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https://www.readbyqxmd.com/read/29222172/proximal-aberrant-crypt-foci-associate-with-synchronous-neoplasia-and-are-primed-for-neoplastic-progression
#1
David A Drew, Allen Mo, James J Grady, Richard G Stevens, Joel B Levine, Bruce M Brenner, Joseph C Anderson, Faripour Forouhar, Michael J O'Brien, Thomas J Devers, Daniel W Rosenberg
Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion found within the human colon. Despite their relatively high frequency in the distal colon, few studies have examined the molecular characteristics of ACF within the proximal colon. In the following study, clinical participants (n=184) were screened for ACF using high-definition chromoendoscopy with contrast dye-spray. Following pathological confirmation, ACF biopsies were subjected to laser-capture microdissection (LCM) and epithelial cells were evaluated for somatic mutations with a customized colorectal cancer mutation panel using DNA-mass spectrometry...
December 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29221474/increased-expression-of-neuregulin-1-in-the-urothelium-of-rat-bladder-with-partial-bladder-outlet-obstruction
#2
Seung Woo Yang, Seong Woo Jeong, Ki Hak Song
BACKGROUND: This study determined whether changes in the expression of neuregulin (NRG) 1, erbB2 tyrosine kinase (ErbB2) and the M2 muscarinic receptor in the urothelium and detrusor muscle of the rat bladder were associated with partial bladder outlet obstruction (PBOO). METHODS: Male Sprague-Dawley rats (body weight 250-300 g) were used and subdivided into control (n = 10) and PBOO groups (n = 20). PBOO was induced for 21 days, and the expression of NRG1, ErbB2 and M2 muscarinic receptor mRNA and protein was evaluated using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting, respectively...
December 8, 2017: BMC Urology
https://www.readbyqxmd.com/read/29219657/the-levels-of-mutant-k-ras-and-mutant-n-ras-are-rapidly-reduced-in-a-beclin1-atg5-dependent-fashion-by-the-irreversible-erbb1-2-4-inhibitor-neratinib
#3
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Cindy Sander, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Paul Dent
The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFRα levels in GBM cells, that was enhanced by sodium valproate...
December 8, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29219616/next-generation-sequencing-approach-to-non-small-cell-lung-carcinoma-yields-more-actionable-alterations
#4
Mitra Mehrad, Somak Roy, Humberto Trejo Bittar, Sanja Dacic
CONTEXT: - Different testing algorithms and platforms for EGFR mutations and ALK rearrangements in advanced-stage lung adenocarcinoma exist. The multistep approach with single-gene assays has been challenged by more efficient next-generation sequencing (NGS) of a large number of gene alterations. The main criticism of the NGS approach is the detection of genomic alterations of uncertain significance. OBJECTIVE: - To determine the best testing algorithm for patients with lung cancer in our clinical practice...
December 8, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29218825/in-vivo-evidence-supporting-a-metastasis-suppressor-role-for-stard13-dlc2-in-erbb2-neu-oncogene-induced-mouse-mammary-tumours
#5
Pratima Basak, Heather Leslie, Rachelle L Dillon, William J Muller, Afshin Raouf, Michael Ra Mowat
Overexpression of dominant oncogenes and the loss of tumor suppressor genes are basic genetic events in the acquisition of the malignant phenotype. The erb-b2 receptor tyrosine kinase 2 (ERBB-2) proto-oncogene is overexpressed in 20-30% of human breast cancers. The StAR related lipid transfer domain containing 13 gene (STARD13), also known as Deleted in Liver Cancer-2 (DLC-2), maps to chromosome band 13q12.3 and is frequently downregulated in human cancers, including 72% of breast cancers. It encodes a RhoGAP protein with sterile α motif (SAM) and StAR-related lipid transfer (START) domains...
December 8, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29217530/the-impact-of-smoking-and-tp53-mutations-in-lung-adenocarcinoma-patients-with-targetable-mutations-the-lung-cancer-mutation-consortium-lcmc2
#6
Dara L Aisner, Lynette M Sholl, Lynne Berry, Michael Rossi, Heidi Chen, Junya Fujimoto, Andre L Moreira, Suresh Ramalingam, Liza C Villaruz, Gregory A Otterson, Eric B Haura, Katerina Politi, Bonnie S Glisson, Jeremy Cetnar, Edward Garon, Joan Schiller, Saiama Waqar, Lecia V Sequist, Julie R Brahmer, Yu Shyr, Kelly Kugler, Ignacio Ivan Wistuba, Bruce E Johnson, John D Minna, Mark G Kris, Paul A Bunn, David J Kwiatkowski
PURPOSE Multiplex genomic profiling is standard of care for patients with advanced lung adenocarcinomas. The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas. PATIENTS AND METHODS Sixteen U.S. institutions enrolled 1367 lung cancer patients in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and immunohistochemistry...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29212173/comprehensive-genomic-sequencing-detects-important-genetic-differences-between-right-sided-and-left-sided-colorectal-cancer
#7
Yoshifumi Shimada, Hitoshi Kameyama, Masayuki Nagahashi, Hiroshi Ichikawa, Yusuke Muneoka, Ryoma Yagi, Yosuke Tajima, Takuma Okamura, Masato Nakano, Jun Sakata, Takashi Kobayashi, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Tetsu Hayashida, Hiromasa Takaishi, Yuko Kitagawa, Eiji Oki, Tsuyoshi Konishi, Fumio Ishida, Shin-Ei Kudo, Jennifer E Ring, Alexei Protopopov, Stephen Lyle, Yiwei Ling, Shujiro Okuda, Takashi Ishikawa, Kohei Akazawa, Kazuaki Takabe, Toshifumi Wakai
Objectives: Anti-epidermal growth factor receptor (EGFR) therapy has been found to be more effective against left-sided colorectal cancer (LCRC) than right-sided colorectal cancer (RCRC). We hypothesized that RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy and tested this using comprehensive genomic sequencing. Materials and methods: A total of 201 patients with either primary RCRC or LCRC were analyzed. We investigated tumors for genetic alterations using a 415-gene panel, which included alterations associated with resistance to anti-EGFR therapy: TK receptors (ERBB2, MET, EGFR, FGFR1, and PDGFRA), RAS pathway (KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and PI3K pathway (PTEN and PIK3CA)...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211816/clinical-outcome-and-molecular-characterisation-of-chemorefractory-metastatic-colorectal-cancer-patients-with-long-term-efficacy-of-regorafenib-treatment
#8
Erika Martinelli, Vincenzo Sforza, Claudia Cardone, Anna Capasso, Anna Nappi, Giulia Martini, Stefania Napolitano, Anna Maria Rachiglio, Nicola Normanno, Salvatore Cappabianca, Alfonso Reginelli, Maurizio Di Bisceglie, Tiziana Pia Latiano, Evaristo Maiello, Michele Orditura, Fernando De Vita, Floriana Morgillo, Fortunato Ciardiello, Teresa Troiani
HASH(0x49401d8) Background: To investigate the potential predictors of response to regorafenib, in chemorefractory metastatic colorectal cancer (mCRC) patients with long-term efficacy from regorafenib treatment. Methods: Retrospective, single institution analysis of patients with chemorefractory mCRC treated with regorafenib, in clinical practice setting. 123 patients were treated and stratified into two groups according to number of cycles received (<7 and ≥7)...
2017: ESMO Open
https://www.readbyqxmd.com/read/29199595/epidermal-growth-factor-receptor-tyrosine-kinase-a-potential-target-in-treatment-of-non-small-cell-lung-carcinoma
#9
REVIEW
Venugopal Vinod Prabhu, Niranjali Devaraj
Lung cancer is responsible for 1.6 million deaths. Approximately 80%-85% of lung cancers are of the non-small-cell variety, which includes squamous cell carcinoma, adenocarcinoma, and large-cell carcinoma. Knowing the stage of cancer progression is a requisite for determining which management approach-surgery, chemotherapy, radiotherapy, and/or immunotherapy-is optimal. Targeted therapeutic approaches with antiangiogenic monoclonal antibodies or tyrosine kinase inhibitors are one option if tumors harbor oncogene mutations...
2017: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29198084/-the-impact-of-molecular-profiling-using-next-generation-sequencing-in-advanced-lung-cancer
#10
Anna Belilovski Rozenblum, Maya Ilouze, Elizabeth Dudnik, Lior Soussan-Gutman, Addie Dvir, Nir Peled
BACKGROUND: In the last decade, important advances in understanding the lung cancer cellular signal pathways have led to the designing of targeted drugs that significantly prolong survival. Recent data shows that 64% of lung adenocarcinomas harbor at least one activating driver mutation, including treatable mutations such as RET, ERBB2 (HER-2) and ROS1 gene mutations, besides the regularly screened ALK and EGFR genes. Next-Generation Sequencing (NGS) reveals more clinically meaningful genomic alterations as compared to currently used diagnostic tests...
November 2017: Harefuah
https://www.readbyqxmd.com/read/29197740/gene-set-enrichment-analysis-and-expression-pattern-exploration-implicate-an-involvement-of-neurodevelopmental-processes-in-bipolar-disorder
#11
Thomas W Mühleisen, Céline S Reinbold, Andreas J Forstner, Lilia I Abramova, Martin Alda, Gulja Babadjanova, Michael Bauer, Paul Brennan, Alexander Chuchalin, Cristiana Cruceanu, Piotr M Czerski, Franziska Degenhardt, Sascha B Fischer, Janice M Fullerton, Scott D Gordon, Maria Grigoroiu-Serbanescu, Paul Grof, Joanna Hauser, Martin Hautzinger, Stefan Herms, Per Hoffmann, Jutta Kammerer-Ciernioch, Elza Khusnutdinova, Manolis Kogevinas, Valery Krasnov, André Lacour, Catherine Laprise, Markus Leber, Jolanta Lissowska, Susanne Lucae, Anna Maaser, Wolfgang Maier, Nicholas G Martin, Manuel Mattheisen, Fermin Mayoral, James D McKay, Sarah E Medland, Philip B Mitchell, Susanne Moebus, Grant W Montgomery, Bertram Müller-Myhsok, Lilijana Oruc, Galina Pantelejeva, Andrea Pfennig, Lejla Pojskic, Alexey Polonikov, Andreas Reif, Fabio Rivas, Guy A Rouleau, Lorena M Schenk, Peter R Schofield, Markus Schwarz, Fabian Streit, Jana Strohmaier, Neonila Szeszenia-Dabrowska, Alexander S Tiganov, Jens Treutlein, Gustavo Turecki, Helmut Vedder, Stephanie H Witt, Thomas G Schulze, Marcella Rietschel, Markus M Nöthen, Sven Cichon
BACKGROUND: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. METHODS: We conducted gene set enrichment analyses (GSEA) using 2...
November 14, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29195807/parallel-evaluation-of-circulating-tumor-dna-and-circulating-tumor-cells-in-metastatic-colorectal-cancer
#12
Giovanni Germano, Gianluca Mauri, Giulia Siravegna, Caroline Dive, Jackie Pierce, Federica Di Nicolantonio, Maurizio D'Incalci, Alberto Bardelli, Salvatore Siena, Andrea Sartore-Bianchi
BACKGROUND: Tissue biopsy is the gold standard for tumor genotyping, but it is an invasive procedure providing a single snapshot into tumor heterogeneity. Liquid biopsy approaches, encompassing the analysis of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs), have been proposed as an alternative, with the potential of providing a comprehensive portrait of the tumor molecular landscape. In metastatic colorectal cancer (mCRC), both CTCs and ctDNA analysis have been investigated, but comparative analyses are limited...
November 1, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29190909/genes-co-amplified-with-erbb2-or-met-as-novel-potential-cancer-promoting-genes-in-gastric-cancer
#13
Mi Jeong Kwon, Ryong Nam Kim, Kyoung Song, Sinyoung Jeon, Hae Min Jeong, Joo Seok Kim, Jinil Han, Sungyoul Hong, Ensel Oh, Jong-Sun Choi, Jungsuk An, Jonathan R Pollack, Yoon-La Choi, Cheol-Keun Park, Young Kee Shin
Gastric cancer (GC), one of the most common cancers worldwide, has a high mortality rate due to limited treatment options. Identifying novel and promising molecular targets is a major challenge that must be overcome if treatment of advanced GC is to be successful. Here, we used comparative genomic hybridization and gene expression microarrays to examine genome-wide DNA copy number alterations (CNAs) and global gene expression in 38 GC samples from old and young patients. We identified frequent CNAs, which included copy number gains on chromosomes 3q, 7p, 8q, 20p, and 20q and copy number losses on chromosomes 19p and 21p...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29190819/the-ectodomain-of-cadherin-11-binds-to-erbb2-and-stimulates-akt-phosphorylation-to-promote-cranial-neural-crest-cell-migration
#14
Ketan Mathavan, Vikram Khedgikar, Vanessa Bartolo, Dominique Alfandari
During development, a multi-potent group of cells known as the cranial neural crest (CNC) migrate to form craniofacial structures. Proper migration of these cells requires proteolysis of cell adhesion molecules, such as cadherins. In Xenopus laevis, preventing extracellular cleavage of cadherin-11 impairs CNC migration. However, overexpression of the soluble cleavage product (EC1-3) is capable of rescuing this phenotype. The mechanism by which EC1-3 promotes CNC migration has not been investigated until now...
2017: PloS One
https://www.readbyqxmd.com/read/29181633/amphiregulin-regulates-proliferation-and-migration-of-her2-positive-breast-cancer-cells
#15
Hannah Schmucker, Walker M Blanding, Julia M Mook, Jessica F Wade, Jang Pyo Park, Kerri Kwist, Hiral Shah, Brian W Booth
PURPOSE: Tumor initiation and progression rely on cellular proliferation and migration. Many factors are involved in these processes, including growth factors. Amphiregulin (AREG) is involved in normal mammary development and the development of estrogen receptor (ER)-positive breast cancer. The aim of this project was to determine if AREG is involved in the proliferation and progression of HER2-positive breast cancer. METHODS: Mouse cell lines MMTV-neu, HC-11 and COMMA-D, as well as human cell lines MCF10A, SKBR3, HCC1954 and BT474 were used...
November 27, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29181055/functions-of-the-ap-2%C3%AE-gene-in-activating-apoptosis-and-inhibiting-proliferation-of-gastric-cancer-cells-both-in-vitro-and-in-vivo
#16
Changqing Zeng, Zhimin Liu, Jian Zhang, Hongwei Fang, Cheng Fang, Yueming Wang, Sharvesh Raj Seeruttun, Jun Chen, Liangxiang Huang, Wei Wang
Introduction: This study was designed to investigate the potential function of the activating protein 2α (AP-2α) gene in controlling the proliferation and apoptosis of gastric cancer. Material and methods: Gastric cancer cell line MCG-803 cells and normal cell line GES-1 cells were selected to transfect pcDNA3.1(+)-AP-2α and pcDNA3.1(+) plasmids, respectively. Both mRNA and protein levels of AP-2α in each group transfected with the pcDNA3.1(+)-AP-2α plasmids were up-regulated after 48 h by real-time PCR and Western blotting analysis, leading to marked proliferation inhibition and significant cell cycle arrest...
October 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29180605/cell-free-dna-and-circulating-tumor-cells-comprehensive-liquid-biopsy-analysis-in-advanced-breast-cancer
#17
Giovanna Rossi, Zhaomei Mu, Alfred Rademaker, Laura Austin, Kimberly S Strickland, Ricardo Lima Barros Costa, Rebecca Nagy, Vittorina Zagonel, Timothy J Taxter, Amir Behdad, Firas H Wehbe, Leonidas C Platanias, William Gradishar, Massimo Cristofanilli
PURPOSE: Liquid biopsy provides a real-time assessment of metastatic breast cancer (MBC). We evaluated the utility of combining circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) to predict prognosis in MBC. EXPERIMENTAL DESIGN: We conducted a retrospective study of 91 patients with locally advanced and MBC. CTCs were enumerated by CellSearch; the plasma-based assay was performed utilizing Guardant360TM and the survival analysis using Kaplan-Meier curves...
November 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29172833/a-systematic-review-of-targeted-agents-for-non-small-cell-lung-cancer
#18
Hannah H Vestergaard, Marcus R Christensen, Ulrik N Lassen
BACKGROUND: advanced-stage non-small cell lung cancer (NSCLC) is characterized by having limited treatment options and thus a poor prognosis. However, new treatment options, in the form of targeted agents (TA), have emerged during recent years. This systematic review aims to provide an overview of the accessible literature in PubMed evaluating TA used on NSCLC patients, and the resulting survival outcomes. METHOD: this systematic literature review was conducted by reviewing all relevant literature in PubMed...
November 25, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29169184/her2-expression-patterns-in-paired-primary-and-metastatic-endometrial-cancer-lesions
#19
Mari Kyllesø Halle, Ingvild Løberg Tangen, Hege Fredriksen Berg, Erling Andre Hoivik, Karen K Mauland, Kanthida Kusonmano, Anna Berg, Antoni Hurtado, Karl Henning Kalland, Anne M Øyan, Ingunn Stefansson, Olav K Vintermyr, Henrica M Werner, Ingfrid S Haldorsen, Jone Trovik, Helga B Salvesen, Camilla Krakstad
BACKGROUND: Despite successful implementation of drugs targeting the human epidermal growth factor receptor 2 (HER2) receptor in breast and gastric cancers, the potential of HER2 as a therapeutic target in other cancers has been less studied, including endometrial cancer. We investigated expression levels of HER2 (ERBB2) in a large cohort of endometrial cancer lesions, also including complex atypical hyperplasia and metastatic lesions. METHODS: 67 precursor lesions, 790 primary endometrial cancers and 383 metastatic lesions were investigated for HER2 expression in relation to clinicopathologic features and outcome...
November 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29163776/mir-1268b-confers-chemosensitivity-in-breast-cancer-by-targeting-erbb2-mediated-pi3k-akt-pathway
#20
Wen-Jie Zhu, Xu Chen, Ya-Wen Wang, Hai-Ting Liu, Ran-Ran Ma, Peng Gao
Chemoresistance represents a major obstacle to effective therapy for breast cancer. Emerging evidences associated aberrantly expressed miRNAs with tumor development and chemoresistance. MiR-1268b has never been studied in any cancers before, and its roles in mediating tumor progression and drug resistance are still unclear. Selected from miRNA microarray and confirmed by real-time quantitative PCR (RT-qPCR), miR-1268b was found to be significantly upregulated in drug sensitive and ERBB2 negative tissues, as well as in breast cancer patients with low clinical stage...
October 27, 2017: Oncotarget
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