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https://www.readbyqxmd.com/read/29146887/targeted-therapy-of-gastroenteropancreatic-neuroendocrine-tumours-preclinical-strategies-and-future-targets
#1
Elke Tatjana Aristizabal Prada, Christoph J Auernhammer
Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mTOR-inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression free survival due to tumor resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP-system are needed. This paper reviews preclinical research models and signaling pathways in NETs of the GEP-system...
November 16, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29140729/gene-expression-and-gene-associations-during-the-development-of-heart-failure-with-preserved-ejection-fraction-in-the-dahl-salt-sensitive-model-of-hypertension
#2
Jeffrey Yim, Hyokeun Cho, Simon W Rabkin
Gene expression and associations were examined in a model of heart failure with preserved ejection fraction (HFpEF), a condition with minimal effective treatment. Genes with at least two studies showing significant changes in Dahl rat with heart failure were examined by meta-analysis. Significantly increased in expression were iNOS, p47phox, ADM, ANP, OPN, ACE, MCP-1, GP91PHOX, ICAM-1, TGF-β1, CTGF, ET-1, p22phox, ETB, BNP, ETA, MMP13, Col1a1, MMP2, TIMP1, Col3a1, Il-1β, β-MHC, ECE1, MMP14, AGT, and MMP9...
November 15, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29101624/genistein-attenuates-pathological-cardiac-hypertrophy-in-vivo-and-in-vitro
#3
Y Meng, Y Zhang, Z Ma, H Zhou, J Ni, H Liao, Q Tang
BACKGROUND: We investigated the effects and underlying mechanisms of genistein on pathological cardiac hypertrophy in vivo and in vitro. MATERIALS AND METHODS: A cardiac hypertrophy model was developed by aortic banding (AB). C57/BL6 mice were randomly assigned to sham + vehicle (CON), sham + genistein (GEN), AB + vehicle (AB), and AB + genistein groups. Genistein (40 mg/kg/day) was administered by gavage for 7 weeks. After assessing the echocardiographic and hemodynamic parameters, mouse hearts were harvested for histopathological and molecular biological analysis...
November 3, 2017: Herz
https://www.readbyqxmd.com/read/29098682/relation-of-nodal-expression-to-the-specification-of-the-dorsal-ventral-axis-and-tissue-patterning-in-the-starfish-patiria-pectinifera
#4
Hiroki Sasaki, Tetsuya Kominami
In this study, we attempted to reveal fundamental aspects of starfish embryogenesis, particularly embryonic axis specification or determination, in Patiria pectinifera. We first cloned PpNodal, which is known to play an important role in the specification of the embryonic axis in a wide range of animals, and studied its expression profile. PpNodal expression was first detected at the mid-blastula stage and showed a single peak around the onset of gastrulation. These features of Nodal expression were shifted to later stages by several hours, compared with those of sea urchin embryos...
November 2, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/29037070/melatonin-promotes-self-renewal-of-nestin-positive-pancreatic-stem-cells-through-activation-of-the-mt2-erk-smad-nestin-axis
#5
Chunyu Bai, Yuhua Gao, Xiangyang Zhang, Wancai Yang, Weijun Guan
Although melatonin has been shown to exhibit a wide variety of biological functions, its effects on promotion of self-renewal in pancreatic stem cells remain unknown. In this study, we incubated murine pancreatic stem cells (PSCs) with various concentrations of melatonin (0.01, 0.1, 1, 10 or 100 μM) to screen for the optimum culture medium for increasing cell proliferation. We found that 10 μM melatonin can significantly increase proliferation and enhance expression of a stem cell marker, nestin, in PSCs via melatonin receptor 2 (MT2)...
October 16, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29034312/tgf-%C3%AE-inhibition-improves-oncolytic-herpes-viroimmunotherapy-in-murine-models-of-rhabdomyosarcoma
#6
Brian Hutzen, Chun-Yu Chen, Pin-Yi Wang, Les Sprague, Hayley M Swain, Julia Love, Joe Conner, Louis Boon, Timothy P Cripe
Oncolytic viruses are an emerging class of cancer therapeutics that couple cytotoxicity with the induction of an anti-tumor immune response. Host-virus interactions are complex and modulated by a tumor microenvironment whose immunosuppressive activities can limit the effectiveness of cancer immunotherapies. In an effort to improve this aspect of oncolytic virotherapy, we combined the oncolytic herpes virus HSV1716 with the transforming growth factor beta receptor 1 (TGF-βR1) inhibitor A8301 to treat syngeneic models of murine rhabdomyosarcoma...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29029263/role-of-stat3-in-skin-fibrosis-and-transforming-growth-factor-beta-signalling
#7
Mesias Pedroza, Sarah To, Shervin Assassi, Minghua Wu, David Tweardy, Sandeep K Agarwal
Objective: SSc is an autoimmune disease characterized by progressive fibrosis of the skin and internal organs. IL-6 and related cytokines that signal through STAT3 have been implicated in the pathogenesis of SSc and mouse models of fibrosis. The aim of this study was to investigate the efficacy of inhibiting STAT3 in the development of fibrosis in two mouse models of skin fibrosis. Methods: Biopsy samples of skin from SSc patients and healthy control subjects were used to determine the expression pattern of phosphotyrosyl (pY705)-STAT3...
September 23, 2017: Rheumatology
https://www.readbyqxmd.com/read/28992339/stat3-inhibition-attenuates-the-progressive-phenotypes-of-alport-syndrome-mouse-model
#8
Tsubasa Yokota, Kohei Omachi, Mary Ann Suico, Misato Kamura, Haruka Kojima, Ryosuke Fukuda, Keishi Motomura, Keisuke Teramoto, Shota Kaseda, Jun Kuwazuru, Toru Takeo, Naomi Nakagata, Tsuyoshi Shuto, Hirofumi Kai
Background: Alport syndrome (AS) is a hereditary, progressive nephritis caused by mutation of type IV collagen. Previous studies have shown that activation of signal transducer and activator of transcription 3 (STAT3) exacerbates other renal diseases, but whether STAT3 activation exacerbates AS pathology is still unknown. Here we aim to investigate the involvement of STAT3 in the progression of AS. Method: Phosphorylated STAT3 expression was assessed by immunoblotting analysis of kidneys and glomeruli of an AS mouse model ( Col4a5 G5X mutant)...
August 17, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28972822/inhibition-of-tgf-%C3%AE-signaling-in-shed-enhances-endothelial-differentiation
#9
J G Xu, T Gong, Y Y Wang, T Zou, B C Heng, Y Q Yang, C F Zhang
Low efficiency of deriving endothelial cells (ECs) from adult stem cells hampers their utilization in tissue engineering studies. The purpose of this study was to investigate whether suppression of transforming growth factor beta (TGF-β) signaling could enhance the differentiation efficiency of dental pulp-derived stem cells into ECs. We initially used vascular endothelial growth factor A (VEGF-A) to stimulate 2 dental pulp-derived stem cells (dental pulp stem cells and stem cells from human exfoliated deciduous teeth [SHED]) and compared their differentiation capacity into ECs...
October 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28913356/expression-profiling-of-cellular-microrna-in-asymptomatic-hbsag-carriers-and-chronic-hepatitis-b-patients
#10
Xianliang Hou, Yan Liang, Jianing Chen, Yingfeng Wei, Ping Zeng, Lin Wang, Chong Lu, Hongyan Diao
BACKGROUND: MicroRNAs (miRNAs) may serve as potential molecular markers to predict liver injury resulting from chronic hepatitis B (CHB). In the present study, we want to study the expression profile and clinical significance of miRNAs at different stages of CHB virus infection. METHODS: Using miRNA microarray, we investigated the global expression profiles of cellular miRNA in asymptomatic hepatitis B antigen carriers (ASCs) and CHB patients, compared with healthy controls (HCs)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28875468/multifunctional-jnk-inhibiting-nanotherapeutics-for-augmented-elastic-matrix-regenerative-repair-in-aortic-aneurysms
#11
Andrew Camardo, Dhruv Seshadri, Tom Broekelmann, Robert Mecham, Anand Ramamurthi
Growth of abdominal aortic aneurysms (AAA), localized aortal wall expansions, is driven by the disruption and subsequent loss of aortal wall elastic fibers by matrix metalloproteases (MMPs). Since elastic fibers do not naturally regenerate or repair, arresting/reversing AAA growth has not been possible. Previously, we showed utility of doxycycline (DOX), an MMP inhibitor drug, to stimulate elastic matrix neoassembly and crosslinking at low microgram per milliliter doses in addition to inhibiting MMPs. We currently show in aneurysmal smooth muscle cell (SMC) cultures that effects of exogenous DOX in this dose range are linked to its upregulation of transforming growth factor beta (TGF-β1) via its inhibition of the regulatory protein c-Jun-N-terminal kinase 2 (JNK 2)...
September 5, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28870615/luspatercept-for-the-treatment-of-anaemia-in-patients-with-lower-risk-myelodysplastic-syndromes-pace-mds-a-multicentre-open-label-phase-2-dose-finding-study-with-long-term-extension-study
#12
MULTICENTER STUDY
Uwe Platzbecker, Ulrich Germing, Katharina S Götze, Philipp Kiewe, Karin Mayer, Jörg Chromik, Markus Radsak, Thomas Wolff, Xiaosha Zhang, Abderrahmane Laadem, Matthew L Sherman, Kenneth M Attie, Aristoteles Giagounidis
BACKGROUND: Myelodysplastic syndromes are characterised by ineffective erythropoiesis. Luspatercept (ACE-536) is a novel fusion protein that blocks transforming growth factor beta (TGF β) superfamily inhibitors of erythropoiesis, giving rise to a promising new investigative therapy. We aimed to assess the safety and efficacy of luspatercept in patients with anaemia due to lower-risk myelodysplastic syndromes. METHODS: In this phase 2, multicentre, open-label, dose-finding study (PACE-MDS), with long-term extension, eligible patients were aged 18 years or older, had International Prognostic Scoring System-defined low or intermediate 1 risk myelodysplastic syndromes or non-proliferative chronic myelomonocytic leukaemia (white blood cell count <13 000/μL), and had anaemia with or without red blood cell transfusion support...
October 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28864263/mechanism-of-chimeric-vaccine-stimulation-of-indoleamine-2-3-dioxygenase-biosynthesis-in-human-dendritic-cells-is-independent-of-tgf-%C3%AE-signaling
#13
Grace E Esebanmen, William H R Langridge
Cholera toxin B subunit fusion to autoantigens such as proinsulin (CTB-INS) down regulate dendritic cell (DC) activation and stimulate synthesis of DC immunosuppressive cytokines. Recent studies of CTB-INS induction of immune tolerance in human DCs indicate that increased biosynthesis of indoleamine 2,3-dioxygenase (IDO1) may play an important role in CTB-INS vaccine suppression of DC activation. Studies in murine models suggest a role for transforming growth factor beta (TGF-β) in the stimulation of IDO1 biosynthesis, for the induction of tolerance in DCs...
September 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28806736/unravelling-the-interplay-of-sphingolipids-and-tgf-%C3%AE-signaling-in-the-human-corneal-stroma
#14
Sarah E Nicholas, Tyler G Rowsey, Shrestha Priyadarsini, Nawajes A Mandal, Dimitrios Karamichos
PURPOSE: To delineate the role of Sphingolipids (SPLs) in the human cornea and their cross-talks with transforming growth factor beta (TGF-β) in order to develop novel, non-invasive therapies. METHODS: Human corneal fibroblasts (HCFs) were harvested from healthy donors, stimulated with Vitamin C to promote extracellular matrix assembly, treated with exogenous sphingosine-1-phosphate (S1P) or sphingosine kinase inhibitor 2 (SPHK I2) and isolated after 4 weeks for further analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28801914/blockade-of-transforming-growth-factor-%C3%AE-signaling-enhances-oncolytic-herpes-simplex-virus-efficacy-in-patient-derived-recurrent-glioblastoma-models
#15
Shinichi Esaki, Fares Nigim, Esther Moon, Samantha Luk, Juri Kiyokawa, William Curry, Daniel P Cahill, Andrew S Chi, A John Iafrate, Robert L Martuza, Samuel D Rabkin, Hiroaki Wakimoto
Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-β) plays vital roles in maintaining GSC stemness and GBM pathogenesis...
December 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28789942/statins-reduce-tgf-beta2-modulation-of-the-extracellular-matrix-in-cultured-astrocytes-of-the-human-optic-nerve-head
#16
Mi-Lyang Kim, Kyung Rim Sung, Jin A Shin, Joo Young Yoon, Joonhee Jang
Statins are cholesterol lowering drugs and have shown beneficial effects on glaucoma. With regard to the mechanism of statin action on glaucoma, we investigated the effects of statins on transforming growth factor-beta 2 (TGF-β2)-induced expression of extracellular matrix (ECM) proteins in human astrocytes of the optic nerve head (ONH) lamina cribrosa (LC). By using primary human ONH astrocytes, we found that both simvastatin and lovastatin inhibited TGF-β2-mediated expression of ECM proteins such as connective tissue growth factor, collagen I, fibronectin, and plasminogen activator inhibitor-1...
November 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28696894/preference-of-aerosolized-pirfenidone-to-oral-intake-an-experimental-model-of-pulmonary-fibrosis-by-paraquat
#17
Rokhsana Rasooli, Hamid Rajaian, Abbas Pardakhty, Ali Mandegary
BACKGROUND: Inhalation drug delivery is a fast, effective, and safe route of delivering medication directly to the lungs. Thanks to the large surface area and highly vascularized epithelium in lung, pulmonary drug delivery has been considered as an effective route to deliver drugs to the systemic circulation. Pirfenidone (PF), an oral antifibrotic agent, has been shown to slow down the progression of the lung fibrosis. Inhalation or intrapulmonary delivery of PF appears to be a good alternative to optimize drug delivery and minimize the dosage, adverse and nonspecific effects...
July 11, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28663339/the-influence-of-connective-tissue-growth-factor-on-rabbit-ligament-injury-repair
#18
X Sun, W Liu, G Cheng, X Qu, H Bi, Z Cao, Q Yu
OBJECTIVES: The injured anterior cruciate ligament (ACL) is thought to exhibit an impaired healing response, and attempts at surgical repair have not been successful. Connective tissue growth factor (CTGF) is reported to be associated with wound healing, probably through transforming growth factor beta 1 (TGF-β1). METHODS: A rabbit ACL injury model was used to study the effect of CTGF on ligament recovery. Quantitative real-time PCR (qRT-PCR) was performed for detection of changes in RNA levels of TGF-β1, type 1 collagen (COL1), type 2 collagen (COL2), SRY-related high mobility group-box gene9 (SOX9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metallopeptidase 13 (MMP-13)...
July 2017: Bone & Joint Research
https://www.readbyqxmd.com/read/28649665/tgf-%C3%AE-target-genes-are-differentially-regulated-in-corneal-epithelial-cells-and-fibroblasts
#19
Xiaoqing Guo, Audrey E K Hutcheon, Jennifer A Tran, James D Zieske
PURPOSE: Transforming growth factor-beta (TGF-β) activates the canonical Smad pathway, which includes the Smad family of proteins and SARA (Smad Anchor for Receptor Activation) and other less understood pathways, including one involving p38(MAPK). The goal of the current research was to determine if corneal epithelial cells and fibroblasts used the classical or alternative TGF-β-signaling pathways. To examine this question, we made use of Trx-SARA, which inhibits native SARA, thus blocking the Smad pathway...
2017: New Front Ophthalmol
https://www.readbyqxmd.com/read/28647356/optimizing-bone-morphogenic-protein-4-mediated-human-embryonic-stem-cell-differentiation-into-trophoblast-like-cells-using-fibroblast-growth-factor-2-and-transforming-growth-factor-%C3%AE-activin-nodal-signalling-inhibition
#20
Mariann Koel, Urmo Võsa, Kaarel Krjutškov, Elisabet Einarsdottir, Juha Kere, Juha Tapanainen, Shintaro Katayama, Sulev Ingerpuu, Viljar Jaks, Ulf-Hakan Stenman, Karolina Lundin, Timo Tuuri, Andres Salumets
Several studies have demonstrated that human embryonic stem cells (hESC) can be differentiated into trophoblast-like cells if exposed to bone morphogenic protein 4 (BMP4) and/or inhibitors of fibroblast growth factor 2 (FGF2) and the transforming growth factor beta (TGF-β)/activin/nodal signalling pathways. The goal of this study was to investigate how the inhibitors of these pathways improve the efficiency of hESC differentiation when compared with basic BMP4 treatment. RNA sequencing was used to analyse the effects of all possible inhibitor combinations on the differentiation of hESC into trophoblast-like cells over 12 days...
September 2017: Reproductive Biomedicine Online
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