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https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#1
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28722233/cooperative-interaction-of-hepatocyte-growth-factor-and-neuregulin-regulates-schwann-cell-migration-and-proliferation-through-grb2-associated-binder-2-in-peripheral-nerve-repair
#2
Yoon Kyoung Shin, So Young Jang, Seoug Hoon Yun, Yun Young Choi, Byeol-A Yoon, Young Rae Jo, So Young Park, Min Gyoung Pak, Joo In Park, Hwan Tae Park
The sequential reactive changes in Schwann cell phenotypes in transected peripheral nerves, including dedifferentiation, proliferation and migration, are essential for nerve repair. Even though the injury-induced migratory and proliferative behaviors of Schwann cells resemble epithelial and mesenchymal transition (EMT) in tumors, the molecular mechanisms underlying this phenotypic change of Schwann cells are still unclear. Here we show that the reactive Schwann cells exhibit migratory features dependent on the expression of a scaffolding oncoprotein Grb2-associated binder-2 (Gab2), which was transcriptionally induced by neuregulin 1-ErbB2 signaling following nerve injury...
July 19, 2017: Glia
https://www.readbyqxmd.com/read/28719033/identification-of-driver-copy-number-alterations-in-diverse-cancer-types-and-application-in-drug-repositioning
#3
Wenbin Zhou, Zhangxiang Zhao, Ruiping Wang, Yue Han, Chengyu Wang, Fan Yang, Ya Han, Haihai Liang, Lishuang Qi, Chenguang Wang, Zheng Guo, Yunyan Gu
Results from numerous studies suggest an important role for somatic copy number alterations (SCNAs) in cancer progression. Our work aimed to identify the drivers (oncogenes or tumor suppressor genes) that reside in recurrently aberrant genomic regions, including a large number of genes or non-coding genes, which remain a challenge for decoding the SCNAs involved in carcinogenesis. Here, we propose a new approach to comprehensively identify drivers, using 8740 cancer samples involving 18 cancer types from The Cancer Genome Atlas (TCGA)...
July 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28718916/the-genetic-landscape-of-endometrial-clear-cell-carcinomas
#4
Deborah F DeLair, Kathleen A Burke, Pier Selenica, Raymond S Lim, Sasinya N Scott, Sumit Middha, Abhinita S Mohanty, Donavan T Cheng, Michael F Berger, Robert A Soslow, Britta Weigelt
Clear cell carcinoma of the endometrium is a rare type of endometrial cancer generally associated with an aggressive clinical behavior. Here we sought to define the repertoire of somatic genetic alterations in endometrial clear cell carcinomas (ECCs) and whether ECCs could be classified into the molecular subtypes described for endometrial endometrioid and serous carcinomas. We performed a rigorous histopathological review, immunohistochemical analysis and massively parallel sequencing targeting 300 cancer-related genes of 32 pure ECCs...
July 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28713927/classifier-of-cross-talk-genes-predicts-the-prognosis-of-hepatocellular-carcinoma
#5
Xiaofeng Zhai, Qingfeng Xue, Qun Liu, Yuyu Guo, Zhe Chen
The present study aimed to establish a prediction model for hepatocellular carcinoma (HCC) based on the cross talk genes from important biological pathways involved in HCC. Differentially expressed genes (DEGs) for HCC were identified from mRNA profiles of GSE36376, which were mapped to protein‑protein interaction (PPI) networks from BioGrid and the human protein reference database. Then critical genes based on the deviation score and the degree of node were selected from the novel PPI network. Cross talk genes were screened from the network established based on the associations of gene‑gene, gene‑pathway and pathway‑pathway...
July 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713919/ganetespib-induces-g2-m-cell-cycle-arrest-and-apoptosis-in-gastric-cancer-cells-through-targeting-of-receptor-tyrosine-kinase-signaling
#6
Harry Lee, Nipun Saini, Amanda B Parris, Ming Zhao, Xiaohe Yang
Heat shock protein 90 (HSP90) regulates several important cellular processes via its repertoire of 'client proteins'. These client proteins have been found to play fundamental roles in signal transduction, cell proliferation, cell cycle progression and survival, as well as other features of malignant cells, such as invasion, tumor angiogenesis and metastasis. Thus, HSP90 is an emerging target for cancer therapy. To this end, we evaluated ganetespib (STA-9090), a novel and potent HSP90 inhibitor, for its activity in gastric cancer cell lines...
July 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28711929/predictive-value-of-molecular-subtyping-in-nmibc-by-rt-qpcr-of-erbb2-esr1-pgr-and-mki67-from-formalin-fixed-tur-biopsies
#7
Johannes Breyer, Ralph Markus Wirtz, Wolfgang Otto, Mark Laible, Kornelia Schlombs, Philipp Erben, Maximilian Christian Kriegmair, Robert Stoehr, Sebastian Eidt, Stefan Denzinger, Maximilian Burger, Arndt Hartmann
Expression of ESR1, PGR, HER2 and Ki67 is important for risk stratification and therapy in breast cancer. Hormone receptor expression can also be found in MIBC, reflecting luminal and basal subtypes of breast cancer. Thus the purpose was to investigate on the mRNA expression of the aforementioned markers and their prognostic value in pT1 bladder cancer. Retrospective analysis of clinical data and Formalin-Fixed Paraffin-Embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder was performed...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28694468/interactome-and-reciprocal-activation-of-pathways-in-topical-mesenchymal-stem-cells-and-the-recipient-cerebral-cortex-following-traumatic-brain-injury
#8
Ping K Lam, Kevin K W Wang, Anthony W I Lo, Cindy S W Tong, Don W C Ching, Kenneth Wong, Zhihui Yang, Themis Kong, Kin K Y Lo, Richard K W Choy, Paul B S Lai, George K C Wong, Wai S Poon
In this study, GFP-MSCs were topically applied to the surface of cerebral cortex within 1 hour of experimental TBI. No treatment was given to the control group. Three days after topical application, the MSCs homed to the injured parenchyma and improved the neurological function. Topical MSCs triggered earlier astrocytosis and reactive microglia. TBI penumbra and hippocampus had higher cellular proliferation. Apoptosis was suppressed at hippocampus at 1 week and reduced neuronal damaged was found in the penumbral at day 14 apoptosis...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28692846/development-of-screen-printed-electrode-based-immunosensor-for-the-detection-of-her2-antigen-in-human-serum-samples
#9
Sagarika Deepthy Tallapragada, Keya Layek, Runu Mukherjee, Kalyan Kumar Mistry, Monidipa Ghosh
In this study, an immunosensor based on screen-printed electrode (SPE) has been developed for the detection of Human Epidermal Growth Factor Receptor-2 (HER2) antigen. The SPEs were fabricated and a sandwich enzyme linked immunosorbent assay (ELISA) format was followed for the construction of the immunosensor. The capture antibody (mouse anti-human ErbB2) was coated onto the electrode surface without any prior surface modification, followed by the addition of recombinant human HER2 antigen. Biotinylated goat anti-human ErbB2 was used as the detection antibody which was linked to streptavidin conjugated horseradish peroxidase (HRP)...
June 30, 2017: Bioelectrochemistry
https://www.readbyqxmd.com/read/28690394/a-software-application-for-mining-and-presenting-relevant-cancer-clinical-trials-per-cancer-mutation
#10
Lisa M Gandy, Jordan Gumm, Amanda L Blackford, Elana J Fertig, Luis A Diaz
ClinicalTrials.org is a popular portal which physicians use to find clinical trials for their patients. However, the current setup of ClinicalTrials.org makes it difficult for oncologists to locate clinical trials for patients based on mutational status. We present CTMine, a system that mines ClinicalTrials.org for clinical trials per cancer mutation and displays the trials in a user-friendly Web application. The system currently lists clinical trials for 6 common genes (ALK, BRAF, ERBB2, EGFR, KIT, and KRAS)...
2017: Cancer Informatics
https://www.readbyqxmd.com/read/28687333/predicting-novel-genes-and-pathways-associated-with-osteosarcoma-by-using-bioinformatics-analysis
#11
Bo Dong, Guozhu Wang, Jie Yao, Puwei Yuan, Wulin Kang, Liqiang Zhi, Xijing He
This aim of this study was to explore novel biomarkers related to osteosarcoma. The mRNA expression profile GSE41293 dataset was downloaded from the Gene Expression Omnibus (GEO) database, which included seven osteosarcoma and six control samples. After preprocessing, the FASTQ format reads of 13 samples were mapped to the reference sequences to screen for unique mapping reads. Differentially expressed genes (DEGs) were selected, which were then used for pathway and protein-protein interaction (PPI) network analyses...
July 4, 2017: Gene
https://www.readbyqxmd.com/read/28684961/natural-history-of-invasive-papillary-breast-carcinoma-followed-for-10-years-a-case-report-and-literature-review
#12
Yong Joon Suh, Hyukjai Shin, Tae Jung Kwon
Diachronic research on untreated breast cancer completely depends on past medical records when no more recent, advanced methods are available. Herein, we report a case of invasive papillary breast carcinoma followed for 10 years in a 59-year-old woman who refused any treatment. The diagnosis was based on core needle biopsies. At the patient's first visit in July 2006, the tumor measured 10.4 × 7.2 × 3.5 cm. It was staged as IIIB (T4bN1). In May 2016, the tumor was staged as IIIC (T4bN3a). In the past 10 years, the tumor has increased to 12...
2017: Case Reports in Medicine
https://www.readbyqxmd.com/read/28683746/multi-omics-of-34-colorectal-cancer-cell-lines-a-resource-for-biomedical-studies
#13
Kaja C G Berg, Peter W Eide, Ina A Eilertsen, Bjarne Johannessen, Jarle Bruun, Stine A Danielsen, Merete Bjørnslett, Leonardo A Meza-Zepeda, Mette Eknæs, Guro E Lind, Ola Myklebost, Rolf I Skotheim, Anita Sveen, Ragnhild A Lothe
BACKGROUND: Colorectal cancer (CRC) cell lines are widely used pre-clinical model systems. Comprehensive insights into their molecular characteristics may improve model selection for biomedical studies. METHODS: We have performed DNA, RNA and protein profiling of 34 cell lines, including (i) targeted deep sequencing (n = 612 genes) to detect single nucleotide variants and insertions/deletions; (ii) high resolution DNA copy number profiling; (iii) gene expression profiling at exon resolution; (iv) small RNA expression profiling by deep sequencing; and (v) protein expression analysis (n = 297 proteins) by reverse phase protein microarrays...
July 6, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28681313/an-independent-survival-prognostic-role-for-human-epidermal-growth-factor-receptor-2-in-gastric-cancer-evidence-from-a-meta-analysis
#14
Y Wang, L He, Y Cheng
BACKGROUND: Some studies have suggested that human epidermal growth factor receptor 2 (HER2) positive is associated with poor outcomes in gastric cancer (GC), whereas another inconsistent studies make the situation confused. This meta-analysis was performed to determine whether HER2 played an independent prognostic role in clinicopathological characteristics and survival outcomes of GC. PATIENTS AND METHODS: Combination of GC and human epidermal growth factor 2 or HER2 or HER2/neu or erbB-2 or cerbB-2 or c-erbB2 or CD340 or p185 were used as key words...
July 5, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28680880/in-vitro-anticancer-effect-of-gedunin-on-human-teratocarcinomal-ntera-2-cancer-stem-like-cells
#15
Luxmiga Tharmarajah, Sameera Ranganath Samarakoon, Meran Keshawa Ediriweera, Poorna Piyathilaka, Kamani Hemamamla Tennekoon, Kanishka Sithira Senathilake, Umapriyatharshini Rajagopalan, Prasanna Bandula Galhena, Ira Thabrew
Gedunin is one of the major compounds found in the neem tree (Azadirachta indica). In the present study, antiproliferative potential of gedunin was evaluated in human embryonal carcinoma cells (NTERA-2, a cancer stem cell model) and peripheral blood mononuclear cells (PBMCs), using Sulforhodamine (SRB) and WST-1 assays, respectively. The effects of gedunin on expression of heat shock protein 90 (HSP90), its cochaperone Cdc37, and HSP client proteins (AKT, ErbB2, and HSF1) were evaluated by real-time PCR. Effects of gedunin on apoptosis were evaluated by (a) apoptosis associated morphological changes, (b) caspase 3/7 expression, (c) DNA fragmentation, (d) TUNEL assay, and (e) real-time PCR of apoptosis related genes (Bax, p53, and survivin)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28680299/the-scaffolding-protein-grb2-associated-binder-1-in-skeletal-muscles-and-terminal-schwann-cells-regulates-postnatal-neuromuscular-synapse-maturation
#16
So Young Park, So Young Jang, Yoon Kyoung Shin, Dong Keun Jung, Byeol A Yoon, Jong Kook Kim, Young Rae Jo, Hye Jeong Lee, Hwan Tae Park
The vertebrate neuromuscular junction (NMJ) is considered as a "tripartite synapse" consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice...
June 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28671339/role-of-erbb-her-family-of-receptor-tyrosine-kinases-in-cholangiocyte-biology
#17
REVIEW
Anna Pellat, Javier Vaquero, Laura Fouassier
The ErbB/HER family comprises four distinct tyrosine kinase receptors, EGFR/ErbB1/HER1, ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4, which trigger intracellular signals at the origin of essential cellular functions including differentiation, proliferation, survival and migration. Epithelial cells, named cholangiocytes, that line intrahepatic and extrahepatic bile ducts, contribute substantially to biliary secretory functions and bile transport. Although ErbB receptors have been widely studied in cholangiocarcinoma (CCA), a malignancy of the biliary tract, knowledge of these receptors in biliary epithelium physiology and in non-malignant cholangiopathies is far from completed...
July 3, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28670859/high-expression-of-cpne3-predicts-adverse-prognosis-in-acute-myeloid-leukemia
#18
Lin Fu, Huaping Fu, Jianlin Qiao, Yifan Pang, Keman Xu, Lei Zhou, Qingyun Wu, Zhenyu Li, Xiaoyan Ke, Kailin Xu, Jinlong Shi
CPNE3, a member of a Ca(2+) -dependent phospholipid-binding protein family, was identified as a ligand of ERBB2 and has a more general role in carcinogenesis. Here, we identified the prognostic significance of CPNE3 expression in acute myeloid leukemia (AML) patients based on two datasets. In the first microarray datasets (n=272), high CPNE3 expression (CPNE3(high) ) was associated with adverse overall survival (OS, P < 0.001) and event-free survival (EFS, P < 0.001) comparing to low CPNE3 expression (CPNE3(low) )...
July 3, 2017: Cancer Science
https://www.readbyqxmd.com/read/28670312/cervical-cancer-neoantigen-landscape-and-immune-activity-is-associated-with-human-papillomavirus-master-regulators
#19
Yong Qin, Suhendan Ekmekcioglu, Marie-Andrée Forget, Lorant Szekvolgyi, Patrick Hwu, Elizabeth A Grimm, Amir A Jazaeri, Jason Roszik
Human papillomaviruses (HPVs) play a major role in development of cervical cancer, and HPV oncoproteins are being targeted by immunotherapies. Although these treatments show promising results in the clinic, many patients do not benefit or the durability is limited. In addition to HPV antigens, neoantigens derived from somatic mutations may also generate an effective immune response and represent an additional and distinct immunotherapy strategy against this and other HPV-associated cancers. To explore the landscape of neoantigens in cervix cancer, we predicted all possible mutated neopeptides in two large sequencing data sets and analyzed whether mutation and neoantigen load correlate with antigen presentation, infiltrating immune cell types, and a HPV-induced master regulator gene expression signature...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28667006/whole-genome-and-epigenomic-landscapes-of-etiologically-distinct-subtypes-of-cholangiocarcinoma
#20
Apinya Jusakul, Ioana Cutcutache, Chern Han Yong, Jing Quan Lim, Mi Ni Huang, Nisha Padmanabhan, Vishwa Nellore, Sarinya Kongpetch, Alvin Wei Tian Ng, Ley Moy Ng, Su Pin Choo, Swe Swe Myint, Raynoo Thanan, Sanjanaa Nagarajan, Weng Khong Lim, Cedric Chuan Young Ng, Arnoud Boot, Mo Liu, Choon Kiat Ong, Vikneswari Rajasegaran, Stefanus Lie, Alvin Soon Tiong Lim, Tse Hui Lim, Jing Tan, Jia Liang Loh, John R McPherson, Narong Khuntikeo, Vajaraphongsa Bhudhisawasdi, Puangrat Yongvanit, Sopit Wongkham, Yasushi Totoki, Hiromi Nakamura, Yasuhito Arai, Satoshi Yamasaki, Pierce K H Chow, Alexander Yaw Fui Chung, London Lucien Peng Jin Ooi, Kiat Hon Lim, Simona Dima, Dan G Duda, Irinel Popescu, Philippe Broet, Sen-Yung Hsieh, Ming-Chin Yu, Aldo Scarpa, Jiaming Lai, Di-Xian Luo, Andre Lopes Carvalho, André Luiz Vettore, Hyungjin Rhee, Young Nyun Park, Ludmil Alexandrov, Raluca Gordan, Steven G Rozen, Tatsuhiro Shibata, Chawalit Pairojkul, Bin Tean Teh, Patrick Tan
Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analysed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined four CCA clusters - Fluke-Positive CCAs (Clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations, conversely Fluke-Negative CCAs (Clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements...
June 30, 2017: Cancer Discovery
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