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https://www.readbyqxmd.com/read/29775598/selective-cytotoxicity-of-the-nampt-inhibitor-fk866-toward-gastric-cancer-cells-with-markers-of-the-epithelial-mesenchymal-transition-due-to-loss-of-naprt
#1
Jooyoung Lee, Hyosil Kim, Jae Eun Lee, Su-Jin Shin, Sejin Oh, Sungjin Kwon, Hakhyun Kim, Yoon Young Choi, Michael A White, Soonmyung Paik, Jae-Ho Cheong, Hyun Seok Kim
BACKGROUND & AIMS: Markers of the epithelial-mesenchymal transition (EMT) in gastric tumor tissues are associated with poor outcomes of patients. We performed a screen to identify pharmacologic compounds that kill gastric cancer cells with EMT-associated gene expression patterns and investigate their mechanisms. METHODS: We identified 29 gastric cancer cell lines with gene expression signature previously associated with an EMT subtype, based on data from RNA sequence analyses, and confirmed their mesenchymal phenotypes of 7 lines (Hs746T, SNU1750, MKN1, SK4, SNU484, SNU668, and YCC11), based in invasive activity and protein markers...
May 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29769421/low-placental-visfatin-expression-is-related-to-impaired-glycaemic-control-and-fetal-macrosmia-in-pregnancies-complicated-by-type-1-diabetes
#2
R Iciek, M Brazert, E Wender-Ozegowska, M Pietryga, J Brazert
Type 1 diabetes mellitus (T1DM) is still related to altered fetal growth and severe maternal complications. We studied the possible role of placental visfatin/nicotinamide phosphoribosyltransferase (NAMPT) in fetal development in T1DM pregnancies, the possible role of placental visfatin in fetal macrosomia. Sixty five pregnant women with T1DM and singleton pregnancy were qualified into the study. Placental visfatin expression was by analysed by RT-PCR. We demonstrated the lowest expression of placental visfatin in women who delivered neonates with birth weight NBW > 4000 g (0...
February 2018: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29761507/upregulation-of-the-adipokine-genes-adipor1-and-spp1-is-related-to-poor-survival-outcomes-in-colorectal-cancer
#3
Eun K Choe, Jin W Yi, Young J Chai, Kyu J Park
BACKGROUND: Obesity is closely associated with colorectal cancer (CRC), but the underlying mechanism is unclear. We thus evaluated the expression of the adipokine gene family in CRC tissues and its clinicopathological implications. METHODS: Correlations between the mRNA expression levels of the adipokine gene family (ADIPOQ, ADIPOR1/2, LEP, LEPR, RETN, RETNLB, RBP4, SFRP5, NAMPT, and SPP1) in CRC tissue and clinicopathologic factors were analyzed using data from The Cancer Genome Atlas database...
May 14, 2018: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29753648/nicotinamide-phosphoribosyltransferase-regulates-cocaine-reward-through-sirtuin-1
#4
Jueying Kong, Changman Du, Linhong Jiang, Wei Jiang, Pengchi Deng, Xue Shao, Baolai Zhang, Yan Li, Ruiming Zhu, Qian Zhao, Dengqi Fu, Hui Gu, Li Luo, Hailei Long, Yinglan Zhao, Xiaobo Cen
Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis in mammals, converts nicotinamide into nicotinamide mononucleotide (NMN). NMN is subsequently converted to NAD, a component that is critical for cell energy metabolism and survival. Sirtuin 1 (SIRT1), an NAD-dependent histone deacetylase, plays an important role in mediating memory and synaptic plasticity. Here, we found that NAMPT was significantly upregulated in the ventral tegmental area (VTA) of cocaine-conditioned mice...
May 10, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29737089/-expression-and-initial-mechanism-of-nicotinamide-phosphoribosyltransferase-nampt-in-dilated-cardiomyopathy
#5
Qing-Yu Dou, Bin Zhou, Ying Pen, Kui Zhang, Xiao-Hui Dai, Ya-Ping Song, Li Rao
OBJECTIVE: To explore nicotinamide phosphoribosyltransferase (NAMPT) expression in dilated cardiomyopathy (DCM) and its initial mechanism in the pathogenesis of DCM. METHODS: The peripheral blood of 131 Chinese patients with DCM confirmed by West China Hospital of Sichuan University during 2010-2013 were collected. 137 cases of Chinese Han healthy persons who were randomly selected in the physical examination center of West China Hospital of Sichuan University as the control group...
January 2018: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29731606/clickable-prodrugs-bearing-potent-and-hydrolytically-cleavable-nicotinamide-phosphoribosyltransferase-inhibitors
#6
Keivan Sadrerafi, Emilia O Mason, Mark W Lee
Purpose: Our previous study indicated that carborane containing small-molecule 1-(hydroxymethyl)-7-(4'-( trans -3″-(3'″-pyridyl)acrylamido)butyl)-1,7-dicarbadodecaborane (hm-MC4-PPEA), was a potent inhibitor of nicotinamide phosphoribosyltransferase (Nampt). Nampt has been shown to be upregulated in most cancers and is a promising target for the treatment of many different types of cancers, including breast cancers. Patients and methods: To increase the selectivity of hm-MC4-PPEA toward cancer cells, three prodrugs were synthesized with different hydrolyzable linkers: ester, carbonate, and carbamate...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29725408/expression-of-nampt-is-associated-with-breast-invasive-ductal-carcinoma-development-and-prognosis
#7
Shao-Jie Zhou, Tie-Qiang Bi, Chun-Xin Qin, Xiao-Qing Yang, Kai Pang
Nicotinamide phosphoribosyltransferase (NAMPT) possesses various functions in human cells, and altered NAMPT expression is associated with human carcinogenesis. The present study detected the expression of NAMPT in normal and cancerous breast tissues from 83 patients using immunohistochemistry, and analyzed its association with the clinicopathological and survival data of the patients. NAMPT was significantly overexpressed in the breast invasive ductal carcinoma tissues compared with adjacent normal mammary gland tissues...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29721988/role-of-sirtuins-in-retinal-function-under-basal-conditions
#8
Jonathan B Lin, Shunsuke Kubota, Raul Mostoslavsky, Rajendra S Apte
Sirtuins are NAD+ -dependent enzymes that govern cellular homeostasis by regulating the acylation status of their diverse target proteins. We recently demonstrated that both rod and cone photoreceptors rely on NAMPT-mediated NAD+ biosynthesis to meet their energetic requirements. Moreover, we found that this NAD+ -dependent retinal homeostasis relies, in part, on maintenance of optimal activity of the mitochondrial sirtuins and of SIRT3 in particular. Nonetheless, it is unknown whether other sirtuin family members also play important roles in retinal homeostasis...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29721178/extracellular-nicotinamide-phosphoribosyltransferase-enampt-is-a-novel-marker-for-patients-with-braf-mutated-metastatic-melanoma
#9
Valentina Audrito, Antonella Managò, Federica Zamporlini, Eliana Rulli, Federica Gaudino, Gabriele Madonna, Stefania D'Atri, Gian Carlo Antonini Cappellini, Paolo Antonio Ascierto, Daniela Massi, Nadia Raffaelli, Mario Mandalà, Silvia Deaglio
Metastatic melanoma carrying BRAF mutations represent a still unmet medical need as success of BRAF inhibitors is limited by development of resistance. Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme in NAD biosynthesis. An extracellular form (eNAMPT) possesses cytokine-like functions and is up-regulated in inflammatory disorders, including cancer. Here we show that eNAMPT is actively released in culture supernatants of melanoma cell lines. Furthermore, cells that become resistant to BRAF inhibitors (BiR) show a significant increase of eNAMPT levels...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29695257/comparative-omics-and-feeding-manipulations-in-chicken-indicate-a-shift-of-the-endocrine-role-of-visceral-fat-towards-reproduction
#10
Susanne Bornelöv, Eyal Seroussi, Sara Yosefi, Sharon Benjamini, Shoval Miyara, Mark Ruzal, Manfred Grabherr, Nima Rafati, Anna-Maja Molin, Ken Pendavis, Shane C Burgess, Leif Andersson, Miriam Friedman-Einat
BACKGROUND: The mammalian adipose tissue plays a central role in energy-balance control, whereas the avian visceral fat hardly expresses leptin, the key adipokine in mammals. Therefore, to assess the endocrine role of adipose tissue in birds, we compared the transcriptome and proteome between two metabolically different types of chickens, broilers and layers, bred towards efficient meat and egg production, respectively. RESULTS: Broilers and layer hens, grown up to sexual maturation under free-feeding conditions, differed 4...
April 26, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29684358/novel-protective-role-of-nicotinamide-phosphoribosyltransferase-in-acetaminophen-induced-acute-liver-injury-in-mice
#11
Li Qin Zhang, Marianne Nsumu, Peixin Huang, Daniel P Heruth, Sean M Riordan, Katherine Shortt, Nini Zhang, Dmitry N Grigoryev, Ding-You Li, Craig A Friesen, Leon Van Haandel, J Steven Leeder, Jody Olson, Shui Qing Ye
Acetaminophen overdose is the most common cause of acute liver injury (ALI) or acute liver failure in the US. Its pathogenetic mechanisms are incompletely understood. Additional studies are warranted to identify new genetic risk factors for more mechanistic insights and new therapeutic target discoveries. The objective of this study was to explore the role and mechanisms of nicotinamide phosphoribosyltransferase (NAMPT) in acetaminophen-induced ALI. C57BL/6 Nampt gene wild-type (Nampt+/+ )-, heterozygous knockout (Nampt+/- )-, and overexpression (NamptOE )-mice were treated with overdose of acetaminophen, followed by histological, biochemical, and transcriptomic evaluation of liver injury...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29663373/nampt-expression-in-osteoblasts-controls-osteoclast-recruitment-in-alveolar-bone-remodeling
#12
Bassam Hassan, Brigitte Baroukh, Annie Llorens, Julie Lesieur, Sandy Ribbes, Catherine Chaussain, Jean-Louis Saffar, Marjolaine Gosset
In bone remodeling, osteoclasts are recruited via increased production of RANKL (receptor activator of nuclear factor-κB ligand) and migrate to the bone surface, aided by matrix metalloproteinases (MMPs). NAMPT (nicotinamide phosphoribosyl transferase), which catalyzes the rate-limiting step in the NAD+ salvage pathway, increases during in vitro osteogenic differentiation and inhibits RANKL-induced osteoclast differentiation. Alveolar bone loss, due to disturbance of the remodeling process, is a major feature of periodontitis...
April 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29662658/cross-resistance-to-diverse-anticancer-nicotinamide-phosphoribosyltransferase-inhibitors-induced-by-fk866-treatment
#13
Yoko Ogino, Akira Sato, Fumiaki Uchiumi, Sei-Ichi Tanuma
Cross-resistance to drugs remains an unsolved problem in cancer chemotherapy. This study elucidates a molecular mechanism of cross-resistance to diverse inhibitors of nicotinamide phosphoribosyltransferase (NAMPT) with anticancer activity. We generated a variant of the human colon cancer cell line HCT116, HCT116RFK866 , which exhibited primary resistance to the potent NAMPT inhibitor FK866, and was approximately 1,000-fold less sensitive to the drug than the parental HCT116. HCT116RFK866 was found to be cross-resistant to diverse NAMPT inhibitors, including CHS-828, GNE-617, and STF-118804...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29653431/inhibition-of-nampt-sensitizes-molt4-leukemia-cells-for-etoposide-treatment-through-the-sirt2-p53-pathway
#14
Theresa Grohmann, Melanie Penke, Stefanie Petzold-Quinque, Susanne Schuster, Sandy Richter, Wieland Kiess, Antje Garten
NAMPT (Nicotinamide phosphoribosyltransferase) catalyses the rate-limiting step in the NAD biosynthesis from nicotinamide and thereby regulates the activity of NAD-dependent enzymes. Cancer cells are highly dependent on NAD for energy and DNA repair processes and are assumed to be more susceptible to an inhibition of NAD synthesis than non-transformed cells. We aimed to investigate whether or not inhibition of NAMPT with its specific inhibitor FK866 can sensitize leukemia cells for chemotherapeutic agents. NAMPT protein abundance, enzymatic activity and NAD concentrations were significantly higher in Jurkat and Molt-4 leukemia cell lines compared to normal peripheral blood mononuclear cells...
April 5, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29608912/glomerular-mitochondrial-changes-in-hiv-associated-renal-injury
#15
Joseph L Bryant, Poornachander R Guda, Girma Asemu, Rogin Subedi, Sugata Ray, Omar S Khalid, Vivek Shukla, Dhruvil Patel, Harry Davis, Vamshi K C Nimmagadda, Tapas K Makar
HIV-associated nephropathy (HIVAN) is an AIDs-related disease of the kidney. HIVAN is characterized by severe proteinuria, podocyte hyperplasia, collapse, glomerular, and tubulointerstitial damage. HIV-1 transgenic (Tg26) mouse is the most popular model to study the HIV manifestations that develop similar renal presentations as HIVAN. Viral proteins, including Tat, Nef, and Vpr play a significant role in renal cell damage. It has been shown that mitochondrial changes are involved in several kidney diseases, and therefore, mitochondrial dysfunction may be implicated in the pathology of HIVAN...
March 30, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29601800/overexpression-of-mir-182-inhibits-ossification-of-ligamentum-flavum-cells-by-targeting-nampt
#16
Qiang Zhang, Yifei Shen, Yuqing Jiang, Shujie Zhao, Dong Zhou, Nanwei Xu
Ossification of the ligamentum flavum (OLF) is a debilitating disease resulting from the development of ectopic bone formation, which leads to the compression of the spinal cord. Nicotinamide phosphoribosyltransferase (NAMPT) was found to be upregulated and microRNA-182 (miR-182) was downregulated in OLF tissue. We investigated the effects of NAMPT and miR-182 expression in OLF cells and the influence on proteins associated with osteogenic differentiation. MiR-182 overexpression inhibited NAMPT, RUNX2, OCN and OPN mRNA and protein expression in OLF cells...
March 27, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29567766/pivotal-role-of-nampt-in-the-switch-of-melanoma-cells-toward-an-invasive-and-drug-resistant-phenotype
#17
Mickaël Ohanna, Mickaël Cerezo, Nicolas Nottet, Karine Bille, Robin Didier, Guillaume Beranger, Baharia Mograbi, Stéphane Rocchi, Laurent Yvan-Charvet, Robert Ballotti, Corine Bertolotto
In BRAFV600E melanoma cells, a global metabolomic analysis discloses a decrease in nicotinamide adenine dinucleotide (NAD+ ) levels upon PLX4032 treatment that is conveyed by a STAT5 inhibition and a transcriptional regulation of the nicotinamide phosphoribosyltransferase (NAMPT) gene. NAMPT inhibition decreases melanoma cell proliferation both in vitro and in vivo, while forced NAMPT expression renders melanoma cells resistant to PLX4032. NAMPT expression induces transcriptomic and epigenetic reshufflings that steer melanoma cells toward an invasive phenotype associated with resistance to targeted therapies and immunotherapies...
March 22, 2018: Genes & Development
https://www.readbyqxmd.com/read/29551635/nampt-mediated-nad-biosynthesis-is-indispensable-for-adipose-tissue-plasticity-and-development-of-obesity
#18
Karen Nørgaard Nielsen, Julia Peics, Tao Ma, Iuliia Karavaeva, Morten Dall, Sabina Chubanava, Astrid L Basse, Oksana Dmytriyeva, Jonas T Treebak, Zachary Gerhart-Hines
OBJECTIVE: The ability of adipose tissue to expand and contract in response to fluctuations in nutrient availability is essential for the maintenance of whole-body metabolic homeostasis. Given the nutrient scarcity that mammals faced for millions of years, programs involved in this adipose plasticity were likely evolved to be highly efficient in promoting lipid storage. Ironically, this previously advantageous feature may now represent a metabolic liability given the caloric excess of modern society...
March 7, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29546048/changes-of-nicotinamide-phosphoribosyltransferase-expressions-in-thyroid-glands-of-patients-with-different-thyroid-pathologies
#19
Nadia Sawicka-Gutaj, Mirosław Andrusiewicz, Agata Czarnywojtek, Joanna Waligórska-Stachura, Maciej Biczysko, Jerzy Skrobisz, Jerzy Sowiński, Marek Ruchała
Purpose: Our aim was to analyze NAMPT expression in thyroid tissue derived from patients with Graves' disease with (GD) and without (GO) orbitopathy, patients with toxic nodular goiters (TNG) and thyroid cancers (TC), and healthy controls. Methods: 153 thyroid tissue samples of consecutive patients who underwent thyroidectomy were collected. Previous therapy with steroids was an exclusion criterion. We collected clinicopathological data of all subjects and we assessed NAMPT expression using qPCR...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29541451/cancer-cell-metabolic-plasticity-allows-resistance-to-nampt-inhibition-but-invariably-induces-dependence-on-ldha
#20
Natthakan Thongon, Chiara Zucal, Vito Giuseppe D'Agostino, Toma Tebaldi, Silvia Ravera, Federica Zamporlini, Francesco Piacente, Ruxanda Moschoi, Nadia Raffaelli, Alessandro Quattrone, Alessio Nencioni, Jean-Francois Peyron, Alessandro Provenzani
Background: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance. Methods: We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, and by exploiting an integrated approach based on genetic, biochemical, and genome wide analyses, we annotated the drug resistance mechanisms...
2018: Cancer & Metabolism
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