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Epithelial to mesenchymal transition tacrolimus

Nadiar Mussin, Seung Cheol Oh, Kwang Woong Lee, Min Young Park, Sooin Seo, Nam Joon Yi, Hyeyoung Kim, Kyung Chul Yoon, Sung Woo Ahn, Hyo Sin Kim, Suk Kyun Hong, Dong Kyu Oh, Kyung Suk Suh
We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies: sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA)...
September 2017: Journal of Korean Medical Science
Malgorzata Kimsa, Barbara Strzalka-Mrozik, Magdalena Kimsa-Dudek, Celina Kruszniewska-Rajs, Joanna Gola, Jolanta Adamska, Urszula Mazurek
BACKGROUND: The transforming growth factor β (TGFβ) family plays an important role in the pathogenesis of many diseases, including fibrotic pathologies of the eyes. The difficulties of surgical procedures contribute to the search for new treatment strategies for proliferative vitreoretinopathy. Therefore, the aim of this study was to investigate the expression profile of TGFβ isoforms, their receptors, and TGFβ-related genes in human retinal pigment epithelial cells (RPE) after tacrolimus (FK-506) treatment in the presence or absence of lipopolysaccharide (LPS)-induced inflammation...
October 2016: Pharmacological Reports: PR
Jason Bennett, Hilary Cassidy, Craig Slattery, Michael P Ryan, Tara McMorrow
Epithelial-mesenchymal transition (EMT), a process which describes the trans-differentiation of epithelial cells into motile mesenchymal cells, is pivotal in stem cell behavior, development and wound healing, as well as contributing to disease processes including fibrosis and cancer progression. Maintenance immunosuppression with calcineurin inhibitors (CNIs) has become routine management for renal transplant patient, but unfortunately the nephrotoxicity of these drugs has been well documented. HK-2 cells were exposed to Tacrolimus (FK506) and EMT markers were assessed by RT PCR and western blot...
April 26, 2016: Journal of Clinical Medicine
Paola Tomei, Valentina Masola, Simona Granata, Gloria Bellin, Pierluigi Carratù, Miriam Ficial, Valentina Anna Ventura, Maurizio Onisto, Onofrio Resta, Giovanni Gambaro, Marco Chilosi, Antonio Lupo, Gianluigi Zaza
BACKGROUND: Everolimus (EVE) is a mammalian target of rapamycin inhibitor (mTOR-I) widely used in transplantation that may determine some severe adverse events, including pulmonary fibrosis. The pathogenic mechanism of mTOR-I-associated pulmonary toxicity is still unclear, but epithelial to mesenchymal transition (EMT) of bronchial/pulmonary cells may play a role. METHODS: Three cell lines-human type II pneumocyte-derived A549, normal bronchial epithelial, and bronchial epithelial homozygous for the delta F508 cystic fibrosis-causing mutation-were treated with EVE or tacrolimus at different concentrations...
December 2016: Journal of Nephrology
Julie Bloch, Marc Hazzan, Cynthia Van der Hauwaert, David Buob, Grégoire Savary, Alexandre Hertig, Viviane Gnemmi, Marie Frimat, Michaël Perrais, Marie-Christine Copin, Franck Broly, Christian Noël, Nicolas Pottier, Christelle Cauffiez, François Glowacki
AIM: The contribution of epithelial-mesenchymal transition (EMT) has been suggested in renal transplant recipients receiving calcineurin inhibitors and developing nephrotoxicity. MATERIALS & METHODS: We assessed whether interindividual variability in tacrolimus pharmacokinetics is associated with the occurrence in tubular cells of two EMT markers (vimentin, β-catenin) detected at 3-month in 140 allograft biopsies. We investigated whether genetic polymorphisms affecting CYP3A5 and ABCB1 influence EMT and kidney fibrosis...
December 2014: Pharmacogenomics
S Romano, S Staibano, A Greco, A Brunetti, G Nappo, G Ilardi, R Martinelli, A Sorrentino, A Di Pace, M Mascolo, R Bisogni, M Scalvenzi, B Alfano, M F Romano
Melanoma is the most aggressive skin cancer; there is no cure in advanced stages. Identifying molecular participants in melanoma progression may provide useful diagnostic and therapeutic tools. FK506 binding protein 51 (FKBP51), an immunophilin with a relevant role in developmental stages, is highly expressed in melanoma and correlates with aggressiveness and therapy resistance. We hypothesized a role for FKBP51 in melanoma invasive behaviour. FKBP51 promoted activation of epithelial-to-mesenchymal transition (EMT) genes and improved melanoma cell migration and invasion...
2013: Cell Death & Disease
A Djamali, S Reese, O Hafez, A Vidyasagar, L Jacobson, W Swain, C Kolehmainen, L Huang, N A Wilson, J R Torrealba
We hypothesized that Nox2, the classical phagocytic NADPH oxidase, plays an important role in calcineurin inhibitor (CNI)-induced renal fibrosis. We tested this hypothesis in vitro, in animal and in human studies. Cyclosporine A (CsA) and tacrolimus (TAC) were associated with greater levels of Nox2 mRNA and epithelial to mesenchymal transition (EMT) in NRK52E cells. CsA increased Nox2, α-SMA and phosphorylated-p38MAPK, Smad3 and NFκB proteins. Nox2 upregulation and EMT were inhibited in TGF-β1 knockout cells suggesting that TGF-β1 is required for Nox2 activation...
August 2012: American Journal of Transplantation
Valerie M Felton, Landon J Inge, Brigham C Willis, Ross M Bremner, Michael A Smith
OBJECTIVE: Obliterative bronchiolitis is the predominant histopathologic finding in patients with chronic rejection after lung transplant. This fibroproliferative transformation within small airways of lung allograft is poorly understood; however, studies suggest epithelial-mesenchymal transition plays a role. Transplant immunosuppressive therapy has been shown to cause epithelial-mesenchymal transition in renal tubular epithelial cells, with subsequent fibrosis. This study explored whether immunosuppressive therapy contributes to epithelial-mesenchymal transition in airway epithelial cells...
February 2011: Journal of Thoracic and Cardiovascular Surgery
J M Rintala, J Savikko, S E Rintala, E von Willebrand
BACKGROUND: Chronic allograft nephropathy (CAN) remains the primary reason for late allograft loss in kidney transplantation. Transforming growth factor beta (TGF-beta) is a major mitogen mediating mesenchymal cell proliferation and epithelial to mesenchymal cell transition in CAN. FK778, an analogue of an active metabolite of leflunomide, is a promising immunosuppressive drug that inhibits de novo pyrimidine biosynthesis. Herein we investigated the effect of FK778 on development of chronic rejection and TGF-beta expression in combination with calcineurin inhibitors cyclosporine (CsA) and tacrolimus (Tac)...
December 2006: Transplantation Proceedings
J M Rintala, J Savikko, S E Rintala, E von Willebrand
BACKGROUND: Acute rejection is the single most important risk factor for the development of subsequent chronic allograft nephropathy (CAN). Both platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) are major mitogens mediating mesenchymal cell proliferation and epithelial to mesenchymal cell transition. Early posttransplant induction of these growth factors may start molecular mechanisms leading to CAN. A new promising immunosuppressive drug, FK778, is an analogue of the active metabolite of leflunamide, which inhibits de novo pyrimidine biosynthesis...
October 2006: Transplantation Proceedings
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