti-cancer target for developing potential novel therapeutics. Several NAMPT inhibitors have been discovered, some of which have been subjected to clinical investigations. Yet, the on-target hematological and retinal toxicities have hampered their clinical development. In this study, we report the discovery of a unique NAMPT inhibitor, LSN3154567. This molecule is highly selective, and has a potent and broad spectrum of anti-cancer activity...
October 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29047090/metabolic-reprogramming-and-redox-signaling-in-pulmonary-hypertension
#18
Lydie Plecitá-Hlavatá, Angelo D'alessandro, Karim El Kasmi, Min Li, Hui Zhang, Petr Ježek, Kurt R Stenmark
Pulmonary hypertension is a complex disease of the pulmonary vasculature, which in severe cases terminates in right heart failure. Complex remodeling of pulmonary arteries comprises the central issue of its pathology. This includes extensive proliferation, apoptotic resistance and inflammation. As such, the molecular and cellular features of pulmonary hypertension resemble hallmark characteristics of cancer cell behavior. The vascular remodeling derives from significant metabolic changes in resident cells, which we describe in detail...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29029387/the-%C3%AE-nad-salvage-pathway-and-pkc-mediated-signaling-influence-localized-parp-1-activity-and-ctcf-poly-adp-ribosylation
#19
David J P Henderson, Jj L Miranda, Beverly M Emerson
Poly(ADP)ribosylation (PARylation) of the chromatin architectural protein CTCF is critical for CTCF-dependent regulation of chromatin boundary and insulator elements. Loss of CTCF PARylation results in epigenetic silencing of certain tumor suppressor genes through destabilization of nearby chromatin boundaries. We investigated the metabolic and mechanistic processes that regulate PARP-1-mediated CTCF PARylation in human cancer cell lines and discovered a key role for the expression and activity of β-NAD+ salvage enzymes, NAMPT and NMNAT-1...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28989670/potent-mechanism-based-sirtuin-2-selective-inhibition-by-an-in-situ-generated-occupant-of-the-substrate-binding-site-selectivity-pocket-and-nad-binding-site
#20
Paolo Mellini, Yukihiro Itoh, Hiroki Tsumoto, Ying Li, Miki Suzuki, Natsuko Tokuda, Taeko Kakizawa, Yuri Miura, Jun Takeuchi, Maija Lahtela-Kakkonen, Takayoshi Suzuki
Sirtuin 2 (SIRT2), a member of the NAD(+)-dependent histone deacetylase family, has recently received increasing attention due to its potential involvement in neurodegenerative diseases and the progression of cancer. Potent and selective SIRT2 inhibitors thus represent desirable biological probes. Based on the X-ray crystal structure of SIRT2 in complex with a previously reported weak inhibitor (6), we identified in this study the potent mechanism-based inactivator KPM-2 (36), which is selective toward SIRT2...
September 1, 2017: Chemical Science
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