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https://www.readbyqxmd.com/read/28522256/sporadic-early-onset-diffuse-gastric-cancers-have-high-frequency-of-somatic-cdh1-alterations-but-low-frequency-of-somatic-rhoa-mutations-compared-with-late-onset-cancers
#1
Soo Young Cho, Jun Won Park, Yang Liu, Young Soo Park, Ju Hee Kim, Hanna Yang, Hyejin Um, Woo Ri Ko, Byung Il Lee, Sun Young Kwon, Seung Wan Ryu, Chae Hwa Kwon, Do Youn Park, Jae-Hyuk Lee, Sang Il Lee, Kyu Sang Song, Hoon Hur, Sang-Uk Han, Heekyung Chang, Su-Jin Kim, Byung-Sik Kim, Jeong-Hwan Yook, Moon-Won Yoo, Beom-Su Kim, In-Seob Lee, Myeong-Cherl Kook, Nina Thiessen, An He, Chip Stewart, Andrew Dunford, Jaegil Kim, Juliann Shih, Gordon Saksena, Andrew D Cherniack, Steven Schumacher, Amaro-Taylor Weiner, Mara Rosenberg, Gad Getz, Eun Gyeong Yang, Min Hee Ryu, Adam J Bass, Hark Kyun Kim
BACKGROUND & AIMS: Early-onset gastric cancer, which develops in younger patients than most gastric cancers, is usually detected at advanced stages, has diffuse histologic features, and occurs more frequently in women. We investigated somatic genomic alterations associated with the unique characteristics of sporadic diffuse gastric cancers (DGCs) from younger patients. METHODS: We conducted whole exome and RNA sequence analyses of 80 resected DGC samples from patients 45 years old or younger in Korea...
May 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28514724/sirna-mediated-inactivation-of-her3-improves-the-antitumour-activity-and-sensitivity-of-gefitinib-in-gastric-cancer-cells
#2
Heng-Heng Yuan, Ying-Nan Yang, Jian-Hua Zhou, Yan-Jing Li, Li-Ying Wang, Jun-Wei Qin, Tao Liu, Zhen-Zhen Li, Qing-Xin Zhou, Xiao-Li Wei, Ting-Ting Zhang, Peng Huang, Wen-Jie Zhang, Lei Liu, Xiao-Xue Du, Yu Han
The human EGFR family consists of four type-1 transmembrane tyrosine kinase receptors: HER1 (EGFR, ErbB1), HER2 (Neu, ErbB2), HER3 (ErbB3), and HER4 (ErbB4). HER3 can dimerize with EGFR, HER2 and even c-Met and likely plays a central role in the response to EGFR-targeted therapy. Because HER3 lacks significant kinase activity and cannot be inhibited by tyrosine kinase inhibitors, neutralizing antibodies and alternative inhibitors of HER3 have been sought as cancer therapeutics. Here, we describe the stable suppression of HER3 mRNA and protein using siRNA...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28480322/data-on-the-effect-of-in-vivo-knockdown-using-artificial-erbb3-mirna-on-remak-bundle-structure
#3
Yuki Miyamoto, Tomohiro Torii, Kazuko Kawahara, Masashi Inoue, Takako Morimoto, Masahiro Yamamoto, Junji Yamauchi
Mature Schwann cells, the peripheral nervous system (PNS) glial cells, have two major roles for neuronal axons (Bunge, 1993) [1]. For large diameter axons, Schwann cells form myelin sheaths with multiple layers. For small diameter axons, they form Remak bundle composed only of single layer of the Schwann cell plasma membrane. In the PNS, ErbB3 forms a dimer with ErbB2 on the Schwann cell plasma membrane. ErbB3 plays a key role in myelination by myelinating Schwann cells, that is to say, its role in myelin thickness...
June 2017: Data in Brief
https://www.readbyqxmd.com/read/28469731/integrated-data-analysis-reveals-potential-drivers-and-pathways-disrupted-by-dna-methylation-in-papillary-thyroid-carcinomas
#4
Caroline Moraes Beltrami, Mariana Bisarro Dos Reis, Mateus Camargo Barros-Filho, Fabio Albuquerque Marchi, Hellen Kuasne, Clóvis Antônio Lopes Pinto, Srikant Ambatipudi, Zdenko Herceg, Luiz Paulo Kowalski, Silvia Regina Rogatto
BACKGROUND: Papillary thyroid carcinoma (PTC) is a common endocrine neoplasm with a recent increase in incidence in many countries. Although PTC has been explored by gene expression and DNA methylation studies, the regulatory mechanisms of the methylation on the gene expression was poorly clarified. In this study, DNA methylation profile (Illumina HumanMethylation 450K) of 41 PTC paired with non-neoplastic adjacent tissues (NT) was carried out to identify and contribute to the elucidation of the role of novel genic and intergenic regions beyond those described in the promoter and CpG islands (CGI)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28450158/the-erbb-family-and-androgen-receptor-signaling-are-targets-of%C3%A2-celecoxib-in-prostate-cancer
#5
Antonella Brizzolara, Roberto Benelli, Roberta Venè, Paola Barboro, Alessandro Poggi, Francesca Tosetti, Nicoletta Ferrari
Inflammation plays a central role in prostate cancer (PCa) development through significant crosstalk between the COX-2-ErbB family receptor network and androgen receptor (AR)-EGFR signaling pathways. The purpose of this work was to determine the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling pathway in androgen-dependent PCa cells and to provide a rationale for its beneficial use in chemopreventive strategies. Functional studies of Celecoxib activity were performed on LNCaP prostate cancer cells...
April 25, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28432142/structural-similarities-between-neuregulin-1-3-isoforms-determine-their-subcellular-distribution-and-signaling-mode-in-central-neurons
#6
Detlef Vullhorst, Tanveer Ahmad, Irina Karavanova, Carolyn Keating, Andres Buonanno
The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants originating from the use of different genes, alternative promoters and splice variants. NRGs have generally been thought to be transported to axons and presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2 accumulates on cell bodies and proximal dendrites, and that NMDAR activity is required for shedding of its ectodomain by metalloproteinases...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28423512/kinase-analysis-of-penile-squamous-cell-carcinoma-on-multiple-platforms-to-identify-potential-therapeutic-targets
#7
Eddy S Yang, Christopher D Willey, Amitkumar Mehta, Michael R Crowley, David K Crossman, Dongquan Chen, Joshua C Anderson, Gurudatta Naik, Deborah L Della Manna, Tiffiny S Cooper, Guru Sonpavde
Penile squamous cell carcinoma (PSCC) is an orphan malignancy with poorly understood biology and suboptimal systemic therapy. Given that kinases may be drivers and readily actionable, we performed comprehensive multiplatform analysis of kinases in PSCC tumor and normal tissue. Fresh frozen tumors were collected from 11 patients with PSCC. After macrodissection to demarcate tumor from normal tissue, the samples underwent multiplatform analysis of kinases. Next Generation Sequencing (NGS) of 517 kinase genes was performed using Agilent Kinome capture and run on the Illumina MiSeq at PE150bp...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421882/inhibition-of-her3-activation-and-tumor-growth-with-a-human-antibody-binding-to-a-conserved-epitope-formed-by-domain-iii-and-iv
#8
Lisa C Schmitt, Alexander Rau, Oliver Seifert, Jonas Honer, Meike Hutt, Simone Schmid, Jonas Zantow, Michael Hust, Stefan Dübel, Monilola A Olayioye, Roland E Kontermann
Human epidermal growth factor receptor 3 (HER3, also known as ErbB3) has emerged as relevant target for antibody-mediated tumor therapy. Here, we describe a novel human antibody, IgG 3-43, recognizing a unique epitope formed by domain III and parts of domain IV of the extracellular region of HER3, conserved between HER3 and mouse ErbB3. An affinity of 11 nM was determined for the monovalent interaction. In the IgG format, the antibody bound recombinant bivalent HER3 with subnanomolar affinity (KD = 220 pM) and HER3-expressing tumor cells with EC50 values in the low picomolar range (27 - 83 pM)...
April 19, 2017: MAbs
https://www.readbyqxmd.com/read/28404378/axl-molecular-targeting-counteracts-aggressiveness-but-not-platinum-resistance-of-ovarian-carcinoma-cells
#9
Cristina Corno, Laura Gatti, Noemi Arrighetti, Nives Carenini, Nadia Zaffaroni, Cinzia Lanzi, Paola Perego
Ovarian carcinoma, the most common gynecological cancer, is characterized by high lethality mainly due to late diagnosis and treatment failure. The efficacy of platinum drug-based therapy in the disease is limited by the occurrence of drug resistance, a phenomenon often associated with increased metastatic potential. Because the Tyr-kinase receptor Axl can be deregulated in ovarian carcinoma and plays a pro-metastatic/anti-apoptotic role, the aim of this study was to examine if Axl inhibition modulates drug resistance and aggressive features of ovarian carcinoma cells, using various pairs of cisplatin-sensitive and -resistant cell lines...
April 9, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28399526/expression-of-the-erbb-family-of-ligands-and-receptors-in-gastric-cancer
#10
Sun-Ju Byeon, Hye Seung Lee, Min-A Kim, Byung Lan Lee, Woo Ho Kim
OBJECTIVE: Gastric cancer (GC) is the second most common cancer and the third leading cause of cancer-related death in Korea. Alterations in the ERBB (homology to the erythroblastoma viral gene product, v-erbB) receptor family and ERBB-related signaling pathways are frequently observed in GC. However, the roles of the ERBB receptors and their ligands in GC are not well established. METHODS: We evaluated the expression levels of various ERBB receptor ligands (i.e...
April 12, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28388586/her2-and-egfr-amplification-and-expression-in-urothelial-carcinoma-occurs-in-distinct-biological-and-molecular-contexts
#11
Pontus Eriksson, Gottfrid Sjödahl, Gunilla Chebil, Fredrik Liedberg, Mattias Höglund
We analyzed a cohort of 599 cases of urothelial carcinoma for EGFR, ERBB2, and ERBB3 gene expression and genomic alterations. The cohort consisted of a reference set (n = 292) comprising all stages and grades and one set (n = 307) of advanced tumors. All cases were previously classified into urothelial carcinoma molecular subtypes. Genomic amplifications were established by array-CGH or in-situ hybridization, and gene expression both at mRNA and protein levels. Clinical HER2 status was independently evaluated using standard clinical procedures...
March 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28369073/her2-signaling-regulates-her2-localization-and-membrane-retention
#12
Jaekwang Jeong, Wonnam Kim, Lark Kyun Kim, Joshua VanHouten, John J Wysolmerski
ErbB2/HER2/Neu is a receptor tyrosine kinase that is overexpressed in 25-30% of human breast cancers, usually associated with amplification of the ERBB2 gene. HER2 has no recognized ligands and heterodimers between HER2 and EGFR (ErbB1/HER1) or HER2 and ErbB3/HER3 are important in breast cancer. Unlike other ErbB family members, HER2 is resistant to internalization and degradation, and remains at the cell surface to signal for prolonged periods after it is activated. Although the mechanisms underlying retention of HER2 at the cell surface are not fully understood, prior studies have shown that, in order to avoid internalization, HER2 must interact with the chaperone, HSP90, and the calcium pump, PMCA2, within specific plasma membrane domains that protrude from the cell surface...
2017: PloS One
https://www.readbyqxmd.com/read/28350117/reduced-expression-of-mir%C3%A2-205%C3%A2-5p-promotes-apoptosis-and-inhibits-proliferation-and-invasion-in-lung-cancer-a549-cells-by-upregulation-of-zeb2-and-downregulation-of-erbb3
#13
Min Jiang, Ting Zhong, Wei Zhang, Zuke Xiao, Guozhu Hu, Hong Zhou, Haibin Kuang
Previous studies have demonstrated that microRNA (miR)-205-5p expression is significantly increased in non‑small cell lung cancer tissues and is associated with tumor differentiation grade. The aim of the present study was to explore the effects of miR‑205‑5p on viability, apoptosis and invasion of lung cancer A549 cells. The hsa‑miR‑205‑5p small interfering RNA (siRNA) inhibitor was transfected into A549 cells and expression of miR‑205‑5p was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338617/egfr-family-members-regulation-of-autophagy-is-at-a-crossroads-of-cell-survival-and-death-in-cancer
#14
REVIEW
Elizabeth Henson, Yongqiang Chen, Spencer Gibson
The epidermal growth factor receptor (EGFR) signaling pathways are altered in many cancers contributing to increased cell survival. These alterations are caused mainly through increased expression or mutation of EGFR family members EGFR, ErbB2, ErbB3, and ErbB4. These receptors have been successfully targeted for cancer therapy. Specifically, a monoclonal antibody against ErbB2, trastuzumab, and a tyrosine kinase inhibitor against EGFR, gefitinib, have improved the survival of breast and lung cancer patients...
March 24, 2017: Cancers
https://www.readbyqxmd.com/read/28322798/neuregulin-1-type-iii-knockout-mice-exhibit-delayed-migration-of-schwann-cell-precursors
#15
Yuki Miyamoto, Tomohiro Torii, Akito Tanoue, Kazuko Kawahara, Miyuki Arai, Hideki Tsumura, Toru Ogata, Motoshi Nagao, Nobuo Terada, Masahiro Yamamoto, Shou Takashima, Junji Yamauchi
In an embryonic developmental stage of the peripheral nervous system (PNS), Schwann cell precursors migrate along neuronal axons to their final destinations. After birth, they eventually wrap around individual axons to form myelin sheaths, which insulate axons to increase the nerve conduction velocity. Some growth factors and adhesion molecules are known to control these developmental stages from in the fish to in the mammal. Neuregulin-1 (NRG1), which is composed of many alternative splicing variants, is such a growth factor...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28320942/egf-and-nrg-induce-phosphorylation-of-her3-erbb3-by-egfr-using-distinct-oligomeric-mechanisms
#16
Bettina van Lengerich, Christopher Agnew, Elias M Puchner, Bo Huang, Natalia Jura
Heteromeric interactions between the catalytically impaired human epidermal growth factor receptor (HER3/ERBB3) and its catalytically active homologs EGFR and HER2 are essential for their signaling. Different ligands can activate these receptor pairs but lead to divergent signaling outcomes through mechanisms that remain largely unknown. We used stochastic optical reconstruction microscopy (STORM) with pair-correlation analysis to show that EGF and neuregulin (NRG) can induce different extents of HER3 clustering that are dependent on the nature of the coexpressed HER receptor...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28304405/the-erbb3-receptor-tyrosine-kinase-negatively-regulates-paneth-cells-by-pi3k-dependent-suppression-of-atoh1
#17
Dana Almohazey, Yuan-Hung Lo, Claire V Vossler, Alan J Simmons, Jonathan J Hsieh, Edie B Bucar, Michael A Schumacher, Kathryn E Hamilton, Ken S Lau, Noah F Shroyer, Mark R Frey
Paneth cells (PCs), a secretory population located at the base of the intestinal crypt, support the intestinal stem cells (ISC) with growth factors and participate in innate immunity by releasing antimicrobial peptides, including lysozyme and defensins. PC dysfunction is associated with disorders such as Crohn's disease and necrotizing enterocolitis, but the specific pathways regulating PC development and function are not fully understood. Here we tested the role of the neuregulin receptor ErbB3 in control of PC differentiation and the ISC niche...
May 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28294470/exome-sequencing-deciphers-a-germline-met-mutation-in-familial-epidermal-growth-factor-receptor-mutant-lung-cancer
#18
Naoki Tode, Toshiaki Kikuchi, Tomohiro Sakakibara, Taizou Hirano, Akira Inoue, Shinya Ohkouchi, Tsutomu Tamada, Tatsuma Okazaki, Akira Koarai, Hisatoshi Sugiura, Tetsuya Niihori, Yoko Aoki, Keiko Nakayama, Kunio Matsumoto, Yoichi Matsubara, Masayuki Yamamoto, Akira Watanabe, Toshihiro Nukiwa, Masakazu Ichinose
Lung cancer accompanied by somatic activating mutations in the epidermal growth factor receptor (EGFR) gene, which is associated with a significant clinical response to the targeted therapy, is frequently found in never-smoking Asian women with adenocarcinoma. Although this implies genetic factors underlying the carcinogenesis, the etiology remains unclear. To gain insight into the pathogenic mechanisms, we sequenced the exomes in the peripheral-blood DNA from six siblings, four affected and two unaffected siblings, of a family with familial EGFR-mutant lung adenocarcinoma...
March 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28286209/esophageal-adenocarcinoma-cells-and-xenograft-tumors-exposed-to-erb-b2-receptor-tyrosine-kinase-2-and-3-inhibitors-activate-transforming-growth-factor-beta-signaling-which-induces-epithelial-to-mesenchymal-transition
#19
Eva A Ebbing, Anne Steins, Evelyn Fessler, Phylicia Stathi, Willem Joost Lesterhuis, Kausilia K Krishnadath, Louis Vermeulen, Jan Paul Medema, Maarten F Bijlsma, Hanneke W M van Laarhoven
BACKGROUND & AIMS: Drugs that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) are the standard treatment of patients with different types of cancer, including HER2-overexpressing gastroesophageal tumors. Unfortunately, cancer cells become resistant to these drugs, so overall these drugs provide little benefit to patients with these tumors. We investigated mechanisms that mediate resistance of esophageal adenocarcinoma (EAC) cells and patient-derived xenograft tumors to ERBB inhibitors...
March 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28285962/the-erk-mapk-pathway-is-overexpressed-and-activated-in-gallbladder-cancer
#20
Kurt Buchegger, Ramón Silva, Jaime López, Carmen Ili, Juan Carlos Araya, Pamela Leal, Priscilla Brebi, Ismael Riquelme, Juan Carlos Roa
Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. Molecular profiling has revealed that the deregulation in the ERK/MAPK signaling pathway plays a crucial role in many disease and malignancies, including GBC. The aim of this study was to measure the expression of ERK1/2 and p-ERK1/2 in a population with high GBC-related mortality, such as the Chilean population, and characterize the protein expression of this ERK/MAPK pathway in seven GBC cell lines. Immunohistochemistry (IHC) for ERK1/2 and p-ERK1/2 was performed in 123 GBC tissues and 37 chronic cholecystitis (CC) tissues...
February 24, 2017: Pathology, Research and Practice
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