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Nicola Maurea, Carmela Coppola, Giovanna Piscopo, Francesca Galletta, Gennaro Riccio, Emanuela Esposito, Claudia De Lorenzo, Michelino De Laurentiis, Paolo Spallarossa, Giuseppe Mercuro
The progress in cancer therapy and the increase in number of long-term survivors reveal the issue of cardiovascular side-effects of anticancer drugs. Cardiotoxicity has become a significant problem, and the risks of adverse cardiac events induced by systemic drugs need to be seriously considered. Potential cardiovascular toxicities linked to anticancer agents include arrhythmias, myocardial ischemia and infarction, hypertension, thromboembolism, left ventricular dysfunction, and heart failure. It has been shown that several anticancer drugs seriously affect the cardiovascular system, such as ErbB2 inhibitors, vascular endothelial growth factor (VEGF) inhibitors, multitargeted kinase inhibitors, Abelson murine leukemia viral oncogene homolog inhibitors, and others...
May 2016: Journal of Cardiovascular Medicine
María S Brea, Romina G Díaz, Daiana S Escudero, Claudia I Caldiz, Enrique L Portiansky, Patricio E Morgan, Néstor G Pérez
BACKGROUND: Myocardial stretch increases force biphasically: the Frank-Starling mechanism followed by the slow force response (SFR). Based on pharmacological strategies, we proposed that epidermal growth factor (EGF) receptor (EGFR or ErbB1) activation is crucial for SFR development. Pharmacological inhibitors could block ErbB4, a member of the ErbB family present in the adult heart. We aimed to specifically test the role of EGFR activation after stretch, with an interference RNA incorporated into a lentiviral vector (small hairpin RNA [shRNA]-EGFR)...
October 15, 2016: Journal of the American Heart Association
Michelangelo Fiorentino, Elisa Gruppioni, Francesco Massari, Francesca Giunchi, Annalisa Altimari, Chiara Ciccarese, Davide Bimbatti, Aldo Scarpa, Roberto Iacovelli, Camillo Porta, Sarhadi Virinder, Giampaolo Tortora, Walter Artibani, Riccardo Schiavina, Andrea Ardizzoni, Matteo Brunelli, Sakari Knuutila, Guido Martignoni
Renal cell cancer (RCC) is characterized by histological and molecular heterogeneity that may account for variable response to targeted therapies. We evaluated retrospectively with a next generation sequencing (NGS) approach using a pre-designed cancer panel the mutation burden of 32 lesions from 22 metastatic RCC patients treated with at least one tyrosine kinase or mTOR inhibitor. We identified mutations in the VHL, PTEN, JAK3, MET, ERBB4, APC, CDKN2A, FGFR3, EGFR, RB1, TP53 genes. Somatic alterations were correlated with response to therapy...
October 10, 2016: Oncotarget
Felipe C Geyer, Samuel H Berman, Caterina Marchiò, Kathleen A Burke, Elena Guerini-Rocco, Salvatore Piscuoglio, Charlotte Ky Ng, Fresia Pareja, Hannah Y Wen, Zoltan Hodi, Stuart J Schnitt, Emad A Rakha, Ian O Ellis, Larry Norton, Britta Weigelt, Jorge S Reis-Filho
Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype, and may give rise to and display somatic genomic alterations typical of high-grade triple-negative breast cancers. Here we report on a comparison of previously published data on eight carcinoma-associated microglandular adenosis and eight acinic cell carcinomas subjected to targeted massively parallel sequencing targeting all exons of 236 genes recurrently mutated in breast cancer and/or DNA repair-related...
October 7, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Yu Gu, Trinh Tran, Sachiko Murase, Andrew Borrell, Alfredo Kirkwood, Elizabeth M Quinlan
: Maturation of excitatory drive onto fast-spiking interneurons (FS INs) in the visual cortex has been implicated in the control of the timing of the critical period for ocular dominance plasticity. However, the mechanisms that regulate the strength of these synapses over cortical development are not understood. Here we use a mouse model to show that neuregulin (NRG) and the receptor tyrosine kinase erbB4 regulate the timing of the critical period. NRG1 enhanced the strength of excitatory synapses onto FS INs, which inhibited ocular dominance plasticity during the critical period but rescued plasticity in transgenics with hypoexcitable FS INs...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Nasrin Majidi Gharenaz, Mansoureh Movahedin, Zohreh Mazaheri, Shahram Pour Beiranvand
BACKGROUND: Nowadays, oocytes and embryos vitrification has become a routine technique. Based on clinical judgment, re-vitrification maybe required. But little is known about re-vitrification impact on genes expression. OBJECTIVE: The impact of re-vitrification on apoptotic and implanting genes, Bax, Bcl-2 and ErbB4, at compaction stage embryos were evaluated in this study. MATERIALS AND METHODS: In this experimental study, 8 cell embryos (n=240) were collected from female mature mice, 60-62 hr post HCG injection...
August 2016: International Journal of Reproductive Biomedicine (Yazd, Iran)
Eun Gene Sun, Kyung Hwa Lee, Yoo-Seung Ko, Hui Jeong Choi, Jung-In Yang, Jae Hyuk Lee, Ik Joo Chung, Yun-Woong Paek, Hangun Kim, Jeong A Bae, Kyung Keun Kim
Understanding the complex biological functions of E3-ubiquitin ligases may facilitate the development of mechanism-based anti-cancer drugs. We recently identified that the KITENIN/ErbB4-Dvl2-c-Jun axis works as a novel unconventional downstream signal of epidermal growth factor (EGF) in colorectal cancer (CRC) tissues. Here we addressed whether E3-ubiquitin ligases are required for operation of this axis. We found that Nrdp1, an E3-ligase for ErbB3/ErbB4, interacted with KITENIN (KAI1 C-terminal interacting tetraspanin) to form a functional KITENIN/ErbB4/Nrdp1 complex and is responsible for down-regulating Dvl2 within this complex...
September 20, 2016: Molecular Carcinogenesis
Yanjun Sun, Taruna Ikrar, Melissa F Davis, Nian Gong, Xiaoting Zheng, Z David Luo, Cary Lai, Lin Mei, Todd C Holmes, Sunil P Gandhi, Xiangmin Xu
Experience alters cortical networks through neural plasticity mechanisms. During a developmental critical period, the most dramatic consequence of occluding vision through one eye (monocular deprivation) is a rapid loss of excitatory synaptic inputs to parvalbumin-expressing (PV) inhibitory neurons in visual cortex. Subsequent cortical disinhibition by reduced PV cell activity allows for excitatory ocular dominance plasticity. However, the molecular mechanisms underlying critical period synaptic plasticity are unclear...
October 5, 2016: Neuron
S J Lubbe, V Escott-Price, A Brice, T Gasser, A M Pittman, J Bras, J Hardy, P Heutink, N M Wood, A B Singleton, D G Grosset, C B Carroll, M H Law, F Demenais, M M Iles, D T Bishop, J Newton-Bishop, N M Williams, H R Morris
A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort...
July 28, 2016: Neurobiology of Aging
Ben Yue, Donglan Cai, Chenchen Liu, Changyi Fang, Dongwang Yan
Long noncoding RNAs act as crucial regulators in plenty of human cancers, yet their potential roles and molecular mechanisms in chemoresistance are poorly understood. This study showed that a novel lncRNA, long intergenic noncoding RNA 152 (Linc00152 ), promoted tumor progression and conferred resistance to oxaliplatin (L-OHP)-induced apoptosis in vitro and in vivo. It antagonized chemosensitivity through acting as a competing endogenous RNA to modulate the expression of miR-193a-3p, and then erb-b2 receptor tyrosine kinase 4 (ERBB4)...
October 18, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Benjamin M Schwenk, Hannelore Hartmann, Alperen Serdaroglu, Martin H Schludi, Daniel Hornburg, Felix Meissner, Denise Orozco, Alessio Colombo, Sabina Tahirovic, Meike Michaelsen, Franziska Schreiber, Simone Haupt, Michael Peitz, Oliver Brüstle, Clemens Küpper, Thomas Klopstock, Markus Otto, Albert C Ludolph, Thomas Arzberger, Peer-Hendrik Kuhn, Dieter Edbauer
Nuclear clearance of TDP-43 into cytoplasmic aggregates is a key driver of neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), but the mechanisms are unclear. Here, we show that TDP-43 knockdown specifically reduces the number and motility of RAB11-positive recycling endosomes in dendrites, while TDP-43 overexpression has the opposite effect. This is associated with delayed transferrin recycling in TDP-43-knockdown neurons and decreased β2-transferrin levels in patient CSF Whole proteome quantification identified the upregulation of the ESCRT component VPS4B upon TDP-43 knockdown in neurons...
September 12, 2016: EMBO Journal
Colm M P O'Tuathaigh, Fabio Fumagalli, Lieve Desbonnet, Francesc Perez-Branguli, Gerard Moloney, Samim Loftus, Claire O'Leary, Emilie Petit, Rachel Cox, Orna Tighe, Gerard Clarke, Donna Lai, Richard P Harvey, John F Cryan, Kevin J Mitchell, Timothy G Dinan, Marco A Riva, John L Waddington
Few studies have addressed likely gene × gene (ie, epistatic) interactions in mediating risk for schizophrenia. Using a preclinical genetic approach, we investigated whether simultaneous disruption of the risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) would produce a disease-relevant phenotypic profile different from that observed following disruption to either gene alone. NRG1 heterozygotes exhibited hyperactivity and disruption to prepulse inhibition, both reversed by antipsychotic treatment, and accompanied by reduced striatal dopamine D2 receptor protein expression, impaired social cognition, and altered glutamatergic synaptic protein expression in selected brain areas...
September 9, 2016: Schizophrenia Bulletin
Andrea Mafficini, Eliana Amato, Ivana Cataldo, Borislav C Rusev, Luca Bertoncello, Vincenzo Corbo, Michele Simbolo, Claudio Luchini, Matteo Fassan, Cinzia Cantù, Roberto Salvia, Giovanni Marchegiani, Giampaolo Tortora, Rita T Lawlor, Claudio Bassi, Aldo Scarpa
OBJECTIVE: To identify molecular prognostic factors and potentially actionable mutations in ampulla of Vater cancer (AVC). BACKGROUND: The largely variable outcomes of AVCs make clinical decisions difficult regarding the need of postsurgical therapy, which is based on morphological and immunohistochemical classification that do not adequately consider the varying degrees of heterogeneity present in many AVCs. No approved targeted therapies for AVC exist, but some show promising results requiring better molecular characterization to identify potential responders...
September 8, 2016: Annals of Surgery
Melanie Kripp, Kirsten Merx, Ralph Markus Wirtz, Timo Gaiser, Sebastian Eidt, Juliana Schwaab, Stefan Post, Frederik Wenz, Andreas Hochhaus, Ralf-Dieter Hofheinz, Philipp Erben
Background. No predictive or prognostic biomarker is available for patients with locally advanced rectal cancer (LARC) undergoing perioperative chemoradiotherapy (CRT). Members of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases EGFR (HER1, ERBB1), HER2 (ERBB2), HER3 (ERBB3), and HER4 (ERBB4) are therapeutic targets in several cancers. The analysis was performed to assess expression levels and study the potential prognostic impact for disease-free and overall survival in patients with LARC...
2016: Gastroenterology Research and Practice
M Hashemi, N Moradi, M Rezaei, S Sanaei, S A M Ziaee, B Narouie, M Sotoudeh, G Bahari, S Ghavami
Genetic polymorphisms in ERBB4 are thought to be associated with cancer susceptibility. In the present study, we aimed to assess the impact of ERBB4 rs12052398 T>C, rs13393577 A>G, rs13424871 A>T, rs16847082 A>G and rs6147150 (12-bp I/D) polymorphisms on risk of prostate cancer (PCa) in a sample of Iranian population. In a case-control study, we enrolled 169 patients with pathologically confirmed PCa and 182 subjects with benign prostatic hyperplasia (BPH). No significant association was found among ERBB4 polymorphisms and risk of PCa...
2016: Cellular and Molecular Biology
Sean P Kennedy, Jordan F Hastings, Jeremy Z R Han, David R Croucher
Each member of the epidermal growth factor receptor (EGFR) family plays a key role in normal development, homeostasis, and a variety of pathophysiological conditions, most notably in cancer. According to the prevailing dogma, these four receptor tyrosine kinases (RTKs; EGFR, ERBB2, ERBB3, and ERBB4) function exclusively through the formation of homodimers and heterodimers within the EGFR family. These combinatorial receptor interactions are known to generate increased interactome diversity and therefore influence signaling output, subcellular localization and function of the heterodimer...
2016: Frontiers in Cell and Developmental Biology
Mayank Jauhri, Akanksha Bhatnagar, Satish Gupta, Yogender Shokeen, Sachin Minhas, Shyam Aggarwal
Mutation frequencies of common genetic alterations in colorectal cancer have been in the spotlight for many years. This study highlights few rare somatic mutations, which possess the attributes of a potential CRC biomarker yet are often neglected. Next-generation sequencing was performed over 112 tumor samples to detect genetic alterations in 31 rare genes in colorectal cancer. Mutations were detected in 26/31 (83.9 %) uncommon genes, which together contributed toward 149 gene mutations in 67/112 (59.8 %) colorectal cancer patients...
October 2016: Medical Oncology
Jessica Edenfield, Christine Schammel, Justin Collins, David Schammel, W Jeff Edenfield
INTRODUCTION: Metaplastic breast carcinoma (MBC) is a rare and aggressive histologic subtype of breast cancer comprising approximately 0.5% to 5.0% of all invasive breast cancers with a poor prognosis and limited therapeutic options. PATIENTS AND METHODS: We investigated MBC at our institution to evaluate outcomes and investigate the molecular profile of our cohort to determine the presence of mutations for which there are targeted therapies. RESULTS: We found our cohort to consist mainly of the matrix-producing variant (72%) with 48% having the stereotypical estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor-2-negative phenotype...
July 25, 2016: Clinical Breast Cancer
Ilianna Zoi, Michalis V Karamouzis, Christos Adamopoulos, Athanasios G Papavassiliou
ErbB family members, ErbB1/EGFR/HER-1, ErbB2/HER-2, ErbB3/HER-3 and ErbB4/HER-4, have been implicated in breast cancer (BC) tumorigenicity. Recently, crucial roles for RANK/RANKL signaling in addition to key downstream factor NF-κB have been demonstrated in mammary tumorigenesis. Here, we present the hypothesis of a novel association between ErbB and RANK pathways in promoting BC. The proposed model alludes to the cross-talk that might occur between RANK and ErbB receptors. This interplay might regulate RANK signaling and consequently, modulate carcinogenesis, mainly in ErbB2 over-expressing BC cells...
October 2016: Trends in Molecular Medicine
Satu Mäki-Nevala, Virinder Kaur Sarhadi, Mikko Rönty, Eeva Kettunen, Kirsti Husgafvel-Pursiainen, Henrik Wolff, Aija Knuuttila, Sakari Knuutila
OBJECTIVES: Non-small cell lung cancer (NSCLC) is a common cancer with a poor prognosis. The aim of this study was to screen Finnish NSCLC tumor samples for common cancer-related mutations by targeted next generation sequencing and to determine their concurrences and associations with clinical features. MATERIALS AND METHODS: Sequencing libraries were prepared from DNA isolated from formalin-fixed, paraffin-embedded tumor material of 425 patients using the AmpliSeq Colon and Lung panel covering mutational hot spot regions of 22 cancer genes...
September 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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