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https://www.readbyqxmd.com/read/28938007/neuropilin-1-modulates-tgf%C3%AE-signaling-to-drive-glioblastoma-growth-and-recurrence-after-anti-angiogenic-therapy
#1
Sam C Kwiatkowski, Paola A Guerrero, Shinya Hirota, Zhihua Chen, John E Morales, Manish Aghi, Joseph H McCarty
Glioblastoma (GBM) is a rapidly progressive brain cancer that exploits the neural microenvironment, and particularly blood vessels, for selective growth and survival. Anti-angiogenic agents such as the vascular endothelial growth factor-A (VEGF-A) blocking antibody bevacizumab yield short-term benefits to patients due to blood vessel regression and stabilization of vascular permeability. However, tumor recurrence is common, and this is associated with acquired resistance to bevacizumab. The mechanisms that drive acquired resistance and tumor recurrence in response to anti-angiogenic therapy remain largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28937434/th17-response-of-borderline-lepromatous-leprosy-inhibits-rash-manifestation-of-dapsone-hypersensitivity-syndrome-case-report
#2
Tamara de Nardo Vanzela, Fred Bernardes Filho, Carlos Gustavo Wambier, Francesca Maia Faria, Norma Tiraboschi Foss, Marco Andrey Cipriani Frade
BACKGROUND: Dapsone hypersensitivity syndrome (DHS) is a rare, but potentially life-threatening reaction to dapsone. OBJECTIVE: Evaluation of immunological factors involved in the sparing of borderline-lepromatous (BL) leprosy patches by the severe exanthema related to DHS. METHODS: The authors describe a 19-year-old man with borderline-lepromatous leprosy with a recent diffuse rash, sparing only the hypochromic patches of leprosy, generalized lymphadenopathy, hepatomegaly, and jaundice 25 days after the start of multibacillary multidrug therapy...
September 11, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28935391/extracellular-vesicles-released-by-mesenchymal-like-prostate-carcinoma-cells-modulate-emt-state-of-recipient-epithelial-like-carcinoma-cells-through-regulation-of-ar-signaling
#3
Ihsan Y El-Sayed, Ahmad Daher, Damien Destouches, Virginie Firlej, Enis Kostallari, Pascale Maillé, Eric Huet, Nathaline Haidar-Ahmad, Guido Jenster, Alexandre de la Taille, Raghida Abou Merhi, Stéphane Terry, Francis Vacherot
Extracellular vesicles released from cancer cells may play an important role in cancer progression by shuttling oncogenic information into recipient cells. However, our knowledge is still fragmentary and there remain numerous questions regarding the mechanisms at play and the functional consequences of these interactions. We have recently established a mesenchymal-like prostate cancer cell line (22Rv1/CR-1; Mes-PCa). In this study, we assessed the effects of the extracellular vesicles released by these cells on recipient androgen-dependent epithelial VCaP prostate cancer cells...
September 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28934877/activin-and-nodal-are-not-suitable-alternatives-to-tgf%C3%AE-for-chondrogenic-differentiation-of-mesenchymal-stem-cells
#4
Laurie M G de Kroon, Esmeralda N Blaney Davidson, Roberto Narcisi, Eric Farrell, Peter M van der Kraan, Gerjo J V M van Osch
Objective Previously, we demonstrated the importance of transforming growth factor-β (TGFβ)-activated SMAD2/3 signaling in chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). However, TGFβ also signals via the SMAD1/5/9 pathway, which is known to induce terminal differentiation of BMSCs. In this study, we investigated whether other SMAD2/3-activating ligands, Activin and Nodal, can induce chondrogenic differentiation of BMSCs without inducing terminal differentiation. Design Activation of SMAD2/3 signaling and chondrogenesis were evaluated in human BMSCs ( N = 3 donors) stimulated with TGFβ, Activin, or Nodal...
October 2017: Cartilage
https://www.readbyqxmd.com/read/28925397/coactosin-like-protein-clp-cotl1-suppresses-breast-cancer-growth-through-activation-of-il-24-perp-and-inhibition-of-non-canonical-tgf%C3%AE-signaling
#5
L Xia, X Xiao, W L Liu, Y Song, T J J Liu, Y J Li, E Zacksenhaus, X J Hao, Y Ben-David
Coactosin-like protein (CLP, or Cotl1), is an F-actin-binding protein, whose role in cancer is largely unknown. Here we show that CLP/Cotl1 is highly expressed in a rat epithelial breast cancer cell line (FE1.3) compared with its mesenchymal counterpart (FE1.2). Knockdown of CLP/Cotl1 in FE1.3 cells increased cell proliferation, whereas its overexpression in FE1.2 cells inhibited proliferation in culture and reduced tumor growth in xenograft assays in mice. Mechanistically, we identified two major pathways through which CLP/Cotl1 exerts its suppressive effects...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28923280/the-roles-of-ubiquitin-modifying-enzymes-in-neoplastic-disease
#6
REVIEW
Nishi Kumari, Patrick William Jaynes, Azad Saei, Prasanna Vasudevan Iyengar, John Lalith Charles Richard, Pieter Johan Adam Eichhorn
The initial experiments performed by Rose, Hershko, and Ciechanover describing the identification of a specific degradation signal in short-lived proteins paved the way to the discovery of the ubiquitin mediated regulation of numerous physiological functions required for cellular homeostasis. Since their discovery of ubiquitin and ubiquitin function over 30years ago it has become wholly apparent that ubiquitin and their respective ubiquitin modifying enzymes are key players in tumorigenesis. The human genome encodes approximately 600 putative E3 ligases and 80 deubiquitinating enzymes and in the majority of cases these enzymes exhibit specificity in sustaining either pro-tumorigenic or tumour repressive responses...
September 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28922951/a-retrospective-study-of-cytokine-profiles-changes-in-mice-with-fviii-inhibitor-development-after-aav-mediated-gene-therapy-in-hemophilia-a-mouse-model
#7
Junjiang Sun, Zhenhua Yuan, Yasmina L Abajas, Dorreen E Szollosi, Genlin Hu, Baolai Hua, Xiao Xiao, Chengwen Li
The development of inhibitory autoantibodies to the infused clotting factor VIII is a major complication for severe hemophilia A management. Novel therapy options for hemophilia have significantly progressed in the last decade and a gene therapy cure for hemophilia is translating into reality. However, mechanistic studies of FVIII autoantibodies (FVIII inhibitors) have lagged behind and remain a challenge for both protein replacement and gene therapy. FVIII inhibitor formation is assumed to be a classical T cell-dependent immune response in which cytokines/chemokines play an important role...
September 19, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28920001/zoledronic-acid-inhibits-nfat-and-il-2-signaling-pathways-in-regulatory-t-cells-and-diminishes-their-suppressive-function-in-patients-with-metastatic-cancer
#8
Dhifaf Sarhan, Caroline Leijonhufvud, Shannon Murray, Kristina Witt, Christina Seitz, Majken Wallerius, Hanjing Xie, Anders Ullén, Ulrika Harmenberg, Elisabet Lidbrink, Charlotte Rolny, John Andersson, Andreas Lundqvist
Regulatory T cells (Treg) suppress anti-tumor immune responses and their infiltration in the tumor microenvironment is associated with inferior prognosis in cancer patients. Thus, in order to enhance anti-tumor immune responses, selective depletion of Treg is highly desired. We found that treatment with zoledronic acid (ZA) resulted in a selective decrease in the frequency of Treg that was associated with a significant increase in proliferation of T cells and natural killer (NK) cells in peripheral blood of patients with metastatic cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28918914/analysis-of-genomes-and-transcriptomes-of-hepatocellular-carcinomas-identifies-mutations-and-gene-expression-changes-in-the-transforming-growth-factor-beta-pathway-short-title-prognostic-significance-of-tgf-%C3%AE-signature-in-liver-cancer
#9
Jian Chen, Sobia Zaidi, Shuyun Rao, Jiun-Sheng Chen, Liem Phan, Patrizia Farci, Xiaoping Su, Kirti Shetty, Jon White, Fausto Zamboni, Xifeng Wu, Asif Rashid, Nagarajan Pattabiraman, Raja Mazumder, Anelia Horvath, Ray-Chang Wu, Shulin Li, Cuiying Xiao, Chu-Xia Deng, David A Wheeler, Bibhuti Mishra, Rehan Akbani, Lopa Mishra
BACKGROUND & AIMS: Development of hepatocellular carcinoma (HCC) is associated with alterations in the transforming growth factor beta (TGFβ) signaling pathway, which regulates liver inflammation and can have tumor suppressor or promoter activities. Little is known about the roles of specific members of this pathway at specific of HCC development. We took an integrated approach to identify and validate the effects of changes in this pathway in HCC and identify therapeutic targets. METHODS: We performed transcriptome analyses for a total of 488 HCCs that include data from The Cancer Genome Atlas...
September 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28918311/structural-basis-for-the-potent-and-selective-binding-of-ldn-212854-to-the-bmp-receptor-kinase-alk2
#10
Eleanor Williams, Alex N Bullock
Individuals with the rare developmental disorder fibrodysplasia ossificans progressiva (FOP) experience disabling heterotopic ossification caused by a gain of function mutation in the intracellular region of the BMP type I receptor kinase ALK2, encoded by the gene ACVR1. Small molecule BMP type I receptor inhibitors that block this ossification in FOP mouse models have been derived from the pyrazolo[1,5-a]pyrimidine scaffold of dorsomorphin. While the first derivative LDN-193189 exhibited pan inhibition of BMP receptors, the more recent compound LDN-212854 has shown increased selectivity for ALK2...
September 12, 2017: Bone
https://www.readbyqxmd.com/read/28915803/tartrate-resistant-acid-phosphatase-trap-acp5-promotes-metastasis-related-properties-via-tgf%C3%AE-2-t%C3%AE-r-and-cd44-in-mda-mb-231-breast-cancer-cells
#11
Anja Reithmeier, Elena Panizza, Michael Krumpel, Lukas M Orre, Rui M M Branca, Janne Lehtiö, Barbro Ek-Rylander, Göran Andersson
BACKGROUND: Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness. METHODS: MDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels...
September 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28915571/p62-plasmid-can-alleviate-diet-induced-obesity-and-metabolic-dysfunctions
#12
Tatiana Halenova, Oleksii Savchuk, Ludmila Ostapchenko, Andrey Chursov, Nathan Fridlyand, Andrey B Komissarov, Franco Venanzi, Sergey I Kolesnikov, Albert A Sufianov, Michael Y Sherman, Vladimir L Gabai, Alexander M Shneider
A high-calorie diet (HCD) induces two mutually exacerbating effects contributing to diet-induced obesity (DIO): impaired glucose metabolism and increased food consumption. A link between the metabolic and behavioral manifestations is not well understood yet. We hypothesized that chronic inflammation induced by HCD plays a key role in linking together the two components of diet-induced pathology. Based on this hypothesis, we tested if a plasmid (DNA vaccine) encoding p62 (SQSTM1) would alleviate DIO including its metabolic and/or food consumption abnormalities...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915063/twist1-in-hypoxia-induced-pulmonary-hypertension-through-tgf%C3%AE-smad-signaling
#13
Tadanori Mammoto, Megan Muyleart, G Ganesh Konduri, Akiko Mammoto
Pulmonary hypertension (PH) is a devastating pulmonary vascular disease characterized by aberrant muscularization of the normally non-muscularized distal pulmonary arterioles. The expression of the transcription factor, Twist1, increases in the lungs of pulmonary arterial hypertension patients. However, the mechanisms by which Twist1 controls the pathogenesis of PH remain unclear. It is becoming clear that endothelial-to-mesenchymal transition (EndMT) contributes to various vascular pathologies including PH; Twist1 is known to mediate EndMT...
September 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28915060/long-non-coding-rna-lnrpt-is-regulated-by-pdgf-bb-and-modulates-proliferation-of-pulmonary-artery-smooth-muscle-cells
#14
Jidong Chen, Jiao Guo, Xiaolei Cui, Yan Dai, Zhixiong Tang, Junle Qu, J Usha Raj, Qinghua Hu, Deming Gou
Pulmonary artery hypertension (PAH) is a rare and fatal disorder with extensive remodeling of pulmonary arteries mediated by hyperproliferation of pulmonary artery smooth muscle cell (PASMC). Aberrant platelet-derived growth factor (PDGF) activity can lead to hyperproliferation of PASMC, however, little is known about the role of long noncoding RNA (lncRNA) in this process. Using RNA sequencing (RNA-seq), we identified 725 lncRNAs in rat PASMC (RPASMC), 95 of which were expressed differentially in response to PDGF-BB treatment...
September 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28912363/tgf%C3%AE-transforming-growth-factor-%C3%AE-blockade-induces-a-human-like-disease-in-a-nondissecting-mouse-model-of-abdominal-aortic-aneurysm
#15
Fabien Lareyre, Marc Clément, Juliette Raffort, Stefanie Pohlod, Meghana Patel, Bruno Esposito, Leanne Master, Alison Finigan, Marie Vandestienne, Nikolaos Stergiopulos, Soraya Taleb, Bram Trachet, Ziad Mallat
OBJECTIVE: Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. APPROACH AND RESULTS: Here, we test this hypothesis in the elastase-induced AAA model in mice...
September 14, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28903341/apobec3g-acts-as-a-therapeutic-target-in-mesenchymal-gliomas-by-sensitizing-cells-to-radiation-induced-cell-death
#16
Yu Wang, Shaofang Wu, Siyuan Zheng, Shuzhen Wang, Arjun Wali, Ravesanker Ezhilarasan, Erik P Sulman, Dimpy Koul, W K Alfred Yung
Genomic, transcriptional, and proteomic analyses of brain tumors reveal that subtypes differ in their pathway activity, progression, and response to therapy. We performed an expression profiling of Glioma Initiating Cells (GICs) and comparative analysis between different groups of GICs indicates major variations in gene expression. Hierarchical clustering analysis revealed groups of GICs reflecting their heterogeneity, and among some of the genes as major regulators of mesenchymal phenotype, we identified ABOBEC3G as one of the most discriminating genes in mesenchymal group...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901584/the-primary-cilium-as-a-signaling-nexus-for-growth-plate-function-and-subsequent-skeletal-development
#17
REVIEW
Emily R Moore, Christopher R Jacobs
The primary cilium is a solitary, antenna-like sensory organelle with many important roles in cartilage and bone development, maintenance, and function. The primary cilium's potential role as a signaling nexus in the growth plate makes it an attractive therapeutic target for diseases and disorders associated with bone development and maintenance. Many signaling pathways that are mediated by the cilium - such as Hh, Wnt, Ihh/PTHrP, TGFβ, BMP, FGF, and Notch - are also known to influence endochondral ossification, primarily by directing growth plate formation and chondrocyte behavior...
September 13, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28899582/fgf2-mediated-attenuation-of-myofibroblast-activation-is-modulated-by-distinct-mapk-signaling-pathways-in-human-dermal-fibroblasts
#18
David M Dolivo, Sara A Larson, Tanja Dominko
BACKGROUND: Previous human and animal studies have demonstrated the ability of exogenously administered basic fibroblast growth factor (FGF2) to act as an antifibrotic agent in the skin. Though the activity of FGF2 as an anti-scarring agent is well-established for fibrotic skin wounds, the mechanisms by which FGF2 exerts these actions are not entirely understood. Canonical FGF2 signaling proceeds in part via FGFR/MAPK pathways in human dermal fibroblasts, and FGF2 has been described to prevent or reverse the fibroblast-to-myofibroblast transition, which is driven by TGFβ signaling and understood to be an important step in the formation of a fibrotic scar in vivo...
September 1, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28895052/the-effects-of-periostin-in-a-rat-model-of-isoproterenol-mediated-cardiotoxicity
#19
Mahmut Sözmen, Alparslan K Devrim, Yonca B Kabak, Tuba Devrim, Mert Sudagidan
Periostin is an extracellular matrix protein from fasciclin family, and it plays an important role in the cell adhesion, migration, and growth of the organism. Periostin prevents apoptosis while stimulating cardiomyocytes. The present study was designed to investigate cardioprotective effects of the recombinant murine periostin peptide administration in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague Dawley rats in 4 groups (n = 21): control group (1), periostin-treated group (2), ISO-treated group (3), and ISO + periostin-treated group (4)...
September 11, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28887922/gramine-inhibits-angiogenesis-and-induces-apoptosis-via-modulation-of-tgf-%C3%AE-signalling-in-7-12-dimethylbenz-a-anthracene-dmba-induced-hamster-buccal-pouch-carcinoma
#20
Arunkumar Ramu, Suresh Kathiresan, Bakrudeen Ali Ahmed
BACKGROUND: Transforming growth factor-β (TGF-β) and its receptors are considered as a novel target in cancer chemotherapy. Gramine, an indole alkaloid, possesses various pharmacological properties including antiproliferative and anticancer. However, the anti-angiogenic property remains unexplored. PURPOSE: The present study was designed to evaluate the anti-angiogenic and apoptosis induction properties of gramine through inhibiting TGF-β on DMBA induced oral squamous cell carcinoma (OSCC) in the hamster buccal pouch (HBP)...
September 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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