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https://www.readbyqxmd.com/read/28329179/research-on-skin-cancer-related-behaviors-and-outcomes-in-the-nih-grant-portfolio-2000-2014-skin-cancer-intervention-across-the-cancer-control-continuum-sci-3c
#1
Frank M Perna, Laura A Dwyer, Gina Tesauro, Jennifer M Taber, Wynne E Norton, Anne M Hartman, Alan C Geller
Importance: The Surgeon General's Call to Action to Prevent Skin Cancer broadly identified research gaps, but specific objectives are needed to further behavioral intervention research. Objective: To review National Institute of Health (NIH) grants targeting skin cancer-related behaviors and relevant outcomes. Design, Setting, and Participants: A portfolio analysis of the title, abstract, specific aims, and research plans of identified grant applications from 2000 to 2014 targeting skin cancer-related behaviors or testing behavioral intervention effects on cancer-relevant outcomes along the cancer continuum...
March 22, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28326081/the-smac-mimetic-bv6-improves-nk-cell-mediated-killing-of-rhabdomyosarcoma-cells-by-simultaneously-targeting-tumor-and-effector-cells
#2
Kyra Fischer, Sara Tognarelli, Stefanie Roesler, Cathinka Boedicker, Ralf Schubert, Alexander Steinle, Thomas Klingebiel, Peter Bader, Simone Fulda, Evelyn Ullrich
Rhabdomyosarcoma (RMS), the most common cancer of connective tissues in pediatrics, is often resistant to conventional therapies. One underlying mechanism of this resistance is the overexpression of Inhibitor of Apoptosis (IAP) proteins, leading to a dysfunctional cell death program within tumor cells. Smac mimetics (SM) are small molecules that can reactivate the cell death program by antagonizing IAP proteins and thereby compensating their overexpression. Here, we report that SM sensitize two RMS cell lines (RD and RH30) toward natural killer (NK) cell-mediated killing on the one hand, and increase the cytotoxic potential of NK cells on the other...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28325600/synthesis-and-anti-cancer-activities-of-new-sulfonamides-4-substituted-triazolyl-nucleosides
#3
Soukaina Alaoui, Maeva Dufies, Mohsine Driowya, Luc Demange, Khalid Bougrin, Guillaume Robert, Patrick Auberger, Gilles Pagès, Rachid Benhida
Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell lines, AICAR is under clinical development for several pathologies, thanks to its original mode of action. Indeed, AICAR induced autophagy cell death and is able, following this mechanism, to circumvent resistance to apoptotic drugs including kinase inhibitors currently on the market...
March 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28322292/a-structure-and-chemical-genomics-based-approach-for-repositioning-of-drugs-against-vcp-p97-atpase
#4
Aldo Segura-Cabrera, Reshmi Tripathi, Xiaoyi Zhang, Lin Gui, Tsui-Fen Chou, Kakajan Komurov
Valosin-containing protein (VCP/p97) ATPase (a.k.a. Cdc48) is a key member of the ER-associated protein degradation (ERAD) pathway. ERAD and VCP/p97 have been implicated in a multitude of human diseases, such as neurodegenerative diseases and cancer. Inhibition of VCP/p97 induces proteotoxic ER stress and cell death in cancer cells, making it an attractive target for cancer treatment. However, no drugs exist against this protein in the market. Repositioning of drugs towards new indications is an attractive alternative to the de novo drug development due to the potential for significantly shorter time to clinical translation...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315326/identification-of-parp14-inhibitors-using-novel-methods-for-detecting-auto-ribosylation
#5
Mariko Yoneyama-Hirozane, Shin-Ichi Matsumoto, Yukio Toyoda, Singh Saikatendu Kumar, Yumi Zama, Kazuko Yonemori, Motomi Oonishi, Tsuyoshi Ishii, Tomohiro Kawamoto
Poly(ADP-ribose) polymerases (PARPs) use nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate to transfer ADP-ribose when it releases nicotinamide as the metabolized product. Enzymes of the PARP family play key roles in detecting and repairing DNA, modifying chromatin, regulating transcription, controlling energy metabolism, and inducing cell death. PARP14, the original member of the PARP family, has been reported to be associated with the development of inflammatory diseases and various cancer types, making it a potential therapeutic target...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28303734/how-badly-did-it-hit-self-assessed-emotional-shock-upon-prostate-cancer-diagnosis-and-psychological-well-being-a-follow-up-at-3-12-and-24-months-after-surgery
#6
Karin Stinesen Kollberg, Ulrica Wilderäng, Thordis Thorsteinsdottir, Jonas Hugosson, Peter Wiklund, Anders Bjartell, Stefan Carlsson, Johan Stranne, Eva Haglind, Gunnar Steineck
BACKGROUND: We were interested in examining if there was a link between self-assessed emotional shock by prostate cancer diagnosis and psychological well-being at 3, 12, and 24 months after surgery. MATERIAL AND METHODS: Information was derived from patients participating in the LAPAroscopic Prostatectomy Robot Open (LAPPRO) trial, Sweden. We analyzed the association between self-assessed emotional shock upon diagnosis and psychological well-being by calculating odds ratios (ORs)...
March 17, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28299833/unsupervised-pharmacophore-modeling-combined-with-qsar-analyses-revealed-novel-low-micromolar-sirt2-inhibitors
#7
Mohammad A Khanfar, Mutasem O Taha
Situin 2 (SIRT2) enzyme is a histone deacetylase that has important role in neuronal development. SIRT2 is clinically validated target for neurodegenerative diseases and some cancers. In this study, exhaustive unsupervised pharmacophore modeling was combined with quantitative structure-activity relationship (QSAR) analysis to explore the structural requirements for potent SIRT2 inhibitors using 146 known SIRT2 ligands. A computational workflow that combines genetic function algorithm with k-nearest neighbor or multiple linear regression was implemented to build self-consistent and predictive QSAR models based on combinations of pharmacophores and physicochemical descriptors...
March 15, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28298901/unveiling-another-missing-piece-in-ebv-driven-lymphomagenesis-ebv-encoded-micrornas-expression-in-eber-negative-burkitt-lymphoma-cases
#8
Lucia Mundo, Maria R Ambrosio, Matteo Picciolini, Giuseppe Lo Bello, Sara Gazaneo, Leonardo Del Porro, Stefano Lazzi, Mohsen Navari, Noel Onyango, Massimo Granai, Cristiana Bellan, Giulia De Falco, Davide Gibellini, Pier P Piccaluga, Lorenzo Leoncini
Epstein-Barr virus (EBV) is a gammaherpesvirus linked to a number of lymphoid and epithelial malignancies, including Burkitt lymphoma (BL) in which its frequency ranges from 30% in sporadic cases to 100% in the endemic ones. The possible contribution of EBV to BL pathogenesis is largely unknown. It has been suggested that EBV may be associated with all of the cases, including those diagnosed as EBV negative by a mechanism of hit-and-run. Early during oncogenesis, viral genes are essential for initiating disease...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28294049/in-silico-analysis-of-amp-activated-protein-kinase-and-ligand-based-virtual-screening-for-identification-of-novel-ampk-activators
#9
Ammarah Ghaffar, Sidra Batool, Gohar Mushtaq, Muhammad Amjad Kamal
BACKGROUND: Adenosine-Monophosphate-Activated protein kinase (AMPK) is a conserved kinase that plays an important role in maintaining the homeostasis of cells. AMPK activation has a positive impact on treatment of diseases such as diabetes, obesity and cancer as well. This observation led to the development of AMPK activators. Certain naturally occurring compounds have also been known to activate AMPK. METHOD: In this study, we retrieved the AMPK activators that includes chemical drugs, xenobiotics and natural compounds and analyzed their interactions with AMPK via docking studies...
March 9, 2017: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/28291344/first-bispecific-inhibitors-of-the-epidermal-growth-factor-receptor-kinase-and-the-nf-%C3%AE%C2%BAb-activity-as-novel-anti-cancer-agents
#10
Mostafa M Hamed, Sarah S Darwish, Jennifer Herrmann, Ashraf H Abadi, Matthias Engel
The activation of the NF-κB transcription factor is a major adaptive response induced upon treatment with EGFR kinase inhibitors, leading to the emergence of resistance in non-small cell lung cancer and other tumor types. To suppress this survival mechanism, we developed new thiourea quinazoline derivatives that are dual inhibitors of both EGFR kinase and the NF-κB activity. Optimization of the hit compound, identified in a NF-κB reporter gene assay, led to compound 9b, exhibiting a cellular IC50 for NF-κB inhibition of 0...
March 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28288156/parameter-estimation-for-multistage-clonal-expansion-models-from-cancer-incidence-data-a-practical-identifiability-analysis
#11
Andrew F Brouwer, Rafael Meza, Marisa C Eisenberg
Many cancers are understood to be the product of multiple somatic mutations or other rate-limiting events. Multistage clonal expansion (MSCE) models are a class of continuous-time Markov chain models that capture the multi-hit initiation-promotion-malignant-conversion hypothesis of carcinogenesis. These models have been used broadly to investigate the epidemiology of many cancers, assess the impact of carcinogen exposures on cancer risk, and evaluate the potential impact of cancer prevention and control strategies on cancer rates...
March 13, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28274247/gossypol-has-anti-cancer-effects-by-dual-targeting-mdm2-and-vegf-in-human-breast-cancer
#12
Jing Xiong, Jiansha Li, Qin Yang, Jun Wang, Tiefen Su, Sheng Zhou
BACKGROUND: Mouse double minute 2 (MDM2) and vascular endothelial growth factor (VEGF) are important molecules involved in tumor progression. We researched potential inhibitors that simultaneously target MDM2 and VEGF. In our recent study involving the performance of high-throughput screening with a fluorescence polarization assay, gossypol was identified as one of the top hits that inhibit protein-RNA binding activity. Because MDM2 is an RNA-binding protein and its targets include VEGF mRNA, we investigated whether gossypol has an inhibitory effect on MDM2-VEGF...
March 9, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28262675/genomic-characterisation-of-e%C3%AE-myc-mouse-lymphomas-identifies-bcor-as-a-myc-co-operative-tumour-suppressor-gene
#13
Marcus Lefebure, Richard W Tothill, Elizabeth Kruse, Edwin D Hawkins, Jake Shortt, Geoffrey M Matthews, Gareth P Gregory, Benjamin P Martin, Madison J Kelly, Izabela Todorovski, Maria A Doyle, Richard Lupat, Jason Li, Jan Schroeder, Meaghan Wall, Stuart Craig, Gretchen Poortinga, Don Cameron, Megan Bywater, Lev Kats, Micah D Gearhart, Vivian J Bardwell, Ross A Dickins, Ross D Hannan, Anthony T Papenfuss, Ricky W Johnstone
The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28258624/trans-oral-robotic-assisted-tongue-base-mucosectomy-for-investigation-of-cancer-of-unknown-primary-in-the-head-and-neck-region-the-uk-experience
#14
Stuart C Winter, Enyi Ofo, Dae Kim, P Silva, Lisa Fraser, James O'Hara, David Meikle, Max Robinson, Vinidh Paleri
INTRODUCTION: The diagnosis of cancer of unknown primary (CUP) in head and neck occurs when the treating clinicians have utilised all available diagnostic tests and failed to identify the origin of the disease. There is no agreed consensus on which diagnostic investigations to use, or the order in which to use them in, although broad recommendations exist. Small tumours arising in the tongue base can be below the limits of resolution of conventional diagnostic techniques. Given the difficulty in targeting the tongue base, current practice involves blind random biopsies, which leads to a variable detection rate...
March 4, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28255604/detection-of-a-new-jcv-strain-of-genotype-a-in-a-subpopulation-of-colorectal-adenocarcinomas-in-tunisia
#15
Wafa Toumi, Alessandro Ripalti, Luigi Ricciardiello, Abderraouf Cherif, Dalila Gargouri, Ahmed Bouhafa, Jamel Kharrat, Slim Jarboui, Hichem Benrhouma, Mohamed Zili, Ridha Khelifa
The etiology of colorectal cancer (CRC) remains elusive in spite of major advances in knowledge of this disease and related risk factors. Several studies report the detection of human polyomavirus JC (JCV) in colorectal tumors and some suggest its association with CRC. Since many known human virus associations with cancer are linked to factors such as ethnic and geographical origin, it is interesting to search for the postulated association of JCV with CRC in different populations and regions. In this perspective, the present work was undertaken to assess the presence of JCV in CRC tumors in Tunisia...
March 3, 2017: New Microbiologica
https://www.readbyqxmd.com/read/28254357/rad-adapt-software-for-modelling-clonogenic-assay-data-in-radiation-biology
#16
Yaping Zhang, Kaiqiang Hu, Jan H Beumer, Christopher J Bakkenist, David Z D'Argenio
We present a comprehensive software program, RAD-ADAPT, for the quantitative analysis of clonogenic assays in radiation biology. Two commonly used models for clonogenic assay analysis, the linear-quadratic model and single-hit multi-target model, are included in the software. RAD-ADAPT uses maximum likelihood estimation method to obtain parameter estimates with the assumption that cell colony count data follow a Poisson distribution. The program has an intuitive interface, generates model prediction plots, tabulates model parameter estimates, and allows automatic statistical comparison of parameters between different groups...
February 20, 2017: DNA Repair
https://www.readbyqxmd.com/read/28253280/the-cyanobacterial-metabolite-nocuolin-a-is-a-natural-oxadiazine-that-triggers-apoptosis-in-human-cancer-cells
#17
Kateřina Voráčová, Jan Hájek, Jan Mareš, Petra Urajová, Marek Kuzma, José Cheel, Andreas Villunger, Alexandra Kapuscik, Marcel Bally, Petr Novák, Martin Kabeláč, Gerhard Krumschnabel, Martin Lukeš, Ludmila Voloshko, Jiří Kopecký, Pavel Hrouzek
Oxadiazines are heterocyclic compounds containing N-N-O or N-N-C-O system within a six membered ring. These structures have been up to now exclusively prepared via organic synthesis. Here, we report the discovery of a natural oxadiazine nocuolin A (NoA) that has a unique structure based on 1,2,3-oxadiazine. We have identified this compound in three independent cyanobacterial strains of genera Nostoc, Nodularia, and Anabaena and recognized the putative gene clusters for NoA biosynthesis in their genomes. Its structure was characterized using a combination of NMR, HRMS and FTIR methods...
2017: PloS One
https://www.readbyqxmd.com/read/28249240/identification-of-novel-dual-specificity-phosphatase-26-inhibitors-by-a-hybrid-virtual-screening-approach-based-on-pharmacophore-and-molecular-docking
#18
Ji-Xia Ren, Zhong Cheng, Yu-Xin Huang, Jing-Feng Zhao, Peng Guo, Zhong-Mei Zou, Yong Xie
Dual-specificity phosphatase 26 (DUSP26) has recently emerged as a target for treatment of human cancers. However, only two small-molecule inhibitors of DUSP26 are known so far, namely NSC-87877 and ethyl-3, 4-dephostatin. DUSP26 contains an N-terminal region (residues 1-60) and a conserved C-terminal catalytic domain (residues 61-211, DUSP26-C). The crystal structure of DUSP26-C, showing a catalytically inactive conformation of the active site, was reported in a previous study. However, the detailed catalytic mechanism of DUSP26 cannot be described based on that structure...
February 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28242581/identification-of-potent-virtual-leads-and-adme-prediction-of-isoxazolidine-podophyllotoxin-derivatives-as-topoisomerase-ii-and-tubulin-inhibitors
#19
Majdi M Bkhaitan, Agha Zeeshan Mirza, Hina Shamshad, Hamed I Ali
Towards the design of new class of podophyllotoxin to target topoisomerase II and tubulin as substantial target in cancer therapy, a series of isoxazolidine podophyllotoxin derivatives were designed. Topoisomerase in complex with etoposide and four β-tubulin in complex with zampanolide, taxol, vinblastine or colchicine were used as targets using GOLD5.2.2 as a docking module. The revealed key structural features of the highest fitness into tubulin domain have been explained as follows: (1) trans orientation of the lactone (ring D) with 5a-β, 8a-α configuration; (2) dioxolane in ring A; (3) free rotation of ring E; (4) α (R) or β (S) configuration has equal fitness in position 5; (5) 4'-OMe; (6) phosphoramide linkage; (7) ethylene bridge between the phosphate and isoxazolidine ring; (8) benzyl moiety at N(2)-position of isoxazolidine ring; and (9) position 5 of isoxazolidine ring accommodated with 6-bromo-9H-purine, 2-amino-6H-purin-6-one, or N-(2-oxopyrimidin-4-yl) acetamide...
February 9, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28231433/discovery-of-a-potent-and-selective-sphingosine-kinase-1-inhibitor-through-the-molecular-combination-of-chemotype-distinct-screening-hits
#20
Mark E Schnute, Matthew D McReynolds, Jeffrey Carroll, Jill Chrencik, Maureen K Highkin, Kaliapan Iyanar, Gina Jerome, John W Rains, Matthew Saabye, Jeffrey A Scholten, Matthew Yates, Marek M Nagiec
Sphingosine kinase (SphK) is the major source of the lipid mediator and G protein-coupled receptor agonist sphingosine-1-phosphate (S1P). S1P promotes cell growth, survival, and migration and is a key regulator of lymphocyte trafficking. Inhibition of S1P signaling has been proposed as a strategy for treatment of inflammatory diseases and cancer. Two different formats of an enzyme-based high-throughput screen yielded two attractive chemotypes capable of inhibiting S1P formation in cells. The molecular combination of these screening hits led to compound 22a (PF-543) with 2 orders of magnitude improved potency...
March 6, 2017: Journal of Medicinal Chemistry
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