keyword
MENU ▼
Read by QxMD icon Read
search

KRAS

keyword
https://www.readbyqxmd.com/read/27923066/somatic-genomics-and-clinical-features-of-lung-adenocarcinoma-a-retrospective-study
#1
Jianxin Shi, Xing Hua, Bin Zhu, Sarangan Ravichandran, Mingyi Wang, Cu Nguyen, Seth A Brodie, Alessandro Palleschi, Marco Alloisio, Gianluca Pariscenti, Kristine Jones, Weiyin Zhou, Aaron J Bouk, Joseph Boland, Belynda Hicks, Adam Risch, Hunter Bennett, Brian T Luke, Lei Song, Jubao Duan, Pengyuan Liu, Takashi Kohno, Qingrong Chen, Daoud Meerzaman, Crystal Marconett, Ite Laird-Offringa, Ian Mills, Neil E Caporaso, Mitchell H Gail, Angela C Pesatori, Dario Consonni, Pier Alberto Bertazzi, Stephen J Chanock, Maria Teresa Landi
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. METHODS AND FINDINGS: We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27922010/mek-inhibitors-block-growth-of-lung-tumours-with-mutations-in-ataxia-telangiectasia-mutated
#2
Michal Smida, Ferran Fece de la Cruz, Claudia Kerzendorfer, Iris Z Uras, Barbara Mair, Abdelghani Mazouzi, Tereza Suchankova, Tomasz Konopka, Amanda M Katz, Keren Paz, Katalin Nagy-Bojarszky, Markus K Muellner, Zsuzsanna Bago-Horvath, Eric B Haura, Joanna I Loizou, Sebastian M B Nijman
Lung cancer is the leading cause of cancer deaths, and effective treatments are urgently needed. Loss-of-function mutations in the DNA damage response kinase ATM are common in lung adenocarcinoma but directly targeting these with drugs remains challenging. Here we report that ATM loss-of-function is synthetic lethal with drugs inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib. Lung cancer cells resistant to MEK inhibition become highly sensitive upon loss of ATM both in vitro and in vivo...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27919956/expression-patterns-of-growth-and-survival-genes-with-prognostic-implications-in-advanced-pancreatic-cancer
#3
Dimitrios Pectasides, Vasiliki Kotoula, George Papaxoinis, Zoi Alexopoulou, Christos Dervenis, Epaminontas Samantas, Kleo Papaparaskeva, Elpida Charalambous, Chrysoula Gkakou, Christos Agalianos, Konstantine T Kalogeras, George Pentheroudakis, George Fountzilas
AIM: The aim of this study was to evaluate the mRNA expression pattern of growth- and survival-related genes and assess their prognostic significance in patients with advanced pancreatic cancer. PATIENTS AND METHODS: In total, 98 patients were included in this retrospective translational research study and were evaluated for Kirsten rat sarcoma viral oncogene homolog (KRAS) mutational status, and v-akt murine thymoma viral oncogene homolog 1 (AKT1), AKT serine/threonine kinase 2 (AKT2), AKT serine/threonine kinase 3 (AKT3), cyclin D1 (CCND1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), hepatocellular growth factor receptor (MET), avian myelomatosis viral oncogene homolog (MYC), nuclear factor kappa B subunit 1 (NFKb1), phosphatase and tensin homolog (PTEN) and mechanistic target of rapamycin (FRAP1) genes mRNA expression...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27916952/high-intra-and-inter-tumoral-heterogeneity-of-ras-mutations-in-colorectal-cancer
#4
Marion Jeantet, David Tougeron, Gaelle Tachon, Ulrich Cortes, Céline Archambaut, Gaelle Fromont, Lucie Karayan-Tapon
Approximately 30% of patients with wild type RAS metastatic colorectal cancer are non-responders to anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR mAbs), possibly due to undetected tumoral subclones harboring RAS mutations. The aim of this study was to analyze the distribution of RAS mutations in different areas of the primary tumor, metastatic lymph nodes and distant metastasis. A retrospective cohort of 18 patients with a colorectal cancer (CRC) was included in the study. Multiregion analysis was performed in 60 spatially separated tumor areas according to the pathological tumor node metastasis (pTNM) staging and KRAS, NRAS and BRAF mutations were tested using pyrosequencing...
December 1, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916938/comprehensive-analysis-of-mirnome-alterations-in-response-to-sorafenib-treatment-in-colorectal-cancer-cells
#5
Anna-Maria Pehserl, Anna Lena Ress, Stefanie Stanzer, Margit Resel, Michael Karbiener, Elke Stadelmeyer, Verena Stiegelbauer, Armin Gerger, Christian Mayr, Marcel Scheideler, Georg C Hutterer, Thomas Bauernhofer, Tobias Kiesslich, Martin Pichler
MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib...
December 1, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27915339/clinicopathological-features-and-predictive-factors-for-colorectal-cancer-outcome-in-the-kingdom-of-saudi-arabia
#6
Abdurrahman Aldiab, Khayal A Al Khayal, Omar A Al Obaid, Ahmed Alsheikh, Khalid Alsaleh, Mohamed Shahid, Hana Alkharji
BACKGROUND/AIMS: Colorectal cancer (CRC) is the most frequent cancer and a leading cause of cancer death in the Kingdom of Saudi Arabia (KSA). To date, no nationwide screening programs have been adopted. This prospective, longitudinal study investigated factors influencing the outcome of CRC in Saudi patients. METHODS: Patients completed a CRC awareness questionnaire. Colonoscopy, CT/MRI, histopathology of tumor biopsies, and KRAS and BRAF testing were performed...
December 3, 2016: Oncology
https://www.readbyqxmd.com/read/27913706/stat1-promotes-kras-colon-tumor-growth-and-susceptibility-to-pharmacological-inhibition-of-translation-initiation-factor-eif4a
#7
Shuo Wang, Cedric Darini, Laurent Désaubry, Antonis E Koromilas
The transcription factor STAT1 displays antitumor functions for certain forms of cancer via immunoregulatory and cell-autonomous pathways. Paradoxically, STAT1 can promote the survival of different tumor types treated with chemotherapeutic drugs through mechanisms that are not clearly defined. Herein, we demonstrate that STAT1 displays prosurvival effects in human KRAS colon tumor cells by regulating pathways that converge on the initiation of mRNA translation. Specifically, STAT1 increases PI3K class IB signaling and promotes the downregulation of the programmed cell death protein 4 (PDCD4), a protein with tumor-suppressive properties...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27913534/myelodysplastic-and-myeloproliferative-disorders-of-childhood
#8
Henrik Hasle
Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure, and reactive conditions...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912827/new-targets-in-non-small-cell-lung-cancer
#9
REVIEW
Soo J Park, Soham More, Ayesha Murtuza, Brian D Woodward, Hatim Husain
With the implementation of genomic technologies into clinical practice, we have examples of the predictive benefit of targeted therapy for oncogene-addicted cancer and identified molecular dependencies in non-small cell lung cancer. The clinical success of tyrosine kinase inhibitors against epidermal growth factor receptor and anaplastic lymphoma kinase activation has shifted treatment emphasize the separation of subsets of lung cancer and genotype-directed therapy. Advances have validated oncogenic driver genes and led to the development of targeted agents...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27911940/isoform-specific-effects-of-wild-type-ras-genes-on-carcinogen-induced-lung-tumorigenesis-in-mice
#10
Jamie D Weyandt, John M Carney, Elizabeth N Pavlisko, MengMeng Xu, Christopher M Counter
The gene KRAS is commonly mutated in lung cancer to encode a constitutively active and oncogenic protein that is well established to initiate and maintain lung tumorigenesis. However, the remaining wild-type KRAS protein, or the other family members HRAS and NRAS, can still be activated in the presence of oncogenic KRAS. Moreover, loss of any one of these three genes has been shown to increase the sensitivity of mice to the carcinogen urethane, which induces Kras mutation-positive early lung lesions. To determine the contribution of progressively disrupting Hras and Nras genes on urethane lung tumorigenesis, mice with different combinations of wild-type and null alleles of Hras and Nras were exposed with urethane and tumor burden was assessed...
2016: PloS One
https://www.readbyqxmd.com/read/27911859/kras-exon-2-codon-13-mutation-is-associated-with-a-better-prognosis-than-codon-12-mutation-following-lung-metastasectomy-in-colorectal-cancer
#11
Stéphane Renaud, Francesco Guerrera, Joseph Seitlinger, Lorena Costardi, Mickaël Schaeffer, Benoit Romain, Claudio Mossetti, Anne Claire-Voegeli, Pier Luigi Filosso, Michèle Legrain, Enrico Ruffini, Pierre-Emmanuel Falcoz, Alberto Oliaro, Gilbert Massard
INTRODUCTION: The utilization of molecular markers as routinely used biomarkers is steadily increasing. We aimed to evaluate the potential different prognostic values of KRAS exon 2 codons 12 and 13 after lung metastasectomy in colorectal cancer (CRC). RESULTS: KRAS codon 12 mutations were observed in 116 patients (77%), whereas codon 13 mutations were observed in 34 patients (23%). KRAS codon 13 mutations were associated with both longer time to pulmonary recurrence (TTPR) (median TTPR: 78 months (95% CI: 50...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27906963/lncrna-rmrp-acts-as-an-oncogene-in-lung-cancer
#12
Qingjun Meng, Mingming Ren, Yanguang Li, Xiang Song
Accumulating studies have demonstrated that long noncoding RNAs (lncRNAs) act a crucial role in the development of tumors. However, the role of lncRNAs in lung cancer remains largely unknown. In this study, we demonstrated that theexpression of RMRP was upregulated in lung adenocarcinoma tissues compared to the matched adjacent normal tissues. Moreover, of 35 lung adenocarcinoma samples, RMRP expression was upregulated in 25 cases (25/35; 71.4%) compared to the adjacent normal tissues. We also showed that RMRP expression was upregulated in lung adenocarcinoma cell lines (A549, SPC-A1, H1299 and H23) compared to the bronchial epithelial cell line (16HBE)...
2016: PloS One
https://www.readbyqxmd.com/read/27905446/genomic-evolution-and-chemoresistance-in-germ-cell-tumours
#13
Amaro Taylor-Weiner, Travis Zack, Elizabeth O'Donnell, Jennifer L Guerriero, Brandon Bernard, Anita Reddy, G Celine Han, Saud AlDubayan, Ali Amin-Mansour, Steven E Schumacher, Kevin Litchfield, Clare Turnbull, Stacey Gabriel, Rameen Beroukhim, Gad Getz, Scott L Carter, Michelle S Hirsch, Anthony Letai, Christopher Sweeney, Eliezer M Van Allen
Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes. GCTs are histologically heterogeneous and distinctly curable with chemotherapy. Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs, but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types...
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27905110/distinct-molecular-landscapes-between-endometrioid-and-non-endometrioid-uterine-carcinomas
#14
Nathaniel L Jones, Joanne Xiu, Sudeshna Chatterjee-Paer, Alexandre Buckley de Meritens, William M Burke, Ana I Tergas, Jason D Wright, June Y Hou
Endometrial carcinoma (EC) is traditionally characterized as endometrioid and non-endometrioid based on histo-pathologic phenotypes. Molecular-based classifications have been proposed, but are not widely implemented. Herein we examine molecular profiles between EC histologic subtypes. 3133 ECs were submitted between March 2011 and July 2014: 1634 Type I and 1226 Type II. In situ hybridization and immunohistochemistry were used to assess copy number and protein expression of selected genes. Sequenced variants in 47 genes were analyzed using the Illumina TruSeq Amplicon Cancer Panel...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27901498/targeting-the-vegf-c-vegfr3-axis-suppresses-slug-mediated-cancer-metastasis-and-stemness-via-inhibition-of-kras-yap1-signaling
#15
REVIEW
Yu-Wen Yeh, Ching-Chia Cheng, Shu-Ting Yang, Chi-Feng Tseng, Ting-Yu Chang, Sin-Ying Tsai, Earl Fu, Chien-Ping Chiang, Li-Chuan Liao, Pei-Wen Tsai, Yung-Luen Yu, Jen-Liang Su
Vascular endothelial growth factor-C (VEGF-C) has been implicated in epithelial-mesenchymal transition (EMT) processes and various human cancers, including skin cancer. Skin cancer is an aggressive human malignancy with increasing incidence worldwide; however, the underlying mechanisms involved in VEGF-C-induced skin cancer stemness and metastasis remain unclear. Here, we report that VEGF-C enhances skin cancer migration, invasion and stemness through Slug up-regulation. Oncomine database analysis indicated that the KRAS/MAPK (mitogen-activated protein kinases) pathway and YAP1 (yes-associated protein 1) expression are positively correlated with metastatic skin cancer...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#16
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27900004/role-of-specific-dna-mutations-in-the-peripheral-blood-of-colorectal-cancer-patients-for-the-assessment-of-tumor-stage-and-residual-disease-following-tumor-resection
#17
Gregor Norcic, Franc Jelenc, Petra Cerkovnik, Vida Stegel, Srdjan Novakovic
In the present study, the detection of tumor-specific KRAS proto-oncogene, GTPase (KRAS) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations in the peripheral blood of colorectal cancer (CRC) patients at all stages and adenomas was used for the estimation of disease stage prior to surgery and for residual disease following surgery. A total of 65 CRC patients were enrolled. The primary tumor tested positive for the specific mutations (KRAS mutations in codons 12, 13, 61, 117 or 146 and BRAF mutations in codon 600) in 35 patients...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899972/efficacy-and-safety-of-aflibercept-in-metastatic-colorectal-cancer-pretreated-with-bevacizumab-a-report-of-five-cases
#18
Julia Alcaide, Mayte Delgado, Marta Legerén, José Miguel Jurado, Isabel Blancas, Teresa Pereda, Jorge López, Margarita Garrido, María J Sánchez, José L García, Antonio Rueda
Aflibercept is a recombinant fusion protein that acts by inhibiting tumoural angiogenesis. Efficacy data obtained in the VELOUR randomised study has contributed to the approval of aflibercept as a second-line metastatic colorectal cancer (mCRC) treatment following an oxaliplatin-based regimen. The present study reports a case series of five patients with mCRC, who were treated in two centres since 2011 in the Compassionate Use Program for aflibercept. All patients had a KRAS mutation and previously received palliative fluoropyrimidine-oxaliplatin-based chemotherapy with bevacizumab...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899805/circulating-tumour-dna-analysis-demonstrates-spatial-mutational-heterogeneity-that-coincides-with-disease-relapse-in-myeloma
#19
S Mithraprabhu, T Khong, M Ramachandran, A Chow, D Klarica, L Mai, S Walsh, D Broemeling, A Marziali, M Wiggin, J Hocking, A Kalff, B Durie, A Spencer
Mutational characterisation in multiple myeloma (MM) currently relies on bone marrow (BM) biopsy, which fails to capture the putative spatial and genetic heterogeneity of this multi-focal disease. Analysis of plasma (PL)-derived circulating free tumour DNA (ctDNA) as an adjunct to BM biopsy, for mutational characterisation and tracking disease progression, was evaluated. Paired BM MM cell DNA and ctDNA from 33 relapsed [RR] and 15 newly diagnosed [ND] patients were analysed for KRAS, NRAS, BRAF and TP53 mutations using the OnTarget™ Mutation Detection (OMD) platform...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899776/-new-classification-for-advanced-colorectal-cancer-using-cancerplex%C3%A2-genomic-tests
#20
Hitoshi Kameyama, Yoshifumi Shimada, Hiroshi Ichikawa, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Shujiro Okuda, Yiwei Ling, Hiroshi Izutsu, Keisuke Kodama, Mitsutaka Nakada, Toshifumi Wakai
Recently, targeted drugs have been developed for the treatment of colorectal cancer(CRC). Among targets, it is well known that KRAS mutations are associated with resistance to epidermal growth factor receptor(EGFR)monoclonal antibodies. However, response rates using anti-EGFR monotherapy for CRC were less than 20-30% in previous clinical studies. Thus, because the RAS/MAP2K/MAPK and PI3K/AKT pathways are associated with CRC resistance to chemotherapy, we analyzed gene mutations in Stage IV CRC patients using a genomic test(CancerPlex®)...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
keyword
keyword
6312
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"