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Epithelial mesenchymal transformation

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https://www.readbyqxmd.com/read/28332047/mechanisms-of-resistance-to-target-therapies-in-non-small-cell-lung-cancer
#1
Francesco Facchinetti, Claudia Proto, Roberta Minari, Marina Garassino, Marcello Tiseo
Targeted therapies are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements, has changed the treatment landscape while improving the prognosis of lung cancer patients. Inevitably, virtually all patients initially treated with targeted therapies develop resistance because of the emergence of an insensitive cellular population, selected by pharmacologic pressure. Diverse mechanisms of resistance, in particular to EGFR, ALK and ROS1 tyrosine-kinase inhibitors (TKIs), have now been discovered and may be classified in three different groups: (1) alterations in the target (such as EGFR T790M and ALK or ROS1 mutations); (2) activation of alternative pathways (i...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28331343/silencing-trim59-inhibits-invasion-migration-and-epithelial-to-mesenchymal-transition-via-tgf-%C3%AE-smad2-3-signaling-pathway-in-bladder-cancer-cells
#2
Wei Chen, Kai Zhao, Chenkui Miao, Aiming Xu, Jianzhong Zhang, Jundong Zhu, Shifeng Su, Zengjun Wang
The evolutionarily conserved genes that encode the tripartite motif (TRIM) protein family are involved in various biological processes, including cellular immunity, inflammatory reaction, antiviral activity, and tumor progression. One member of this protein family, Trim59, has been reported as a novel biomarker for the occurrence and progression of multiple human carcinomas, such as lung cancer, gastric cancer, cervical cancer, and osteosarcoma. However, little is known about the relationship between Trim59 and bladder carcinogenesis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28331066/ketamine-induced-bladder-fibrosis-involves-epithelial-to-mesenchymal-transition-mediated-by-transforming-growth-factor-%C3%AE-1
#3
Junpeng Wang, Yang Chen, Di Gu, Guihao Zhang, Jiawei Chen, Jie Zhao, Peng Wu
Bladder wall fibrosis is a major complication of ketamine-induced cystitis (KC), but the underlying pathogenesis is poorly understood. The aim of the present study was to elucidate the mechanism of ketamine-induced fibrosis in association with epithelial-to-mesenchymal transition (EMT) mediated by transforming growth factor-β1 (TGF-β1). Sprague-Dawley rats were randomly distributed into four groups, which received saline, ketamine, ketamine combined with a TGF-β receptor (TβR) inhibitor (SB505124) for 16 weeks, or 12 weeks of ketamine and 4 weeks of abstinence...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28329136/chronic-resveratrol-treatment-inhibits-mrc5-fibroblast-sasp-related-protumoral-effects-on-melanoma-cells
#4
Beatrice Menicacci, Anna Laurenzana, Anastasia Chillà, Francesca Margheri, Silvia Peppicelli, Elisabetta Tanganelli, Gabriella Fibbi, Lisa Giovannelli, Mario Del Rosso, Alessandra Mocali
Cellular senescence is related to organismal aging and is observed after DNA damaging cancer therapies, that induce tumor-suppressive modifications, but it is characterized by a strong increase in secreted factors, termed the "senescence-associated secretory phenotype" (SASP). Particularly, SASP from stroma senescent fibroblasts creates a cancer-favoring microenvironment, providing targets for anti-cancer interventions. In the present article, chronic treatment (5 weeks) with 5 µM resveratrol has been used to modulate senescence-related protumoral features of MRC5 fibroblasts, reducing SASP-related interleukins IL1α, IL1β, IL6, and IL8; transforming-growth-factor-β (TGFβ); matrix metallo-proteinases MMP3 and MMP2; urokinase plasminogen activator (uPA); receptor proteins uPAR, IL6R, insulin growth factor receptor-1 (IGF-1R), TGFβ-R2, and CXCR4...
January 20, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28326594/hypoacetylation-of-acetyl-histone-h3-h3k9ac-as-marker-of-poor-prognosis-in-oral-cancer
#5
Liana Preto Webber, Vivian Petersen Wagner, Marina Curra, Pablo Agustin Vargas, Luise Meurer, Vinícius Coelho Carrard, Cristiane Helena Squarize, Rogério Moraes Castilho, Manoela Domingues Martins
AIMS: Epigenetics refers to changes in cell characteristics that occur independently of modifications to the DNA sequence. Oral carcinogenesis is influenced by modifications in epigenetic mechanisms, including changes in histones, which are proteins that support chromatin remodeling for the dynamic regulation of gene expression and silencing. The dysregulation of histone acetylation can lead to the uncontrolled activity of different genes, thereby triggering events associated with malignant transformation...
March 22, 2017: Histopathology
https://www.readbyqxmd.com/read/28315789/involvement-of-epithelial-mesenchymal-transition-afforded-by-activation-of-lox-1-tgf-%C3%AE-1-klf6-signaling-pathway-in-diabetic-pulmonary-fibrosis
#6
Xiao-Zhou Zou, Zhi-Cheng Gong, Ting Liu, Fang He, Tian-Tian Zhu, Dai Li, Wei-Fang Zhang, Jun-Lin Jiang, Chang-Ping Hu
BACKGROUND AND OBJECTIVE: Diabetic pulmonary fibrosis is a severe disease that increases mortality risk of diabetes. However, the molecular mechanisms leading to pulmonary fibrosis in diabetes are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in streptozotocin (STZ)-induced rat pulmonary fibrosis. METHODS: The rat model of diabetic pulmonary fibrosis was established by intraperitoneal injection of a single dose of STZ (35 mg/kg)...
March 15, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315334/bapx1-mediates-transforming-growth-factor-%C3%AE-induced-epithelial-mesenchymal-transition-and-promotes-a-malignancy-phenotype-of-gastric-cancer-cells
#7
Shi Ouyang, Guodong Zhu, Lei Ouyang, Yuhao Luo, Rui Zhou, Changqie Pan, Jianping Bin, Yulin Liao, Wangjun Liao
The homeoprotein Bapx1 is an important regulator of gastroduodenal tract morphogenesis. Here, we investigated how Bapx1 influences gastric cancer (GC) prognosis and elucidated the underlying mechanisms. Bapx1 expression was greater in GC tissues compared to adjacent non-tumor tissues and expression was positively correlated with mortality, lymph node and distance metastasis. Silencing Bapx1 diminished cell invasion/migration and decreased mesenchymal phenotypes. Transforming growth factor-β (TGF-β) induced Bapx1 expression and epithelial-mesenchymal transition (EMT) in GC cells...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28314256/hydrogen-peroxide-enhances-tgf%C3%AE-mediated-epithelial-to-mesenchymal-transition-in-human-mammary-epithelial-mcf-10a-cells
#8
Daisuke Iizuka, Megumi Sasatani, Mary Helen Barcellos-Hoff, Kenji Kamiya
AIM: This study investigated the effect of reactive oxygen species (ROS) on transforming growth factor (TGF)-β-mediated epithelial-to-mesenchymal transition (EMT) in order to clarify the influence of ROS and TGFβ on the induction of dysplasia and ultimately, tumorigenesis. MATERIALS AND METHODS: Confluent MCF-10A human mammary epithelial cells were treated with H2O2 for 1 h, then reseeded at low density in the presence of TGFβ and cultured until confluence. RESULTS: Hydrogen peroxide (H2O2, 250 μM) enhanced TGFβ-mediated EMT, as evidenced by increased expression of EMT-associated transcription factors, which was accompanied by increased nuclear localization of phosphorylated SMAD family member 2 (SMAD2) and up-regulation of the TGFβ signaling pathway components mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303918/effects-of-matrix-stiffness-on-epithelial-to-mesenchymal-transition-like-processes-of-endometrial-epithelial-cells-implications-for-the-pathogenesis-of-endometriosis
#9
Sachiko Matsuzaki, Claude Darcha, Jean-Luc Pouly, Michel Canis
Endometriosis is defined as the presence of endometrial glands and stroma within extrauterine sites. Our previous study revealed an epithelial to mesenchymal transition (EMT)-like process in red peritoneal endometriosis, whereas membrane localization of E-cadherin was well maintained in epithelial cells of deep infiltrating endometriosis (DIE). Here we show that endometrial epithelial cells (EEE) grown on polyacrylamide gel substrates (PGS) of 2 kilopascal (kPa), a soft matrix, initiate a partial EMT-like process with transforming growth factor-β1 (TGF-β1) stimulation...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302679/disrupting-androgen-receptor-signaling-induces-snail-mediated-epithelial-mesenchymal-plasticity-in-prostate-cancer
#10
Lu Miao, Lin Yang, Rui Li, Daniel Nava Rodrigues, Mateus Crespo, Jer-Tsong Hsieh, Wayne D Tilley, Johann S de Bono, Luke A Selth, Ganesh V Raj
Epithelial to mesenchymal plasticity (EMP) has been linked to metastasis, stemness, and drug resistance. In prostate cancer (PCa), EMP has been associated with both suppression and activation of androgen receptor (AR) signaling. Here we investigated the effect of the potent AR antagonist enzalutamide on EMP in multiple preclinical models of PCa and patient tissues. Enzalutamide treatment significantly enhanced the expression of EMP drivers (ZEB1, ZEB2, Snail, Twist, and FOXC2) and mesenchymal markers (N-cadherin, fibronectin, and vimentin) in PCa cells, enhanced PCa cell migration, and induced PCa transformation to a spindle, fibroblast-like morphology...
March 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28289061/tgf-%C3%AE-family-signaling-in-ductal-differentiation-and-branching-morphogenesis
#11
Kaoru Kahata, Varun Maturi, Aristidis Moustakas
Epithelial cells contribute to the development of various vital organs by generating tubular and/or glandular architectures. The fully developed forms of ductal organs depend on processes of branching morphogenesis, whereby frequency, total number, and complexity of the branching tissue define the final architecture in the organ. Some ductal tissues, like the mammary gland during pregnancy and lactation, disintegrate and regenerate through periodic cycles. Differentiation of branched epithelia is driven by antagonistic actions of parallel growth factor systems that mediate epithelial-mesenchymal communication...
March 13, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28288400/c-phycocyanin-suppresses-transforming-growth-factor-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-human-epithelial-cells
#12
Dhamotharan Pattarayan, Dheeran Rajarajan, Sivanantham Ayyanar, Rajaguru Palanichamy, Rajasekaran Subbiah
BACKGROUND: Epithelial mesenchymal transition (EMT) is a process through which epithelial cells undergo multiple biochemical changes, causing them to differentiate into a mesenchymal-cell phenotype. This process has been shown to contribute to the development of fibrotic diseases. C-phycocyanin (C-PC) is a phycobiliprotein extracted from Spirulina platensis. This study was done to investigate the effect of C-PC on transforming growth factor-β1 (TGF-β1)-induced EMT and an EMT associated proliferation in human epithelial cell lines...
January 5, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28288136/oncostatin-m-promotes-cancer-cell-plasticity-through-cooperative-stat3-smad3-signaling
#13
D J Junk, B L Bryson, J M Smigiel, N Parameswaran, C A Bartel, M W Jackson
Increasing evidence supports the idea that cancer cell plasticity promotes metastasis and tumor recurrence, resulting in patient mortality. While it is clear that the tumor microenvironment (TME) contributes to cancer cell plasticity, the specific TME factors most actively controlling plasticity remain largely unknown. Here, we performed a screen to identify TME cytokines and growth factors that promote epithelial-mesenchymal plasticity, and acquisition of cancer stem cell (CSC) properties. Of 28 TME cytokines and growth factors tested, we identified Oncostatin M (OSM) as the most potent inducer of mesenchymal/CSC properties...
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
#14
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/28285503/development-of-urinary-bladder-pre-neoplasia-by-schistosoma-haematobium-eggs-and-chemical-carcinogen-in-mice
#15
Bayissa Chala, Min-Ho Choi, Kyung Chul Moon, Hyung Suk Kim, Cheol Kwak, Sung-Tae Hong
Schistosoma haematobium is a biocarcinogen of human urinary bladder (UB). The present study investigated developing UB cancer mouse model by injecting S. haematobium eggs into the bladder wall and introduction of chemical carcinogens. Histopathological findings showed mild hyperplasia to epithelial vacuolar change, and high grade dysplasia. Squamous metaplasia was observed in the S. haematobium eggs+NDMA group at week 12 but not in other groups. Immunohistochemistry revealed significantly high expression of Ki-67 in urothelial epithelial cells of the S...
February 2017: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/28267878/quantification-of-substrate-and-cellular-strains-in-stretchable-3d-cell-cultures-an-experimental-and-computational-framework
#16
P González-Avalos, M Mürnseer, J Deeg, A Bachmann, J Spatz, S Dooley, R Eils, E Gladilin
The mechanical cell environment is a key regulator of biological processes . In living tissues, cells are embedded into the 3D extracellular matrix and permanently exposed to mechanical forces. Quantification of the cellular strain state in a 3D matrix is therefore the first step towards understanding how physical cues determine single cell and multicellular behaviour. The majority of cell assays are, however, based on 2D cell cultures that lack many essential features of the in vivo cellular environment. Furthermore, nondestructive measurement of substrate and cellular mechanics requires appropriate computational tools for microscopic image analysis and interpretation...
March 7, 2017: Journal of Microscopy
https://www.readbyqxmd.com/read/28260014/baicalin-ameliorates-renal-fibrosis-via-inhibition-of-transforming-growth-factor-%C3%AE-1-production-and-downstream-signal-transduction
#17
Long Zheng, Chao Zhang, Long Li, Chao Hu, Mushuang Hu, Niyazi Sidikejiang, Xuanchuan Wang, Miao Lin, Ruiming Rong
Previous studies have demonstrated the potential antifibrotic effects of baicalin in vitro, via examination of 21 compounds isolated from plants. However, its biological activity and underlying mechanisms of action in vivo remain to be elucidated. The present study aimed to evaluate the effect of baicalin on renal fibrosis in vivo, and the potential signaling pathways involved. A unilateral ureteral obstruction (UUO)‑induced renal fibrosis model was established using Sprague‑Dawley rats. Baicalin was administrated intraperitoneally every 2 days for 10 days...
February 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28259913/1-25-oh-2d3-vdr-attenuates-high-glucose%C3%A2-induced-epithelial%C3%A2-mesenchymal-transition-in-human-peritoneal-mesothelial-cells-via-the-tgf%C3%AE-smad3-pathway
#18
Lina Yang, Lan Wu, Xiuli Zhang, Ye Hu, Yi Fan, Jianfei Ma
Epithelial-mesenchymal transition (EMT) has been recognized to accelerate peritoneal membrane dysfunction. 1,25(OH)2D3/vitamin D receptor (VDR) is important for preventing various types of EMT in vivo. However, its function on EMT and inflammation of human peritoneal mesothelial cells (HPMCs) remains to be elucidated. Therefore, the present study investigated the effects of 1,25(OH)2D3/VDR on high glucose (HG)‑induced EMT and inflammation in HPMCs and the underlying molecular mechanism. It was determined that HG reduced VDR expression, increased inflammatory cytokine expression, including transforming growth factor β (TGFβ) and interleukin‑6 (IL‑6) and phosphorylated‑SMAD family member 3 (p‑Smad3) expression...
March 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28259823/evaluation-of-permeability-alteration-and-epithelial-mesenchymal-transition-induced-by-transforming-growth-factor-%C3%AE-1-in-a549-nci-h441-and-calu-3-cells-development-of-an-in-vitro-model-of-respiratory-epithelial-cells-in-idiopathic-pulmonary-fibrosis
#19
Kohei Togami, Kotaro Yamaguchi, Sumio Chono, Hitoshi Tada
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease, which is accompanied by changes in lung structure. With regard to treatment, aerosolized drugs administered intrapulmonarily are rapidly distributed into the plasma and do not remain in the lungs due to damage to the alveolar epithelium that occurs from pulmonary fibrosis. In this study, we sought to develop an in vitro model of respiratory epithelial cells in IPF for the evaluation of the intrapulmonary distribution of aerosolized drugs...
March 1, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28258635/cinnamomum-cassia-extracts-reverses-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-human-lung-adenocarcinoma-cells-and-suppresses-tumor-growth-in-vivo
#20
Chin-Yin Lin, Yi-Hsien Hsieh, Shun-Fa Yang, Shu-Chen Chu, Pei-Ni Chen, Yih-Shou Hsieh
Metastasis is the most common cause of cancer-related mortality in patients, and epithelial-mesenchymal transition (EMT) is essential for cancer metastasis and antidrug resistance. Cinnamomum cassia has several antioxidative, anti-inflammatory, and anticancer biological effects. However, the anti-EMT effect of C. cassia in human lung carcinoma is rarely reported. In this study, we determined whether C. cassia extracts (CCE) reduces the EMT and tumor growth of human lung adenocarcinoma cells. CCE inhibited the transforming growth factor (TGF)-β1-induced cell motility and invasiveness of A549 and H1299 cells by repressing matrix metalloproteinase-2 and urokinase-type plasminogen activator as well as impaired cell adhesion to collagen...
March 4, 2017: Environmental Toxicology
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