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https://www.readbyqxmd.com/read/28096336/%C3%AE-catenin-haploinsufficiency-promotes-mammary-tumorigenesis-in-an-erbb2-positive-basal-breast-cancer-model
#1
Bui Tung, Babette Schade, Robert D Cardiff, Olulanu H Aina, Virginie Sanguin-Gendreau, William J Muller
Aberrant activation of β-catenin through its activity as a transcription factor has been observed in a large proportion of human malignancies. Despite the improved understanding of the β-catenin signaling pathway over the past three decades, attempts to develop therapies targeting β-catenin remain challenging, and none of these targeted therapies have advanced to the clinic. In this study, we show that part of the challenge in antagonizing β-catenin is caused by its dual functionality as a cell adhesion molecule and a signaling molecule...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28088512/ros1-fusions-rarely-overlap-with-other-oncogenic-drivers-in-non-small-cell-lung-cancer
#2
Jessica J Lin, Lauren L Ritterhouse, Siraj M Ali, Mark Bailey, Alexa B Schrock, Justin F Gainor, Lorin A Ferris, Mari Mino-Kenudson, Vincent A Miller, Anthony J Iafrate, Jochen K Lennerz, Alice T Shaw
INTRODUCTION: Chromosomal rearrangements involving the ROS proto-oncogene 1 receptor tyrosine kinase gene (ROS1) define a distinct molecular subset of non-small cell lung cancer (NSCLC) with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in epidermal growth factor receptor (EGFR) and KRAS proto-oncogene (KRAS). METHODS: We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma kinase (ALK)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088409/genome-wide-association-analysis-and-pathways-enrichment-for-lactation-persistency-in-canadian-holstein-cattle
#3
D N Do, N Bissonnette, P Lacasse, F Miglior, M Sargolzaei, X Zhao, E M Ibeagha-Awemu
Lactation persistency (LP), defined as the rate of declining milk yield after milk peak, is an economically important trait for dairy cattle. Improving LP is considered a good alternative method for increasing overall milk production because it does not cause the negative energy balance and other health issues that cows experience during peak milk production. However, little is known about the biology of LP. A genome-wide association study (GWAS) and pathway enrichment were used to explore the genetic mechanisms underlying LP...
January 11, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28077399/her2-testing-and-clinical-decision-making-in-gastroesophageal-adenocarcinoma-guideline-from-the-college-of-american-pathologists-american-society-for-clinical-pathology-and-american-society-of-clinical-oncology
#4
REVIEW
Angela N Bartley, Mary Kay Washington, Christina B Ventura, Nofisat Ismaila, Carol Colasacco, Al B Benson, Alfredo Carrato, Margaret L Gulley, Dhanpat Jain, Sanjay Kakar, Helen J Mackay, Catherine Streutker, Laura Tang, Megan Troxell, Jaffer A Ajani
CONTEXT: ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA. OBJECTIVES: To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making...
December 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28067668/adaptor-proteins-numb-and-numbl-promote-cell-cycle-withdrawal-by-targeting-erbb2-for-degradation
#5
Maretoshi Hirai, Yoh Arita, C Jane McGlade, Kuo-Fen Lee, Ju Chen, Sylvia M Evans
Failure of trabecular myocytes to undergo appropriate cell cycle withdrawal leads to ventricular noncompaction and heart failure. Signaling of growth factor receptor ERBB2 is critical for myocyte proliferation and trabeculation. However, the mechanisms underlying appropriate downregulation of trabecular ERBB2 signaling are little understood. Here, we have found that the endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae. Loss of NUMB and NUMBL resulted in a partial block of late endosome formation, resulting in sustained ERBB2 signaling and STAT5 activation...
January 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28065942/neuregulin-1-erbb-module-in-c-bouton-synapses-on-somatic-motor-neurons-molecular-compartmentation-and-response-to-peripheral-nerve-injury
#6
Anna Casanovas, Sara Salvany, Víctor Lahoz, Olga Tarabal, Lídia Piedrafita, Raimundo Sabater, Sara Hernández, Jordi Calderó, Josep E Esquerda
The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display an endoplasmic reticulum-related subsurface cistern (SSC) adjacent to the postsynaptic membrane. Besides cholinergic molecules, a constellation of proteins involved in different signal-transduction pathways are clustered at C-type synaptic sites (M2 muscarinic receptors, Kv2.1 potassium channels, Ca(2+) activated K(+) [SK] channels, and sigma-1 receptors [S1R]), but their collective functional significance so far remains unknown...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28060735/the-natural-compound-fucoidan-from-new-zealand-undaria-pinnatifida-synergizes-with-the-erbb-inhibitor-lapatinib-enhancing-melanoma-growth-inhibition
#7
Varsha Thakur, Jun Lu, Giuseppe Roscilli, Luigi Aurisicchio, Manuela Cappelletti, Emiliano Pavoni, William Lindsey White, Barbara Bedogni
Melanoma remains one of the most aggressive and therapy-resistant cancers. Finding new treatments to improve patient outcomes is an ongoing effort. We previously demonstrated that melanoma relies on the activation of ERBB signaling, specifically of the ERBB3/ERBB2 cascade. Here we show that melanoma tumor growth is inhibited by 60% over controls when treated with lapatinib, a clinically approved inhibitor of ERBB2/EGFR. Importantly, tumor growth is further inhibited to 85% when the natural compound fucoidan from New Zealand U...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28057171/predicting-high-impact-pharmacological-targets-by-integrating-transcriptome-and-text-mining-features
#8
Anatoly Mayburd, Ancha Baranova
PURPOSE: Novel, "outside of the box" approaches are needed for evaluating candidate molecules, especially in oncology. Throughout the years of 2000-2010, the efficiency of drug development fell to barely acceptable levels, and in the second decade of this century, levels have improved only marginally. This dismal condition continues despite unprecedented progress in the development of a variety of high-throughput tools, computational methods, aggregated databases, drug repurposing programs and innovative chemistries...
October 2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28052061/integrated-genomic-characterization-of-oesophageal-carcinoma
#9
(no author information available yet)
Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas...
January 4, 2017: Nature
https://www.readbyqxmd.com/read/28052030/the-angiotensin-ii-type-1-receptor-antagonist-telmisartan-inhibits-cell-proliferation-and-tumor-growth-of-esophageal-adenocarcinoma-via-the-ampk%C3%AE-mtor-pathway-in-vitro-and-in-vivo
#10
Shintaro Fujihara, Asahiro Morishita, Kana Ogawa, Tomoko Tadokoro, Taiga Chiyo, Kiyohito Kato, Hideki Kobara, Hirohito Mori, Hisakazu Iwama, Tsutomu Masaki
Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB). This drug inhibits cancer cell proliferation, but the underlying mechanisms in various cancers, including esophageal cancer, remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human esophageal cancer cell proliferation in vitro and in vivo. We assessed the effects of telmisartan on human esophageal adenocarcinoma (EAC) cells using the cell lines OE19, OE33, and SKGT-4...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28050146/personalized-oncogenomics-in-the-management-of-gastrointestinal-carcinomas-early-experiences-from-a-pilot-study
#11
B S Sheffield, B Tessier-Cloutier, H Li-Chang, Y Shen, E Pleasance, K Kasaian, Y Li, S J M Jones, H J Lim, D J Renouf, D G Huntsman, S Yip, J Laskin, M Marra, D F Schaeffer
BACKGROUND: Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. METHODS: We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma...
December 2016: Current Oncology
https://www.readbyqxmd.com/read/28049018/transactivation-of-the-epidermal-growth-factor-receptor-in-responses-to-myocardial-stress-and-cardioprotection
#12
REVIEW
Melissa E Reichelt, Shannon O'Brien, Walter G Thomas, John P Headrick
The epidermal growth factor receptor (EGFR) family comprises the ErbB1 (EGFR) and ErbB4 receptors as well as the 'co-receptors' ErbB2 (which does not bind EGF ligands) and ErbB3 (which lack tyrosine kinase activity). This family of receptors is essential for cardiac development, myocardial, renal and vascular function, and cardiac responses to physiological and pathological perturbations. The EGFR appears critical in protecting cardiac cells from injury, while considerable attention has focussed on neuregulin/ErbB4 signalling in potentially ameliorating cardiomyopathy/heart failure...
December 31, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28039535/use-of-droplet-digital-pcr-for-quantitative-and-automatic-analysis-of-the-her2-status-in-breast-cancer-patients
#13
Kazutaka Otsuji, Takeshi Sasaki, Atsushi Tanaka, Akiko Kunita, Masako Ikemura, Keisuke Matsusaka, Keiichiro Tada, Masashi Fukayama, Yasuyuki Seto
PURPOSE: Digital polymerase chain reaction (dPCR) has been used to yield an absolute measure of nucleic acid concentrations. Recently, a new method referred to as droplet digital PCR (ddPCR) has gained attention as a more precise and less subjective assay to quantify DNA amplification. We demonstrated the usefulness of ddPCR to determine HER2 gene amplification of breast cancer. METHODS: In this study, we used ddPCR to measure the HER2 gene copy number in clinical formalin-fixed paraffin-embedded samples of 41 primary breast cancer patients...
December 30, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28035320/clinical-significance-of-early-changes-in%C3%A2-circulating-tumor-cells-from-patients-receiving-first-line-cisplatin-based-chemotherapy-for-metastatic-urothelial-carcinoma
#14
Emanuela Fina, Andrea Necchi, Patrizia Giannatempo, Maurizio Colecchia, Daniele Raggi, Maria Grazia Daidone, Vera Cappelletti
Background: The therapeutic paradigm of metastatic urothelial carcinoma (UC) is rapidly shifting and new biomarkers are needed to enhance patient selection. Objective: Early identification of dynamic predictors of outcome may be a key to optimize the sequence of effective therapies in metastatic UC patients. Methods: Blood samples from patients receiving first-line MVAC chemotherapy were collected at baseline (T0) and after 2 cycles (T2). Samples were processed by immunomagnetic beads (AdnaTest ProstateCancerSelect kit) and the expression of EPCAM, MUC1 and ERBB2 was studied using multiplex-PCR...
October 27, 2016: Bladder Cancer
https://www.readbyqxmd.com/read/28034454/comprehensive-genomic-sequencing-and-the-molecular-profiles-of-clinically-advanced-breast-cancer
#15
Jeffrey S Ross, Laurie M Gay
Targeting specific mutations that have arisen within a tumour is a promising means of increasing the efficacy of treatments, and breast cancer is no exception to this new paradigm of personalised medicine. Traditional DNA sequencing methods used to characterise clinical cancer specimens and impact treatment decisions are highly sensitive, but are often limited in their scope to known mutational hot spots. Next-generation sequencing (NGS) technologies can also test for these well-known hot spots, as well as identifying insertions and deletions, copy number changes such as ERBB2 (HER2) gene amplification, and a wide array of fusion or rearrangement events...
December 26, 2016: Pathology
https://www.readbyqxmd.com/read/28031413/let-7-status-is-crucial-for-parp1-expression-in-her2-overexpressing-breast-tumors
#16
Monica E Wielgos, Rajani Rajbhandari, Tiffiny S Cooper, Shi Wei, Susan E Nozell, Eddy S Yang
: HER2+ breast tumors have been shown to express elevated levels of poly (ADPribose) polymerase 1 (PARP1) protein. Yet, the mechanism by which PARP1 is upregulated in HER2+ breast cancer is unknown. Here, knockdown of HER2 (ERBB2) in HER2+ breast cancer cells resulted in a reduction in PARP1 protein. Conversely, ectopic overexpression of HER2 in a non-HER2 overexpressing cell line resulted in increased PARP1 protein. Alterations in HER2 expression had no significant effect on PARP1 transcript levels...
December 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28027945/next-generation-assessment-of-erbb2-human%C3%A2-epidermal-growth-factor-receptor-2-amplification-status-clinical-validation-in-the-context-of-a-hybrid-capture-based-comprehensive-solid-tumor-genomic-profiling-assay
#17
Dara S Ross, Ahmet Zehir, Donavan T Cheng, Ryma Benayed, Khedoudja Nafa, Jaclyn F Hechtman, Yelena Y Janjigian, Britta Weigelt, Pedram Razavi, David M Hyman, José Baselga, Michael F Berger, Marc Ladanyi, Maria E Arcila
Establishing ERBB2 [human epidermal growth factor receptor 2 (HER2)] amplification status in breast and gastric carcinomas is essential to patients' treatment plans. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) constitute the current standard for assessment. With further advancements in genomic medicine, new clinically relevant biomarkers are rapidly emerging and options for targeted therapy are increasing in patients with advanced disease, driving the need for comprehensive molecular profiling...
December 24, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28027822/semaphorin-4d-enhances-angiogenic-potential-and-suppresses-osteo-odontogenic-differentiation-of-human-dental-pulp-stem-cells
#18
Ting Zou, Waruna Lakmal Dissanayaka, Shan Jiang, Shuai Wang, Boon Chin Heng, Xiaojing Huang, Chengfei Zhang
INTRODUCTION: To investigate the roles of semaphorin 4D (Sema4D)/plexin-B1 signaling on the angiogenic potential and osteo-/odontogenic differentiation of human dental pulp stem cells (DPSCs) and to uncover the corresponding molecular mechanisms. METHODS: DPSCs were treated with Sema4D (10 μg/mL) for different time durations. Osteo-/odontogenic differentiation was assessed by quantifying alkaline phosphatase activity, mineralized nodule formation, and osteo-/odontogenic gene (ALP, Col1A1, BSP, RUNX2, and DSPP) and protein (Col1A1 and DSPP) expression...
December 24, 2016: Journal of Endodontics
https://www.readbyqxmd.com/read/28007036/genomic-landscape-of-colorectal-cancer-in-japan-clinical-implications-of-comprehensive-genomic-sequencing-for-precision-medicine
#19
Masayuki Nagahashi, Toshifumi Wakai, Yoshifumi Shimada, Hiroshi Ichikawa, Hitoshi Kameyama, Takashi Kobayashi, Jun Sakata, Ryoma Yagi, Nobuaki Sato, Yuko Kitagawa, Hiroyuki Uetake, Kazuhiro Yoshida, Eiji Oki, Shin-Ei Kudo, Hiroshi Izutsu, Keisuke Kodama, Mitsutaka Nakada, Julie Tse, Meaghan Russell, Joerg Heyer, Winslow Powers, Ruobai Sun, Jennifer E Ring, Kazuaki Takabe, Alexei Protopopov, Yiwei Ling, Shujiro Okuda, Stephen Lyle
BACKGROUND: Comprehensive genomic sequencing (CGS) has the potential to revolutionize precision medicine for cancer patients across the globe. However, to date large-scale genomic sequencing of cancer patients has been limited to Western populations. In order to understand possible ethnic and geographic differences and to explore the broader application of CGS to other populations, we sequenced a panel of 415 important cancer genes to characterize clinically actionable genomic driver events in 201 Japanese patients with colorectal cancer (CRC)...
December 22, 2016: Genome Medicine
https://www.readbyqxmd.com/read/28006840/copy-number-variations-in-dcc-18q-and-erbb2-17q-are-associated-with-disease-free-survival-in-microsatellite-stable-colon-cancer
#20
David Sefrioui, Thomas Vermeulin, France Blanchard, Caroline Chapusot, Ludivine Beaussire, Laura Armengol-Debeir, Richard Sesboué, Alice Gangloff, Mohamed Hebbar, Marie-Christine Copin, Estelle Houivet, Lilian Schwarz, Florian Clatot, Jean-Jacques Tuech, Jacques Bénichou, Laurent Martin, Anne-Marie Bouvier, Jean-Christophe Sabourin, Nasrin Sarafan-Vasseur, Thierry Frébourg, Côme Lepage, Pierre Michel, Frédéric Di Fiore
We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q, and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS)...
December 22, 2016: International Journal of Cancer. Journal International du Cancer
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