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https://www.readbyqxmd.com/read/28538219/molecular-alterations-in-patients-with-pulmonary-adenocarcinoma-presenting-with-malignant-pleural-effusion-at-the-first-diagnosis
#1
Erika F Rodriguez, Maryam Shabihkhani, Jamal Carter, Zahra Maleki
OBJECTIVES: The aim of this study was to report cytologic and molecular features of pulmonary adenocarcinoma patients presenting with a malignant pleural effusion at the first diagnosis. STUDY DESIGN: Patients who had a cytopathologic diagnosis conclusive for lung adenocarcinoma for the first time on their pleural fluid specimen, and molecular testing done, were studied. The control group consisted of patients with a malignant pleural effusion that developed during disease progression...
May 25, 2017: Acta Cytologica
https://www.readbyqxmd.com/read/28537922/cooperative-but-distinct-early-co-signaling-events-originate-from-erbb2-and-erbb1-receptors-upon-trastuzumab-treatment-in-breast-cancer-cells
#2
Paola Bagnato, Alessia Castagnino, Katia Cortese, Maria Bono, Silvia Grasso, Grazia Bellese, Tiziana Daniele, Richard Lundmark, Paola Defilippi, Patrizio Castagnola, Carlo Tacchetti
ERBB2 receptor belongs to the ERBB tyrosine kinase receptor family. At variance to the other family members, ERBB2 is a constitutively active orphan receptor. Upon ligand binding and activation, ERBB receptors form homo- or hetero-dimers with the other family members, including ERBB2, promoting an intracellular signaling cascade. ERBB2 is the preferred dimerization partner and ERBB2 heterodimers signaling is stronger and longer acting compared to heterodimers between other ERBB members. The specific contribution of ERBB2 in heterodimer signaling is still undefined...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28531814/targeting-egfr-her2-heterodimerization-with-a-novel-anti-her2-domain-ii-iii-antibody
#3
Xiaojie Yu, Lingfei Wang, Yafeng Shen, Chao Wang, Yajun Zhang, Yanchun Meng, Yang Yang, Beibei Liang, Bo Zhou, Huajing Wang, Huafeng Wei, Changhai Lei, Shi Hu, Bohua Li
HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. Despite the effectiveness of trastuzumab, its efficacy remains variable and often modest. Thus, there is an urgent need to improve ErbB2-targeting therapy. Here, we describe a novel anti-HER2 antibody, 7C3, which was developed using hybridoma technique. Structural analysis confirms that the epitope of this antibody is in domain II/III of HER2...
May 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28521404/silencing-tak1-alters-gene-expression-signatures-in-bladder-cancer-cells
#4
Jimin Chen, Nan Zhang, Jiaming Wen, Zhewei Zhang
The aim of the present study was to identify the differentially expressed genes (DEGs) that are induced by the silencing of transforming growth factor-β-activated kinase 1 (TAK1) in bladder cancer cells and to analyze the potential biological effects. Dataset GSE52452 from mutant fibroblast growth factor receptor 3 (FGFR3) bladder cancer cells transfected with control siRNA or TAK1-specific siRNA was downloaded from Gene Expression Omnibus. The DEGs between the two groups were identified using Limma package following data pre-processing by Affy in Bioconductor...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28514745/combating-acquired-resistance-to-trastuzumab-by-an-anti-erbb2-fully-human-antibody
#5
Chao Wang, Lingfei Wang, Xiaojie Yu, Yajun Zhang, Yanchun Meng, Huajing Wang, Yang Yang, Jie Gao, Huafeng Wei, Jian Zhao, Cuihua Lu, Han Chen, Yanping Sun, Bohua Li
Trastuzumab resistance is a common problem that impedes the effectiveness of trastuzumab in ErbB2-amplified cancers. About 70% of ErbB2-amplified breast cancers do not respond to trastuzumab (de novo resistance), and the majority of the trastuzumab-responsive cancers progress within 1 year (acquired resistance). Different mechanisms exist between de novo and acquired resistance. Innate resistance mechanisms are mainly independent of ErbB2 receptor activity, and acquired resistance involves with alterations depending on ErbB2 activity...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514724/sirna-mediated-inactivation-of-her3-improves-the-antitumour-activity-and-sensitivity-of-gefitinib-in-gastric-cancer-cells
#6
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/28504299/what-we-know-about-stage-ii-and-iii-colon-cancer-it-s-still-not-enough
#7
Alberto Puccini, Martin D Berger, Wu Zhang, Heinz-Josef Lenz
The introduction of oxaliplatin as adjuvant treatment for stage III colon cancer in 2004 has been the last practice changing progress in adjuvant treatment for patients with early colon cancer. Since then, many prognostic and predictive biomarkers have been studied, but only DNA mismatch repair status has been validated as having an important prognostic value. Accordingly, TNM and clinical-pathological patterns, such as pT4 lesions and lymph node sampling <12 nodes, are the main factors that guide physicians' choice regarding adjuvant treatment...
May 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28501855/extracellular-ph-is-a-biomarker-enabling-detection-of-breast-cancer-and-liver-cancer-using-cest-mri
#8
Miaomiao Chen, Chaoying Chen, Zhiwei Shen, Xiaolei Zhang, Yanzi Chen, Fengfeng Lin, Xilun Ma, Caiyu Zhuang, Yifei Mao, Haochuan Gan, Peidong Chen, Xiaodan Zong, Renhua Wu
Extracellular pH (pHe) decrease is associated with tumor growth, invasion, metastasis, and chemoresistance, which can be detected by chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). Here, we demonstrated that ioversol CEST MRI can be exploited to achieve pHe mapping of the liver cancer microenvironment. In in vitro studies, we firstly explored whether ioversol signal is pH-dependent, and calculated the function equation between the CEST effects of ioversol and pH values, in the range of 6...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28501091/update-on-gastroesophageal-adenocarcinoma-targeted-therapies
#9
REVIEW
Steven B Maron, Daniel V T Catenacci
Gastroesophageal cancer (GEC) remains a major cause of cancer-related mortality worldwide. Although the incidence of distal gastric adenocarcinoma (GC) is declining in the United States, proximal esophagogastric junction adenocarcinoma (EGJ) incidence is rising. GC and EGJ, together, are treated uniformly in the metastatic setting as GEC. Overall survival in the metastatic setting remains poor, with few molecular targeted approaches having been successfully incorporated into routine care to date-only first-line anti-HER2 therapy for ERBB2 amplification and second-line anti-VEGFR2 therapy...
June 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28493713/cetuximab-prevents-methotrexate-induced-cytotoxicity-in-vitro-through-epidermal-growth-factor-dependent-regulation-of-renal-drug-transporters
#10
Pedro Caetano-Pinto, Amer Jamalpoor, Janneke Ham, Anastasia Goumenou, Monique Mommersteeg, Dirk Pijnenburg, Rob Ruijtenbeek, Natalia Sánchez-Romero, Bertrand van Zelst, Sandra Heil, Jitske Jansen, Martijn J Wilmer, Carla M L van Herpen, Rosalinde Masereeuw
The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells over-expressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4) and P-glycoprotein (P-gp) in methotrexate handling upon EGF and/or cetuximab treatment...
May 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28492066/progression-inference-for-somatic-mutations-in-cancer
#11
Leif E Peterson, Tatiana Kovyrshina
Computational methods were employed to determine progression inference of genomic alterations in commonly occurring cancers. Using cross-sectional TCGA data, we computed evolutionary trajectories involving selectivity relationships among pairs of gene-specific genomic alterations such as somatic mutations, deletions, amplifications, downregulation, and upregulation among the top 20 driver genes associated with each cancer. Results indicate that the majority of hierarchies involved TP53, PIK3CA, ERBB2, APC, KRAS, EGFR, IDH1, VHL, etc...
April 2017: Heliyon
https://www.readbyqxmd.com/read/28490348/an-international-reproducibility-study-validating-quantitative-determination-of-erbb2-esr1-pgr-and-mki67-mrna-in-breast-cancer-using-mammatyper%C3%A2
#12
Zsuzsanna Varga, Annette Lebeau, Hong Bu, Arndt Hartmann, Frederique Penault-Llorca, Elena Guerini-Rocco, Peter Schraml, Fraser Symmans, Robert Stoehr, Xiaodong Teng, Andreas Turzynski, Reinhard von Wasielewski, Claudia Gürtler, Mark Laible, Kornelia Schlombs, Heikki Joensuu, Thomas Keller, Peter Sinn, Ugur Sahin, John Bartlett, Giuseppe Viale
BACKGROUND: Accurate determination of the predictive markers human epidermal growth factor receptor 2 (HER2/ERBB2), estrogen receptor (ER/ESR1), progesterone receptor (PgR/PGR), and marker of proliferation Ki67 (MKI67) is indispensable for therapeutic decision making in early breast cancer. In this multicenter prospective study, we addressed the issue of inter- and intrasite reproducibility using the recently developed reverse transcription-quantitative real-time polymerase chain reaction-based MammaTyper® test...
May 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28489587/ngs-based-identification-of-mutational-hotspots-for-targeted-therapy-in-anaplastic-thyroid-carcinoma
#13
Vera Tiedje, Saskia Ting, Thomas Herold, Sarah Synoracki, Soeren Latteyer, Lars C Moeller, Denise Zwanziger, Martin Stuschke, Dagmar Fuehrer, Kurt Werner Schmid
CONTEXT: Anaplastic thyroid carcinoma (ATC) represents one of the most aggressive carcinomas with no consistent survival benefit when treated with conventional radiochemotherapy. Approaches targeting "oncogene addiction" of ATC are increasingly explored and first promising results have been reported in single case studies. OBJECTIVE: To determine the prevalence of mutations in known thyroid oncogenes and signalling pathways amendable to targeted therapy in a large cohort of ATC...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28485554/identification-of-aca-28-a-1-acetoxychavicol-acetate-analogue-compound-as-a-novel-modulator-of-erk-mapk-signaling-which-preferentially-kills-human-melanoma-cells
#14
Ryosuke Satoh, Kanako Hagihara, Kazuki Matsuura, Yoshiaki Manse, Ayako Kita, Tatsuki Kunoh, Takashi Masuko, Mariko Moriyama, Hiroyuki Moriyama, Genzoh Tanabe, Osamu Muraoka, Reiko Sugiura
The extracellular signal-regulated kinase (ERK) signaling pathway is essential for cell proliferation and is frequently deregulated in human tumors such as melanoma. Melanoma remains incurable despite the use of conventional chemotherapy; consequently, development of new therapeutic agents for melanoma is highly desirable. Here, we carried out a chemical genetic screen using a fission yeast phenotypic assay and showed that ACA-28, a synthetic derivative of 1'-acetoxychavicol acetate (ACA), which is a natural ginger compound, effectively inhibited the growth of melanoma cancer cells wherein ERK MAPK signaling is hyperactivated due to mutations in the upstream activating regulators...
May 9, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28485381/regulation-of-cardiomyocyte-behavior-in-zebrafish-trabeculation-by-neuregulin-2a-signaling
#15
S Javad Rasouli, Didier Y R Stainier
Trabeculation is crucial for cardiac muscle growth in vertebrates. This process requires the Erbb2/4 ligand Neuregulin (Nrg), secreted by the endocardium, as well as blood flow/cardiac contractility. Here, we address two fundamental, yet unresolved, questions about cardiac trabeculation: why does it initially occur in the ventricle and not the atrium, and how is it modulated by blood flow/contractility. Using loss-of-function approaches, we first show that zebrafish Nrg2a is required for trabeculation, and using a protein-trap line, find that it is expressed in both cardiac chambers albeit with different spatiotemporal patterns...
May 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28480322/data-on-the-effect-of-in-vivo-knockdown-using-artificial-erbb3-mirna-on-remak-bundle-structure
#16
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/28476488/improving-pertuzumab-production-by-gene-optimization-and-proper-signal-peptide-selection
#17
Amin Ramezani, Elham Mahmoudi Maymand, Mahsa Yazdanpanah-Samani, Ahmad Hosseini, Fatemeh Sadat Toghraie, Abbas Ghaderi
Using proper signal peptide and codon optimization are important factors that must be considered when designing the vector to increase protein expression in Chinese Hamster Ovary (CHO) cells. The aim of the present study is to investigate how to enhance Pertuzumab production through heavy and light chain coding gene optimization and proper signal peptide selection. First, CHO-K1 cells were transiently transfected with whole-antibody-gene-optimized, variable-regions-optimized and non-optimized constructs and then we employed five different signal peptides to improve the secretion efficiency of Pertuzumab...
May 3, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28473715/rationally-co-targeting-divergent-pathways-in-kras-wild-type-colorectal-cancers-by-canscript-technology-reveals-tumor-dependence-on-notch-and-erbb2
#18
Nilesh Brijwani, Misti Jain, Muthu Dhandapani, Farrah Zahed, Pragnashree Mukhopadhyay, Manjusha Biswas, Deepak Khatri, Vinod D Radhakrishna, Biswanath Majumder, Padhma Radhakrishnan, Saravanan Thiyagarajan
KRAS mutation status can distinguish between metastatic colorectal carcinoma (mCRC) patients who may benefit from therapies that target the epidermal growth factor receptor (EGFR), such as cetuximab. However, patients whose tumors harbor mutant KRAS (codons 12/13, 61 and 146) are often excluded from EGFR-targeted regimens, while other patients with wild type KRAS will sometimes respond favorably to these same drugs. These conflicting observations suggest that a more robust approach to individualize therapy may enable greater frequency of positive clinical outcome for mCRC patients...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28472989/circulating-mutational-portrait-of-cancer-manifestation-of-aggressive-clonal-events-in-both-early-and-late-stages
#19
Meng Yang, Umit Topaloglu, W Jeffrey Petty, Matthew Pagni, Kristie L Foley, Stefan C Grant, Mac Robinson, Rhonda L Bitting, Alexandra Thomas, Angela T Alistar, Rodwige J Desnoyers, Michael Goodman, Carol Albright, Mercedes Porosnicu, Mihaela Vatca, Shadi A Qasem, Barry DeYoung, Ville Kytola, Matti Nykter, Kexin Chen, Edward A Levine, Edgar D Staren, Ralph B D'Agostino, Robin M Petro, William Blackstock, Bayard L Powell, Edward Abraham, Boris Pasche, Wei Zhang
BACKGROUND: Solid tumors residing in tissues and organs leave footprints in circulation through circulating tumor cells (CTCs) and circulating tumor DNAs (ctDNA). Characterization of the ctDNA portraits and comparison with tumor DNA mutational portraits may reveal clinically actionable information on solid tumors that is traditionally achieved through more invasive approaches. METHODS: We isolated ctDNAs from plasma of patients of 103 lung cancer and 74 other solid tumors of different tissue origins...
May 4, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28472234/comparison-of-breast-cancer-molecular-features-and-survival-by-african-and-european-ancestry-in-the-cancer-genome-atlas
#20
Dezheng Huo, Hai Hu, Suhn K Rhie, Eric R Gamazon, Andrew D Cherniack, Jianfang Liu, Toshio F Yoshimatsu, Jason J Pitt, Katherine A Hoadley, Melissa Troester, Yuanbin Ru, Tara Lichtenberg, Lori A Sturtz, Carl S Shelley, Christopher C Benz, Gordon B Mills, Peter W Laird, Craig D Shriver, Charles M Perou, Olufunmilayo I Olopade
Importance: African Americans have the highest breast cancer mortality rate. Although racial difference in the distribution of intrinsic subtypes of breast cancer is known, it is unclear if there are other inherent genomic differences that contribute to the survival disparities. Objectives: To investigate racial differences in breast cancer molecular features and survival and to estimate the heritability of breast cancer subtypes. Design, Setting, and Participants: Among a convenience cohort of patients with invasive breast cancer, breast tumor and matched normal tissue sample data (as of September 18, 2015) were obtained from The Cancer Genome Atlas...
May 4, 2017: JAMA Oncology
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