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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/29342254/distinctive-desmoplastic-3d-morphology-associated-with-brafv600e-in-papillary-thyroid-cancers
#3
M Tarabichi, A Antoniou, S Le Pennec, D Gacquer, N de Saint Aubain, L Craciun, T Cielen, I Laios, D Larsimont, G Andry, J E Dumont, C Maenhaut, V Detours
Context: Although 60% of papillary thyroid carcinomas are BRAFV600E mutant (PTCV600E), the higher aggressiveness of these cancers is still debated. Objective: In PTCV600E we aimed to further characterize the extent of the stroma and its activation, the 3D tumor-stroma interface, and the proliferation rates of tumor and stromal fibroblasts. Design: We analyzed exomes, trancriptomes and images of 364 PTC from The Cancer Genome Atlas (TCGA), including 211 PTCV600E; stained 22 independent PTC for BRAFV600E and Ki67; sequenced the exomes and stained BRAFV600E in 5 primary tumor blocks and 4 nodal metastases from one PTCV600E patient; and reconstructed the 3D volumes of one tumor and one metastatic blocks at histological resolution...
January 12, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29342249/splice-expression-variation-analysis-seva-for-inter-tumor-heterogeneity-of-gene-isoform-usage-in-cancer
#4
Bahman Afsari, Theresa Guo, Michael Considine, Liliana Florea, Luciane T Kagohara, Genevieve L Stein-O'Brien, Dylan Kelley, Emily Flam, Kristina D Zambo, Patrick K Ha, Donald Geman, Michael F Ochs, Joseph A Califano, Daria A Gaykalova, Alexander V Favorov, Elana J Fertig
Motivation: Current bioinformatics methods to detect changes in gene isoform usage in distinct phenotypes compare the relative expected isoform usage in phenotypes. These statistics model differences in isoform usage in normal tissues, which have stable regulation of gene splicing. Pathological conditions, such as cancer, can have broken regulation of splicing that increases the heterogeneity of the expression of splice variants. Inferring events with such differential heterogeneity in gene isoform usage requires new statistical approaches...
January 12, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29342193/analysis-of-copy-number-loss-of-the-erbb4-receptor-tyrosine-kinase-in-glioblastoma
#5
DeAnalisa C Jones, Adriana Scanteianu, Matthew DiStefano, Mehdi Bouhaddou, Marc R Birtwistle
Current treatments for glioblastoma multiforme (GBM)-an aggressive form of brain cancer-are minimally effective and yield a median survival of 14.6 months and a two-year survival rate of 30%. Given the severity of GBM and the limitations of its treatment, there is a need for the discovery of novel drug targets for GBM and more personalized treatment approaches based on the characteristics of an individual's tumor. Most receptor tyrosine kinases-such as EGFR-act as oncogenes, but publicly available data from the Cancer Cell Line Encyclopedia (CCLE) indicates copy number loss in the ERBB4 RTK gene across dozens of GBM cell lines, suggesting a potential tumor suppressor role...
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/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
#8
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/29341832/racial-differences-in-21-gene-recurrence-scores-among-patients-with-hormone-receptor-positive-node-negative-breast-cancer
#9
Andreana N Holowatyj, Michele L Cote, Julie J Ruterbusch, Kristina Ghanem, Ann G Schwartz, Fawn D Vigneau, David H Gorski, Kristen S Purrington
Purpose The 21-gene recurrence score (RS) breast cancer assay is clinically used to quantify risk of 10-year distant recurrence by category (low, < 18; intermediate, 18 to 30; high, ≥ 31) for treatment management among women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative, lymph node-negative breast cancer. Although non-Hispanic black (NHB) women have worse prognosis compared with non-Hispanic white (NHW) women, the equivalency of 21-gene RS across racial groups remains unknown...
January 17, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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
#10
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/29341452/contribution-of-mlh1-constitutional-methylation-for-lynch-syndrome-diagnosis-in-patients-with-tumor-mlh1-downregulation
#11
Diana Pinto, Carla Pinto, Joana Guerra, Manuela Pinheiro, Rui Santos, Hege Marie Vedeld, Zeremariam Yohannes, Ana Peixoto, Catarina Santos, Pedro Pinto, Paula Lopes, Ragnhild Lothe, Guro Elisabeth Lind, Rui Henrique, Manuel R Teixeira
Constitutional epimutation of the two major mismatch repair genes, MLH1 and MSH2, has been identified as an alternative mechanism that predisposes to the development of Lynch syndrome. In the present work, we aimed to investigate the prevalence of MLH1 constitutional methylation in colorectal cancer (CRC) patients with abnormal expression of the MLH1 protein in their tumors. In a series of 38 patients who met clinical criteria for Lynch syndrome genetic testing, with loss of MLH1 expression in the tumor and with no germline mutations in the MLH1 gene (35/38) or with tumors presenting the BRAF p...
January 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29341428/epigenetic-silencing-of-tap1-in-aldefluor-breast-cancer-stem-cells-contributes-to-their-enhanced-immune-evasion
#12
Mohammad Sultan, Dejan Vidovic, Arianne S Paine, Thomas T Huynh, Krysta M Coyle, Margaret L Thomas, Brianne M Cruickshank, Cheryl A Dean, Derek R Clements, Youra Kim, Kristin Lee, Shashi A Gujar, Ian C Weaver, Paola Marcato
Avoiding detection and destruction by immune cells is key for tumor initiation and progression. The important role of cancer stem cells (CSC) in tumor initiation has been well established, yet their ability to evade immune detection and targeting is only partly understood. To investigate the ability of breast CSCs to evade immune detection we identified a highly tumorigenic population in a spontaneous murine mammary tumor based on increased aldehyde dehydrogenase (ALDH) activity. We performed tumor growth studies in immunocompetent and immunocompromised mice...
January 17, 2018: Stem Cells
https://www.readbyqxmd.com/read/29341374/validation-of-the-digital-pcr-system-in-tyrosine-kinase-inhibitor-resistant-egfr-mutant-non-small-cell-lung-cancer
#13
Katsuhiro Masago, Shiro Fujita, Akito Hata, Chiyuki Okuda, Yuko Yoshizumi, Reiko Kaji, Nobuyuki Katakami, Yukio Hirata, Yasushi Yatabe
The aim of this study was to compare the accuracy of the QuantStudio 3D Digital polymerase chain reaction (dPCR) system and a PCR-based next generation sequencing (NGS) system for detecting a secondary mutation in the epidermal growth factor receptor (EGFR) gene T790M in non-small cell lung cancer (NSCLC) patients previously diagnosed with EGFR-activating mutations. Twenty-five patients with NSCLC previously treated with EGFR-TKIs were examined. The patients were treated daily with either erlotinib or gefitinib...
January 17, 2018: Pathology International
https://www.readbyqxmd.com/read/29341317/apoptosis-induction-in-k562-human-myelogenous-leukaemia-cells-is-connected-to-the-modulation-of-wnt-%C3%AE-catenin-signalling-by-bhx-a-novel-pyrazoline-derivative
#14
Hanmei Bao, Qing Zhang, Yibo Du, Cai Zhang, Hui Xu, Zhongling Zhu, Zhao Yan
OBJECTIVES: The goal of this study was to explore the effects of BHX on human chronic myeloid leukaemia (CML) cells and to elucidate the underlying molecular mechanism. MATERIALS AND METHODS: CML cell line K562 cells were treated with BHX. The effects of BHX on cell proliferation, apoptosis and cell cycle were detected. Subsequently, the caspase, ATP activity, Ca2+ , ROS and mitochondrial membrane potential (MMP) levels treated with various concentrations of BHX were analysed...
January 16, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29341215/microrna181c-inhibits-prostate-cancer-cell-growth-and-invasion-by-targeting-multiple-erk-signaling-pathway-components
#15
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/29341159/clinicopathological-genomic-and-immunological-factors-in-colorectal-cancer-prognosis
#16
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/29341152/meta-analysis-of-the-prognostic-value-of-cpg-island-methylator-phenotype-in-gastric-cancer
#17
REVIEW
A G M T Powell, S Soul, A Christian, W G Lewis
BACKGROUND: CpG island methylator phenotype (CIMP) has been identified as a distinct molecular subtype of gastric cancer, yet associations with survival are conflicting. A meta-analysis was performed to estimate the prognostic significance of CIMP. METHODS: Embase, MEDLINE, PubMed, PubMed Central and Cochrane databases were searched systematically for studies related to the association between CIMP and survival in patients undergoing potentially curative resection for gastric cancer...
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
#18
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/29341149/quality-of-life-implications-of-risk-reducing-cancer-surgery
#19
REVIEW
A M Altman, J Y C Hui, T M Tuttle
BACKGROUND: Modern advances in genetic sequencing techniques have allowed for increased availability of genetic testing for hereditary cancer syndromes. Consequently, more people are being identified as mutation carriers and becoming aware of their increased risk of malignancy. Testing is commonplace for many inheritable cancer syndromes, and with that comes the knowledge of being a gene carrier for some patients. With increased risk of malignancy, many guidelines recommend that gene carriers partake in risk reduction strategies, including risk-reducing surgery for some syndromes...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29341146/defining-the-molecular-pathology-of-pancreatic-body-and-tail-adenocarcinoma
#20
S B Dreyer, N B Jamieson, R Upstill-Goddard, P J Bailey, C J McKay, A V Biankin, D K Chang
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a dismal disease, with very little improvement in survival over the past 50 years. Recent large-scale genomic studies have improved understanding of the genomic and transcriptomic landscape of the disease, yet very little is known about molecular heterogeneity according to tumour location in the pancreas; body and tail PDACs especially tend to have a significantly worse prognosis. The aim was to investigate the molecular differences between PDAC of the head and those of the body and tail of the pancreas...
January 2018: British Journal of Surgery
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