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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
Tiantian Zhang, Yogesh R Suryawanshi, Dennis H Kordish, Helene M Woyczesczyk, David Jeng, Karim Essani
Neuregulin (NRG), an epidermal growth factor is known to promote the growth of various cell types, including human melanoma cells through ErbB family of tyrosine kinases receptors. Tanapoxvirus (TPV)-encoded protein TPV-15L, a functional mimic of NRG, also acts through ErbB receptors. Here, we show that the TPV-15L protein promotes melanoma proliferation. TPV recombinant generated by deleting the 15L gene (TPVΔ15L) showed replication ability similar to that of wild-type TPV (wtTPV) in owl monkey kidney cells, human lung fibroblast (WI-38) cells, and human melanoma (SK-MEL-3) cells...
October 13, 2016: Virus Genes
Mincione Gabriella, Di Marcantonio Maria Carmela, Tarantelli Chiara, Savino Luca, Ponti Donatella, Marchisio Marco, Lanuti Paola, Sancilio Silvia, Calogero Antonella, Di Pietro Roberta, Muraro Raffaella
Epidermal Growth Factor Receptor (EGFR), a member of the ErbB family of receptor tyrosine kinase (RTK) proteins, is aberrantly expressed or deregulated in tumors and plays pivotal roles in cancer onset and metastatic progression. ZNF216 gene has been identified as one of Immediate Early Genes (IEGs) induced by RTKs. Overexpression of ZNF216 protein sensitizes 293 cell line to TNF-α induced apoptosis. However, ZNF216 overexpression has been reported in medulloblastomas and metastatic nasopharyngeal carcinomas...
October 6, 2016: Oncotarget
E Vandendriessche, G Van De Putte, R Van Den Broecke, Etm De Jonge
AIM: Intra and inter tumour heterogeneity is a known feature in cancer because tumour cells undergo changes at genetic and epigenetic level as they spread from their primary tumour site. Adjuvant treatment protocols in breast cancer are currently based on the biological characteristics of the primary tumour, which in most cases has been removed surgically. Considering tumour heterogeneity in metastases we examined the present status of knowledge regarding measurable differences in tumour profiling between the primary breast tumour and its synchronous axillary lymph node metastases (ALNM) and if so whether adjuvant therapy directed towards the tumour characteristics of the ALNM instead of those of the primary tumour is more effective...
December 28, 2015: Facts, Views & Vision in ObGyn
Anna E Kersh, Maiko Sasaki, Lee A Cooper, Haydn T Kissick, Brian P Pollack
Advances in molecular pathology have changed the landscape of oncology. The ability to interrogate tissue samples for oncogene amplification, driver mutations, and other molecular alterations provides clinicians with an enormous level of detail about their patient's cancer. In some cases, this information informs treatment decisions, especially those related to targeted anti-cancer therapies. However, in terms of immune-based therapies, it is less clear how to use such information. Likewise, despite studies demonstrating the pivotal role of neoantigens in predicting responsiveness to immune checkpoint blockade, it is not known if the expression of neoantigens impacts the response to targeted therapies despite a growing recognition of their diverse effects on immunity...
2016: Frontiers in Pharmacology
Xin Yin, Su-Su Zheng, Lan Zhang, Xiao-Ying Xie, Yan Wang, Bo-Heng Zhang, Weizhong Wu, Shuangjian Qiu, Zheng-Gang Ren
Hepatocellular carcinoma (HCC) is the most prevalent and malignant type of liver cancer. Besides the high incidence, the resistance to chemotherapy is a major problem that leads to the high mortality of HCC. Recently, aberrant expression of long noncoding RNAs (lncRNAs) has been considered as a primary feature of many types of cancer. However, the genome-wide expression pattern and associated functional implications of lncRNAs in chemo-resistant HCC cells remain unknown. In this study, we identified 120 differentially expressed lncRNAs with 61 up-regulated and 59 down-regulated (fold change>2, p<0...
October 8, 2016: Gene
Gennady M Verkhivker
Protein kinases are versatile molecule switches that govern functional processes in signal transduction networks and regulate fundamental biological processes of cell cycle and organism development. The continuous growth of biological information and a remarkable breath of structural, genetic, and pharmacological studies on protein kinase genes have significantly advanced our knowledge of the kinase activation, drug binding and allosteric mechanisms underlying kinase regulation and interactions in signaling cascades...
October 6, 2016: Current Medicinal Chemistry
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
Malihe Hasanzadeh, Norrie Sharifi, Marjaneh Farazestanian, Seyed Saman Nazemian, Faezeh Madani Sani
BACKGROUND: Finding a tumor marker to predict the aggressive behavior of molar pregnancy in early stages has yet been a topic for studies. OBJECTIVES: In this survey we planned to study patients with molar pregnancy to 1) assess the p53 and c-erbB-2 expression in trophoblastic tissue, 2) to study the relationship between their expression intensity and progression of a molar pregnancy to gestational trophoblastic neoplasia, and 3) to determine a cut off value for the amount of p53 and c-erbB-2 expression which might correlate with aggressive behavior of molar pregnancy...
June 2016: Iranian Journal of Cancer Prevention
Huairong Zhang, Bo Gao, Bingyin Shi
Aim. We aim to identify protein kinases involved in the pathophysiology of papillary thyroid carcinoma (PTC) in order to provide potential therapeutic targets for kinase inhibitors and unfold possible molecular mechanisms. Materials and Methods. The gene expression profile of GSE27155 was analyzed to identify differentially expressed genes and mapped onto human protein kinases database. Correlation of kinases with PTC was addressed by systematic literature search, GO and KEGG pathway analysis. Results. The functional enrichment analysis indicated that "mitogen-activated protein kinases pathway" expression was extremely enriched, followed by "neurotrophin signaling pathway," "focal adhesion," and "GnRH signaling pathway...
2016: Disease Markers
Stephen R Adams, Howard C Yang, Elamprakash N Savariar, Joe Aguilera, Jessica L Crisp, Karra A Jones, Michael A Whitney, Scott M Lippman, Ezra E W Cohen, Roger Y Tsien, Sunil J Advani
Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression...
October 4, 2016: Nature Communications
Jun Chen, Taisei Kinoshita, Juthamas Sukbuntherng, Betty Y Chang, Laurence Elias
Ibrutinib is a potent, small-molecule Bruton's tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies. Ibrutinib covalently binds to Cys481 in the ATP-binding domain of BTK. This cysteine residue is conserved among 9 other tyrosine kinases, including HER2 and EGFR, which can be targeted. Screening large panels of cell lines demonstrated that ibrutinib was growth inhibitory against some solid tumor cells, including those inhibited by other HER2/EGFR inhibitors. Among sensitive cell lines, breast cancer lines with HER2 overexpression were most potently inhibited by ibrutinib (<100 nM); additionally the IC50s were lower than that of lapatinib and dacomitinib...
September 27, 2016: Molecular Cancer Therapeutics
Reiner Hoppe, Ping Fan, Florian Büttner, Stefan Winter, Amit K Tyagi, Heather Cunliffe, V Craig Jordan, Hiltrud Brauch
Aromatase inhibitor (AI) resistance during breast cancer treatment is mimicked by MCF-7:5C (5C) and MCF-7:2A (2A) cell lines that grow spontaneously. Survival signaling is reconfigured but cells are vulnerable to estradiol (E2)-inducible apoptosis. These model systems have alterations of stress related pathways including the accumulation of endoplasmic reticulum, oxidative, and inflammatory stress that occur prior to E2-induced apoptosis. We investigated miRNA expression profiles of 5C and 2A to characterize their AI resistance phenotypes...
September 17, 2016: Oncotarget
Qi Wang, Kaishi Satomi, Ji Eun Oh, Barbara Hutter, Benedikt Brors, Nicolle Diessl, Hai-Kun Liu, Stephan Wolf, Otmar Wiestler, Paul Kleihues, Bernd Koelsch, Andrea Kindler-Röhrborn, Hiroko Ohgaki
A single dose of N-ethyl-N-nitrosourea (ENU) during late prenatal or early postnatal development induces a high incidence of malignant schwannomas and gliomas in rats. Although T->A mutations in the transmembrane domain of the Neu (c-ErbB-2) gene are the driver mutations in ENU-induced malignant schwannomas, the molecular basis of ENU-induced gliomas remains enigmatic. We performed whole-genome sequencing of gliomas that developed in three BDIV and two BDIX rats exposed to a single dose of 80 mg ENU/kg body weight on postnatal day one...
October 2016: American Journal of Pathology
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
Feliciano Barron, Martha de la Torre-Vallejo, Rosa Luz Luna-Palencia, Andres F Cardona, Oscar Arrieta
INTRODUCTION: Lung cancer tumors present EGFR mutations associated with an increased response rate to tyrosine kinase inhibitors (TKIs). Afatinib acts as an irreversible pan-ErbB-TKI. AREAS COVERED: This review summarizes the results of clinical trials in NSCLC regarding its safety and efficacy. EXPERT OPINION: Afatinib in 40mg doses is highly effective in patients with NSCLC and EGFR mutations, improving progression-free survival and disease-related symptoms compared to chemotherapy...
September 16, 2016: Expert Opinion on Drug Safety
Yuichi Ohnishi, Hiroki Yasui, Kenji Kakudo, Masami Nozaki
Lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR)/ErbB2, has antiproliferative effects and is used to treat patients with ErbB2-positive metastatic breast cancer. In the present study, we examined the effects of lapatinib on growth of oral and prostate cancer cells. Oral squamous cell carcinoma (OSCC) cell lines HSC3, HSC4 and Ca9-22 were sensitive to the antiproliferative effects of lapatinib in anchorage-dependent culture, but the OSCC cell lines KB and SAS and the prostate cancer cell line DU145 were resistant to lapatinib...
September 7, 2016: Oncology Reports
Christos Yapijakis, Maria Adamopoulou, Konstantina Tasiouka, Costas Voumvourakis, George Stranjalis
BACKGROUND/AIM: A deeper understanding of the complex molecular pathology of brain malignancies is needed in order to develop more effective and targeted therapies of these highly lethal disorders. In an effort to further enlighten the molecular pathology of brain oncogenesis involving the her-2 (erbB-2/neu/ngl)/N-ras/nf1 pathway, we screened the genotypes of specimens from various types of brain tumors. MATERIALS AND METHODS: The studied specimens included 35 biopsies of four general categories: 13 neuroglial tumors (4 astrocytomas, 2 oligodendrogliomas, 7 glioblastomas multiforme), 14 meningiomas, 3 other nervous system tumors (2 schwannomas, 1 craniopharyngioma) and 5 metastatic tumors (such as lung carcinomas and chronic myelocytic leukemia)...
September 2016: Anticancer Research
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
Benjamin Goeppert, Christina Ernst, Constance Baer, Stephanie Roessler, Marcus Renner, Arianeb Mehrabi, Mohammadreza Hafezi, Anita Pathil, Arne Warth, Albrecht Stenzinger, Wilko Weichert, Marion Bähr, Rainer Will, Peter Schirmacher, Christoph Plass, Dieter Weichenhan
Cholangiocarcinoma (CC) is a rare malignancy of the extrahepatic or intrahepatic biliary tract with an outstanding poor prognosis. Non-surgical therapeutic regimens result in minimally improved survival of CC patients. Global genomic analyses identified a few recurrently mutated genes, some of them in genes involved in epigenetic patterning. In a previous study, we demonstrated global DNA methylation changes in CC, indicating major contribution of epigenetic alterations to cholangiocarcinogenesis. Here, we aimed at the identification and characterization of CC-related, differentially methylated regions (DMRs) in potential microRNA promoters and of genes targeted by identified microRNAs...
September 3, 2016: Epigenetics: Official Journal of the DNA Methylation Society
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