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Mario I Fernández, Stephen B Williams, Daniel L Willis, Rebecca S Slack, Rian J Dickstein, Sahil Parikh, Edmund Chiong, Arlene O Siefker-Radtke, Charles C Guo, Bogdan A Czerniak, David J McConkey, Jay B Shah, Louis L Pisters, H Barton Grossman, Colin P N Dinney, Ashish M Kamat
OBJECTIVE: To analyze survival in clinically localized, surgically resectable micropapillary bladder cancer patients undergoing radical cystectomy with and without neoadjuvant chemotherapy and develop risk strata based on outcome data. PATIENTS AND METHODS: A review of our database identified 103 patients with surgically resectable (≤cT4acN0cM0) micropapillary bladder cancer who underwent radical cystectomy. Survival estimates were calculated using Kaplan-Meier method and compared using log-rank tests...
October 18, 2016: BJU International
Kirsten A M White, Li Luo, Todd A Thompson, Salina Torres, Chien-An Andy Hu, Nancy E Thomas, Jenna Lilyquist, Hoda Anton-Culver, Stephen B Gruber, Lynn From, Klaus J Busam, Irene Orlow, Peter A Kanetsky, Loraine D Marrett, Richard P Gallagher, Lidia Sacchetto, Stefano Rosso, Terence Dwyer, Anne E Cust, Colin B Begg, Marianne Berwick
Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0...
October 17, 2016: Cancer Medicine
Brian H Shirts, Colin C Pritchard, Tom Walsh
Every single-nucleotide change compatible with life is present in the human population today. Understanding these rare human variants defines an extraordinary challenge for genetics and medicine. The new clinical practice of sequencing many genes for hereditary cancer risk has illustrated the utility of clinical next-generation sequencing in adults, identifying more medically actionable variants than single-gene testing. However, it has also revealed a linear relationship between the length of DNA evaluated and the number of rare 'variants of uncertain significance' reported...
October 11, 2016: Trends in Molecular Medicine
Meng Chen, Nathaniel Rothman, Yuanqing Ye, Jian Gu, Paul A Scheet, Maosheng Huang, David W Chang, Colin P Dinney, Debra T Silverman, Jonine D Figueroa, Stephen J Chanock, Xifeng Wu
Genome-wide association studies (GWAS) are designed to identify individual regions associated with cancer risk, but only explain a small fraction of the inherited variability. Alternative approach analyzing genetic variants within biological pathways has been proposed to discover networks of susceptibility genes with additional effects. The gene set enrichment analysis (GSEA) may complement and expand traditional GWAS analysis to identify novel genes and pathways associated with bladder cancer risk. We selected three GSEA methods: Gen-Gen, Aligator, and the SNP Ratio Test to evaluate cellular signaling pathways involved in bladder cancer susceptibility in a Texas GWAS population...
July 2016: Genes & Cancer
Colin Thomas, Yingbiao Ji, Niraj Lodhi, Elena Kotova, Aaron Dan Pinnola, Konstantin Golovine, Peter Makhov, Kate Pechenkina, Vladimir Kolenko, Alexei V Tulin
The clinical potential of PARP-1 inhibitors has been recognized >10years ago, prompting intensive research on their pharmacological application in several branches of medicine, particularly in oncology. However, natural or acquired resistance of tumors to known PARP-1 inhibitors poses a serious problem for their clinical implementation. Present study aims to reignite clinical interest to PARP-1 inhibitors by introducing a new method of identifying highly potent inhibitors and presenting the largest known collection of structurally diverse inhibitors...
October 4, 2016: EBioMedicine
Sarah E Allison, Yongjuan Chen, Nenad Petrovic, Stefanie Zimmermann, Bjoern Moosmann, Mirko Jansch, Pei H Cui, Colin R Dunstan, Peter I Mackenzie, Michael Murray
Secondary metastases are the leading cause of mortality in patients with breast cancer. Cytochrome P450 (CYP) 2J2 (CYP2J2) is upregulated in many human tumors and generates epoxyeicosanoids from arachidonic acid that promote tumorigenesis and metastasis, but at present there is little information on the genes that mediate these actions. In this study MDA-MB-468 breast cancer cells were stably transfected with CYP2J2 (MDA-2J2 cells) and Affymetrix microarray profiling was undertaken. We identified 182 genes that were differentially expressed in MDA-2J2 cells relative to control (MDA-CTL) cells (log[fold of control]≥2)...
October 5, 2016: International Journal of Biochemistry & Cell Biology
Jordi Remon, Nicolas Girard, Julien Mazieres, Eric Dansin, Eric Pichon, Laurent Greillier, Catherine Dubos, Colin R Lindsay, Benjamin Besse
No abstract text is available yet for this article.
October 6, 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Victoria L Camus, Grant D Stewart, William H Nailon, Duncan B McLaren, Colin J Campbell
Correction for 'Measuring the effects of fractionated radiation therapy in a 3D prostate cancer model system using SERS nanosensors' by Victoria L. Camus, et al., Analyst, 2016, 141, 5056-5061.
October 3, 2016: Analyst
Ronald J Hause, Colin C Pritchard, Jay Shendure, Stephen J Salipante
Microsatellite instability (MSI), the spontaneous loss or gain of nucleotides from repetitive DNA tracts, is a diagnostic phenotype for gastrointestinal, endometrial, and colorectal tumors, yet the landscape of instability events across a wider variety of cancer types remains poorly understood. To explore MSI across malignancies, we examined 5,930 cancer exomes from 18 cancer types at more than 200,000 microsatellite loci and constructed a genomic classifier for MSI. We identified MSI-positive tumors in 14 of the 18 cancer types...
October 3, 2016: Nature Medicine
Harshali Patil, Shailaja Gada Saxena, Colin J Barrow, Jagat R Kanwar, Arnab Kapat, Rupinder K Kanwar
Colorectal cancer (CRC) is a major health burden worldwide. The optimal approach to the diagnosis, management, and treatment of CRC involves multidisciplinary and integrated management practices. The field is rapidly changing because of recent advancements in delineating the molecular basis of tumorigenesis, introduction of targeted therapy, varied patient response to mainstay chemotherapeutics, biological drugs, and the effective combination regimes being used for treatment. Recent meta-analysis studies, which tend to establish few clinically useful predictor biomarkers, identify inconsistent results and limitations of the trials...
September 28, 2016: Drug Discovery Today
Andrea K Miyahira, Sameek Roychowdhury, Sangeeta Goswami, Joseph E Ippolito, Saul J Priceman, Colin C Pritchard, Karen S Sfanos, Sumit K Subudhi, Jonathan W Simons, Kenneth J Pienta, Howard R Soule
INTRODUCTION: The 2016 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer," was held from June 23 to June 26, 2016, in Coronado, California. METHODS: For the 4th year in a row, the Prostate Cancer Foundation (PCF) hosted the CHPCA Meeting, a think tank-structured scientific conference, which focuses on a specific topic of critical unmet need on the biology and treatment of advanced prostate cancer...
September 28, 2016: Prostate
Jonathan Oh, Minal Barve, Carolyn M Matthews, E Colin Koon, Thomas P Heffernan, Bruce Fine, Elizabeth Grosen, Melanie K Bergman, Evelyn L Fleming, Leslie R DeMars, Loyd West, Daniel L Spitz, Howard Goodman, Kenneth C Hancock, Gladice Wallraven, Padmasini Kumar, Ernest Bognar, Luisa Manning, Beena O Pappen, Ned Adams, Neil Senzer, John Nemunaitis
OBJECTIVES: The majority of women with Stage III/IV ovarian cancer who achieve clinical complete response with frontline standard of care will relapse within 2years. Vigil immunotherapy, a GMCSF/bi-shRNA furin DNA engineered autologous tumor cell (EATC) product, demonstrated safety and induction of circulating activated T-cells against autologous tumor in Phase I trial Senzer et al. (2012, 2013) . Our objectives for this study include evaluation of safety, immune response and recurrence free survival (RFS)...
September 24, 2016: Gynecologic Oncology
Gary M Williams, Colin Berry, Michele Burns, Joao Lauro Viana de Camargo, Helmut Greim
Glyphosate has been rigorously and extensively tested for carcinogenicity by administration to mice (five studies) and to rats (nine studies). Most authorities have concluded that the evidence does not indicate a cancer risk to humans. The International Agency for Research on Cancer (IARC), however, evaluated some of the available data and concluded that glyphosate probably is carcinogenic to humans. The expert panel convened by Intertek assessed the findings used by IARC, as well as the full body of evidence and found the following: (1) the renal neoplastic effects in males of one mouse study are not associated with glyphosate exposure, because they lack statistical significance, strength, consistency, specificity, lack a dose-response pattern, plausibility, and coherence; (2) the strength of association of liver hemangiosarcomas in a different mouse study is absent, lacking consistency, and a dose-response effect and having in high dose males only a significant incidence increase which is within the historical control range; (3) pancreatic islet-cell adenomas (non-significant incidence increase), in two studies of male SD rats did not progress to carcinomas and lacked a dose-response pattern (the highest incidence is in the low dose followed by the high dose); (4) in one of two studies, a non-significant positive trend in the incidence of hepatocellular adenomas in male rats did not lead to progression to carcinomas; (5) in one of two studies, the non-significant positive trend in the incidence of thyroid C-cell adenomas in female rats was not present and there was no progression of adenomas to carcinomas at the end of the study...
September 2016: Critical Reviews in Toxicology
Gary M Williams, Marilyn Aardema, John Acquavella, Sir Colin Berry, David Brusick, Michele M Burns, Joao Lauro Viana de Camargo, David Garabrant, Helmut A Greim, Larry D Kier, David J Kirkland, Gary Marsh, Keith R Solomon, Tom Sorahan, Ashley Roberts, Douglas L Weed
The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies...
September 2016: Critical Reviews in Toxicology
Colin Thomas, Sujana Movva
Patients diagnosed with metastatic soft-tissue sarcoma (STS) have a poor prognosis. Additionally, after failure of first-line therapy, there are relatively few treatment options from which to choose. The novel tubulin-binding drug, eribulin, with a unique mechanism of action from taxanes or vinca alkaloids, has shown clinical activity in several different types of cancers. Eribulin has been approved by the US Food and Drug Administration (FDA) for patients with metastatic breast cancer previously treated with an anthracycline or a taxane and has recently been FDA approved for patients with unresectable or metastatic liposarcoma who have failed a previous anthracycline regimen...
2016: OncoTargets and Therapy
Wei Hseun Yeap, Kok Loon Wong, Noriko Shimasaki, Esmeralda Chi Yuan Teo, Jeffrey Kim Siang Quek, Hao Xiang Yong, Colin Phipps Diong, Antonio Bertoletti, Yeh Ching Linn, Siew Cheng Wong
Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcγ receptors (FcγRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcγRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16- expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies...
September 27, 2016: Scientific Reports
Colin P Bergstrom, Brian Ruffell, Christine M T Ho, Celestia S Higano, William J Ellis, Mark Garzotto, Tomasz M Beer, Julie N Graff
The aims of this study were to report the clinical outcomes in a cohort of men with high-risk prostate cancer treated with neoadjuvant docetaxel and mitoxantrone 10 years after treatment, identify pretreatment clinical parameters that may be predictors of recurrence, and describe tumor-infiltrating leukocytes present in radical prostatectomy specimens. We conducted a phase I/II study of neoadjuvant docetaxel and mitoxantrone before radical prostatectomy in high-risk localized prostate cancer to determine the feasibility of this combination and predictors of prostate cancer recurrence after cytotoxic chemotherapy...
September 23, 2016: Anti-cancer Drugs
Yashar S Niknafs, Sumin Han, Teng Ma, Corey Speers, Chao Zhang, Kari Wilder-Romans, Matthew K Iyer, Sethuramasundaram Pitchiaya, Rohit Malik, Yasuyuki Hosono, John R Prensner, Anton Poliakov, Udit Singhal, Lanbo Xiao, Steven Kregel, Ronald F Siebenaler, Shuang G Zhao, Michael Uhl, Alexander Gawronski, Daniel F Hayes, Lori J Pierce, Xuhong Cao, Colin Collins, Rolf Backofen, Cenk S Sahinalp, James M Rae, Arul M Chinnaiyan, Felix Y Feng
Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1...
2016: Nature Communications
Marcel Smid, F Germán Rodríguez-González, Anieta M Sieuwerts, Roberto Salgado, Wendy J C Prager-Van der Smissen, Michelle van der Vlugt-Daane, Anne van Galen, Serena Nik-Zainal, Johan Staaf, Arie B Brinkman, Marc J van de Vijver, Andrea L Richardson, Aquila Fatima, Kim Berentsen, Adam Butler, Sancha Martin, Helen R Davies, Reno Debets, Marion E Meijer-Van Gelder, Carolien H M van Deurzen, Gaëtan MacGrogan, Gert G G M Van den Eynden, Colin Purdie, Alastair M Thompson, Carlos Caldas, Paul N Span, Peter T Simpson, Sunil R Lakhani, Steven Van Laere, Christine Desmedt, Markus Ringnér, Stefania Tommasi, Jorunn Eyford, Annegien Broeks, Anne Vincent-Salomon, P Andrew Futreal, Stian Knappskog, Tari King, Gilles Thomas, Alain Viari, Anita Langerød, Anne-Lise Børresen-Dale, Ewan Birney, Hendrik G Stunnenberg, Mike Stratton, John A Foekens, John W M Martens
A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome...
2016: Nature Communications
Iris Sze Ue Luk, Raunak Shrestha, Hui Xue, Yuwei Wang, Fang Zhang, Dong Lin, Anne Haegert, Rebecca Wu, Xin Dong, Colin C Collins, Amina Zoubeidi, Martin E Gleave, Peter W Gout, Yuzhuo Wang
PURPOSE: Enzalutamide (ENZ) resistance has emerged as a major problem in the management of castration-resistant prostate cancer (CRPC). Research on therapy resistance of CRPCs has primarily focussed on the androgen receptor pathway. In contrast, there is limited information on anti-apoptotic mechanisms that may facilitate the treatment resistance. The Inhibitor of Apoptosis Protein (IAP) family is well recognized for its role in promoting treatment resistance of cancers by inhibiting drug-induced apoptosis...
September 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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