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TGF beta inhibitors

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https://www.readbyqxmd.com/read/28230858/ngs-based-transcriptome-profiling-reveals-biomarkers-for-companion-diagnostics-of-the-tgf-%C3%AE-receptor-blocker-galunisertib-in-hcc
#1
Yuan Cao, Rahul Agarwal, Francesco Dituri, Luigi Lupo, Paolo Trerotoli, Serena Mancarella, Peter Winter, Gianluigi Giannelli
Transforming growth factor-beta (TGF-β) signaling has gained extensive interest in hepatocellular carcinoma (HCC). The small molecule kinase inhibitor galunisertib, targeting the TGF-β receptor I (TGF-βRI), blocks HCC progression in preclinical models and shows promising effects in ongoing clinical trials. As the drug is not similarly effective in all patients, this study was aimed at identifying new companion diagnostics biomarkers for patient stratification. Next-generation sequencing-based massive analysis of cDNA ends was used to investigate the transcriptome of an invasive HCC cell line responses to TGF-β1 and galunisertib...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28228478/an-engineered-tgf-%C3%AE-monomer-that-functions-as-a-dominant-negative-to-block-tgf-%C3%AE-signaling
#2
Sun Kyung Kim, Lindsey Barron, Cynthia S Hinck, Elyse M Petrunak, Kristin E Cano, Avinash Thangirala, Brian Iskra, Molly Brothers, Machell Vonberg, Belinda Leal, Blair Richter, Ravindra Kodali, Alex B Taylor, Shoucheng Du, Christopher O Barnes, Traian Sulea, Guillermo Calero, P John Hart, Matthew J Hart, Borries Demeler, Andrew P Hinck
The transforming growth factor beta isoforms, TGF-β1, -β2, and -β3 are small secreted homodimeric signaling proteins with essential roles in regulating the adaptive immune system and maintaining the extracellular matrix. However, dysregulation of the TGF-β pathway is responsible for promoting the progression of several human diseases, including cancer and fibrosis. In spite of the known importance of TGF-βs in promoting disease progression, no inhibitors have been approved for use in humans. Herein, we describe an engineered TGF-β monomer, lacking the heel helix, a structural motif essential for binding the TGF-β type I receptor, TβRI, but dispensible for binding the other receptor required for TGF-β signaling, the TGF-β type II receptor, TβRII, as an alternative therapeutic modality for blocking TGF-β signaling in humans...
February 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28214889/regulatory-role-of-mirna-375-in-expression-of-bmp15-gdf9-receptors-and-its-effect-on-proliferation-and-apoptosis-of-bovine-cumulus-cells
#3
Hongyan Chen, Chang Liu, Hao Jiang, Yan Gao, Mingqiang Xu, Jiawei Wang, Siyuan Liu, Yao Fu, Xulei Sun, Jiajun Xu, Jiabao Zhang, Lisheng Dai
BACKGROUND: Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are members of the transforming growth factor beta (TGF-β) superfamily. Through autocrine and paracrine mechanisms, these two factors can regulate cell differentiation, proliferation, and other functions in the ovary locally. Furthermore, GDF9 and BMP15 play vital roles in follicular growth, atresia, ovulation, fertilization, reproduction, and maintenance. Numerous studies have demonstrated a synergy between BMP15 and GDF9...
January 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213007/effect-of-dasatinib-on-emt-mediated-mechanism-of-resistance-against-egfr-inhibitors-in-lung-cancer-cells
#4
Yuichi Sesumi, Kenichi Suda, Hiroshi Mizuuchi, Yoshihisa Kobayashi, Katsuaki Sato, Masato Chiba, Masaki Shimoji, Kenji Tomizawa, Toshiki Takemoto, Tetsuya Mitsudomi
OBJECTIVE: The epithelial to mesenchymal transition (EMT) is associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in certain non-small cell lung cancers that harbor EGFR mutations. Because no currently available drugs specifically kill cancer cells via EMT, novel treatment strategies that overcome or prevent EMT are needed. A recent report suggested that dasatinib (an ABL/Src kinase inhibitor) inhibits EMT induced by transforming growth factor (TGF)-beta in lung cancer cells (Wilson et al...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28207279/angiotensin-converting-inhibitors-and-angiotensin-ii-receptor-blockers-and-longitudinal-change-in-percent-emphysema-on-computed-tomography-the-mesa-lung-study
#5
Megha A Parikh, Carrie P Aaron, Eric A Hoffman, Joseph E Schwartz, Jaime Madrigano, John H M Austin, Ravi Kalhan, Gina Lovasi, Karol Watson, Karen Hinckley Stukovsky, R Graham Barr
RATIONALE: Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death in the United States. Emphysema on computed tomography (CT) is associated with increased morbidity and mortality in patients with and without spirometrically defined COPD but no available medications target emphysema.  Transforming growth factor beta (TGF-β) and endothelial dysfunction are implicated in emphysema pathogenesis, and angiotensin II receptor blockers (ARB) inhibit TGF-β, improve endothelial function and restore airspace architecture in murine models...
February 16, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28195144/concomitant-underexpression-of-tgfbr2-and-overexpression-of-htert-are-associated-with-poor-prognosis-in-cervical-cancer
#6
Hui Yang, Hongyan Zhang, Yahua Zhong, Qiaoli Wang, Lei Yang, Hong Kang, Xiaojia Gao, Haijun Yu, Conghua Xie, Fuxiang Zhou, Yunfeng Zhou
The human telomerase reverse transcriptase (hTERT) is highly expressed in a variety of tumors. The transforming growth factor beta receptor type II (TGFBR2) is a downstream protein of transforming growth factor beta (TGF-β) which suppresses telomerase activity. However, the relevance of survival to the expression of TGFBR2, hTERT or TGFBR2/hTERT has not been previously investigated in cervical cancer tissues. Our study showed that patients with low level of TGFBR2 were associated with poor prognosis (HR = 1...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28146373/osthole-inhibited-tgf-%C3%AE-induced-epithelial-mesenchymal-transition-emt-by-suppressing-nf-%C3%AE%C2%BAb-mediated-snail-activation-in-lung-cancer-a549-cells
#7
Haitao Feng, Jin-Jian Lu, Yitao Wang, Lixia Pei, Xiuping Chen
Epithelial-mesenchymal transition (EMT), the transdifferentiation of epithelial cells into mesenchymal cells, has been implicated in the metastasis and provides novel strategies for cancer therapy. Osthole (OST), a dominant active constituent of Chinese herb Cnidium monnieri, has been reported to inhibit cancer metastasis while the mechanisms remains unclear. Here, we studied the inhibitory effect and mechanisms of OST on TGF-β1-induced EMT in A549 cells. Cells were treated with TGF-β1 in the absence and presence of OST...
February 1, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28139522/ovarian-fibrosis-a-phenomenon-of-concern
#8
REVIEW
Feng Zhou, Li-Bing Shi, Song-Ying Zhang
OBJECTIVE: Ovarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition of extracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis. DATA SOURCES: We searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-β1), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-γ), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28124643/rapamycin-inhibits-transforming-growth-factor-beta-1-induced-myofibroblast-differentiation-via-the-phosphorylated-phosphatidylinositol-3-kinase-mammalian-target-of-rapamycin-signal-pathways-in-nasal-polyp-derived-fibroblasts
#9
Dong-Yn Ko, Jae-Min Shin, Ji-Young Um, Byungjin Kang, Il-Ho Park, Heung-Man Lee
PURPOSE: Rapamycin has antiproliferative and antifibrogenic effects in vitro and in vivo. The purpose of this study was to evaluate the effects of rapamycin on transforming growth factor (TGF) beta 1 induced myofibroblast differentiation (alpha smooth-muscle actin [SMA]), extracellular matrix production, and collagen contraction in nasal polyp-derived fibroblasts (NPDF). The underlying molecular mechanisms of rapamycin were also determined in NPDFs. METHODS: NPDFs were grown in culture and transformed into myofibroblasts by using TGF beta 1 (5 ng/mL)...
November 1, 2016: American Journal of Rhinology & Allergy
https://www.readbyqxmd.com/read/28120574/relaxin-modulates-the-expression-of-mmps-and-timps-in-fibroblasts-of-patients-with-carpal-tunnel-syndrome
#10
Young Mi Kang, Hwan Mo Lee, Seong Hwan Moon, Ho Kang, Yun Rak Choi
PURPOSE: The aim of this study was to investigate the anti-fibrotic effect of relaxin in subsynovial fibroblasts activated by transforming growth factor beta (TGF-β). MATERIALS AND METHODS: To test the anti-fibrotic effect of an adenovirus-relaxin construct (Ad-RLN) on subsynovial fibroblasts in vitro, cells from subsynovial connective tissue of patients with carpal tunnel syndrome were activated with TGF-β1 and exposed to Ad-RLN (as a therapeutic gene) or adenovirus-lacZ construct (as a marker gene) for four hours...
March 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28114966/tgf-%C3%AE-1-induced-differentiation-of-shed-into-functional-smooth-muscle-cells
#11
Jian Guang Xu, Shao Yue Zhu, Boon Chin Heng, Waruna Lakmal Dissanayaka, Cheng Fei Zhang
BACKGROUND: Adequate vascularization is crucial for supplying nutrition and discharging metabolic waste in freshly transplanted tissue-engineered constructs. Obtaining the appropriate building blocks for vascular tissue engineering (i.e. endothelial and mural cells) is a challenging task for tissue neovascularization. Hence, we investigated whether stem cells from human exfoliated deciduous teeth (SHED) could be induced to differentiate into functional vascular smooth muscle cells (vSMCs)...
January 23, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28110870/combined-treatment-with-zingerone-and-its-novel-derivative-synergistically-inhibits-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-migration-and-invasion-of-human-hepatocellular-carcinoma-cells
#12
Young-Joo Kim, Youngsic Jeon, Taejung Kim, Won-Chul Lim, Jungyeob Ham, Young Nyun Park, Tae-Jin Kim, Hyeonseok Ko
The epithelial-mesenchymal transition (EMT) is an important cellular process during which polarized epithelial cells become motile mesenchymal cells, which promote cancer metastasis. Ginger, the rhizome of Zingiber officinale, is extensively used in cooking worldwide and also as a traditional medicinal herb with antioxidant, anti-inflammatory and anticancer properties. Several pungent compounds have been identified in ginger, including zingerone, which has anticancer potential. However, the role of zingerone in EMT is unclear...
December 20, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28092987/emerging-treatment-approaches-for-myeloma-related-bone-disease
#13
Maria Gavriatopoulou, Meletios A Dimopoulos, Efstathios Kastritis, Evangelos Terpos
Multiple myeloma is characterized by the presence of osteolytic lesions that leads to devastating skeletal-related events in the majority of patients. Myeloma bone disease is attributed to increased osteoclastic and suppressed osteoblastic activity. Areas covered: Bisphosphonates remain the main treatment option, however they have limitations on their own. Understanding the pathogenesis of myeloma bone disease may provide a roadmap for new therapeutic approaches. The pathway of RANKRANKLOPG pathway has revealed denosumab, a monoclonal antibody targeting RANKL as a novel emerging therapy for myeloma-related bone disease...
January 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28090659/the-effect-of-intradetrusor-botulinum-neurotoxin-type-a-on-urinary-ngf-tgf-beta-1-timp-2-levels-in-children-with-neurogenic-detrusor-overactivity-due-to-myelodysplasia
#14
Tuncay Top, Cagri Akin Sekerci, Banu Isbilen-Basok, Yiloren Tanidir, Ilker Tinay, Ferruh Kemal Isman, Cem Akbal, Ferruh Simsek, Tufan Tarcan
AIMS: The aim of this study was to determine the value of urine nerve growth factor (NGF), transforming growth factor beta 1 (TGF-Beta-1), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) levels to predict the urodynamic profile before and after botulinum neurotoxin type A (BoNT-A) treatment in children with myelodysplasia. METHODS: This prospective study included 15 children with myelodysplasia who underwent intradetrusor BoNT-A injections due to neurogenic detrusor overactivity (NDOA)...
January 16, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28086769/effect-of-ginseng-extract-on-the-tgf-%C3%AE-1-signaling-pathway-in-ccl4-induced-liver-fibrosis-in-rats
#15
Mohamed M Hafez, Sherifa S Hamed, Manal F El-Khadragy, Zeinab K Hassan, Salim S Al Rejaie, Mohamed M Sayed-Ahmed, Naif O Al-Harbi, Khalid A Al-Hosaini, Mohamed M Al-Harbi, Ali R Alhoshani, Othman A Al-Shabanah, Shakir Dekhal Alsharari
BACKGROUND: Liver diseases are major global health problems. Ginseng extract has antioxidant, immune-modulatory and anti-inflammatory activities. This study investigated the effect of ginseng extract on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: Male Wistar rats were divided into four groups: control group, ginseng group, CCl4 group and CCl4 + ginseng group. Liver injury was induced by the intraperitoneal (I.P) injection of 3 ml/kg CCl4 (30% in olive oil) weekly for 8 weeks...
January 13, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28075040/n-acetyl-seryl-aspartyl-lysyl-proline-mediates-the-anti-fibrotic-properties-of-captopril-in-unilateral-ureteric-obstructed-balb-c-mice
#16
Gary Cw Chan, Hao Jia Wu, Kam Wa Chan, Stella Yiu, Ailis Zou, Xiao Ru Huang, Hui Yao Lan, Kar Neng Lai, Sydney Cw Tang
BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEi) are widely employed to deter the progression of chronic kidney disease (CKD). Besides controlling hypertension and reduction of intra-glomerular pressure, ACEi appear to have anti-fibrotic effects in the renal cortex. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), an endogenous tetrapeptide that is degraded by ACE, has also been shown to ameliorate the pro-fibrotic phenotype displayed in CKD in our recent study. Whether the anti-fibrotic properties of ACEi are mediated by Ac-SDKP has not been fully investigated...
January 11, 2017: Nephrology
https://www.readbyqxmd.com/read/28065853/sitagliptin-inhibit-human-lymphocytes-proliferation-and-th1-th17-differentiation-in-vitro
#17
Marcelo Maia Pinheiro, Caroline Lais Stoppa, Claudete Justina Valduga, Cristina Eunice Okuyama, Renata Gorjão, Regina Mara Silva Pereira, Susana Nogueira Diniz
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin...
March 30, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28060893/positioning-of-tacrolimus-for-the-treatment-of-diabetic-nephropathy-based-on-computational-network-analysis
#18
Constantin Aschauer, Paul Perco, Andreas Heinzel, Judith Sunzenauer, Rainer Oberbauer
OBJECTIVE: To evaluate tacrolimus as therapeutic option for diabetic nephropathy (DN) based on molecular profile and network-based molecular model comparisons. MATERIALS AND METHODS: We generated molecular models representing pathophysiological mechanisms of DN and tacrolimus mechanism of action (MoA) based on literature derived data and transcriptomics datasets. Shared enriched molecular pathways were identified based on both model datasets. A newly generated transcriptomics dataset studying the effect of tacrolimus on mesangial cells in vitro was added to identify mechanisms in DN pathophysiology...
2017: PloS One
https://www.readbyqxmd.com/read/28042775/inhibition-of-epithelial-mesenchymal-transition-in-response-to-treatment-with-metformin-and-y27632-in-breast-cancer-cell-lines
#19
Camila Leonel, Lívia Carvalho Ferreira, Thaiz Ferraz Borin, Marina Gobbe Moschetta, Gabriela Scavacini Freitas, Michel Raineri Haddad, João Antonio de Camargos Pinto Robles, Debora Aparecida Pires de Campos Zuccari
BACKGROUND: ROCK-1 expression is associated with the malignant character of tumors, while inhibiting this molecule results in a significant suppression of tumor metastasis. Likewise, transforming growth factor beta (TGF-β) is associated with this malignancy by having the ability to induce epithelial-mesenchymal transition (EMT). Metformin, a drug used in the treatment of diabetes, has previously been shown to inhibit EMT in breast cancer cells. OBJECTIVE: The aim of this study is to evaluate the TGF-β1 action model for induction of EMT and the action of metformin and ROCK-1 inhibitor (Y27632) in EMT process in breast cancer cell lines...
January 2, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28008250/a-polyethylenimine-modified-carboxyl-poly-styrene-acrylamide-copolymer-nanosphere-for-co-delivering-of-cpg-and-tgf-%C3%AE-receptor-i-inhibitor-with-remarkable-additive-tumor-regression-effect-against-liver-cancer-in-mice
#20
Shuyan Liang, Jun Hu, Yuanyuan Xie, Qing Zhou, Yanhong Zhu, Xiangliang Yang
Cancer immunotherapy based on nanodelivery systems has shown potential for treatment of various malignancies, owing to the benefits of tumor targeting of nanoparticles. However, induction of a potent T-cell immune response against tumors still remains a challenge. In this study, polyethylenimine-modified carboxyl-styrene/acrylamide (PS) copolymer nano-spheres were developed as a delivery system of unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides and transforming growth factor-beta (TGF-β) receptor I inhibitors for cancer immunotherapy...
2016: International Journal of Nanomedicine
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