Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 35 for “"Smad4"”.
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TGFβ signalling in microglia and the impact of microglia-specific Smad4 deletion
… signalling in microglia and the regulation of Smad4-mediated microglial functions, and their subsequent impact on central nervous system (CNS) homeostasis, neurodevelopment, and neuroinflammation. The study comprehensively describes the TGFβ signalling pathway in microglia, analyzing the …
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Dissecting the impact of SMAD4 loss and KRAS mutations in pancreatic ductal adenocarcinoma
… in four key genes: KRAS, TP53, CDKN2A and SMAD4; which have been shown to shape stromal composition. Lack of representation of complex genetic profiles in pre-clinical models of PDAC, which focus on Kras G12D and Trp53 mutations, alongside limited consideration of CAF heterogeneity, have …
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The study of tumor-derived Smad4 mutations in transforming growth factor β (TGF-β) signaling
This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).
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Tumour suppression mediated through DPC4, p53 and APC
Mutations in the tumour suppressor genes SMAD4 (or DPC4, deleted in pancreatic cancer locus 4), APC (adenomatous polyposis coli) and p53 have been implicated in pancreatic cancer in humans. This thesis firstly documents the in vivo effects of mutations in these genes singly and in combination …
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Interactions between BMP and Canonical Wnt Signaling Regulate Critical Stages of the Osteoblast Lifecycle
… of osteoprogenitors, by focusing on Smad4, a central mediator of the greater TGF-beta/BMP pathway. Acute, tamoxifen-induced deletion of <italic>Smad4</italic> in otherwise normal osteoblasts in mice activates proliferation of predominantly post-mitotic <italic>Osterix+</italic> cells …
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Deconvoluting genetic variants associated with aortic disease using stem cell models
… and mothers against decapentaplegic homolog 4 (SMAD4, 51076665 C>T) were selected. CRISPR-Cas9 genetic editing introduced these mutations into wild type iPSC lines. The mutant lines were differentiated into vascular smooth muscle cells (VSMC), analysed with a multi-omic approach, and the …
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The Role and Mechanism of The Homeobox Gene Dlx4 In Transforming Growth Factor-B Resistance In Cancer
… by directly binding to Smad4 and to Sp1. Binding of DLX4 to Smad4 prevented Smad4 from forming transcriptional complexes with Smad2 and Smad3, whereas binding of DLX4 to Sp1 inhibited DNA-binding activity of Sp1. In addition, DLX4 induced expression of c-myc, a repressor …
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The Mechanism of Tumorigenesis In The Immortalized Human Pancreatic Cell Lines: Cell Culture Models of Human Pancreatic Cancer
… and p14 (40%), inactivation p53 (50-75%) and Smad4 (55%). However, the role of these signature gene alterations in PDAC is still not well understood, especially, how these genetic lesions individually or in combination contribute mechanistically to human pancreatic oncogenesis is still …
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Comparative Morphological and Immunohistochemical Analysis of Benign and Malignant Epithelial Colon Tumors // Сравнителен морфологичен и имунохистохимичен анализ на бенигнени и малигнени епителни тумори на дебелото черво
… експресия на протеини APC, p53, SMAD4, MSH2 и BRAF при доброкачествени и злокачествени епителни тумори на дебелото черво във връзка с клинико-морфологичните показатели и ролята им в туморната инициация и прогресия. Получихме следните резултати: с редуциране площта на експресия на …
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The activin a pathway in fetal testis development and dysgenesis in the mouse
… A, I produced mouse models lacking expression of Smad4, a central component of TGFβ superfamily signaling, in specific cell types within the testis. Deletion of Smad4 from the Sertoli cell epithelium recapitulated the fetal testis cord dysgenesis present in Inhba-/- mice, indicating the Sertoli …
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Epithelial to Mesenchymal Transition As A Predictor of Response to Polo-Like Kinase 1 Inhibition-Induced Apoptosis In Non-Small Cell Lung Carcinoma
… NSCLC cell lines and we identified β-Catenin, SMAD4 and PDK1 to be differentially regulated between epithelial and mesenchymal NSCLC cell lines after PLK1 inhibition. We tested the role of β-Catenin, SMAD4 and PDK1 in PLK1 inhibition induced apoptosis in NSCLC.</p> <p>Here, we demonstrate that …
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CROSSTALK BETWEEN LYSOPHOSPATIDIC ACID (LPA) AND TRANSFORMING GROWTH FACTOR BETA (TGFβ) IN BREAST AND OVARIAN CANCER CELLS
… cell migration. Knockdown of Smad3 or Smad4 with small hairpin RNA (shRNA) eliminated the inhibitory effects of TGFβ on the LPA1 expression and LPA-dependent cell migration. There are two potential TGFβ inhibitory elements (TIE) (-40 bp and -401 bp) present in the human LPA1 gene …
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Serum Regulation of Inhibitor of DNA Binding/Differentiation 1 Expression by a BMP Pathway and BMP Responsive El
… of the BMP pathway by siRNA depletion of Smad4, treatment with the BMP antagonist noggin, or the BMP receptor inhibitor dorsomorphin blocked serum induction of Id1. Further, BMP2 is sufficient to induce Id1 expression. Given reports that SRC inhibitors can block Id1 expression, we tested …
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Expression of Leukemia/Lymphoma Related Factor (LRF) in Human Breast Carcinoma
… LRF significantly increased TGF-βRII and Smad4 expression. It also activated and interacted with the active p65 subunit of NF-κB. Overexpressed LRF also upregulated the expression of the cyclin A, down- regulated p21CIP/WAF expression and induced cell cycle arrest in the G2 phase. Further …
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A Context-Forward In Vivo Functional Genomics Platform For Target Discovery and Establishing Vulnerability Context In Pancreatic Cancer
… we validated PCEN-informed dependences (SMAD4, ZEB1, ILK) associated to the basal-like subtype intratumorally. Silencing these targets resulted in a significant and direction shift in the differential signature spectrum towards a more classical profile, coinciding with phenotypic …
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The Role of ECSIT in Mitochondrial Dysfunction Mediated Cardiomyopathy
… protein pathway through interaction with SMAD4 allowing for normal embryonic development. It also functions as a mitochondrial complex I assembly factor and loss of function leads to a reduction in fully assembled complex I. As part of a large scale ENU mutagenesis screen, The Harwell …
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Molecular Mechanisms Underlying The Transcriptional Regulation of T Helper 17 and Regulatory T Cells
… of TGF-b, we found that while Smad2, Smad3 and Smad4 are required for the generation of iTreg cells, only Smad2 is indispensable for the induction of IL-17-producing cells, suggesting that TGF-b induces these T helper lineages through differential signaling pathways. Thus, our findings describe …
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Smad Proteins and theTgf-Beta Signaling Pathway During In Vitro Progression of Hpv16-Immortalized Human Keratinocytes' and 'Microarray Gene Expression Profiling of Exfoliated Cervical Cells'
… TGF-β induced nuclear trafficking of Smad3 and Smad4, and phosphorylation of Smad2 are affected during in vitro progression. We did not find any consistent decrease in protein expression of Smad2, Smad3 or Smad4; or increase in protein expression of inhibitory Smad7 that paralleled the …
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The Role of Bone Morphogenetic Protein (BMP) Signalling in Lung Cancer and Lung Regeneration
… normal lung epithelial cells while BMP4, BMP5, Smad4 and Id-1 expression were increased. We hypothesized BMPR-IB plays an anti-proliferative role during early tumour progression. To characterise the function of BMPR-IB in lung cells, the gene was cloned from mouse lung cDNA and an …
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Effects of nerve growth factor on TGF-Beta,Smad signal transduction in PC12 cells
… to the nucleus and activates transcription in a Smad4-dependent manner. Negative regulation is provided by Smad7 which was found to act as a potent inhibitor of Smad signaling not only in TGF-ß- but also in NGF-mediated cascades. The potential of NGF to activate the Smad pathway independent of …
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