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https://www.readbyqxmd.com/read/28106883/pten-deficiency-permits-the-formation-of-pancreatic-cancer-in-the-absence-of-autophagy
#1
Mathias T Rosenfeldt, Jim O'Prey, Lucia Flossbach, Colin Nixon, Jennifer P Morton, Owen J Sansom, Kevin M Ryan
No abstract text is available yet for this article.
January 20, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28104720/when-dizziness-becomes-sinister-oropharyngeal-carcinoma-presenting-as-a-paraneoplastic-neurological-disorder
#2
Li Yong, Panagiotis Asimakopoulos, Colin Mumford, Ioanna Fragkandrea Nixon
Paraneoplastic neurological disorders are uncommon presentations of head and neck cancers. We present a case of a 68-year-old male patient who presented with dizziness, nausea and memory problems. MRI of his brain showed bilateral cerebellar leptomeningeal enhancing signal abnormality with cervical lymphadenopathy. CT imaging of his neck raised the suspicion of a tonsillar primary, which was later confirmed on biopsy. His poorly differentiated HPV positive squamous cell carcinoma was treated with chemoradiotherapy...
January 19, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28102366/aurora-kinase-a-is-a-biomarker-for-bladder-cancer-detection-and-contributes-to-its-aggressive-behavior
#3
Aaron Mobley, Shizhen Zhang, Jolanta Bondaruk, Yan Wang, Tadeusz Majewski, Nancy P Caraway, Li Huang, Einav Shoshan, Guermarie Velazquez-Torres, Giovanni Nitti, Sangkyou Lee, June Goo Lee, Enrique Fuentes-Mattei, Daniel Willis, Li Zhang, Charles C Guo, Hui Yao, Keith Baggerly, Yair Lotan, Seth P Lerner, Colin Dinney, David McConkey, Menashe Bar-Eli, Bogdan Czerniak
The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098411/an-efficient-basket-trial-design
#4
Kristen M Cunanan, Alexia Iasonos, Ronglai Shen, Colin B Begg, Mithat Gönen
The landscape for early phase cancer clinical trials is changing dramatically because of the advent of targeted therapy. Increasingly, new drugs are designed to work against a target such as the presence of a specific tumor mutation. Because typically only a small proportion of cancer patients will possess the mutational target, but the mutation is present in many different cancers, a new class of basket trials is emerging, whereby the drug is tested simultaneously in different baskets, that is, subgroups of different tumor types...
January 18, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28097472/proceedings-of-the-third-international-molecular-pathological-epidemiology-mpe-meeting
#5
REVIEW
Peter T Campbell, Timothy R Rebbeck, Reiko Nishihara, Andrew H Beck, Colin B Begg, Alexei A Bogdanov, Yin Cao, Helen G Coleman, Gordon J Freeman, Yujing J Heng, Curtis Huttenhower, Rafael A Irizarry, N Sertac Kip, Franziska Michor, Daniel Nevo, Ulrike Peters, Amanda I Phipps, Elizabeth M Poole, Zhi Rong Qian, John Quackenbush, Harlan Robins, Peter K Rogan, Martha L Slattery, Stephanie A Smith-Warner, Mingyang Song, Tyler J VanderWeele, Daniel Xia, Emily C Zabor, Xuehong Zhang, Molin Wang, Shuji Ogino
Molecular pathological epidemiology (MPE) is a transdisciplinary and relatively new scientific discipline that integrates theory, methods, and resources from epidemiology, pathology, biostatistics, bioinformatics, and computational biology. The underlying objective of MPE research is to better understand the etiology and progression of complex and heterogeneous human diseases with the goal of informing prevention and treatment efforts in population health and clinical medicine. Although MPE research has been commonly applied to investigating breast, lung, and colorectal cancers, its methodology can be used to study most diseases...
January 17, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28073598/hdac10-as-a-potential-therapeutic-target-in-ovarian-cancer
#6
Muhtadi M Islam, Tapahsama Banerjee, Colin Z Packard, Shweta Kotian, Karuppaiyah Selvendiran, David E Cohn, Jeffrey D Parvin
OBJECTIVE: We analyzed histone deacetylase 10 (HDAC10) for function in the context of the DNA damage response in BRCA1-null ovarian cancer cells as well as evaluated the potential of general HDAC inhibitors in primary ovarian carcinoma cells. HDAC10 had previously been shown to be highly stimulatory to the process of homology directed repair in HeLa cells, and in this study we investigated whether HDAC10 could impact in vitro the response to anticancer therapies. We hypothesized that the loss of HDAC10 would sensitize cells to platinum therapy...
January 7, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28071659/acg-clinical-guideline-treatment-of-helicobacter-pylori-infection
#7
William D Chey, Grigorios I Leontiadis, Colin W Howden, Steven F Moss
Helicobacter pylori (H. pylori) infection is a common worldwide infection that is an important cause of peptic ulcer disease and gastric cancer. H. pylori may also have a role in uninvestigated and functional dyspepsia, ulcer risk in patients taking low-dose aspirin or starting therapy with a non-steroidal anti-inflammatory medication, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura. While choosing a treatment regimen for H. pylori, patients should be asked about previous antibiotic exposure and this information should be incorporated into the decision-making process...
January 10, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28069876/targeting-plk1-to-enhance-efficacy-of-olaparib-in-castration-resistant-prostate-cancer
#8
Xiaoqi Liu, Jie Li, Ruixin Wang, Yifan Kong, Meaghan M Broman, Colin Carlock, Long Chen, Zhiguo Li, Elia Farah, Timothy L Ratliff
Olaparib is a FDA-approved PARP inhibitor (PARPi) that has shown promise as a synthetic lethal treatment approach for BRCA-mutant castration-resistant prostate cancer (CRPC) in clinical use. However, emerging data has also shown that even BRCA-mutant cells may be resistant to PARPi. The mechanistic basis for these drug resistances is poorly understood. Polo-like kinase 1 (Plk1), a critical regulator of many cell cycle events, is significantly elevated upon castration of mice carrying xenograft prostate tumors...
January 9, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28068672/genomic-hallmarks-of-localized-non-indolent-prostate-cancer
#9
Michael Fraser, Veronica Y Sabelnykova, Takafumi N Yamaguchi, Lawrence E Heisler, Julie Livingstone, Vincent Huang, Yu-Jia Shiah, Fouad Yousif, Xihui Lin, Andre P Masella, Natalie S Fox, Michael Xie, Stephenie D Prokopec, Alejandro Berlin, Emilie Lalonde, Musaddeque Ahmed, Dominique Trudel, Xuemei Luo, Timothy A Beck, Alice Meng, Junyan Zhang, Alister D'Costa, Robert E Denroche, Haiying Kong, Shadrielle Melijah G Espiritu, Melvin L K Chua, Ada Wong, Taryne Chong, Michelle Sam, Jeremy Johns, Lee Timms, Nicholas B Buchner, Michèle Orain, Valérie Picard, Helène Hovington, Alexander Murison, Ken Kron, Nicholas J Harding, Christine P'ng, Kathleen E Houlahan, Kenneth C Chu, Bryan Lo, Francis Nguyen, Constance H Li, Ren X Sun, Richard de Borja, Christopher I Cooper, Julia F Hopkins, Shaylan K Govind, Clement Fung, Daryl Waggott, Jeffrey Green, Syed Haider, Michelle A Chan-Seng-Yue, Esther Jung, Zhiyuan Wang, Alain Bergeron, Alan Dal Pra, Louis Lacombe, Colin C Collins, Cenk Sahinalp, Mathieu Lupien, Neil E Fleshner, Housheng H He, Yves Fradet, Bernard Tetu, Theodorus van der Kwast, John D McPherson, Robert G Bristow, Paul C Boutros
Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries...
January 19, 2017: Nature
https://www.readbyqxmd.com/read/28061747/gtb-an-online-genome-tolerance-browser
#10
Hashem A Shihab, Mark F Rogers, Michael Ferlaino, Colin Campbell, Tom R Gaunt
BACKGROUND: Accurate methods capable of predicting the impact of single nucleotide variants (SNVs) are assuming ever increasing importance. There exists a plethora of in silico algorithms designed to help identify and prioritize SNVs across the human genome for further investigation. However, no tool exists to visualize the predicted tolerance of the genome to mutation, or the similarities between these methods. RESULTS: We present the Genome Tolerance Browser (GTB, http://gtb...
January 6, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28056180/clonality-inference-from-single-tumor-samples-using-low-coverage-sequence-data
#11
Nilgun Donmez, Salem Malikic, Alexander W Wyatt, Martin E Gleave, Colin C Collins, S Cenk Sahinalp
Inference of intra-tumor heterogeneity can provide valuable insight into cancer evolution. Somatic mutations detected by sequencing can help estimate the purity of a tumor sample and reconstruct its subclonal composition. Although several methods have been developed to infer intra-tumor heterogeneity, the majority of these tools rely on variant allele frequencies as estimated via ultra-deep sequencing from multiple samples of the same tumor. In practice, obtaining sequencing data from a large number of samples per patient is only feasible in a few cancer types such as liquid tumors, or in rare cases involving solid tumors selected for research...
January 5, 2017: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/28039486/cd147-a-small-molecule-transporter-ancillary-protein-at-the-crossroad-of-multiple-hallmarks-of-cancer-and-metabolic-reprogramming
#12
Agnieszka A Kendrick, Johnathon Schafer, Monika Dzieciatkowska, Travis Nemkov, Angelo D Alessandro, Deepika Neelakantan, Heide L Ford, Chad G Pearson, Colin D Weekes, Kirk C Hansen, Elan Z Eisenmesser
Increased expression of CD147 in pancreatic cancer has been proposed to play a critical role in cancer progression via CD147 chaperone function for lactate monocarboxylate transporters (MCTs). Here, we show for the first time that CD147 interacts with membrane transporters beyond MCTs and exhibits a protective role for several of its interacting partners. CD147 prevents its interacting partner's proteasome-dependent degradation and correct plasma membrane localization through CD147 transmembrane (TM) region...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28008216/understanding-genetic-breast-cancer-risk-processing-loci-of-the-brca-gist-intelligent-tutoring-system
#13
Christopher R Wolfe, Valerie F Reyna, Colin L Widmer, Elizabeth M Cedillos-Whynott, Priscila G Brust-Renck, Audrey M Weil, Xiangen Hu
The BRCA Gist Intelligent Tutoring System helps women understand and make decisions about genetic testing for breast cancer risk. BRCA Gist is guided by Fuzzy-Trace Theory, (FTT) and built using AutoTutor Lite. It responds differently to participants depending on what they say. Seven tutorial dialogues requiring explanation and argumentation are guided by three FTT concepts: forming gist explanations in one's own words, emphasizing decision-relevant information, and deliberating the consequences of decision alternatives...
July 2016: Learning and Individual Differences
https://www.readbyqxmd.com/read/28002667/discovery-of-a-potent-cell-penetrant-and-selective-p300-cbp-associated-factor-pcaf-general-control-non-derepressible-5-gcn5-bromodomain-chemical-probe
#14
Philip G Humphreys, Paul Bamborough, Chun-Wa Chung, Peter D Craggs, Laurie J Gordon, Paola Grandi, Thomas G Hayhow, Jameed Hussain, Katherine L Jones, Matthew Lindon, Anne-Marie Michon, Jessica F Renaux, Colin J Suckling, David F Tough, Rab K Prinjha
p300/CREB binding protein associated factor (PCAF/KAT2B) and general control non-derepressible 5 (GCN5/KAT2A) are multidomain proteins that have been implicated in retroviral infection, inflammation pathways and cancer development. However, outside of viral replication, little is known about the dependence of these effects on the C-terminal bromodomain. Herein, we report GSK4027 as a chemical probe for the PCAF/GCN5 bromodomain, together with GSK4028 as an enantiomeric negative control. The probe was optimized from a weakly potent, non-selective pyridazinone hit to deliver high potency for the PCAF/GCN5 bromodomain, high solubility, cellular target engagement and ≥18000 fold selectivity over the BET family, together with ≥70 fold selectivity over the wider bromodomain families...
December 21, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27990167/relative-bioavailability-of-three-formulations-of-galunisertib-administered-as-monotherapy-in-patients-with-advanced-or-metastatic-cancer
#15
Ivelina Gueorguieva, Ann Cleverly, Durisala Desaiah, Analia Azaro, Joan Seoane, Irene Braña, Elisabet Sicart, Colin Miles, Michael M Lahn, Malcolm I Mitchell, Jordi Rodon
OBJECTIVE: Galunisertib (LY2157299 monohydrate), an inhibitor of the transforming growth factor β (TGFβ) pathway, is currently under investigation in several clinical trials involving multiple tumor types. The primary objective of this study was to assess relative bioavailability of two new galunisertib formulations developed using the roller compaction (RC) dry-milled (RCD) and RC slurry-milled (RCS) processes, compared with the existing formulation developed using the high-sheer wet granulation (HSWG) process...
2016: Drugs in Context
https://www.readbyqxmd.com/read/27987404/diagnostic-accuracy-of-cancer-antigen-125-ca125-for-endometriosis-in-symptomatic-women-a-multi-center-study
#16
Martin Hirsch, James M N Duffy, Christine S Deguara, Colin J Davis, Khalid S Khan
STUDY OBJECTIVE: To assess the diagnostic accuracy of serum Cancer Antigen 125 (CA 125)≥30units/milliliter (u/ml) for diagnosing endometriosis in symptomatic women. STUDY DESIGN: Prospective observational cohort study including patients with symptoms of pelvic pain or subfertility undergoing elective diagnostic laparoscopy at two tertiary referral hospitals. We excluded patients suspected to have other gynecological pathology. We evaluated the accuracy of serum CA 125 (index test) with histologically confirmed endometriosis (reference standard)...
December 5, 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/27978560/prevalence-and-spectrum-of-germline-cancer-susceptibility-gene-mutations-among-patients-with-early-onset-colorectal-cancer
#17
Rachel Pearlman, Wendy L Frankel, Benjamin Swanson, Weiqiang Zhao, Ahmet Yilmaz, Kristin Miller, Jason Bacher, Christopher Bigley, Lori Nelsen, Paul J Goodfellow, Richard M Goldberg, Electra Paskett, Peter G Shields, Jo L Freudenheim, Peter P Stanich, Ilene Lattimer, Mark Arnold, Sandya Liyanarachchi, Matthew Kalady, Brandie Heald, Carla Greenwood, Ian Paquette, Marla Prues, David J Draper, Carolyn Lindeman, J Philip Kuebler, Kelly Reynolds, Joanna M Brell, Amy A Shaper, Sameer Mahesh, Nicole Buie, Kisa Weeman, Kristin Shine, Mitchell Haut, Joan Edwards, Shyamal Bastola, Karen Wickham, Karamjit S Khanduja, Rosemary Zacks, Colin C Pritchard, Brian H Shirts, Angela Jacobson, Brian Allen, Albert de la Chapelle, Heather Hampel
Importance: Hereditary cancer syndromes infer high cancer risks and require intensive cancer surveillance, yet the prevalence and spectrum of these conditions among unselected patients with early-onset colorectal cancer (CRC) is largely undetermined. Objective: To determine the frequency and spectrum of cancer susceptibility gene mutations among patients with early-onset CRC. Design, Setting, and Participants: Overall, 450 patients diagnosed with colorectal cancer younger than 50 years were prospectively accrued from 51 hospitals into the Ohio Colorectal Cancer Prevention Initiative from January 1, 2013, to June 20, 2016...
December 15, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27975152/phase-i-ii-study-of-refametinib-bay-86-9766-in-combination-with-gemcitabine-in-advanced-pancreatic-cancer
#18
Jean-Luc Van Laethem, Hanno Riess, Jacek Jassem, Michael Haas, Uwe M Martens, Colin Weekes, Marc Peeters, Paul Ross, John Bridgewater, Bohuslav Melichar, Stefano Cascinu, Piotr Saramak, Patrick Michl, David Van Brummelen, Alberto Zaniboni, Wollf Schmiegel, Svein Dueland, Marius Giurescu, Vittorio L Garosi, Katrin Roth, Anke Schulz, Henrik Seidel, Prabhu Rajagopalan, Michael Teufel, Barrett H Childs
BACKGROUND: Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer. METHODS: Phase I comprised dose escalation, followed by phase II expansion. Refametinib and gemcitabine plasma levels were analyzed for pharmacokinetics. KRAS mutational status was determined from circulating tumor DNA...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27969514/ps01-47-pet-volumetric-prognostic-index-may-be-the-most-significant-survival-factor-in-non-small-cell-lung-cancer-treated-with-chemoradiation-topic-radiation-oncology
#19
Li Yan, Hong Zhang, Maurice King, Huanmei Wu, Colin Huang, Wenhu Pi, Yonglin Pu, Mark Tan, Feng-Ming Spring Kong
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27965871/using-specialist-screening-practitioners-ssps-to-increase-uptake-of-the-bowel-scope-flexible-sigmoidoscopy-screening-programme-a-study-protocol-for-a-feasibility-single-stage-phase-ii-trial
#20
Lesley M McGregor, Hanna Skrobanski, Hayley Miller, Mary Ritchie, Lindy Berkman, Stephen Morris, Colin Rees, Christian von Wagner
BACKGROUND: The NHS Bowel Scope Screening (BSS) programme offers men and women aged 55 years a once-only flexible sigmoidoscopy (FS), a test that can help reduce colorectal cancer (CRC) incidence and mortality. However, the benefits of BSS are contingent on uptake. This National Institute for Health Research-funded single-stage phase II trial will test the feasibility of using patient navigation (PN), an intervention that offers support to patients to overcome barriers to healthcare, to increase BSS uptake within a socially deprived area of England...
2016: Pilot and Feasibility Studies
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