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https://www.readbyqxmd.com/read/27923064/sparse-regression-based-structure-learning-of-stochastic-reaction-networks-from-single-cell-snapshot-time-series
#1
Anna Klimovskaia, Stefan Ganscha, Manfred Claassen
Stochastic chemical reaction networks constitute a model class to quantitatively describe dynamics and cell-to-cell variability in biological systems. The topology of these networks typically is only partially characterized due to experimental limitations. Current approaches for refining network topology are based on the explicit enumeration of alternative topologies and are therefore restricted to small problem instances with almost complete knowledge. We propose the reactionet lasso, a computational procedure that derives a stepwise sparse regression approach on the basis of the Chemical Master Equation, enabling large-scale structure learning for reaction networks by implicitly accounting for billions of topology variants...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27922280/ganetespib-for-small-cell-lung-cancer
#2
Deepa S Subramaniam, Eiran A Warner, Giuseppe Giaccone
Heat shock proteins (Hsps) are part of a complex network of chaperone proteins that are critically involved in the conformational maturation of intracellular proteins and regulate their degradation via the proteasome system Hsps (especially Hsp70 and Hsp90) are upregulated in many cancers and are potentially attractive therapeutic targets. Ganetespib is a potent non-geldanamycin analogue, and avoids the toxicities associated with older analogues due to its small molecular weight, lipophilicity and the absence of the benzoquinone moiety; strong pre-clinical data support its evaluation in lung cancer, especially small cell lung cancer (SCLC)...
December 6, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27922122/identification-of-critical-paralog-groups-with-indispensable-roles-in-the-regulation-of-signaling-flow
#3
Dezso Modos, Johanne Brooks, David Fazekas, Eszter Ari, Tibor Vellai, Peter Csermely, Tamas Korcsmaros, Katalin Lenti
Extensive cross-talk between signaling pathways is required to integrate the myriad of extracellular signal combinations at the cellular level. Gene duplication events may lead to the emergence of novel functions, leaving groups of similar genes - termed paralogs - in the genome. To distinguish critical paralog groups (CPGs) from other paralogs in human signaling networks, we developed a signaling network-based method using cross-talk annotation and tissue-specific signaling flow analysis. 75 CPGs were found with higher degree, betweenness centrality, closeness, and 'bowtieness' when compared to other paralogs or other proteins in the signaling network...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922078/malat1-and-hotair-long-non-coding-rnas-play-opposite-role-in-estrogen-mediated-transcriptional-regulation-in-prostate-cancer-cells
#4
Aurora Aiello, Lorenza Bacci, Agnese Re, Cristian Ripoli, Francesco Pierconti, Francesco Pinto, Riccardo Masetti, Claudio Grassi, Carlo Gaetano, Pier Francesco Bassi, Alfredo Pontecorvi, Simona Nanni, Antonella Farsetti
In the complex network of nuclear hormone receptors, the long non-coding RNAs (lncRNAs) are emerging as critical determinants of hormone action. Here we investigated the involvement of selected cancer-associated lncRNAs in Estrogen Receptor (ER) signaling. Prior studies by Chromatin Immunoprecipitation (ChIP) Sequencing showed that in prostate cancer cells ERs form a complex with the endothelial nitric oxide synthase (eNOS) and that in turn these complexes associate with chromatin in an estrogen-dependent fashion...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921393/the-role-of-the-microvascular-network-structure-on-diffusion-and-consumption-of-anti-cancer-drugs
#5
P Mascheroni, R Penta
We investigate the impact of microvascular geometry on the transport of drugs in solid tumors, focusing on the diffusion and consumption phenomena. We embrace recent advances in the asymptotic homogenization literature starting from a double Darcy, double advection-diffusion-reaction system of partial differential equations that is obtained exploiting the sharp length separation between the intercapillary distance and the average tumor size. The geometric information on the microvascular network is encoded into effective hydraulic conductivities and diffusivities, which are numerically computed by solving periodic cell problems on appropriate microscale representative cells...
December 6, 2016: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/27920729/transcriptional-network-architecture-of-breast-cancer-molecular-subtypes
#6
Guillermo de Anda-Jáuregui, Tadeo E Velázquez-Caldelas, Jesús Espinal-Enríquez, Enrique Hernández-Lemus
Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27919915/chemoprevention-of-colorectal-cancer-in-individuals-with-previous-colorectal-neoplasia-systematic-review-and-network-meta-analysis
#7
Parambir S Dulai, Siddharth Singh, Evelyn Marquez, Rohan Khera, Larry J Prokop, Paul J Limburg, Samir Gupta, Mohammad Hassan Murad
OBJECTIVE:  To assess the comparative efficacy and safety of candidate agents (low and high dose aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), calcium, vitamin D, folic acid, alone or in combination) for prevention of advanced metachronous neoplasia (that is, occurring at different times after resection of initial neoplasia) in individuals with previous colorectal neoplasia, through a systematic review and network meta-analysis. DATA SOURCES:  Medline, Embase, Web of Science, from inception to 15 October 2015; clinical trial registries...
December 5, 2016: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/27919796/the-bad-seed-gardener-deubiquitinases-in-the-cancer-stem-cell-signaling-network-and-therapeutic-resistance
#8
REVIEW
Guan-Zhong Qiu, Wei Sun, Ming-Zhu Jin, Jing Lin, Pei-Gang Lu, Wei-Lin Jin
Tumors are comprised of highly heterogeneous populations of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumors in vivo. These rare cancer stem cells (CSCs) have been regarded as the "bad seeds" accounted for tumor initiation, progression, metastasis, relapse and therapeutic resistance. CSC-targeted therapy seems to be a better avenue for radical cure of cancer. Deubiquitinases (DUBs), specifically disassembling ubiquitin chains, have been demonstrated to play an important role in rigidly maintaining the balance between ubiquitination and deubiquitination for protein quality control and homeostasis in normal circumstances...
December 2, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27919789/unravelling-a-p73-regulated-network-the-role-of-a-novel-p73-dependent-target-mir3158-in-cancer-cell-migration-and-invasiveness
#9
Sotiris Galtsidis, Stella Logotheti, Athanasia Pavlopoulou, Christos P Zampetidis, Georgia Papachristopoulou, Andreas Scorilas, Borek Vojtesek, Vassilis Gorgoulis, Vassilis Zoumpourlis
The transcription factor p73 is homologous to the well-known tumor-suppressor p53. The p73-regulated networks are of significant clinical interest, because they may substitute for impaired p53-regulated networks which are commonly perturbed in cancer. Herein, we aimed to characterize a p73-regulated network that mediates cell migration and restores anti-oncogenic responses in p53-mutant cancer cells. In this study, we demonstrate that p73 regulates a network underlying cell migration, which consists of MIR34A/MIR3158/vimentin/β-catenin/lef1...
December 2, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27919654/american-brachytherapy-society-brachytherapy-treatment-recommendations-for-locally-advanced-cervix-cancer-for-low-income-and%C3%A2-middle-income-countries
#10
Gita Suneja, Derek Brown, Amy Chang, Beth Erickson, Elena Fidarova, Surbhi Grover, Umesh Mahantshetty, Subir Nag, Kailash Narayan, Memory Bvochora-Nsingo, Celia Viegas, Akila N Viswanathan, Ming Yin Lin, David Gaffney
PURPOSE: Most cervix cancer cases occur in low-income and middle-income countries (LMIC), and outcomes are suboptimal, even for early stage disease. Brachytherapy plays a central role in the treatment paradigm, improving both local control and overall survival. The American Brachytherapy Society (ABS) aims to provide guidelines for brachytherapy delivery in resource-limited settings. METHODS AND MATERIALS: A panel of clinicians and physicists with expertise in brachytherapy administration in LMIC was convened...
December 2, 2016: Brachytherapy
https://www.readbyqxmd.com/read/27919584/assessment-of-population-exposure-to-pm2-5-for-mortality-in-china-and-its-public-health-benefit-based-on-benmap
#11
Li Chen, Mengshuang Shi, Shuang Gao, Suhuan Li, Jian Mao, Hui Zhang, Yanling Sun, Zhipeng Bai, Zhongliang Wang
Along with the rapid socioeconomic development, air pollution in China has become a severe problem. One component of air pollution, in particular, PM2.5 has aroused wide public concern because of its high concentration. In this study, data were collected from over 900 monitoring sites of the newly constructed PM2.5 monitoring network in China. The interpolation methods were used to simulate the PM2.5 exposure level of China especially in rural areas, thus reflecting the spatial variation of PM2.5 pollution...
December 2, 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27918645/redox-and-ph-dual-responsive-polymer-based-nanoparticles-for-in-vivo-drug-delivery
#12
Chung Yen Ang, Si Yu Tan, Cathleen Teh, Jia Min Lee, Mun Fei Eddy Wong, Qiuyu Qu, Li Qing Poh, Menghuan Li, Yuanyuan Zhang, Vladimir Korzh, Yanli Zhao
Responsive nanomaterials have emerged as promising candidates as drug delivery vehicles in order to address biomedical diseases such as cancer. In this work, polymer-based responsive nanoparticles prepared by a supramolecular approach are loaded with doxorubicin (DOX) for the cancer therapy. The nanoparticles contain disulfide bonds within the polymer network, allowing the release of the DOX payload in a reducing environment within the endoplasm of cancer cells. In addition, the loaded drug can also be released under acidic environment...
December 5, 2016: Small
https://www.readbyqxmd.com/read/27917343/a-new-bioinformatic-insight-into-the-associated-proteins-in-psychiatric-disorders
#13
Wenlong Zhao, Wenjing Yang, Shuanglin Zheng, Qiong Hu, Ping Qiu, Xinghua Huang, Xiaoqian Hong, Fenghua Lan
BACKGROUND: Psychiatric diseases severely affect the quality of patients' lives and bring huge economic pressure to their families. Also, the great phenotypic variability among these patients makes it difficult to investigate the pathogenesis. Nowadays, bioinformatics is hopeful to be used as an effective tool for the diagnosis of psychiatric disorders, which can identify sensitive biomarkers and explore associated signaling pathways. METHODS: In this study, we performed an integrated bioinformatic analysis on 1945 mental-associated proteins including 91 secreted proteins and 593 membrane proteins, which were screened from the Universal Protein Resource (Uniport) database...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27916857/in-silico-characterization-of-mirna-and-long-non-coding-rna-interplay-in-multiple-myeloma
#14
Domenica Ronchetti, Martina Manzoni, Katia Todoerti, Antonino Neri, Luca Agnelli
The identification of deregulated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In addition, the cross-regulation between lncRNAs and miRNAs has begun to emerge, and theoretical and experimental studies have demonstrated the competing endogenous RNA (ceRNA) activity of lncRNAs as natural miRNA decoys in pathophysiological conditions, including cancer. Currently, information concerning lncRNA and miRNA interplay in MM is virtually absent...
November 29, 2016: Genes
https://www.readbyqxmd.com/read/27916711/implementation-of-a-surgeon-level-comparative-quality-performance-review-to-improve-positive-surgical-margin-rates-during-radical-prostatectomy
#15
Richard S Matulewicz, Jeffrey J Tosoian, C J Stimson, Ashley E Ross, Meera Chappidi, Tamara L Lotan, Elizabeth Humphreys, Alan W Partin, Edward M Schaeffer
PURPOSE: Success in the era of value-based payment will depend on the capacity of health systems to improve quality while controlling costs. Comparative quality performance review (CQPR) can be used to drive improvements in surgical outcomes and thereby reduce costs. We sought to determine the efficacy of CQPR to improve a surgeon-level measure of surgical oncologic quality: positive surgical margin (PSM) rate at the time of radical prostatectomy (RP). METHODS: Between 1-1-2015 and 12-31-15, eight surgeons performing consecutive RP at a single high-volume institution were included...
December 1, 2016: Journal of Urology
https://www.readbyqxmd.com/read/27916548/high-expression-of-cpt1a-predicts-adverse-outcomes-a-potential-therapeutic-target-for-acute-myeloid-leukemia
#16
Jinlong Shi, Huaping Fu, Zhilong Jia, Kunlun He, Lin Fu, Weidong Wang
Carnitine palmitoyl transferase 1A (CPT1A) protein catalyzes the rate-limiting step of Fatty-acid oxidation (FAO) pathway, which can promote cell proliferation and suppress apoptosis. Targeting CPT1A has shown remarkable anti-leukemia activity. But, its prognostic value remains unclear in Acute Myeloid Leukemia (AML). In two independent cohorts of cytogenetically normal AML (CN-AML) patients, compared to low expression of CPT1A (CPT1A(low)), high expression of CPT1A (CPT1A(high)) was significantly associated with adverse outcomes, which was also shown in European Leukemia Network (ELN) Intermediate-I category...
November 22, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27916436/utility-of-a-multidisciplinary-tumor-board-in-the-management-of-pancreatic-and-upper-gastrointestinal-diseases-an-observational-study
#17
David G Brauer, Matthew S Strand, Dominic E Sanford, Vladimir M Kushnir, Kian-Huat Lim, Daniel K Mullady, Benjamin R Tan, Andrea Wang-Gillam, Ashley E Morton, Marianna B Ruzinova, Parag J Parikh, Vamsi R Narra, Kathryn J Fowler, Majella B Doyle, William C Chapman, Steven S Strasberg, William G Hawkins, Ryan C Fields
BACKGROUND & OBJECTIVES: Multidisciplinary tumor boards (MDTBs) are frequently employed in cancer centers but their value has been debated. We reviewed the decision-making process and resource utilization of our MDTB to assess its utility in the management of pancreatic and upper gastrointestinal tract conditions. METHODS: A prospectively-collected database was reviewed over a 12-month period. The primary outcome was change in management plan as a result of case discussion...
December 1, 2016: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/27916347/new-treatment-strategy-with-nuclear-factor-%C3%AE%C2%BAb-inhibitor-for-pancreatic-cancer
#18
Takashi Horiuchi, Tadashi Uwagawa, Yoshihiro Shirai, Nobuhiro Saito, Ryota Iwase, Koichiro Haruki, Hiroaki Shiba, Toya Ohashi, Katsuhiko Yanaga
BACKGROUND: Because of difficulties with early diagnosis, most patients with pancreatic cancer receive chemotherapy. The National Comprehensive Cancer Network guidelines (version 2.2015) suggest therapy with gemcitabine (GEM) plus nab-paclitaxel (nPTX) as a category 1 recommendation for metastatic pancreatic ductal adenocarcinoma. According to the results of many studies, the activation of chemotherapeutic agents-induced nuclear factor-κB (NF-κB) causes chemoresistance. Hence, we hypothesized that the addition of nafamostat mesilate (NM), a potent NF-κB inhibitor, to GEM/nPTX therapy could enhance the antitumor effect in the treatment of pancreatic ductal adenocarcinoma...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27915976/strategies-to-strike-survival-networks-in-cancer
#19
Marzia Pennati, Graziella Cimino-Reale, Laura Gatti, Giuliana Cassinelli
The machinery that maintains cellular and tissue homeostasis in a healthy individual is recruited and hijacked by cancer cells to support tumor growth and progression. Activation of often unpredictable alternative or complementary signaling pathways allows cancer cells to bypass the intrinsic self-destructive machinery and the limited replicative potential present in every cell for correct homeostasis maintenance. Therefore, evasion/resistance to apoptosis/cell death, self-sufficiency in growth/survival signals, and limitless replicative potential remain undoubted hallmarks of cancer, contributing to drug resistance...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27914987/tetrabromobisphenol-a-activates-the-hepatic-interferon-pathway-in-rats
#20
J K Dunnick, D L Morgan, S A Elmore, K Gerrish, A Pandiri, T V Ton, K R Shockley, B A Merrick
Tetrabromobisphenol A (TBBPA) is a widely used flame retardant in printed circuit boards, paper, and textiles. In a two-year study, TBBPA showed evidence of uterine tumors in female Wistar-Han rats and liver and colon tumors in B6C3F1 mice. In order to gain further insight into early gene and pathway changes leading to cancer, we exposed female Wistar Han rats to TBBPA at 0, 25, 250, or 1000mg/kg (oral gavage in corn oil, 5X/week) for 13 weeks. Because at the end of the TBBPA exposure period, there were no treatment-related effects on body weights, liver or uterus lesions, and liver and uterine organ weights were within 10% of controls, only the high dose animals were analyzed...
November 30, 2016: Toxicology Letters
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