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J Xu, B J Hartley, P Kurup, A Phillips, A Topol, M Xu, C Ononenyi, E Foscue, S-M Ho, T D Baguley, N Carty, C S Barros, U Müller, S Gupta, P Gochman, J Rapoport, J A Ellman, C Pittenger, B Aronow, A C Nairn, M W Nestor, P J Lombroso, K J Brennand
The brain-specific tyrosine phosphatase, STEP (STriatal-Enriched protein tyrosine Phosphatase) is an important regulator of synaptic function. STEP normally opposes synaptic strengthening by increasing N-methyl D-aspartate glutamate receptor (NMDAR) internalization through dephosphorylation of GluN2B and inactivation of the kinases extracellular signal-regulated kinase 1/2 and Fyn. Here we show that STEP61 is elevated in the cortex in the Nrg1(+/-) knockout mouse model of schizophrenia (SZ). Genetic reduction or pharmacological inhibition of STEP prevents the loss of NMDARs from synaptic membranes and reverses behavioral deficits in Nrg1(+/-) mice...
October 18, 2016: Molecular Psychiatry
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
Elfriede Bollschweiler, Arnulf H Hölscher, Till Herbold, Ralf Metzger, Hakan Alakus, Henner Schmidt, Uta Drebber, Ute Warnecke-Eberz
OBJECTIVE: The aim of this study was to evaluate the predictive value of a single or combination of biomarker(s) for histopathologic non-response to neoadjuvant chemoradiation in esophageal cancer. SUMMARY OF BACKGROUND DATA: Patients without response to neoadjuvant chemoradiation for esophageal cancer have no prognostic benefits, but experience time delays and risk side effects. METHODS: Inclusion criteria for this prospective diagnostic study were patients with cT3,Nx,M0, esophageal squamous cell or adenocarcinoma and planned neoadjuvant chemoradiation (5- fluorouracil, cisplatin, 40Gy) followed by 2-field transthoracic esophagectomy...
November 2016: Annals of Surgery
Kaye Showler, Mayumi Nishimura, Kazuhiro Daino, Tatsuhiko Imaoka, Yukiko Nishimura, Takamitsu Morioka, Benjamin J Blyth, Toshiaki Kokubo, Masaru Takabatake, Maki Fukuda, Hitomi Moriyama, Shizuko Kakinuma, Masahiro Fukushi, Yoshiya Shimada
The PI3K/AKT pathway is one of the most important signaling networks in human breast cancer, and since it was potentially implicated in our preliminary investigations of radiation-induced rat mammary carcinomas, our aim here was to verify its role. We included mammary carcinomas induced by the chemical carcinogen 1-methyl-1-nitrosourea to determine whether any changes were radiation-specific. Most carcinomas from both groups showed activation of the PI3K/AKT pathway, but phosphorylation of AKT1 was often heterogeneous and only present in a minority of carcinoma cells...
October 13, 2016: Journal of Radiation Research
Michael P Chu, J Randolph Hecht, Dennis Slamon, Zev A Wainberg, Yung-Jue Bang, Paulo M Hoff, Alberto Sobrero, Shukui Qin, Karen Afenjar, Vincent Houe, Karen King, Sheryl Koski, Karen Mulder, Julie Price Hiller, Andrew Scarfe, Jennifer Spratlin, Yingjie J Huang, Saba Khan-Wasti, Neil Chua, Michael B Sawyer
Importance: Capecitabine is an oral cytotoxic chemotherapeutic commonly used across cancer subtypes. As with other oral medications though, it may suffer from drug interactions that could impair its absorption. Objective: To determine if gastric acid suppressants such as proton pump inhibitors (PPIs) may impair capecitabine efficacy. Design, Setting, and Participants: This secondary analysis of TRIO-013, a phase III randomized trial, compares capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer (GEC); patients were randomized 1:1 between CapeOx with or without lapatinib...
October 13, 2016: JAMA Oncology
Shira Toledano, Huayi Lu, Agustina Palacio, Boaz Kigel, Ofra Kessler, Gilad Allon, Yoreh Barak, Gera Neufeld, Shlomit Schaal
Abnormal subretinal choroidal neovascularization (CNV) is a major cause of blindness in exudative age-related macular degeneration (AMD). Current anti-angiogenic treatments by VEGF sequestering agents have been successful, but a significant proportion of patients do not respond well to these treatments, and the response of others diminishes over time, suggesting that additional anti-angiogenic agents that function by separate mechanisms may be of use to such patients. We have previously found that a point mutated form of semaphorin-3E resistant to cleavage by furin like pro-protein convertases (UNCL-Sema3E) displays potent anti-angiogenic properties...
October 7, 2016: Experimental Eye Research
Matthias Christgen, Jana L van Luttikhuizen, Mieke Raap, Peter Braubach, Lars Schmidt, Danny Jonigk, Friedrich Feuerhake, Ulrich Lehmann, Brigitte Schlegelberger, Hans H Kreipe, Doris Steinemann
HER2/ERBB2 amplification/overexpression determines the eligibility of breast cancer patients to HER2-targeted therapy. This study evaluates the agreement between ERBB2 copy number assessment by fluorescence in situ hybridization, a standard method recommended by the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP), and newly available DNA extraction-based methods. A series of n=29 formalin-fixed paraffin-embedded breast cancers were subjected to ERBB2 copy number assessment by fluorescence in situ hybridization (FISH, Vysis, Abbott)...
October 3, 2016: Oncotarget
Ramesh Babu Telugu, Amit Kumar Chowhan, Nandyala Rukmangadha, Rashmi Patnayak, Bobbidi Venkata Phaneendra, Bodapati Chandra Mowliswara Prasad, Mandyam Kumaraswamy Reddy
BACKGROUND: Meningiomas are common slow-growing primary central nervous system tumors that arise from the meningothelial cells of the arachnoid and spinal cord. Human epidermal growth factor receptor 2 (HER2) or HER2/neu (also known as c-erbB2) is a 185-kD transmembrane glycoprotein with tyrosine kinase activity expressed in meningiomas and various other tumors. It can be used in targeted therapy for HER2/neu positive meningiomas. AIM: To correlate the expression of HER2/neu protein in meningiomas with gender, location, histological subtypes, and grade...
October 2016: Journal of Neurosciences in Rural Practice
Hellyeh Hamidi, Mika Pietilä, Johanna Ivaska
Cancer is a complex disease and progresses within a dynamically evolving extracellular matrix that controls virtually every aspect of the tumour and tumour-associated cells. Interactions with the extracellular microenvironment are predominately mediated by a family of cell-surface transmembrane receptors called integrins. Integrin-matrix engagement leads to the formation of adhesion plaques, consisting of signalling and adaptor proteins, at the plasma membrane that link the extracellular matrix to the regulation of the cell cytoskeleton...
September 29, 2016: British Journal of Cancer
Debora Fumagalli, David Venet, Michail Ignatiadis, Hatem A Azim, Marion Maetens, Françoise Rothé, Roberto Salgado, Ian Bradbury, Lajos Pusztai, Nadia Harbeck, Henry Gomez, Tsai-Wang Chang, Maria Antonia Coccia-Portugal, Serena Di Cosimo, Evandro de Azambuja, Lorena de la Peña, Paolo Nuciforo, Jan C Brase, Jens Huober, José Baselga, Martine Piccart, Sherene Loi, Christos Sotiriou
Importance: In neoadjuvant trials, treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancers with dual HER2 blockade resulted in increased pathologic complete response (pCR) rates compared with each targeted agent alone. Amplification and/or overexpression of HER2 currently remains the only biomarker for therapeutic decisions, but it is insufficient to explain the heterogeneous response to anti-HER2 agents. Objective: To investigate the ability of clinically and biologically relevant genes and gene signatures (GSs) measured by RNA sequencing to predict the efficacy of anti-HER2 agents...
September 29, 2016: JAMA Oncology
Andrew Rankin, Samuel J Klempner, Rachel Erlich, James X Sun, Axel Grothey, Marwan Fakih, Thomas J George, Jeeyun Lee, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, Siraj M Ali, Alexa B Schrock
INTRODUCTION: A KRAS mutation represented the first genomic biomarker to predict lack of benefit from anti-epidermal growth factor receptor (EGFR) antibody therapy in advanced colorectal cancer (CRC). Expanded RAS testing has further refined the treatment approach, but understanding of genomic alterations underlying primary and acquired resistance is limited and further study is needed. MATERIALS AND METHODS: We prospectively analyzed 4,422 clinical samples from patients with advanced CRC, using hybrid-capture based comprehensive genomic profiling (CGP) at the request of the individual treating physicians...
September 28, 2016: Oncologist
Monica Benvenuto, Rosanna Mattera, Laura Masuelli, Gloria Taffera, Orlando Andracchio, Ilaria Tresoldi, Paolo Lido, Maria Gabriella Giganti, Justyna Godos, Andrea Modesti, Roberto Bei
Racemic Gossypol [(±)-GOS], composed of both (-)-GOS and (+)-GOS, is a small BH3-mimetic polyphenol derived from cotton seeds. (±)-GOS has been employed and well tolerated by cancer patients. Head and neck carcinoma (HNC) represents one of the most fatal cancers worldwide, and a significant proportion of HNC expresses high levels of antiapoptotic Bcl-2 proteins. In this study, we demonstrate that (±)-GOS inhibits cell proliferation and induces apoptosis and autophagy of human pharynx, tongue, and salivary gland cancer cell lines and of mouse salivary gland cancer cells (SALTO)...
September 27, 2016: International Journal of Food Sciences and Nutrition
Lingfei Wang, Xiaojie Yu, Jian Dong, Yanchun Meng, Yang Yang, Huajing Wang, Chao Wang, Yajun Zhang, Yirong Zhao, Jian Zhao, Hao Wang, Cuihua Lu, Bohua Li
Despite of the effectiveness of the anti-ErbB2 humanized antibody trastuzumab, trastuzumab resistance emerges as a major and common clinical problem. Thus, circumventing trastuzumab resistance has become an urgent need. Recently, Src inhibitor saracatinib has drawn great attention for its key role in trastuzumab response. As shown in our previous study, H2-18, an anti-ErbB2 antibody, could potently induce programmed cell death (PCD) in trastuzumab-resistant breast cancer cells. Here we combined H2-18 and a Src inhibitor, saracatinib, and studied the antitumor activity of this drug combination in trastuzumab-resistant breast cancer cell lines...
October 21, 2016: Biochemical and Biophysical Research Communications
Sakshi Jasra, Mateusz Opyrchal, Larry Norton, Rutika Mehta
No abstract text is available yet for this article.
August 18, 2016: Clinical Breast Cancer
Shu-Xia Li, Yan-Qi Yang, Li-Jian Jin, Zhi-Gang Cai, Zheng Sun
INTRODUCTION: The aim of this study was to detect the survivin, carcinoembryonic antigen (CEA) and ErbB2 in the saliva, serum and local tumor-exfoliated cells of oral squamous cell carcinoma (OSCC) patients, for providing reliable tumor markers for the early detection of oral malignant cancer. MATERIALS AND METHODS: The saliva, serum, and local tumor-exfoliated cell samples of 26 OSCC patients without chemotherapy and 10 non-cancer patients were collected in Department of Oral and Maxillofacial Surgery, School of Stomatology, Peking University...
September 16, 2016: Cancer Biomarkers: Section A of Disease Markers
Marine De Paoli, Selma Gogalic, Ursula Sauer, Claudia Preininger, Hardev Pandha, Guy Simpson, Andras Horvath, Christophe Marquette
Purpose. Nonmuscle invasive bladder cancer (BCa) has a high recurrence rate requiring lifelong surveillance. Urinary biomarkers are promising as simple alternatives to cystoscopy for the diagnosis of recurrent bladder cancer. However, no single marker can achieve the required accuracy. The purpose of this study was to select a multiparameter panel, comprising urinary biomarkers and clinical parameters, for BCa recurrence diagnosis. Experimental Design. Candidate biomarkers were measured in urine samples of BCa patients with recurrence and BCa patients without recurrence...
2016: Disease Markers
Laura J Tafe, Kirsten J Pierce, Jason D Peterson, Francine de Abreu, Vincent A Memoli, Candice C Black, Jason R Pettus, Jonathan D Marotti, Edward J Gutmann, Xiaoying Liu, Keisuke Shirai, Konstantin H Dragnev, Christopher I Amos, Gregory J Tsongalis
Detection of somatic mutations in non-small cell lung cancers (NSCLCs), especially adenocarcinomas, is important for directing patient care when targeted therapy is available. Here, we present our experience with genotyping NSCLC using the Ion Torrent Personal Genome Machine (PGM) and the AmpliSeq Cancer Hotspot Panel v2. We tested 453 NSCLC samples from 407 individual patients using the 50 gene AmpliSeq Cancer Hotspot Panel v2 from May 2013 to July 2015. Using 10 ng of DNA, up to 11 samples were simultaneously sequenced on the Ion Torrent PGM (316 and 318 chips)...
September 2016: Neoplasia: An International Journal for Oncology Research
Clément Chevalier, Serge Roche, Christine Bénistant
ERBB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2) amplification is associated with invasive breast cancer. We discovered that TOM1L1 (target of myb1-like 1) and ERBB2 co-amplification defines a novel mechanism involved in breast cancer metastatic progression. Upregulation of the vesicular trafficking protein TOM1L1 enhances plasma membrane delivery of membrane-type 1 matrix metalloprotease (MT1-MMP) for efficient extracellular matrix degradation and tumor cell dissemination.
July 2016: Molecular & Cellular Oncology
Johanne Tremblay, Carole G Campion, Thomas Verissimo, Suzanne Cossette, Hiroyuki Matsuda, Pavel Hamet
OBJECTIVE: Epidermal growth factor receptor (EGFR) signaling plays a dual role in hypertension-induced kidney damage. EGFR is critically involved in angiotensin II-induced renal lesions and fibrosis but is also engaged in kidney tissue repair. Consequently, targeting EGFR in renal diseases is complex because even if inhibition of EGFR activity would be beneficial, a minimal EGFR activity is needed to recover from harmful insults. Our group has identified HCaRG (Hypertension-related, Calcium-Regulated Gene) whose expression is increased in kidneys of hypertensive rats and mice...
September 2016: Journal of Hypertension
Juliano Coelho de Oliveira Zakir, Luiz Augusto Casulari, José Wilson Corrêa Rosa, João Willy Corrêa Rosa, Paulo Andrade de Mello, Albino Verçosa de Magalhães, Luciana Ansaneli Naves
Although some pituitary adenomas may have an aggressive behavior, the vast majority are benign. There are still controversies about predictive factors regarding the biological behavior of these particular tumors. This study evaluated potential markers of invasion and proliferation compared to current classification patterns and epidemiogeographical parameters. The study included 50 patients, operated on for tumors greater than 30 mm, with a mean postoperative follow-up of 15.2 ± 4.8 years. Pituitary magnetic resonance was used to evaluate regrowth, invasion, and extension to adjacent tissue...
2016: International Journal of Endocrinology
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