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https://www.readbyqxmd.com/read/28339086/identification-of-novel-mutations-in-endometrial-cancer-patients-by-whole-exome-sequencing
#1
Ya-Sian Chang, Hsien-Da Huang, Kun-Tu Yeh, Jan-Gowth Chang
The aim of the present study was to identify genomic alterations in Taiwanese endometrial cancer patients. This information is vitally important in Taiwan, where endometrial cancer is the second most common gynecological cancer. We performed whole-exome sequencing on DNA from 14 tumor tissue samples from Taiwanese endometrial cancer patients. We used the Genome Analysis Tool kit software package for data analysis, and the dbSNP, Catalogue of Somatic Mutations in Cancer (COSMIC) and The Cancer Genome Atlas (TCGA) databases for comparisons...
March 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28339023/lead-exposure-and-plasma-mrna-expression-in-erbb2-gene
#2
Margherita Ferrante, Caterina Ledda, Gea Oliveri Conti, Maria Fiore, Venerando Rapisarda, Chiara Copat, Giuseppe Sole, Nivea Terzo, Salvatore Travali
Epidemiologic data for carcinogenicity in those exposed to lead (Pb) suggests relations with cancers although the totality of the evidence is inconsistent. Alterations in the expression of ERBB receptors have been studied during the development and malignant transformation of different kinds of human tumors where they induce proliferation, angiogenesis and metastasis generation. Relevant clinical data demonstrate the role of ERBB2 receptors in the development and malignancy of human cancers. Therefore, the objective of the present investigation is to give more information on the link between plasma mRNA expression in ERBB2 gene and lead blood levels in a healthy population...
March 24, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28334857/co-cultures-with-stem-cell-derived-human-sensory-neurons-reveal-regulators-of-peripheral-myelination
#3
Alex J Clark, Malte S Kaller, Jorge Galino, Hugh J Willison, Simon Rinaldi, David L H Bennett
Effective bidirectional signalling between axons and Schwann cells is essential for both the development and maintenance of peripheral nerve function. We have established conditions by which human induced pluripotent stem cell-derived sensory neurons can be cultured with rat Schwann cells, and have produced for the first time long-term and stable myelinating co-cultures with human neurons. These cultures contain the specialized domains formed by axonal interaction with myelinating Schwann cells, such as clustered voltage-gated sodium channels at the node of Ranvier and Shaker-type potassium channel (Kv1...
February 15, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28333948/epigenomic-annotation-of-noncoding-mutations-identifies-mutated-pathways-in-primary-liver-cancer
#4
Rebecca F Lowdon, Ting Wang
Evidence that noncoding mutation can result in cancer driver events is mounting. However, it is more difficult to assign molecular biological consequences to noncoding mutations than to coding mutations, and a typical cancer genome contains many more noncoding mutations than protein-coding mutations. Accordingly, parsing functional noncoding mutation signal from noise remains an important challenge. Here we use an empirical approach to identify putatively functional noncoding somatic single nucleotide variants (SNVs) from liver cancer genomes...
2017: PloS One
https://www.readbyqxmd.com/read/28316823/a-new-solvate-of-afatinib-a-specific-inhibitor-of-the-erbb-family-of-tyrosine-kinases
#5
Matthias Zeller, Gabriel Lima Barros de Araujo, Trev Parker, Amrinder Singh Rai, Stephen R Byrn
Afatinib (systematic name: N-{4-(3-chloro-4-fluoro-anilino)-7-[(tetra-hydro-furan-3-yl)-oxy]quinazolin-6-yl}-4-(di-methyl-amino)-but-2-enamide), is a specific in-hibitor of the ErbB family of tyrosine kinases. The free base form crystallizes from aceto-nitrile as a mixed water-aceto-nitrile solvent, C24H25ClFN5O3·0.25C2H3N·2H2O. It crystallizes with two independent mol-ecules (A and B) in the asymmetric unit of the chiral space group P4212, but exhibits close to perfect pseudo-inversion symmetry, emulating P4/ncc that relates the two mol-ecules to each other...
March 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28316082/dacomitinib-induced-diarrhoea-is-associated-with-altered-gastrointestinal-permeability-and-disruption-in-ileal-histology-in-rats
#6
Ysabella Z A Van Sebille, Rachel J Gibson, Hannah R Wardill, Kate R Secombe, Imogen A Ball, Dorothy M K Keefe, John W Finnie, Joanne M Bowen
Dacomitinib - an irreversible pan-ErbB tyrosine kinase inhibitor (TKI) - causes diarrhoea in 75% of patients. Dacomitinib-induced diarrhoea has not previously been investigated and the mechanisms remain poorly understood. The present study aimed to develop an in-vitro and in-vivo model of dacomitinib-induced diarrhoea to investigate underlying mechanisms. T84 cells were treated with 1-4 μM dacomitinib and resistance and viability were measured using transepithelial electrical resistance (TEER) and XTT assays...
March 17, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28306722/distinct-erbb2-receptor-populations-differentially-interact-with-beta1-integrin-in-breast-cancer-cell-models
#7
Andrés Martín Toscani, Rocío G Sampayo, Federico Martín Barabas, Federico Fuentes, Marina Simian, Federico Coluccio Leskow
ErbB2 is a member of the ErbB family of tyrosine kinase receptors that plays a major role in breast cancer progression. Located at the plasma membrane, ErbB2 forms large clusters in spite of the presence of growth factors. Beta1 integrin, membrane receptor of extracellular matrix proteins, regulates adhesion, migration and invasiveness of breast cancer cells. Physical interaction between beta1 integrin and ErbB2 has been suggested although published data are contradictory. The aim of the present work was to study the interaction between ErbB2 and beta1 integrin in different scenarios of expression and activation...
2017: PloS One
https://www.readbyqxmd.com/read/28301080/hsp90-inhibitor-auy922-can-reverse-fulvestrant-induced-feedback-reaction-in-human-breast-cancer-cells
#8
Jingchao Bai, Guanglin Zhou, Yufan Qiu, Yunhui Hu, Jingjing Liu, Jing Zhao, Sheng Zhang, Jin Zhang
Hormone therapy has become one of the main strategy for breast cancer, however, many estrogen receptor(ER) positive patients ends in tumor collapse due to initial or acquired resistance to hormone treatment, which includes Fulvestrant. Here we report that ErbB Receptors and downstream PI3K/AKT and ERK pathway have been reactivated after treatment of Fulvestrant in ER positive MCF-7 and T47D cells, which are related to Fulvestrant resistance. HSP90 is a universally expressed chaperone protein and plays a vital role in both normal and cancer cells, HSP90 inhibitor AUY922 can reverse this feedback reactivation effect of Fulvestrant by targeting multiple proteins related in ErbB Receptors, PI3K/AKT and ERK pathway, which is much better than single targeting inhibitors...
March 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28286519/erbb-proteins-as-molecular-target-of-dietary-phytochemicals-in-malignant-diseases
#9
REVIEW
Alexandru Filippi, Oana-Alina Ciolac, Constanța Ganea, Maria-Magdalena Mocanu
ErbB proteins overexpression, in both normal and mutated forms, is associated with invasive forms of cancer prone to metastasis and with stronger antiapoptotic mechanisms and therefore more challenging to treat. Downstream effectors of ErbB receptors mediating these phenotypic traits include MAPK, STAT, and PI3K/AKT/mTOR pathways. Various phytochemical compounds were studied for their large number of biological effects including anticancer activity. Among these compounds, epigallocatechin-3-gallate (EGCG), the main catechin from green tea leaves, and curcumin, component of the curry powder, constituted the object of numerous studies...
2017: Journal of Oncology
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
#10
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 (PDX) tumors to ERBB inhibitors...
March 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28284947/behavioral-characterization-of-blocking-the-erbb-signaling-during-adolescent-and-adulthood-in-reward-liking-preference-and-reward-related-learning
#11
Hagar Tadmor, Idit Golani, Eshkar Dvir, Ilana Kremer, Alon Shamir
Adolescence is a critical period in brain development. During this critical period the seeking for hedonic activities is increased, and their activity signals are stronger than the regulatory signals of judgment and reasoning. We recently reported that alteration of ErbB signaling during this period led to elevated striatal dopamine levels and reduced preference for sweetness without affecting locomotor activity and exploratory behavior. In the current study, we extend our findings and explore whether inhibition of the ErbB pathway during adolescence or adulthood also affects alcohol preference (hedonic "liking"), avoidance learning, and motivational reward "wanting"...
March 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28280367/clarifying-the-molecular-mechanism-associated-with-carfilzomib-resistance-in-human-multiple-myeloma-using-microarray-gene-expression-profile-and-genetic-interaction-network
#12
Zhihong Zheng, Tingbo Liu, Jing Zheng, Jianda Hu
Carfilzomib is a Food and Drug Administration-approved selective proteasome inhibitor for patients with multiple myeloma (MM). However, recent studies indicate that MM cells still develop resistance to carfilzomib, and the molecular mechanisms associated with carfilzomib resistance have not been studied in detail. In this study, to better understand its potential resistant effect and its underlying mechanisms in MM, microarray gene expression profile associated with carfilzomib-resistant KMS-11 and its parental cell line was downloaded from Gene Expression Omnibus database...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28279416/cardio-oncology-related-to-heart-failure-epidermal-growth-factor-receptor-target-based-therapy
#13
REVIEW
Benjamin Kenigsberg, Varun Jain, Ana Barac
Cancer therapy targeting the epidermal growth factor receptor (EGFR)/erythroblastic leukemia viral oncogene B (ErbB)/human EGFR receptor (HER) family of tyrosine kinases has been successfully used in treatment of several malignancies. The ErbB pathways play a role in the maintenance of cardiac homeostasis. This article summarizes current knowledge about EGFR/ErbB/HER receptor-targeted cancer therapeutics focusing on their cardiotoxicity profiles, molecular mechanisms, and implications in clinical cardio-oncology...
April 2017: Heart Failure Clinics
https://www.readbyqxmd.com/read/28275713/axonal-type-iii-nrg1-controls-glutamate-synapse-formation-and-glua2-trafficking-in-hippocampal-accumbens-connections
#14
Chongbo Zhong, Wendy Akmentin, Chuang Du, Lorna W Role, David A Talmage
Altered neuregulin 1 (Nrg1)/ErbB signaling and glutamatergic hypofunction have been implicated in the pathophysiology of schizophrenia. Here, we employed gene chimeric ventral hippocampus (vHipp)-nucleus accumbens (nAcc) coculture from mouse, electrophysiology, immunocytochemistry, FM1-43 vesicle fusion, and electron microscopy techniques to examine the pre- and postsynaptic mechanisms of genetic deficits in Nrg1/ErbB signaling-induced glutamatergic dysfunctions. Reduced presynaptic type III Nrg1 expression along vHipp axons decreases the number of glutamate synapses and impairs GluA2 trafficking in the postsynaptic nAcc neurons, resulting in decreased frequency and amplitude of miniature EPSCs (mEPSCs)...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28275299/dysregulation-of-mrna-profile-in-cisplatin-resistant-gastric-cancer-cell-line-sgc7901
#15
Xiao-Que Xie, Qi-Hong Zhao, Hua Wang, Kang-Sheng Gu
AIM: To explore novel therapeutic target of cisplatin resistance in human gastric cancer. METHODS: The sensitivity of SGC7901 cells and cisplatin-resistant SGC7901 cells (SGC7901/DDP) for cisplatin were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. High-quality total RNA which isolated from SGC7901/DDP cells and SGC7901 cells were used for mRNA microarray analysis. Results were analyzed bioinformatically to predict their roles in the development of cisplatin resistance and the expression of 13 dysregulated mRNAs we selected were validated by quantitative real-time polymerase chain reaction (qRT-PCR)...
February 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28271613/qiliqiangxin-protects-against-anoxic-injury-in-cardiac-microvascular-endothelial-cells-via-nrg-1-erbb-pi3k-akt-mtor-pathway
#16
Jingfeng Wang, Jingmin Zhou, Yanyan Wang, Chunjie Yang, Mingqiang Fu, Jingjing Zhang, Xueting Han, Zhiming Li, Kai Hu, Junbo Ge
Cardiac microvascular endothelial cells (CMECs) are important angiogenic components and are injured rapidly after cardiac ischaemia and anoxia. Cardioprotective effects of Qiliqiangxin (QL), a traditional Chinese medicine, have been displayed recently. This study aims to investigate whether QL could protect CMECs against anoxic injury and to explore related signalling mechanisms. CMECs were successfully cultured from Sprague-Dawley rats and exposed to anoxia for 12 hrs in the absence and presence of QL. Cell migration assay and capillary-like tube formation assay on Matrigel were performed, and cell apoptosis was determined by TUNEL assay and caspase-3 activity...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28265860/neuregulin1%C3%AE-effects-on-brain-tissue-via-erk5-dependent-mapk-pathway-in-a-rat-model-of-cerebral-ischemia-reperfusion-injury
#17
Ning Gu, Keli Ge, Cui Hao, Yaqing Ji, Hongyun Li, Yunliang Guo
Neuregulin1β (NRG1β), a member of the excitomotor of tyrosine kinase receptor (erbB) family, was recently shown to play a neuroprotective role in cerebral ischemia-reperfusion injury. The present study analyzed the effects and its possible signaling pathway of NRG1β on brain tissues after cerebral ischemia-reperfusion injury. A focal cerebral ischemic model was established by inserting a monofilament thread to achieve middle cerebral artery occlusion, followed by an NRG1β injection via the internal carotid artery...
April 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28243590/second-line-treatment-of-nsclc-the-pan-erbb-inhibitor-afatinib-in-times-of-shifting-paradigms
#18
REVIEW
Jens Köhler
In contrast to the established role of epidermal growth factor receptor (EGFR) inhibitors for the first-line treatment of patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR blockade and of EGFR molecular testing in the second-line treatment remains less clear. The irreversible pan-ErbB family inhibitor afatinib (Gi(l)otrif(®)) was recently FDA- and EMA-approved for the second-line treatment of NSCLC with squamous cell histology irrespective of the EGFR mutational status (LUX-Lung 8)...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28236760/differential-expression-of-circular-rnas-in-glioblastoma-multiforme-and-its-correlation-with-prognosis
#19
Junle Zhu, Jingliang Ye, Lei Zhang, Lili Xia, Hongkang Hu, Heng Jiang, Zhiping Wan, Fei Sheng, Yan Ma, Wen Li, Jun Qian, Chun Luo
OBJECTIVE: The present study aimed to explore the expression profiles of circular RNAs (circRNAs) in glioblastoma multiforme (GBM) in an attempt to identify potential core genes in the pathogenesis of this tumor. METHODS: Differentially expressed circRNAs were screened between tumor tissues from five GBM patients and five normal brain samples using Illumina Hiseq. Bioinformatics analysis was used to analyze their potential function. CircBRAF was further detected in different WHO grades glioma tissues and normal brain tissues...
April 2017: Translational Oncology
https://www.readbyqxmd.com/read/28235801/the-scaffolding-protein-nherf1-regulates-the-stability-and-activity-of-the-tyrosine-kinase-her2
#20
Jaekwang Jeong, Joshua N Vanhouten, Wonnam Kim, Pamela Dann, Catherine Sullivan, Jungmin Choi, W Bruce Sneddon, Peter A Friedman, John J Wysolmerski
Unlike other ErbB family members, ErbB2/HER2/Neu (HER2) is not internalized but remains on the cell surface when activated. This allows for prolonged signaling and contributes to its transforming ability. Previous studies have shown that the calcium pump, PMCA2, interacts with HER2 within membrane protrusions and is required for the retention of HER2 on the cell surface. In this study, we knocked down NHERF1 expression in breast cancer cells lines and examined whether the scaffolding protein, NHERF1, interacts with PMCA2 and HER2...
February 24, 2017: Journal of Biological Chemistry
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