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https://www.readbyqxmd.com/read/28454347/effect-of-cigarette-smoke-exposure-and-mutant-kras-overexpression-on-pancreatic-cell-proliferation
#1
Howard P Glauert, R Scott Elliott, Sung Gu Han, Mark Athey, Eun Y Lee, C Gary Gairola
Pancreatic cancer is the fourth leading cause of cancer-associated mortality. The major risk factor for pancreatic cancer is cigarette smoking. Kras mutations are commonly observed in human pancreatic cancers. The present study examined the hypothesis that exposure to cigarette smoke and overexpression of a mutant Kras gene in the pancreas affects pancreatic cell proliferation in mice. Mice overexpressing the mutant Kras gene (KRas(G12D)) in the pancreas as well as wild-type mice were exposed to environmental tobacco smoke for 2 weeks...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454346/microrna-134-targets-kras-to-suppress-breast-cancer-cell-proliferation-migration-and-invasion
#2
Xiaomei Su, Ling Zhang, Hua Li, Peng Cheng, Yajie Zhu, Zhen Liu, Yu Zhao, Hongyu Xu, Dong Li, Hui Gao, Tao Zhang
The expression patterns and functions of microRNA-134 (miR-134) have been previously studied in numerous types of cancer. To the best of our knowledge, this is the first study of miR-134 in human breast cancer. In the present study, the expression patterns, biological functions and underlying molecular mechanisms of miR-134 in human breast cancer were investigated. Reverse transcription-quantitative polymerase chain reaction evaluated the expression of miR-134 in human breast cancer tissues, matched normal adjacent tissues, breast cancer cell lines and a normal mammary epithelial cell line...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453697/prediction-of-overall-survival-in-stage-ii-and-iii-colon-cancer-beyond-tnm-system-a-retrospective-pooled-biomarker-study
#3
R Dienstmann, M J Mason, F A Sinicrope, A I Phipps, S Tejpar, A Nesbakken, S A Danielsen, A Sveen, D D Buchanan, M Clendenning, C Rosty, B Bot, S R Alberts, J Milburn Jessup, R A Lothe, M Delorenzi, P A Newcomb, D Sargent, J Guinney
Background: TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. Patients and methods: After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3 (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782)...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28453690/subgroups-and-prognostication-in-stage-iii-colon-cancer-future-perspectives-for-adjuvant-therapy
#4
E Auclin, A Zaanan, D Vernerey, R Douard, C Gallois, P Laurent-Puig, F Bonnetain, J Taieb
Since the MOSAIC study, oxaliplatin-based adjuvant chemotherapy has been the standard treatment of stage III colon cancer. Combination therapy with fluoropyrimidines and oxaliplatin has improved overall survival (OS) and reduced the risk of recurrence in patients with resected stage III colon cancer. However, only 20% of patients really benefit from adjuvant chemotherapy, exposing 80% of patients to unnecessary toxicity. Recent analyses of large multicenter adjuvant studies have focused on the prognostication of OS and disease-free survival in stage III colon cancer in order to reduce over-treatment and to find more accurate prognostic tools than those used for adjuvant treatment decision-making in stage II disease...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28453558/tumor-targeted-sn38-inhibits-growth-of-early-stage-non-small-cell-lung-cancer-nsclc-in-a-kras-p53-transgenic-mouse-model
#5
Alexander Y Deneka, Leora Haber, Meghan C Kopp, Anna V Gaponova, Anna S Nikonova, Erica A Golemis
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, with a 5-year survival of only ~16%. Potential strategies to address NSCLC mortality include improvements in early detection and prevention, and development of new therapies suitable for use in patients with early and late stage diagnoses. Controlling the growth of early stage tumors could yield significant clinical benefits for patients with comorbidities that make them poor candidates for surgery: however, many drugs that limit cancer growth are not useful in the setting of long-term use or in comorbid patients, because of associated toxicities...
2017: PloS One
https://www.readbyqxmd.com/read/28453434/follicular-morphological-characteristics-may-be-associated-with-invasion-in-follicular-thyroid-neoplasms-with-papillary-like-nuclear-features
#6
Nuray Can, Mehmet Celik, Yavuz Atakan Sezer, Filiz Ozyilmaz, Semra Ayturk, Ebru Tastekin, Necdet Sut, Hakan Gurkan, Funda Ustun, Buket Yilmaz Bulbul, Sibel Guldiken, Fulya Oz Puyan
The newly proposed nomenclature and diagnostic criteria for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could improve the consistency and accuracy of diagnosing this entity. Diagnosis of NIFTP requires evaluation of the complete tumor border or capsule. The presence of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear features has been recently discussed by many authors...
April 28, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28453411/pooled-analysis-of-the-prognostic-and-predictive-effects-of-tp53-comutation-status-combined-with-kras-or-egfr-mutation-in-early-stage-resected-non-small-cell-lung-cancer-in-four-trials-of-adjuvant-chemotherapy
#7
Frances A Shepherd, Benjamin Lacas, Gwénaël Le Teuff, Pierre Hainaut, Pasi A Jänne, Jean-Pierre Pignon, Thierry Le Chevalier, Lesley Seymour, Jean-Yves Douillard, Stephen Graziano, Elizabeth Brambilla, Robert Pirker, Martin Filipits, Robert Kratzke, Jean-Charles Soria, Ming-Sound Tsao
Purpose Our previous work evaluated individual prognostic and predictive roles of TP53, KRAS, and EGFR in non-small-cell lung cancer (NSCLC). In this analysis, we explore the prognostic and predictive roles of TP53/KRAS and TP53/EGFR comutations in randomized trials of adjuvant chemotherapy versus observation. Patients and Methods Mutation analyses (wild-type [WT] and mutant) for TP53, KRAS, and EGFR were determined in blinded fashion in multiple laboratories. Primary and secondary end points of pooled analysis were overall survival and disease-free survival...
April 28, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28449008/extended-ras-analysis-and-correlation-with-overall-survival-in-advanced-pancreatic-cancer
#8
Michael Haas, Steffen Ormanns, Sibylle Baechmann, Anna Remold, Stephan Kruger, Christoph B Westphalen, Jens T Siveke, Patrick Wenzel, Anna Melissa Schlitter, Irene Esposito, Detlef Quietzsch, Michael R Clemens, Erika Kettner, Ruediger P Laubender, Andreas Jung, Thomas Kirchner, Stefan Boeck, Volker Heinemann
BACKGROUND: Mutations in the KRAS gene can be detected in about 70-90% of pancreatic cancer (PC) cases. Whether these mutations have a prognostic or predictive value remains elusive. Furthermore, the clinical relevance of the extended RAS (KRAS+NRAS) mutational status is unclear in PC. METHODS: We prospectively defined a PC patient population who received erlotinib-free chemotherapy regimens. A statistically significant difference between KRAS wild-type and KRAS mutated tumours in at least 160 patients in this population would support the assumption of a rather prognostic role of KRAS...
April 27, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28448866/function-of-microrna-143-in-different-signal-pathways-in-cancer-new-insights-into-cancer-therapy
#9
REVIEW
Leila Karimi, Behzad Mansoori, Dariush Shanebandi, Ali Mohammadi, Mahyar Aghapour, Behzad Baradaran
MicroRNAs (miRNAs) are small non-coding RNAs which participate in the post-transcriptional regulation of gene expression. They play important roles in cellular events such as growth and differentiation. Deregulation of miRNAs is frequently evident in human cancers where their aberrant expression is associated with uncontrolled proliferation, metastasis, impaired cell cycle and DNA damage response. The miRNAs are important in cancer as ∼50% of miRNA genes are located in cancer-associated regions such as fragile sites of genome...
April 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28448556/a-highly-specific-and-sensitive-massive-parallel-sequencer-based-test-for-somatic-mutations-in-non-small-cell-lung-cancer
#10
Yoshiaki Inoue, Jun Shiihara, Hitoshi Miyazawa, Hiromitsu Ohta, Megumi Higo, Yoshiaki Nagai, Kunihiko Kobayashi, Yasuo Saijo, Masanori Tsuchida, Mitsuo Nakayama, Koichi Hagiwara
Molecular targeting therapy for non-small cell lung cancer (NSCLC) has clarified the importance of mutation testing when selecting treatment regimens. As a result, multiple-gene mutation tests are urgently needed. We developed a next-generation sequencer (NGS)-based, multi-gene test named the MINtS for investigating driver mutations in both cytological specimens and snap-frozen tissue samples. The MINtS was used to investigate the EGFR, KRAS, BRAF genes from DNA, and the ERBB2, and the ALK, ROS1, and RET fusion genes from RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28448388/consideration-of-kras-mutational-status-may-enhance-the-prognostic-impact-of-indeterminate-extrahepatic-disease-in-the-lungs-as-identified-by-18fdg-pet-scan-in-patients-with-colorectal-liver-metastases
#11
Georgios A Margonis, Nikolaos Andreatos, Timothy M Pawlik, Matthew J Weiss
No abstract text is available yet for this article.
April 26, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28448128/total-chemical-synthesis-and-folding-of-all-l-and-all-d-variants-of-oncogenic-kras-g12v
#12
Adam Marc Levinson, John H McGee, Andrew G Roberts, Gardner Creech, Ting Wang, Michael T Peterson, Ronald C Hendrickson, Gregory L Verdine, Samuel J Danishefsky
The Ras proteins are essential GTPases involved in the regulation of cell proliferation and survival. Mutated oncogenic forms of Ras alter effector binding and innate GTPase activity, leading to deregulation of downstream signal transduction. Mutated forms of Ras are involved in approximately 30% of human cancers. Despite decades of effort to develop direct Ras inhibitors, Ras has long been considered 'undruggable' due to its high affinity for GTP and its lack of hydrophobic binding pockets. Herein, we report a total chemical synthesis of all-L- and all-D-amino acid biotinylated variants of oncogenic mutant KRas(G12V)...
April 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28447565/risk-factors-for-brain-metastases-in-patients-with-metastatic-colorectal-cancer
#13
Troels Dreier Christensen, Jesper Andreas Palshof, Finn Ole Larsen, Estrid Høgdall, Tim Svenstrup Poulsen, Per Pfeiffer, Benny Vittrup Jensen, Mette Karen Yilmaz, Ib Jarle Christensen, Dorte Nielsen
BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict later risk of developing BM. Furthermore, we wished to estimate the incidence of BM in long-term surviving patients. MATERIAL AND METHODS: We conducted a retrospective study on a Danish multicenter cohort of patients with mCRC who received cetuximab and irinotecan (CetIri) as third-line treatment...
May 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28447195/salivary-mir-16-mir-191-and-mir-223-intuitive-indicators-of-dominant-ovarian-follicles-in-buffaloes
#14
Prashant Singh, Naresh Golla, Pankaj Singh, Vijay Simha Baddela, Subhash Chand, Rubina Kumari Baithalu, Dheer Singh, Suneel Kumar Onteru
Estrus or sexual receptivity determination is utmost important for efficient breeding programs for female buffaloes. Prominent estrus behavioral symptoms are the result of several molecular and neuroendocrine events involving the ovary and the brain. Expression of estrus behavior is poor in buffaloes during the summer season. Hence, the discovery of biomarkers specific to the estrus stage or its related ovarian events, like the presence of dominant ovarian follicle, is helpful for developing an easy estrus determination method...
April 26, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28446878/computational-model-predicts-the-effects-of-targeting-cellular-metabolism-in-pancreatic-cancer
#15
Mahua Roy, Stacey D Finley
Reprogramming of energy metabolism is a hallmark of cancer that enables the cancer cells to meet the increased energetic requirements due to uncontrolled proliferation. One prominent example is pancreatic ductal adenocarcinoma, an aggressive form of cancer with an overall 5-year survival rate of 5%. The reprogramming mechanism in pancreatic cancer involves deregulated uptake of glucose and glutamine and other opportunistic modes of satisfying energetic demands in a hypoxic and nutrient-poor environment. In the current study, we apply systems biology approaches to enable a better understanding of the dynamics of the distinct metabolic alterations in KRAS-mediated pancreatic cancer, with the goal of impeding early cell proliferation by identifying the optimal metabolic enzymes to target...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28446505/clinical-features-and-outcomes-of-patients-with-colorectal-cancers-harboring-nras-mutations
#16
Andrea Cercek, Maria Ignez Braghiroli, Joanne F Chou, Jaclyn F Hechtman, Nancy E Kemeny, Leonard Saltz, Marinela Capanu, Rona Yaeger
Purpose: NRAS mutations are now routinely included in RAS testing prior to EGFR (epidermal growth factor receptor) inhibitor therapy for metastatic colorectal cancer (mCRC).  The clinical implications of NRAS mutation beyond lack of response to anti-EGFR therapy, however, are not known.  We undertook this study to determine the clinical features and treatment outcomes of patients with NRAS mutant mCRC.<br />Experimental Design: We reviewed clinical characteristics, concurrent mutations, and outcomes for all mCRC cases with NRAS mutations undergoing standard genotyping at our institution from 2008-2015...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28446242/activity-of-distinct-growth-factor-receptor-network-components-in-breast-tumors-uncovers-two-biologically-relevant-subtypes
#17
Mumtahena Rahman, Shelley M MacNeil, David F Jenkins, Gajendra Shrestha, Sydney R Wyatt, Jasmine A McQuerry, Stephen R Piccolo, Laura M Heiser, Joe W Gray, W Evan Johnson, Andrea H Bild
BACKGROUND: The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns. METHODS: Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD)...
April 26, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28445990/prognostic-value-of-tumor-mutations-in-radically-treated-locally-advanced-non-small-cell-lung-cancer-patients
#18
Angela Boros, Ludovic Lacroix, Benjamin Lacas, Julien Adam, Jean-Pierre Pignon, Caroline Caramella, David Planchard, Vincent de Montpreville, Eric Deutsch, Antonin Levy, Benjamin Besse, Cécile Le Pechoux
INTRODUCTION: Chemo-radiation is standard treatment in locally advanced non-small cell lung cancers (NSCLC). The prognostic value of mutations has been poorly explored in this population. RESULTS: Clinical data were collected from 190 patients and mutational profiles were obtained in 78 of them; 58 (74%) were males, 31 (40%) current smokers, 47/31 stage IIIA/IIIB and 40 (51%) adenocarcinoma. The following mutations were identified: EGFR 12% (9/78), KRAS 15% (12/78), BRAF 5% (3/65), PI3KCA 2% (1/57), NRAS 3% (1/32), and ALK+ (FISH) 4% (2/51)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445137/monitoring-of-kras-mutated-ctdna-to-discriminate-pseudo-progression-from-true-progression-during-anti-pd-1-treatment-of-lung-adenocarcinoma
#19
Nicolas Guibert, Julien Mazieres, Myriam Delaunay, Anne Casanova, Magali Farella, Laura Keller, Gilles Favre, Anne Pradines
OBJECTIVES: Pseudo-progression is a rare but worrying situation for both clinicians and patients during immunotherapy. Dedicated ir-RECIST criteria have been established to improve this situation. However, this can be sometimes considered inadequate and patients experiencing true progression may then receive inefficient treatments. Additional reliable tools to discriminate pseudo from true progression are thus needed. So far, no biomarker has been identified to distinguish pseudo from true progression...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445136/selective-eradication-of-cancer-cells-by-delivery-of-adenovirus-based-toxins
#20
Shiran Shapira, Assaf Shapira, Diana Kazanov, Gil Hevroni, Sarah Kraus, Nadir Arber
BACKGROUND AND OBJECTIVE: KRAS mutation is an early event in colorectal cancer carcinogenesis. We previously reported that a recombinant adenovirus, carrying a pro-apoptotic gene (PUMA) under the regulation of Ets/AP1 (RAS-responsive elements) suppressed the growth of cancer cells harboring hyperactive KRAS. We propose to exploit the hyperactive RAS pathway, rather than to inhibit it as was previously tried and failed repeatedly. We aim to improve efficacy by substituting PUMA with a more potent toxin, the bacterial MazF-MazE toxin-antitoxin system, under a very tight regulation...
April 7, 2017: Oncotarget
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