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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
#1
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/28050146/personalized-oncogenomics-in-the-management-of-gastrointestinal-carcinomas-early-experiences-from-a-pilot-study
#2
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
#3
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/28036286/her3-and-linc00052-interplay-promotes-tumor-growth-in-breast-cancer
#4
Ahmad Salameh, Xuejun Fan, Byung-Kwon Choi, Shu Zhang, Ningyan Zhang, Zhiqiang An
Here we report that the lncRNA LINC00052 expression correlates positively with HER3/ErbB3 levels in breast cancer cells. Gene silencing of LINC00052 diminished both LINC00052 and HER3 expression and reduced cancer cell growth in vitro and in vivo. LINC00052 overexpression promoted cancer cell growth in vitro and in vivo and increased HER3-mediated downstream signaling. Importantly, neutralization of HER3 signaling with HER3 targeting monoclonal antibodies blocked LINC00052 mediated cancer cell proliferation in vitro and tumor growth in vivo, suggesting LINC00052 promoting cancer growth through HER3 signaling...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031425/phase-ib-study-of-safety-and-pharmacokinetics-of-the-pi3k-inhibitor-sar245408-with-the-her3-neutralizing-human-antibody-sar256212-in-patients-with-solid-tumors
#5
Vandana G Abramson, Jeffrey G Supko, Tarah Ballinger, James M Cleary, John F Hilton, Sara Tolaney, Nicole G Chau, Daniel C Cho, Joanne J Lager, Joseph Pearlberg, Geoffrey I Shapiro, Carlos L Arteaga
PURPOSE: This phase Ib study was designed to determine the maximum tolerated dose, safety, preliminary efficacy, and pharmacokinetics of the HER3 (ErbB3) monoclonal antibody SAR256212 in combination with the oral phosphoinositide 3-kinase (PI3K) inhibitor SAR245408 for patients with metastatic or locally advanced solid tumors. EXPERIMENTAL DESIGN: Patients received the combination of intravenous SAR256212 and oral SAR245408 in a 3+3 dose escalation design until occurrence of disease progression or dose-limiting toxicity...
December 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28004068/-up-regulation-of-erbb3-binding-protein-1-inhibits-the-growth-of-esophageal-carcinoma-cells
#6
Hao Jiang, Dong-Ping Liu, Dong Xie, Dong-Zhi Wei
The objective of this study was to investigate the role of ErbB3-binding protein 1 (Ebp1) in the growth of esophageal squamous cell carcinoma (ESCC) cells and the underlying mechanism. Eca109 and KYSE150 cells were transfected with lentiviral vector carrying Ebp1 gene. The mRNA levels of Ebp1 in esophageal cancer tissues and paired adjacent normal tissues were examined by real-time PCR. The growth and viability of esophageal carcinoma cells were assessed using MTT and crystal violet assays, respectively. Clone-forming abilities of Eca109 and KYSE150 cells were analyzed by soft agar assay...
December 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/27998236/randomized-phase-ii-trial-of-seribantumab-in-combination-with-paclitaxel-in-patients-with-advanced-platinum-resistant-or-refractory-ovarian-cancer
#7
Joyce F Liu, Isabelle Ray-Coquard, Frederic Selle, Andrés M Poveda, David Cibula, Hal Hirte, Felix Hilpert, Francesco Raspagliesi, Laurence Gladieff, Philipp Harter, Salvatore Siena, Josep Maria Del Campo, Isabelle Tabah-Fisch, Joseph Pearlberg, Victor Moyo, Kaveh Riahi, Rachel Nering, William Kubasek, Bambang Adiwijaya, Akos Czibere, R Wendel Naumann, Robert L Coleman, Ignace Vergote, Gavin MacBeath, Eric Pujade-Lauraine
Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) -mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab...
December 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27988307/interleukin-6-and-neuregulin-1-as-regulators-of-utrophin-expression-via-the-activation-of-nrg-1-erbb-signaling-pathway-in-mdx-cells
#8
Nevenka Juretić, Josefina Díaz, Felipe Romero, Gustavo González, Enrique Jaimovich, Nora Riveros
Duchenne muscular dystrophy (DMD) is a neuromuscular disease originated by mutations in the dystrophin gene. A promising therapeutic approach deals with functional substitution of dystrophin by utrophin, a structural homolog that might be able to compensate dystrophin absence in DMD muscle fibers. It has been described that both interleukin-6 (IL-6) and neuregulin-1 (NRG-1; Heregulin-HRG) induce utrophin expression in skeletal muscle. We investigated a possible functional link among IL-6, NRG-1 and utrophin, in normal (C57) and dystrophic (mdx) skeletal muscle cells...
December 15, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27906435/down-regulation-of-microrna-143-is-associated-with-colorectal-cancer-progression
#9
J-W Bai, H-Z Xue, C Zhang
OBJECTIVE: Colorectal cancer (CRC) is one of the most prevalent carcinomas worldwide. Tumor metastasis and recurrence are leading causes of CRC-related deaths. Given the role of microRNA (miRNA) in CRC invasion and metastasis, we explored the association between miRNA-143 expression and clinicopathologic characteristics in CRC, as well as the effects of miRNA-143 on CRC cell invasion in vitro. MATERIALS AND METHODS: Quantitative real-time PCR was conducted to assess the expression of miR-143 in tissue specimens and cell lines...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27906180/mir-148a-3p-represses-proliferation-and-emt-by-establishing-regulatory-circuits-between-erbb3-akt2-c-myc-and-dnmt1-in-bladder-cancer
#10
Xiao Wang, Zhen Liang, Xin Xu, Jiangfeng Li, Yi Zhu, Shuai Meng, Shiqi Li, Song Wang, Bo Xie, Alin Ji, Ben Liu, Xiangyi Zheng, Liping Xie
miR-148a-3p downregulation has emerged as a critical factor in cancer progression yet, the underlying mechanisms of miR-148a-3p expression pattern and its function in bladder cancer remains to be elucidated. Here, we illustrate that miR-148a-3p is frequently downregulated in bladder cancer and that its expression may be regulated by DNA methylation. DNA methyltransferase 1 (DNMT1) and miR-148a-3p function in a positive feedback loop in bladder cancer. miR-148a-3p overexpression functions as a tumor suppressor in bladder cancer cells...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27845906/specific-micro-rna-expression-patterns-distinguish-the-basal-and-luminal-subtypes-of-muscle-invasive-bladder-cancer
#11
Andrea E Ochoa, Woonyoung Choi, Xiaoping Su, Arlene Siefker-Radtke, Bogdan Czerniak, Colin Dinney, David J McConkey
The roles of non-coding RNAs in controlling clinical and biological heterogeneity in bladder cancer remain unclear. We used TCGA's published dataset (n = 405 tumors) as a discovery cohort and created a new validation cohort to define the miRNA expression patterns in the basal and luminal molecular subtypes of muscle-invasive bladder cancer (MIBC). We identified 63 miRNAs by PAM, which optimally identified basal and luminal tumors. The targets of the top luminal miRNAs were activators of EMT (ZEB1, ZEB2) and basal subtype transcription (IL-6, EGFR, STAT3), whereas the targets of the top basal miRNAs were involved in adipogenesis pathways and luminal breast cancer (ERBB2, ERBB3)...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27843803/randomized-phase-ii-study-of-duligotuzumab-mehd7945a-vs-cetuximab-in-squamous-cell-carcinoma-of-the-head-and-neck-mehgan-study
#12
Jérôme Fayette, Lori Wirth, Cristina Oprean, Anghel Udrea, Antonio Jimeno, Danny Rischin, Christopher Nutting, Paul M Harari, Tibor Csoszi, Dana Cernea, Paul O'Brien, William D Hanley, Amy V Kapp, Maria Anderson, Elicia Penuel, Bruce McCall, Andrea Pirzkall, Jan B Vermorken
BACKGROUND: Duligotuzumab, a novel dual-action humanized IgG1 antibody that blocks ligand binding to epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3), inhibits signaling from all ligand-dependent HER dimers, and can elicit antibody-dependent cell-mediated cytotoxicity. High tumor-expression of neuregulin 1 (NRG1), a ligand to HER3, may enhance sensitivity to duligotuzumab. METHODS: This multicenter, open-label, randomized phase II study (MEHGAN) evaluated drug efficacy in patients with recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) progressive on/after chemotherapy and among patients with NRG1-high tumors...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27784795/the-potential-roles-of-long-noncoding-rnas-lncrna-in-glioblastoma-development
#13
Shuang Liu, Ramkrishna Mitra, Ming-Ming Zhao, Wenhong Fan, Christine M Eischen, Feng Yin, Zhongming Zhao
Long noncoding RNA (lncRNA) may contribute to the initiation and progression of tumor. In this study, we first systematically compared lncRNA and mRNA expression between glioblastoma and paired normal brain tissues using microarray data. We found 27 lncRNA and 82 mRNA significantly upregulated in glioblastoma, as well as 198 lncRNA and 285 mRNA significantly downregulated in glioblastoma. We identified 138 coexpressed lncRNA-mRNA pairs from these differentially expressed lncRNA and genes. Subsequent pathway analysis of the lncRNA-paired genes indicated that EphrinB-EPHB, p75-mediated signaling, TNFα/NF-κB, and ErbB2/ErbB3 signaling pathways might be altered in glioblastoma...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27776045/microrna-148a-suppresses-the-proliferation-and-migration-of-pancreatic-cancer-cells-by-down-regulating-erbb3
#14
Hui Feng, Yalei Wang, Jiaojiao Su, Hongwei Liang, Chen-Yu Zhang, Xi Chen, Weiyan Yao
OBJECTIVES: ErbB3 (HER3) has been associated with pancreatic cancer progression, but little is known about its regulatory mechanisms. We investigated whether microRNAs (miRNAs) regulate levels of ErbB3 in pancreatic cancer cells. METHODS: We used bioinformatic analyses to search for miRNAs that can potentially target ERBB3. Furthermore, the biological consequences of the targeting of ERBB3 by miR-148a were examined by cell proliferation and migration assays in vitro...
October 2016: Pancreas
https://www.readbyqxmd.com/read/27770702/modulation-of-hcv-replication-and-translation-by-erbb3-binding-protein1-isoforms
#15
Priya Mishra, Updesh Dixit, Ashutosh K Pandey, Alok Upadhyay, Virendra N Pandey
We recently identified a cell-factor, ErbB3 binding protein 1 (Ebp-1), which specifically interacts with the viral RNA genome and modulates HCV replication and translation. Ebp1 has two isoforms, p48, and p42, that result from differential splicing. We found that both isoforms interact with HCV proteins NS5A and NS5B, as well as cell-factor PKR. The p48 isoform, which localizes in the cytoplasm and nuclei, promoted HCV replication, whereas the shorter p42 isoform, which resides exclusively in the cytoplasm, strongly inhibited HCV replication...
October 19, 2016: Virology
https://www.readbyqxmd.com/read/27756321/egfr-transactivation-contributes-to-neuroinflammation-in-streptococcus-suis-meningitis
#16
Xiao-Pei Yang, Ji-Yang Fu, Rui-Cheng Yang, Wen-Tong Liu, Tao Zhang, Bo Yang, Ling Miao, Bei-Bei Dou, Chen Tan, Huan-Chun Chen, Xiang-Ru Wang
BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic bacterial pathogen in both humans and animals, which can cause high morbidity and mortality. Meningitis is one of the major clinical manifestations of SS2 infection. However, the specific process of SS2 meningitis and its molecular mechanisms remain unclear. Epidermal growth factor receptor (EGFR) has been reported to initiate transduction of intracellular signals and regulate host inflammatory responses. Whether and how EGFR contributes to the development of S...
October 19, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27743014/membrane-protein-quantity-control-at-the-endoplasmic-reticulum
#17
Ignat Printsev, Daniel Curiel, Kermit L Carraway
The canonical function of the endoplasmic reticulum-associated degradation (ERAD) system is to enforce quality control among membrane-associated proteins by targeting misfolded secreted, intra-organellar, and intramembrane proteins for degradation. However, increasing evidence suggests that ERAD additionally functions in maintaining appropriate levels of a subset of membrane-associated proteins. In this 'quantity control' capacity, ERAD responds to environmental cues to regulate the proteasomal degradation of specific ERAD substrates according to cellular need...
October 14, 2016: Journal of Membrane Biology
https://www.readbyqxmd.com/read/27709558/dna-copy-number-alterations-gene-expression-changes-and-disease-free-survival-in-patients-with-colorectal-cancer-a-10-year-follow-up
#18
Elisabetta Bigagli, Carlotta De Filippo, Cinzia Castagnini, Simona Toti, Francesco Acquadro, Francesco Giudici, Marilena Fazi, Piero Dolara, Luca Messerini, Francesco Tonelli, Cristina Luceri
BACKGROUND: DNA copy number alterations (CNAs) and gene expression changes have amply been encountered in colorectal cancers (CRCs), but the extent at which CNAs affect gene expression, as well as their relevance for tumor development, are still poorly defined. Here we aimed at assessing the clinical relevance of these parameters in a 10 year follow-up study. METHODS: Tumors and normal adjacent colon mucosa, obtained at primary surgery from 21 CRC patients, were subjected to (i) high-resolution array CGH (a-CGH) for the detection of CNAs and (ii) microarray-based transcriptome profiling for the detection of gene expression (GE) changes...
December 2016: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/27662660/genomic-characterization-of-liver-metastases-from-colorectal-cancer-patients
#19
José María Sayagués, Luís Antonio Corchete, María Laura Gutiérrez, Maria Eugenia Sarasquete, María Del Mar Abad, Oscar Bengoechea, Encarna Fermiñán, María Fernanda Anduaga, Sofia Del Carmen, Manuel Iglesias, Carmen Esteban, María Angoso, Jose Antonio Alcazar, Jacinto García, Alberto Orfao, Luís Muñoz-Bellvis
Metastatic dissemination is the most frequent cause of death of sporadic colorectal cancer (sCRC) patients. Genomic abnormalities which are potentially characteristic of such advanced stages of the disease are complex and so far, they have been poorly described and only partially understood. We evaluated the molecular heterogeneity of sCRC tumors based on simultaneous assessment of the overall GEP of both coding mRNA and non-coding RNA genes in primary sCRC tumor samples from 23 consecutive patients and their paired liver metastases...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27658374/cadm3-necl-1-interferes-with-the-activation-of-the-pi3-kinase-akt-signaling-cascade-and-inhibits-schwann-cell-myelination-in-vitro
#20
Ming-Shuo Chen, Hyosung Kim, Léonard Jagot-Lacoussiere, Patrice Maurel
Axo-glial interactions are critical for myelination and the domain organization of myelinated fibers. Cell adhesion molecules belonging to the Cadm family, and in particular Cadm3 (axonal) and its heterophilic binding partner Cadm4 (Schwann cell), mediate these interactions along the internode. Using targeted shRNA-mediated knockdown, we show that the removal of axonal Cadm3 promotes Schwann cell myelination in the in vitro DRG neuron/Schwann cell myelinating system. Conversely, over-expressing Cadm3 on the surface of DRG neuron axons results in an almost complete inability by Schwann cells to form myelin segments...
December 2016: Glia
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