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Cancer susceptibility

Jocelyn P Wong, Jason R Todd, Martina A Finetti, Frank McCarthy, Malgorzata Broncel, Simon Vyse, Maciej T Luczynski, Stephen Crosier, Karen A Ryall, Kate Holmes, Leo S Payne, Frances Daley, Patty Wai, Andrew Jenks, Barbara Tanos, Aik-Choon Tan, Rachael C Natrajan, Daniel Williamson, Paul H Huang
Subunits of the SWI/SNF chromatin remodeling complex are mutated in a significant proportion of human cancers. Malignant rhabdoid tumors (MRTs) are lethal pediatric cancers characterized by a deficiency in the SWI/SNF subunit SMARCB1. Here, we employ an integrated molecular profiling and chemical biology approach to demonstrate that the receptor tyrosine kinases (RTKs) PDGFRα and FGFR1 are coactivated in MRT cells and that dual blockade of these receptors has synergistic efficacy. Inhibitor combinations targeting both receptors and the dual inhibitor ponatinib suppress the AKT and ERK1/2 pathways leading to apoptosis...
October 25, 2016: Cell Reports
Sérgio Ferreira de Lima, Mayara Mansur Fernandes Tavares, Jamilly Lopes de Macedo, Renata Santos de Oliveira, Sandra de Andrade Heráclio, Maria de Mascena Diniz Maia, Paulo Roberto Eleutério de Souza, Ronald Moura, Sergio Crovella
Human papillomavirus (HPV) infections are strongly associated with the development of cervical intraepithelial neoplasias and invasive cervical cancer. Polymorphisms in cytokine-encoding genes and behavioural cofactors could play an important role in protecting an individual against viral infections and cancer. Here, we investigated whether IL-6 -174 G>C, IL-8 +396 G>T, and TGF-β1 +869 G>C and +915 G>C polymorphisms were associated with susceptibility to HPV infection in women from north-east (Pernambuco) Brazil...
October 24, 2016: Memórias do Instituto Oswaldo Cruz
Christina M Mariaselvam, Ryad Tamouza, Rajagopal Krishnamoorthy, Dominique Charron, Durga Prasanna Misra, Vikramraj K Jain, Vir Singh Negi
INTRODUCTION: NKG2D (KLRK1) is a C-type lectin receptor present on NK cells, γδ, CD8(+) and CD4(+) T cells. Upon ligand binding, NKG2D mediates activatory and co-stimulatory signals to NK cells and activated CD4+ T cells, respectively. Polymorphisms in NKG2D predispose to infectious diseases, cancer, transplantation and autoimmune disorders. We studied the influence of this NK receptor polymorphism on predisposition to and modification of the disease phenotype in patients with Rheumatoid Arthritis (RA)...
October 26, 2016: Clinical and Experimental Immunology
Joanne Kotsopoulos, Christian Singer, Steven A Narod
BRCA1 mutation carriers face a high lifetime risk of breast cancer, estimated at 60 % compared to 10 % in the general population. BRCA1 breast cancers typically have an aggressive course (i.e., high-grade, triple-negative) and are associated with a poor prognosis. At present, primary prevention is limited to prophylactic removal of the unaffected breasts. Effective chemopreventive strategies are not yet available. Emerging evidence suggests that BRCA1 mutation carriers have high circulating levels of progesterone which may play a role in their susceptibility to breast cancer...
October 25, 2016: Breast Cancer Research and Treatment
Oliver J Gurney-Champion, Thijs Bruins Slot, Eelco Lens, Astrid van der Horst, Remy Klaassen, Hanneke W M van Laarhoven, Geertjan van Tienhoven, Jeanin E van Hooft, Aart J Nederveen, Arjan Bel
PURPOSE: Biliary stents may cause susceptibility artifacts, gradient-induced artifacts, and radio frequency (RF) induced artifacts on magnetic resonance images, which can hinder accurate target volume delineation in radiotherapy. In this study, the authors investigated and quantified the magnitude of these artifacts for stents of different materials. METHODS: Eight biliary stents made of nitinol, platinum-cored nitinol, stainless steel, or polyethylene from seven vendors, with different lengths (57-98 mm) and diameters (3...
October 2016: Medical Physics
Kirsi Määttä, Tommi Rantapero, Anna Lindström, Matti Nykter, Minna Kankuri-Tammilehto, Satu-Leena Laasanen, Johanna Schleutker
A remarkable proportion of factors causing genetic predisposition to breast cancer (BC) are unknown in non-BRCA1/2 families. Exome sequencing was performed for 13 high-risk Finnish hereditary breast and/or ovarian cancer (HBOC) families to detect variants contributing to BC susceptibility. After filtering, 18 candidate variants in DNA damage response (DDR) pathway genes were screened in 129 female HBOC patients, up to 989 female controls, and 31 breast tumours by Sanger sequencing/TaqMan assays. In addition, two variants were further studied in 49 male BC patients and 909 male controls...
October 26, 2016: European Journal of Human Genetics: EJHG
Ho Jae Lee, Jong Min Park, Ki Baik Hahm
Background/Aims: Transforming growth factor-beta (TGF-β) is a cytokine implicated in the susceptibility, development, and progression of gastrointestinal cancer and certain other neoplasms. In the later stages of cancer, TGF-β not only acts as a bystander of host-immune response, but also contributes to cell growth, invasion, and metastasis. In the current study, we generated gastric mucosal cells that stably express Smad7, and explored the Helicobacter pylori-associated biological changes between mock-transfected and Smad7-transfected RGM1 cells...
October 25, 2016: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
Roger Chou, Shelley Selph, David I Buckley, Rongwei Fu, Jessica C Griffin, Sara Grusing, John L Gore
PURPOSE: To systematically review the comparative effectiveness of fluorescent versus white light cystoscopy on bladder cancer clinical outcomes. METHODS: Systematic literature searches of Ovid MEDLINE (January 1990 through September 2015), Cochrane databases, and reference lists were performed. Fourteen randomized trials of fluorescent cystoscopy using 5-amimolevulinic acid (5-ALA) or hexaminolevulinic acid (HAL) versus white light cystoscopy for diagnosis of initial or recurrent bladder cancer that reported bladder cancer recurrence, progression, mortality, and harms were selected for review...
October 22, 2016: Journal of Urology
Melissa Ellermann, Janelle C Arthur
Iron is an essential micronutrient for most life forms including the majority of resident bacteria of the microbiota and their mammalian hosts. Bacteria have evolved numerous mechanisms to competitively acquire iron within host environments, such as the secretion of small molecules known as siderophores that can solubilize iron for bacterial use. However, siderophore biosynthesis and acquisition is not a capability equally harbored by all resident bacteria. Moreover, the structural diversity of siderophores creates variability in the susceptibility to host mechanisms that serve to counteract siderophore-mediated iron acquisition and limit bacterial growth...
October 22, 2016: Free Radical Biology & Medicine
Katharina Wimmer, Thorsten Rosenbaum, Ludwine Messiaen
Constitutional mismatch repair (MMR) deficiency (CMMRD) is a rare childhood cancer susceptibility syndrome resulting from biallelic germline loss-of-function mutations in one of the MMR genes. Individuals with CMMRD have a high risk to develop a broad spectrum of malignancies and frequently display features reminiscent of neurofibromatosis type 1 (NF1). Evaluation of the clinical findings of genetically proven CMMRD patients shows that not only multiple café-au-lait macules but any of the diagnostic features of NF1 may be present in a CMMRD patient...
October 25, 2016: Clinical Genetics
Elizabeth M Kass, Pei Xin Lim, Hildur R Helgadottir, Mary Ellen Moynahan, Maria Jasin
The mammary gland undergoes significant proliferative stages after birth, but little is known about how the developmental changes impact DNA double-strand break (DSB) repair. Mutations in multiple genes involved in homology-directed repair (HDR), considered a particularly accurate pathway for repairing DSBs, are linked to breast cancer susceptibility, including BRCA2. Using reporter mice that express an inducible endonuclease, we find that HDR is particularly robust in mammary tissue during puberty and pregnancy, accounting for 34-40% of detected repair events, more than in other tissues examined...
October 25, 2016: Nature Communications
Marie Eliade, Jeremy Skrzypski, Amandine Baurand, Caroline Jacquot, Geoffrey Bertolone, Catherine Loustalot, Charles Coutant, France Guy, Pierre Fumoleau, Yannis Duffourd, Laurent Arnould, Alexandra Delignette, Marie-Martine Padéano, Côme Lepage, Géraldine Raichon-Patru, Axelle Boudrant, Marie-Christine Bône-Lépinoy, Anne-Laure Villing, Aurélie Charpin, Karine Peignaux, Sandy Chevrier, Frédérique Vegran, François Ghiringhelli, Romain Boidot, Nicolas Sevenet, Sarab Lizard, Laurence Faivre
Until recently, the molecular diagnosis of hereditary breast and ovarian cancer (HBOC) was mostly based on BRCA1/2 testing. Next generation sequencing and the recent discovery of new genes involved in HBOC now permit the transfer of genomic capture targeting multiple candidate genes from research to clinical use. However, the implications for the management of patients and their families have not been extensively studied, in particular since some of these genes are not well-established cancer predisposing genes...
October 15, 2016: Oncotarget
A Cruz-Bermúdez, R J Vicente-Blanco, E Gonzalez-Vioque, M Provencio, M Á Fernández-Moreno, R Garesse
The potential role of the mitochondrial genome has recently attracted interest because of its high mutation frequency in tumors. Different aspects of mtDNA make it relevant for cancer's biology, such as it encodes a limited but essential number of genes for OXPHOS biogenesis, it is particularly susceptible to mutations, and its copy number can vary. Moreover, most ROS in mitochondria are produced by the electron transport chain. These characteristics place the mtDNA in the center of multiple signaling pathways, known as mitochondrial retrograde signaling, which modifies numerous key processes in cancer...
October 24, 2016: Clinical & Translational Oncology
Mthulisi Khuphe, Clare S Mahon, Paul D Thornton
The glucoseamine-initiated ring-opening polymerisation of amino acid N-carboxyanhydrides and O-carboxanhydrides to yield amphiphilic block copolymers that are capable of self-assembly in aqueous solution to form well-defined, glucose-presenting, particles is reported. The particles formed are susceptible to enzyme-mediated (lipase and protease) and pH-induced degradation, and can selectively bind the lectin concanavalin A. Consequently, such glycoparticles are of significance for the controlled release of payload molecules in response to an acidic environment, for instance cancerous tissue, and upon interaction with target enzymes...
October 25, 2016: Biomaterials Science
B R Cardoso, D J Hare, A I Bush, B R Roberts
Glutathione peroxidase 4 (GPx4) is an antioxidant enzyme reported as an inhibitor of ferroptosis, a recently discovered non-apoptotic form of cell death. This pathway was initially described in cancer cells and has since been identified in hippocampal and renal cells. In this Perspective, we propose that inhibition of ferroptosis by GPx4 provides protective mechanisms against neurodegeneration. In addition, we suggest that selenium deficiency enhances susceptibility to ferroptotic processes, as well as other programmed cell death pathways due to a reduction in GPx4 activity...
October 25, 2016: Molecular Psychiatry
Haiping Liu, Dan Lyu, Yan Zhang, Lianbing Sheng, Ning Tang
Cervical cancer is the second most common cancer and the third leading cause of cancer-related death among females in less developed countries. Studies have shown that the single-nucleotide polymorphisms of interleukin 6 might be associated with cervical cancer risk. A total of 710 articles from EMBASE, EBSCO, Web of science, PubMed, Springer link, and Chinese National Knowledge Infrastructure databases were reviewed in our study. A meta-analysis on the associations between interleukin 6 rs1800795 polymorphism and cervical cancer risk was carried out by comparison using 5 genetic models...
October 24, 2016: Technology in Cancer Research & Treatment
Ankit Malik, Deepika Sharma, Qifan Zhu, Rajendra Karki, Clifford S Guy, Peter Vogel, Thirumala-Devi Kanneganti
Inflammatory bowel diseases (IBD) affect over 5 million individuals in the industrialized world, with an increasing incidence rate worldwide. IBD also predisposes affected individuals to development of colorectal cancer, which is a leading cause of cancer-related deaths in adults. Mutations in genes encoding molecules in the IL-33 signaling pathway are associated with colitis and colitis-associated cancer (CAC), but how IL-33 modulates gut homeostasis is unclear. Here, we have shown that Il33-deficient mice are highly susceptible to colitis and CAC...
October 24, 2016: Journal of Clinical Investigation
Yanwen Wang, Yongfeng Yang, Yihan Zhu, Li Li, Fei Chen, Li Zhang
CONTEXT: Polymorphisms of IL-32 related closely to tumoregenesis. MATERIALS AND METHODS: Two IL-32 polymorphisms (rs12934561 and rs28372698) and mRNA expression were conducted by SNP genotype assay and real-time PCR in 423 lung cancer patients and 437 controls. RESULTS: T allele of rs28372698 associated significantly with poor prognosis in moderate and well differentiation lung cancer patients. TT genotype of rs12934561 related closely to poor survival status in squamous carcinoma...
October 24, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Liwen Hu, Xinyue Yao, Yi Shen
Accumulating epidemiological evidence indicates that the quantitative changes in human mitochondrial DNA (mtDNA) copy number could affect the genetic susceptibility of malignancies in a tumor-specific manner, but the results are still elusive. To provide a more precise estimation on the association between mtDNA copy number and risk of diverse malignancies, a meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95% confidence intervals (95% CI). A total of 36 case-control studies involving 11,847 cases and 15,438 controls were finally included in the meta-analysis...
October 24, 2016: Scientific Reports
Steffen Grampp, James L Platt, Victoria Lauer, Rafik Salama, Franziska Kranz, Viviana K Neumann, Sven Wach, Christine Stöhr, Arndt Hartmann, Kai-Uwe Eckardt, Peter J Ratcliffe, David R Mole, Johannes Schödel
Clear cell renal cell carcinoma (ccRCC) is characterized by loss of function of the von Hippel-Lindau tumour suppressor (VHL) and unrestrained activation of hypoxia-inducible transcription factors (HIFs). Genetic and epigenetic determinants have an impact on HIF pathways. A recent genome-wide association study on renal cancer susceptibility identified single-nucleotide polymorphisms (SNPs) in an intergenic region located between the oncogenes MYC and PVT1. Here using assays of chromatin conformation, allele-specific chromatin immunoprecipitation and genome editing, we show that HIF binding to this regulatory element is necessary to trans-activate MYC and PVT1 expression specifically in cells of renal tubular origins...
October 24, 2016: Nature Communications
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