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https://www.readbyqxmd.com/read/29342309/prognostic-power-of-a-tumor-differentiation-gene-signature-for-bladder-urothelial-carcinomas
#1
Qianxing Mo, Fotis Nikolos, Fengju Chen, Zoe Tramel, Yu-Cheng Lee, Kazukuni Hayashi, Jing Xiao, Jianjun Shen, Keith Syson Chan
Background: Muscle-invasive bladder cancers (MIBCs) cause approximately 150 000 deaths per year worldwide. Survival for MIBC patients is heterogeneous, with no clinically validated molecular markers that predict clinical outcome. Non-MIBCs (NMIBCs) generally have favorable outcome; however, a portion progress to MIBC. Hence, development of a prognostic tool that can guide decision-making is crucial for improving clinical management of bladder urothelial carcinomas. Methods: Tumor grade is defined by pathologic evaluation of tumor cell differentiation, and it often associates with clinical outcome...
January 12, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29342271/melodi-mining-enriched-literature-objects-to-derive-intermediates
#2
Benjamin Elsworth, Karen Dawe, Emma E Vincent, Ryan Langdon, Brigid M Lynch, Richard M Martin, Caroline Relton, Julian P T Higgins, Tom R Gaunt
Background: The scientific literature contains a wealth of information from different fields on potential disease mechanisms. However, identifying and prioritizing mechanisms for further analytical evaluation presents enormous challenges in terms of the quantity and diversity of published research. The application of data mining approaches to the literature offers the potential to identify and prioritize mechanisms for more focused and detailed analysis. Methods: Here we present MELODI, a literature mining platform that can identify mechanistic pathways between any two biomedical concepts...
January 12, 2018: International Journal of Epidemiology
https://www.readbyqxmd.com/read/29342233/quantumclone-clonal-assessment-of-functional-mutations-in-cancer-based-on-a-genotype-aware-method-for-clonal-reconstruction
#3
Paul Deveau, Leo Colmet Daage, Derek Oldridge, Virginie Bernard, Angela Bellini, Mathieu Chicard, Nathalie Clement, Eve Lapouble, Valerie Combaret, Anne Boland, Vincent Meyer, Jean-Francois Deleuze, Isabelle Janoueix-Lerosey, Emmanuel Barillot, Olivier Delattre, John Maris, Gudrun Schleiermacher, Valentina Boeva
Motivation: In cancer, clonal evolution is assessed based on information coming from single nucleotide variants and copy number alterations. Nonetheless, existing methods often fail to accurately combine information from both sources to truthfully reconstruct clonal populations in a given tumor sample or in a set of tumor samples coming from the same patient. Moreover, previously published methods detect clones from a single set of variants. As a result, compromises have to be done between stringent variant filtering (reducing dispersion in variant allele frequency estimates, VAFs) and using all biologically relevant variants...
January 12, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29342230/metformin-as-an-anti-cancer-agent-actions-and-mechanisms-targeting-cancer-stem-cells
#4
Nipun Saini, Xiaohe Yang
Metformin, a first line medication for type II diabetes, initially entered the spotlight as a promising anti-cancer agent due to epidemiologic reports that found reduced cancer risk and improved clinical outcomes in diabetic patients taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Recently, the anti-cancer potential of metformin has gained increasing interest due to its inhibitory effects on cancer stem cells (CSCs), which are associated with tumor metastasis, drug resistance, and relapse...
October 7, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29342165/increased-colon-cancer-risk-after-severe-salmonella-infection
#5
Lapo Mughini-Gras, Michael Schaapveld, Jolanda Kramers, Sofie Mooij, E Andra Neefjes-Borst, Wilfrid van Pelt, Jacques Neefjes
BACKGROUND: Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. METHODS AND FINDINGS: We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection...
2018: PloS One
https://www.readbyqxmd.com/read/29342159/prediction-of-novel-target-genes-and-pathways-involved-in-bevacizumab-resistant-colorectal-cancer
#6
Precious Takondwa Makondi, Chia-Hwa Lee, Chien-Yu Huang, Chi-Ming Chu, Yu-Jia Chang, Po-Li Wei
Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs)...
2018: PloS One
https://www.readbyqxmd.com/read/29342134/chromosomal-instability-drives-metastasis-through-a-cytosolic-dna-response
#7
Samuel F Bakhoum, Bryan Ngo, Ashley M Laughney, Julie-Ann Cavallo, Charles J Murphy, Peter Ly, Pragya Shah, Roshan K Sriram, Thomas B K Watkins, Neil K Taunk, Mercedes Duran, Chantal Pauli, Christine Shaw, Kalyani Chadalavada, Vinagolu K Rajasekhar, Giulio Genovese, Subramanian Venkatesan, Nicolai J Birkbak, Nicholas McGranahan, Mark Lundquist, Quincey LaPlant, John H Healey, Olivier Elemento, Christine H Chung, Nancy Y Lee, Marcin Imielenski, Gouri Nanjangud, Dana Pe'er, Don W Cleveland, Simon N Powell, Jan Lammerding, Charles Swanton, Lewis C Cantley
Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342116/vegf-signaling-in-neurological-disorders
#8
REVIEW
Joon W Shim, Joseph R Madsen
Vascular endothelial growth factor (VEGF) is a potent growth factor playing diverse roles in vasculogenesis and angiogenesis. In the brain, VEGF mediates angiogenesis, neural migration and neuroprotection. As a permeability factor, excessive VEGF disrupts intracellular barriers, increases leakage of the choroid plexus endothelia, evokes edema, and activates the inflammatory pathway. Recently, we discovered that a heparin binding epidermal growth factor like growth factor (HB-EGF)-a class of EGF receptor (EGFR) family ligands-contributes to the development of hydrocephalus with subarachnoid hemorrhage through activation of VEGF signaling...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29342108/different-lipid-regulation-in-ovarian-cancer-inhibition-of-the-immune-system
#9
Christina Wefers, Tjitske Duiveman-de Boer, Petra L M Zusterzeel, Leon F A G Massuger, David Fuchs, Ruurd Torensma, Craig E Wheelock, I Jolanda M de Vries
Lipid metabolism is altered in several cancer settings leading to different ratios of intermediates. Ovarian cancer is the most lethal gynecological malignancy. Cancer cells disperse in the abdominal space and ascites occurs. T cells obtained from ascites are unable to proliferate after an antigenic stimulus. The proliferation of ascites-derived T cells can be restored after culturing the cells for ten days in normal culture medium. No pathway aberrancies were detected. The acellular fraction of ascites can inhibit the proliferation of autologous as well as allogeneic peripheral blood lymphocytes, indicating the presence of soluble factors that interfere with T cell functionality...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29342092/metabolic-alterations-in-cancer-cells-and-the-emerging-role-of-oncometabolites-as-drivers-of-neoplastic-change
#10
REVIEW
Zhengqiu Zhou, Elochukwu Ibekwe, Yevgen Chornenkyy
The mitochondrion is an important organelle and provides energy for a plethora of intracellular reactions. Metabolic dysregulation has dire consequences for the cell, and alteration in metabolism has been identified in multiple disease states-cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of oxygen, undergo glycolysis by reprogramming their metabolism-termed "aerobic glycolysis". Alterations in metabolism enable cancer cells to gain a growth advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic acids and lipids...
January 17, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29341930/activation-of-estrogen-receptor-beta-er%C3%AE-regulates-the-expression-of-n-cadherin-e-cadherin-and-%C3%AE-catenin-in-androgen-independent-prostate-cancer-cells
#11
Rafael de Souza Silva, Ana Paola G Lombardi, Deborah Simão de Souza, Carolina M Vicente, Catarina S Porto
The aim of the present study was to investigate the impact of the activation of estrogen receptors on expression and localization of N-cadherin, E-cadherin and non-phosphorylated β-catenin in androgen-independent prostate cancer cells (PC-3 and DU-145) and in human post pubertal prostate epithelial cells (PNT1A). Expression of N-cadherin was detected in PNT1A and PC-3 cells, but not in DU-145 cells. E-cadherin was detected only in DU-145 cells and β-catenin was detected in all cells studied. N-cadherin and β-catenin were located preferentially in the cellular membrane of PNT1A cells and in the cytoplasm of PC-3 cells...
January 13, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29341903/emerging-roles-and-mechanisms-of-foxc2-in-cancer
#12
REVIEW
Teng Wang, Lei Zheng, Qian Wang, Yan-Wei Hu
Forkhead box protein C2 (FOXC2), a transcription factor of the forkhead/winged-helix family, is required for embryonic and prenatal development. FOXC2 acts as a crucial modulator during both angiogenesis and lymphangiogenesis via multiple angiogenic and lymphangiogenic pathways, respectively. Although recent studies have shed light on the emerging role of FOXC2 in cancer, very little is known about the precise underlying mechanisms. The purpose of this review is to summarize the current understanding of FOXC2 and provide potential mechanistic explanations of the relationship between FOXC2 and cancer, as well as discuss the prospect for future research in the promising prognostic value of FOXC2 in cancer...
January 13, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29341469/downregulation-of-csn6-attenuates-papillary-thyroid-carcinoma-progression-by-reducing-wnt-%C3%AE-catenin-signaling-and-sensitizes-cancer-cells-to-fh535-therapy
#13
Duo Wen, Tian Liao, Ben Ma, Ning Qu, Rong-Liang Shi, Zhong-Wu Lu, Yu-Long Wang, Wen-Jun Wei, Qing-Hai Ji
The incidence of thyroid cancer has increased worldwide at a rate higher than that of any other cancer. CSN6 is overexpressed in many types of cancers, and such expression is linked to oncogenic activity. However, the detailed biological functions of CSN6 in papillary thyroid cancer (PTC) have not been well characterized. We investigated CSN6 expression in PTC specimens and cell lines. We used short-hairpin RNA-mediated gene silencing to explore the biological effects of CSN6 depletion in PTC cells. The combined effects of CSN6 silencing and FH535 therapy were assessed in terms of cell viability...
January 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29341321/interleukin-6-contributes-to-chemoresistance-in-mda-mb-231-cells-via-targeting-hif-1%C3%AE
#14
Ke Wang, Xue Zhu, Kai Zhang, Yongxiang Yin, Yu Chen, Ting Zhang
Chemoresistance is a critical challenge in the clinical treatment of triple-negative breast cancer (TNBC). It has been well documented that inflammatory mediators from tumor microenvironment are involved in the pathogenesis of TNBC and might be related to chemoresistance of cancer cells. In this study, the contribution of interleukin-6 (IL-6), one of the principal oncogenic molecules, in chemoresistance of a TNBC cell line MDA-MB-231 was first investigated. The results showed that IL-6 treatment could induce upregulation of HIF-1α via the activation of STAT3 in MDA-MB-231 cells, which consequently contributed to its effect against chemotherapeutic drug-induced cytotoxicity and cell apoptosis...
January 17, 2018: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29341247/secretory-expression-of-negative-regulatory-region-of-human-notch1-in-e-coli-and-preparation-of-a-functional-polyclonal-antibody
#15
Dengyang Zhang, Tianzhu Sun, Jingyun Yan, Xuanjun Wang, Jun Sheng
Notch signaling is a highly conserved pathway existed in multicellular organisms. It plays roles in normal human body development, human cancer initiation, progression and metastasis. The Notch negative regulatory region (NRR) is critical for Notch signaling, and cleavage at the S2 site in the NRR ultimately leads to the activation of Notch signaling. To study the function of human NRR1, we expressed the recombinant human NRR1 (rhNRR1) domain in Escherichia coli. After purification, rhNRR1 was obtained with approximately 94% purity according to SDS-PAGE analysis...
January 17, 2018: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/29341215/microrna181c-inhibits-prostate-cancer-cell-growth-and-invasion-by-targeting-multiple-erk-signaling-pathway-components
#16
Zhengzheng Su, Mengni Zhang, Miao Xu, Xinglan Li, Junya Tan, Yunyi Xu, Xiuyi Pan, Ni Chen, Xueqin Chen, Qiao Zhou
BACKGROUND: The ERK signaling pathway is frequently deregulated in tumorigenesis, mostly by classical mechanisms such as gene mutation of its components (eg, RAS and RAF). However, whether and how multiple key components of ERK pathway are regulated by microRNAs are not clear. METHODS: We firstly predicted post-transcriptional regulation of multiple key components of the ERK signaling pathway by miR181c through bioinformatics analysis, and then confirmed the post-transcriptional regulation by dual luciferase reporter gene assays and Western blot analysis...
January 16, 2018: Prostate
https://www.readbyqxmd.com/read/29341212/differential-role-of-pten-in-transforming-growth-factor-%C3%AE-tgf-%C3%AE-effects-on-proliferation-and-migration-in-prostate-cancer-cells
#17
Mawiyah N Kimbrough-Allah, Ana C Millena, Shafiq A Khan
BACKGROUND: Transforming growth factor-β (TGF-β) acts as a tumor suppressor in normal epithelial cells but as a tumor promoter in advanced prostate cancer cells. PI3-kinase pathway mediates TGF-β effects on prostate cancer cell migration and invasion. PTEN inhibits PI3-kinase pathway and is frequently mutated in prostate cancers. We investigated possible role(s) of PTEN in TGF-β effects on proliferation and migration in prostate cancer cells. METHODS: Expression of PTEN mRNA and proteins were determined using RT-PCR and Western blotting in RWPE1 and DU145 cells...
January 16, 2018: Prostate
https://www.readbyqxmd.com/read/29341159/clinicopathological-genomic-and-immunological-factors-in-colorectal-cancer-prognosis
#18
REVIEW
K M Marks, N P West, E Morris, P Quirke
BACKGROUND: Numerous factors affect the prognosis of colorectal cancer (CRC), many of which have long been identified, such as patient demographics and the multidisciplinary team. In more recent years, molecular and immunological biomarkers have been shown to have a significant influence on patient outcomes. Whilst some of these biomarkers still require ongoing validation, if proven to be worthwhile they may change our understanding and future management of CRC. The aim of this review was to identify the key prognosticators of CRC, including new molecular and immunological biomarkers, and outline how these might fit into the whole wider context for patients...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29341150/effect-of-akt-activation-and-experimental-pharmacological-inhibition-on-responses-to-neoadjuvant-chemoradiotherapy-in-rectal-cancer
#19
F C Koyama, C M Lopes Ramos, F Ledesma, V A F Alves, J M Fernandes, B B Vailati, G P São Julião, A Habr-Gama, J Gama-Rodrigues, R O Perez, A A Camargo
BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is one of the preferred initial treatment strategies for locally advanced rectal cancer. Responses are variable, and most patients still require surgery. The aim of this study was to identify molecular mechanisms determining poor response to CRT. METHODS: Global gene expression and pathway enrichment were assessed in pretreatment biopsies from patients with non-metastatic cT2-4 N0-2 rectal cancer within 7 cm of the anal verge...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29341110/eurogin-roadmap-2017-triage-strategies-for-the-management-of-hpv-positive-women-in-cervical-screening-programmes
#20
REVIEW
K Cuschieri, G Ronco, A Lorincz, L Smith, G Ogilvie, L Mirabello, F Carozzi, H Cubie, N Wentzensen, P Snijders, M Arbyn, J Monsonego J, S Franceschi
Cervical cancer screening will rely, increasingly, on HPV testing as a primary screen. The requirement for triage tests which can delineate clinically significant infection is thus prescient. In this EUROGIN 2017 roadmap, justification behind the most evidenced triages is outlined, as are challenges for implementation. Cytology is the triage with the most follow-up data; the existence of an HR-HPV positive, cytology negative group presents a challenge and re-testing intervals for this group (and choice of re-test) require careful consideration...
January 17, 2018: International Journal of Cancer. Journal International du Cancer
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