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https://www.readbyqxmd.com/read/28316082/dacomitinib-induced-diarrhoea-is-associated-with-altered-gastrointestinal-permeability-and-disruption-in-ileal-histology-in-rats
#1
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
#2
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/28300085/the-scaffold-protein-p140cap-limits-erbb2-mediated-breast-cancer-progression-interfering-with-rac-gtpase-controlled-circuitries
#3
Silvia Grasso, Jennifer Chapelle, Vincenzo Salemme, Simona Aramu, Isabella Russo, Nicoletta Vitale, Ludovica Verdun di Cantogno, Katiuscia Dallaglio, Isabella Castellano, Augusto Amici, Giorgia Centonze, Nanaocha Sharma, Serena Lunardi, Sara Cabodi, Federica Cavallo, Alessia Lamolinara, Lorenzo Stramucci, Enrico Moiso, Paolo Provero, Adriana Albini, Anna Sapino, Johan Staaf, Pier Paolo Di Fiore, Giovanni Bertalot, Salvatore Pece, Daniela Tosoni, Stefano Confalonieri, Manuela Iezzi, Paola Di Stefano, Emilia Turco, Paola Defilippi
The docking protein p140Cap negatively regulates tumour cell features. Its relevance on breast cancer patient survival, as well as its ability to counteract relevant cancer signalling pathways, are not fully understood. Here we report that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2-positive tumour cell progression, impairing tumour onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation...
March 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28288875/the-histone-h2a-isoform-hist2h2ac-is-a-novel-regulator-of-proliferation-and-epithelial-mesenchymal-transition-in-mammary-epithelial-and-in-breast-cancer-cells
#4
Fátima Liliana Monteiro, Rui Vitorino, Jun Wang, Hugo Cardoso, Hugo Laranjeira, Joana Simões, Margarida Caldas, Rui Henrique, Francisco Amado, Cecilia Williams, Carmen Jerónimo, Luisa A Helguero
Proliferation and differentiation are controlled through chromatin remodelling. Therefore, there is an enormous biological significance and clinical value in understanding how specific signalling pathways are affected by histone replacement in the nucleosome. In this work, mass spectrometry was used to screen HC11 mammary epithelial cells for changes in histone levels throughout cell differentiation. The canonical histone isoform Histone H2A type 2-C (Hist2h2ac) was found only in undifferentiated/proliferating cells...
March 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28288164/bayesian-model-of-signal-rewiring-reveals-mechanisms-of-gene-dysregulation-in-acquired-drug-resistance-in-breast-cancer
#5
A K M Azad, Alfons Lawen, Jonathan M Keith
Small molecule inhibitors, such as lapatinib, are effective against breast cancer in clinical trials, but tumor cells ultimately acquire resistance to the drug. Maintaining sensitization to drug action is essential for durable growth inhibition. Recently, adaptive reprogramming of signaling circuitry has been identified as a major cause of acquired resistance. We developed a computational framework using a Bayesian statistical approach to model signal rewiring in acquired resistance. We used the p1-model to infer potential aberrant gene-pairs with differential posterior probabilities of appearing in resistant-vs-parental networks...
2017: PloS One
https://www.readbyqxmd.com/read/28288133/mta1-modulated-by-mir-30e-contributes-to-epithelial-to-mesenchymal-transition-in-hepatocellular-carcinoma-through-an-erbb2-dependent-pathway
#6
L Deng, J Tang, H Yang, C Cheng, S Lu, R Jiang, B Sun
MTA1 is a metastasis-associated protein, which is essential to epithelial-to-mesenchymal transition (EMT). However, information concerning its up- and downstream regulation is rare. We investigated its upstream regulation and downstream effector in human hepatocellular carcinoma (HCC). In total, 94 paired HCC and adjacent tissue samples were involved in the study, and the results indicated that decreased miR-30e levels were associated with increased MTA1 levels in human HCC. miR-30e exerted its regulation of MTA1 transcription by binding to its 3'-untranslated region, and was negatively associated with EMT...
March 13, 2017: Oncogene
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
#7
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/28285962/the-erk-mapk-pathway-is-overexpressed-and-activated-in-gallbladder-cancer
#8
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
https://www.readbyqxmd.com/read/28272674/the-role-of-egfr-hepatocyte-growth-factor-receptor-c-met-c-erbb2-her2-neu-and-clinicopathological-parameters-in-the-pathogenesis-and-prognosis-of-chordoma
#9
Zeynep Tosuner, Süheyla Uyar Bozkurt, Türker Kiliç, Baran Yilmaz
OBJECTIVE: Chordoma is a rare malignant bone tumor with a poor outcome. Although radiotherapy and gamma knife surgery have been used for treatment, providing a cure for the tumor is not easy, because of the frequent recurrences. Molecular targeted therapy against tyrosine kinases has been effective in the treatment of malignancies such as breast and lung cancers and brain tumors. We aimed to analyse the histopathological features of chordomas and the immunoexpression profiles of the three receptor tyrosine kinases of EGFR, c-Met and c-Erb-B2 in chordomas...
February 4, 2017: Türk Patoloji Dergisi
https://www.readbyqxmd.com/read/28271613/qiliqiangxin-protects-against-anoxic-injury-in-cardiac-microvascular-endothelial-cells-via-nrg-1-erbb-pi3k-akt-mtor-pathway
#10
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/28271309/mutational-studies-on-single-circulating-tumor-cells-isolated-from-the-blood-of-inflammatory-breast-cancer-patients
#11
Catherine Bingham, Sandra V Fernandez, Patricia Fittipaldi, Paul W Dempsey, Karen J Ruth, Massimo Cristofanilli, R Katherine Alpaugh
PURPOSE: The molecular characterization of circulating tumor cells (CTCs) is critical to identify the key drivers of cancer metastasis and devising therapeutic approaches, particularly for inflammatory breast cancer (IBC) which is usually diagnosed at advance stages and progresses rapidly. METHODS: Genomic alterations in tumor tissue samples were studied using Foundation One™. Single CTCs were isolated using CellSearch followed by single-cell isolation by DEPArray™...
March 7, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28266931/biliary-adenofibroma-of-liver-morphology-tumor-genetics-and-outcomes-in-6-cases
#12
Thomas Arnason, Darrell R Borger, Christopher Corless, Catherine Hagen, A John Iafrate, Hala Makhlouf, Joseph Misdraji, Heidi Sapp, Wilson M Tsui, Ian R Wanless, Tania Zuluaga Toro, Gregory Y Lauwers
Biliary adenofibroma is a rare primary hepatic neoplasm, recognized in the World Health Organization classification, although only 14 cases have been reported to date. This series includes extended follow-up from 2 of the early case reports and 4 novel cases. Clinical history and histology were reviewed in all 6 cases. Tumor DNA was analyzed for point mutations by multiplex polymerase chain reaction and copy number alterations by array comparative genomic hybridization. The patients included 4 females and 2 males presenting between 46 and 83 years of age, with tumors ranging from 7 to 16 cm in diameter...
April 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28266149/iodne-an-integrated-optimization-method-for-identifying-the-deregulated-subnetwork-for-precision-medicine-in-cancer
#13
S Mounika Inavolu, J Renbarger, M Radovich, V Vasudevaraja, G H Kinnebrew, S Zhang, L Cheng
Subnetwork analysis can explore complex patterns of entire molecular pathways for the purpose of drug target identification. In this article, the gene expression profiles of a cohort of patients with breast cancer are integrated with protein-protein interaction (PPI) networks using, simultaneously, both edge scoring and node scoring. A novel optimization algorithm, integrated optimization method to identify deregulated subnetwork (IODNE), is developed to search for the optimal dysregulated subnetwork of the merged gene and protein network...
March 7, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28265829/a-multicenter-study-of-a-fluorescence-in-situ-hybridization-probe-set-for-diagnosing-high-grade-dysplasia-and-adenocarcinoma-in-barrett-s-esophagus
#14
John M Poneros, Adam S Faye, Emily G Barr Fritcher, Ananda Sen, Sharmila Anandasabapathy, Robert S Bresalier, Norman Marcon, D Kim Turgeon, Henry Appelman, Daniel Normolle, Larry E Morrison, Dean E Brenner, Kevin C Halling
BACKGROUND AND AIMS: Preliminary single-institution data suggest that fluorescence in situ hybridization (FISH) may be useful for detecting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EA) in patients with Barrett's esophagus (BE). This multicenter study aims to validate the measurement of polysomy (gain of at least two loci) by FISH as a way to discriminate degrees of dysplasia in BE specimens. METHODS: Tissue specimens were collected from four different hospitals and read by both the local pathology department ("Site diagnosis") and a single central pathologist ("Review diagnosis") at a separate institution...
March 6, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28263756/neuregulin-1%C3%AE-induces-proliferation-survival-and-paracrine-signaling-in-normal-human-cardiac-ventricular-fibroblasts
#15
Annet Kirabo, Sergey Ryzhov, Manisha Gupte, Seng Sengsayadeth, Richard J Gumina, Douglas B Sawyer, Cristi L Galindo
Neuregulin-1β (NRG-1β) is critical for cardiac development and repair, and recombinant forms are currently being assessed as possible therapeutics for systolic heart failure. We previously demonstrated that recombinant NRG-1β reduces cardiac fibrosis in an animal model of cardiac remodeling and heart failure, suggesting that there may be direct effects on cardiac fibroblasts. Here we show that NRG-1β receptors (ErbB2, ErbB3, and ErbB4) are expressed in normal human cardiac ventricular (NHCV) fibroblast cell lines...
March 3, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28261057/molecular-mechanisms-involved-in-schwann-cell-plasticity
#16
REVIEW
Angélique Boerboom, Valérie Dion, Alain Chariot, Rachelle Franzen
Schwann cell incredible plasticity is a hallmark of the utmost importance following nerve damage or in demyelinating neuropathies. After injury, Schwann cells undergo dedifferentiation before redifferentiating to promote nerve regeneration and complete functional recovery. This review updates and discusses the molecular mechanisms involved in the negative regulation of myelination as well as in the reprogramming of Schwann cells taking place early following nerve lesion to support repair. Significant advance has been made on signaling pathways and molecular components that regulate SC regenerative properties...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28243898/identification-of-frequent-somatic-mutations-in-inflammatory-breast-cancer
#17
Naoko Matsuda, Bora Lim, Ying Wang, Savitri Krishnamurthy, Wendy Woodward, Ricardo H Alvarez, Anthony Lucci, Vicente Valero, James M Reuben, Funda Meric-Bernstam, Naoto T Ueno
PURPOSE: Inflammatory breast cancer is an aggressive form of breast cancer that shows distinct clinical features from non-inflammatory breast cancer. Genomic understanding of inflammatory breast cancer will shed light on biological targets for this disease. Our objective was to identify targeted hotspot mutations using multiplex genome sequencing in inflammatory breast cancer and compare the findings with those for patients with non-inflammatory breast cancer to further recognize novel targets...
February 27, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28242701/correction-for-tung-et-al-%C3%AE-catenin-haploinsufficiency-promotes-mammary-tumorigenesis-in-an-erbb2-positive-basal-breast-cancer-model
#18
(no author information available yet)
No abstract text is available yet for this article.
February 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28235801/the-scaffolding-protein-nherf1-regulates-the-stability-and-activity-of-the-tyrosine-kinase-her2
#19
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
https://www.readbyqxmd.com/read/28235789/erbb-signaling-attenuates-pro-inflammatory-activation-of-non-classical-monocytes
#20
Sergey Ryzhov, Anton Matafonov, Cristi L Galindo, Qinkun Zhang, Truc-Linh Tran, Daniel P Lenihan, Carrie Geisberg Lenneman, Igor Feoktistov, Douglas B Sawyer
Immune activation in chronic systolic heart failure (HF) correlates with disease severity and prognosis. Recombinant neuregulin-1 (NRG-1) is being developed as a possible therapy for HF based on activation of ERBB receptors in cardiac cells. Work in animal models of HF led us to hypothesize that there may be direct effects of NRG-1 on immune system activation and inflammation. We investigated the expression of ERBB receptors and the effect of the recombinant NRG-1 isoform glial growth factor 2 (GGF2) in subpopulations of peripheral blood mononuclear cells in subjects with HF...
February 24, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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