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https://www.readbyqxmd.com/read/28249894/targeting-cd38-suppresses-induction-and-function-of-t-regulatory-cells-to-mitigate-immunosuppression-in-multiple-myeloma
#1
Xiaoyan Feng, Li Zhang, Chirag Acharya, Gang An, Kenneth Wen, Luqui Qiu, Nikhil C Munshi, Yu-Tzu Tai, Kenneth C Anderson
PURPOSE: We study CD38 levels in immunosuppressive CD4+CD25highFoxp3+ Tregs and further define immune modulating effects of a therapeutic CD38 monoclonal antibody (mAb) Isatuximab (Isa)/SAR650984 in multiple myeloma (MM). EXPERIMENTAL DESIGN: We evaluated percentages of CD38-expressing subsets in Tregs from normal donors and MM patients. PBMCs were then treated with Isa with or without Lenalidomide (Len) or Pomalidomide (Pom) to identify their impact on percentage and immunosuppressive activity of Tregs on CD4+CD25- T cells (Tcons)...
March 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28159920/tgfbeta-and-mirna-regulation-in-familial-and-sporadic-breast-cancer
#2
Katia Danza, Simona De Summa, Rosamaria Pinto, Brunella Pilato, Orazio Palumbo, Massimo Carella, Ondina Popescu, Maria Digennaro, Rosanna Lacalamita, Stefania Tommasi
The term 'BRCAness' was introduced to identify sporadic malignant tumors sharing characteristics similar to those germline BRCA-related. Among all mechanisms attributable to BRCA1 expression silencing, a major role has been assigned to microRNAs. MicroRNAs role in familial and sporadic breast cancer has been explored but few data are available about microRNAs involvement in homologous recombination repair control in these breast cancer subgroups. Our aim was to seek microRNAs associated to pathways underlying DNA repair dysfunction in breast cancer according to a family history of the disease...
January 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28119430/a-transcriptional-program-for-detecting-tgfbeta-induced-emt-in-cancer
#3
Momeneh Foroutan, Joseph Cursons, Soroor Hediyeh-Zadeh, Erik W Thompson, Melissa J Davis
Most cancer deaths are due to metastasis, and epithelial-to-mesenchymal transition (EMT) plays a central role in driving cancer cell metastasis. EMT is induced by different stimuli, leading to different signaling patterns and therapeutic responses. Transforming growth factor beta (TGFbeta) is one of the best-studied drivers of EMT, and many drugs are available to target this signalling pathway. A comprehensive bioinformatics approach was employed to derive a signature for TGFbeta-induced EMT which can be used to score TGFbeta-driven EMT in cells and clinical specimens...
January 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108836/smad-dependent-signaling-plays-a-detrimental-role-in-a-fly-model-of-smarcb1-deficiency-and-the-biology-of-atypical-teratoid-rhabdoid-tumors
#4
Astrid Jeibmann, Jacqueline Schulz, Kristin Eikmeier, Pascal D Johann, Katharina Thiel, Isabel Tegeder, Oliver Ambrée, Michael C Frühwald, Stefan M Pfister, Marcel Kool, Werner Paulus, Martin Hasselblatt
Atypical teratoid/rhabdoid tumors (ATRT) are highly malignant brain tumors arising in young children. The majority of ATRT is characterized by inactivation of the chromatin remodeling complex member SMARCB1 (INI1/hSNF5). Little is known, however, on downstream pathways involved in the detrimental effects of SMARCB1 deficiency which might also represent targets for treatment. Using Drosophila melanogaster and the Gal4-UAS system, modifier screens were performed in order to identify the role of SMAD dependent signaling in the lethal phenotype associated with knockdown of snr1, the fly homolog of SMARCB1...
January 20, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28078601/inhibition-of-epithelial-mesenchymal-transition-and-metastasis-by-combined-tgfbeta-knockdown-and-metformin-treatment-in-a-canine-mammary-cancer-xenograft-model
#5
Camila Leonel, Thaiz Ferraz Borin, Lívia de Carvalho Ferreira, Marina Gobbe Moschetta, Marcio Chaim Bajgelman, Alicia M Viloria-Petit, Debora Aparecida Pires de Campos Zuccari
Epithelial mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties, generating metastases. Transforming growth factor beta (TGF-β) is associated with this malignancy by having the ability to induce EMT. Metformin, has been shown to inhibit EMT in breast cancer cells. Based on this evidence we hypothesize that treatment with metformin and the silencing of TGF-β, inhibits the EMT in cancer cells. Canine metastatic mammary tumor cell line CF41 was stably transduced with a shRNA-lentivirus, reducing expression level of TGF-β1...
January 11, 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28049736/glp-1-analogue-induced-weight-loss-does-not-improve-obesity-induced-at-dysfunction
#6
Emilie Pastel, Laura J McCulloch, Rebecca Ward, Shivam Joshi, Kim M Gooding, Angela C Shore, Katarina Kos
Glucagon-like peptide-1 (GLP-1) analogues aid weight loss which improves obesity-associated adipose tissue (AT) dysfunction. GLP-1 treatment may however also directly influence AT which expresses GLP-1 receptors. This study aimed to assess the impact of GLP-1 analogue treatment on subcutaneous AT inflammatory and fibrotic responses, compared to weight loss by calorie reduction (control). Among the 39 participants with type 2 diabetes recruited, 30 age-matched participants were randomised to 4 months treatment with Liraglutide (n=22) or calorie restriction-based on dietetic counselling (n=8)...
January 3, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27934856/bulk-cell-density-and-wnt-tgfbeta-signalling-regulate-mesendodermal-patterning-of-human-pluripotent-stem-cells
#7
Henning Kempf, Ruth Olmer, Alexandra Haase, Annika Franke, Emiliano Bolesani, Kristin Schwanke, Diana Robles-Diaz, Michelle Coffee, Gudrun Göhring, Gerald Dräger, Oliver Pötz, Thomas Joos, Erik Martinez-Hackert, Axel Haverich, Falk F R Buettner, Ulrich Martin, Robert Zweigerdt
In vitro differentiation of human pluripotent stem cells (hPSCs) recapitulates early aspects of human embryogenesis, but the underlying processes are poorly understood and controlled. Here we show that modulating the bulk cell density (BCD: cell number per culture volume) deterministically alters anteroposterior patterning of primitive streak (PS)-like priming. The BCD in conjunction with the chemical WNT pathway activator CHIR99021 results in distinct paracrine microenvironments codifying hPSCs towards definitive endoderm, precardiac or presomitic mesoderm within the first 24 h of differentiation, respectively...
December 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27893804/tgfbeta-induces-binucleation-polyploidization-in-hepatocytes-through-a-src-dependent-cytokinesis-failure
#8
Marco De Santis Puzzonia, Angela Maria Cozzolino, Germana Grassi, Francesca Bisceglia, Raffaele Strippoli, Giulia Guarguaglini, Franca Citarella, Benedetto Sacchetti, Marco Tripodi, Alessandra Marchetti, Laura Amicone
In all mammals, the adult liver shows binucleated as well as mononucleated polyploid hepatocytes. The hepatic polyploidization starts after birth with an extensive hepatocyte binucleation and generates hepatocytes of several ploidy classes. While the functional significance of hepatocyte polyploidy is becoming clearer, how it is triggered and maintained needs to be clarified. Aim of this study was to identify a major inducer of hepatocyte binucleation/polyploidization and the cellular and molecular mechanisms involved...
2016: PloS One
https://www.readbyqxmd.com/read/27679942/influence-of-duodenogastric-reflux-in-the-gastric-mucosa-histological-changes-of-rats-infected-with-helicobacter-pylori
#9
José Carlos Ribeiro DE Araujo, Jorge José DE Carvalho, Humberto Oliveira Serra
OBJECTIVE: to evaluate the influence of Duodenal reflux in histological changes of the gastric mucosa of rats infected with Helicobacter pylori submitted to pyloroplasty. METHODS: after two weeks of acclimation, we infected 30 male Wistar rats with Helicobacter pylori. We randomly divided them into three groups: one submitted to pyloroplasty, another to partial gastrectomy and the third, only infected, was not operated. After six months of surgery, euthanasia was carried out...
July 2016: Revista do Colégio Brasileiro de Cirurgiões
https://www.readbyqxmd.com/read/27671336/integrated-genetic-epigenetic-and-transcriptional-profiling-identifies-molecular-pathways-in-the-development-of-laterally-spreading-tumors
#10
Luke B Hesson, Benedict Ng, Peter Zarzour, Sameer Srivastava, Chau-To Kwok, Deborah Packham, Andrea C Nunez, Dominik Beck, Regina Ryan, Ashraf Dower, Caroline E Ford, John E Pimanda, Mathew A Sloane, Nicholas J Hawkins, Michael J Bourke, Jason W H Wong, Robyn L Ward
Laterally spreading tumors (LST) are colorectal adenomas that develop into extremely large lesions with predominantly slow progression to cancer, depending on lesion subtype. Comparing and contrasting the molecular profiles of LSTs and colorectal cancers offers an opportunity to delineate key molecular alterations that drive malignant transformation in the colorectum. In a discovery cohort of 11 LSTs and paired normal mucosa, we performed a comprehensive and unbiased screen of the genome, epigenome, and transcriptome followed by bioinformatics integration of these data and validation in an additional 84 large, benign colorectal lesions...
December 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27510179/selective-expansion-of-regulatory-t-cells-during-lenalidomide-treatment-of-myelodysplastic-syndrome-with-isolated-deletion-5q
#11
MULTICENTER STUDY
Ekaterina Balaian, Claudia Schuster, Claudia Schönefeldt, Ulrich Germing, Detlef Haase, Sebastian Tuve, Rainer Ordemann, Gerhard Ehninger, Martin Bornhäuser, Uta Oelschlaegel, Brigitte Mohr, Malte von Bonin, Uwe Platzbecker, Martin Wermke
Lenalidomide (LEN) leads to erythroid improvement in the majority of patients with myelodysplastic syndrome and isolated deletion of the long arm of chromosome 5 (MDS-del(5q)). This effect is believed to be exerted via its immunomodulatory properties, although the precise nature is still incompletely understood. We prospectively performed immune profiling in the bone marrow and blood of MDS-del(5q) patients undergoing LEN therapy for a median of 6 cycles. Therapy with LEN led to a significant increase in the median absolute lymphocyte count (1...
October 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27369649/association-of-traf1-c5-with-risk-of-uveitis-in-juvenile-idiopathic-arthritis
#12
Yves-Marie Pers, Pierre Le Blay, Catherine Ludwig, Cécile Rittore, Gautier Tejedor, Randy Foliwe, Michel Rodiere, Christian Jorgensen, Isabelle Touitou
OBJECTIVES: Numerous single nucleotide polymorphisms (SNPs) have been associated with JIA, but few of these studies were replicated. We conducted a candidate-gene approach study to assess if some SNPs could be related to clinical subtypes or other clinical features of the juvenile idiopathic arthritis (JIA) such as the risk of uveitis, ANA positivity and the age at onset. METHODS: SNPs in six genes were analysed: PTPN22, STAT4, TRAF1-C5, TGFbeta, TNFAIP3, and C12orf30...
June 28, 2016: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/27335065/smad-signaling-is-required-for-structural-integrity-of-the-female-reproductive-tract-and-uterine-function-during-early-pregnancy-in-mice
#13
Amanda Rodriguez, Swamy K Tripurani, Jason C Burton, Caterina Clementi, Irina Larina, Stephanie A Pangas
Pregnancy is a complex physiological process tightly controlled by the interplay among hormones, morphogens, transcription factors, and signaling pathways. Although recent studies using genetically engineered mouse models have revealed that ligands and receptors of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) signaling pathways are essential for multiple reproductive events during pregnancy, the functional role of SMAD transcription factors, which serve as the canonical signaling platform for the TGFbeta/BMP pathways, in the oviduct and uterus is undefined...
August 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27334756/annexin-a6-protein-is-downregulated-in-human-hepatocellular-carcinoma
#14
Elisabeth M Meier, Lisa Rein-Fischboeck, Rebekka Pohl, Josef Wanninger, Andrew J Hoy, Thomas Grewal, Kristina Eisinger, Sabrina Krautbauer, Gerhard Liebisch, Thomas S Weiss, Christa Buechler
Annexin A6 (AnxA6) is a lipid-binding protein highly expressed in the liver, regulating cholesterol homeostasis and signaling pathways with a role in liver physiology. Here, we analyzed whether hepatic AnxA6 levels are affected by pathological conditions that are associated with liver dysfunction and liver injury. AnxA6 levels in the fatty liver of mice fed a high-fat diet, in ob/ob and db/db animals and in human fatty liver are comparable to controls. Similarly, AnxA6 levels appear unaffected in murine nonalcoholic steatohepatitis and human liver fibrosis...
July 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27149845/distinct-signaling-requirements-for-the-establishment-of-esc-pluripotency-in-late-stage-episcs
#15
Damir Jacob Illich, Miao Zhang, Andrei Ursu, Rodrigo Osorno, Kee-Pyo Kim, Juyong Yoon, Marcos J Araúzo-Bravo, Guangming Wu, Daniel Esch, Davood Sabour, Douglas Colby, Kathrin S Grassme, Jiayu Chen, Boris Greber, Susanne Höing, Wiebke Herzog, Slava Ziegler, Ian Chambers, Shaorong Gao, Herbert Waldmann, Hans R Schöler
It has previously been reported that mouse epiblast stem cell (EpiSC) lines comprise heterogeneous cell populations that are functionally equivalent to cells of either early- or late-stage postimplantation development. So far, the establishment of the embryonic stem cell (ESC) pluripotency gene regulatory network through the widely known chemical inhibition of MEK and GSK3beta has been impractical in late-stage EpiSCs. Here, we show that chemical inhibition of casein kinase 1alpha (CK1alpha) induces the conversion of recalcitrant late-stage EpiSCs into ESC pluripotency...
April 14, 2016: Cell Reports
https://www.readbyqxmd.com/read/26663515/master-regulators-in-primary-skin-fibroblast-fate-reprogramming-in-a-human-ex-vivo-model-of-chronic-wounds
#16
Maïté Noizet, Emilie Lagoutte, Marlène Gratigny, Marielle Bouschbacher, Isabelle Lazareth, Hugues Roest Crollius, Xavier Darzacq, Claire Dugast-Darzacq
Fibroblasts are important players in regulating tissue homeostasis. In the dermis, they are involved in wound healing where they differentiate into contractile myofibroblasts leading to wound closure. In nonhealing chronic wounds, fibroblasts fail to undertake differentiation. We established and used a human ex vivo model of chronic wounds where fibroblasts can undergo normal myofibroblast differentiation, or take on a nondifferentiable pathological state. At the whole genome scale, we identified the genes that are differentially regulated in these two cell fates...
March 2016: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/26493868/microarray-analyses-reveal-marked-differences-in-growth-factor-and-receptor-expression-between-8-cell-human-embryos-and-pluripotent-stem-cells
#17
Antonis Vlismas, Ritsa Bletsa, Despina Mavrogianni, Georgina Mamali, Maria Pergamali, Vasiliki Dinopoulou, George Partsinevelos, Peter Drakakis, Dimitris Loutradis, Ann A Kiessling
Previous microarray analyses of RNAs from 8-cell (8C) human embryos revealed a lack of cell cycle checkpoints and overexpression of core circadian oscillators and cell cycle drivers relative to pluripotent human stem cells [human embryonic stem cells/induced pluripotent stem (hES/iPS)] and fibroblasts, suggesting growth factor independence during early cleavage stages. To explore this possibility, we queried our combined microarray database for expression of 487 growth factors and receptors. Fifty-one gene elements were overdetected on the 8C arrays relative to hES/iPS cells, including 14 detected at least 80-fold higher, which annotated to multiple pathways: six cytokine family (CSF1R, IL2RG, IL3RA, IL4, IL17B, IL23R), four transforming growth factor beta (TGFB) family (BMP6, BMP15, GDF9, ENG), one fibroblast growth factor (FGF) family [FGF14(FH4)], one epidermal growth factor member (GAB1), plus CD36, and CLEC10A...
January 15, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/26459048/gli2-cell-specific-activity-is-controlled-at-the-level-of-transcription-and-rna-processing-consequences-to-cancer-metastasis
#18
Helle Sadam, Urmas Liivas, Anna Kazantseva, Priit Pruunsild, Jekaterina Kazantseva, Tõnis Timmusk, Toomas Neuman, Kaia Palm
High activity of GLI family zinc finger protein 2 (GLI2) promotes tumor progression. Removal of the repressor domain at the N terminus (GLI2∆N) by recombinant methods converts GLI2 into a powerful transcriptional activator. However, molecular mechanisms leading to the formation of GLI2∆N activator proteins have not been established. Herein we report for the first time that the functional activities of GLI2 are parted into different protein isoforms by alternative promoter usage, selection of alternative splicing, transcription initiation and termination sites...
January 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26457375/systemic-sclerosis-from-pathogenesis-to-targeted-therapy
#19
REVIEW
Christopher P Denton
Systemic sclerosis (scleroderma) leads to morbidity and mortality through a combination of inflammation, fibrosis and vascular damage leading to internal organ complications affecting the heart, lung, kidneys and bowel. More than half of those diagnosed ultimately die from the disease. Current treatments focus on broad spectrum immunosuppression or organ-based therapy for complication such as lung fibrosis, pulmonary or systemic hypertension. Targeting peptide mediators such as endothelin-1 have already led to licensed effective therapies for SSc vasculopathy...
July 2015: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/26366208/wwtr1-ww-domain-containing-transcription-regulator-1
#20
Yulei Zhao, Xiaolong Yang
WWTR1 (also called TAZ in publications. Therefore, TAZ is used in the following description) is a WW domaing-containing transcriptional coactivator, which was first identified as a 14-3-3 binding protein. TAZ is the downstream component in the Hippo pathway, and also has been found to interact with different pathways, such as Wnt, TGFbeta, etc. TAZ is involved in mesenchymal stem cell differentiation as well as tumorigenesis. High level of TAZ has been found in different cancers, such as breast cancer, colon cancer, lung cancer, etc...
November 1, 2014: Atlas of Genetics and Cytogenetics in Oncology and Haematology
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