Search results for "SIGNALING PATHWAY"
showing 10 items of 284 documents
The Insulin Receptor Substrate 1 (Irs1) in Intestinal Epithelial Differentiation and in Colorectal Cancer
2012
Colorectal cancer (CRC) is associated with lifestyle factors that affect insulin/IGF signaling, of which the insulin receptor substrate 1 (IRS1) is a key transducer. We investigated expression, localization and pathologic correlations of IRS1 in cancer-uninvolved colonic epithelium, primary CRCs with paired liver metastases and in vitro polarizing Caco2 and HT29 cells. IRS1 mRNA and protein resulted higher, relative to paired mucosa, in adenomas of familial adenomatous polyposis patients and in CRCs that overexpressed c-MYC, ß-catenin, InsRß, and IGF1R. Analysis of IRS1 immunostaining in 24 cases of primary CRC with paired colonic epithelium and hepatic metastasis showed that staining inten…
Extracellular Nampt promotes macrophage survival via a nonenzymatic interleukin-6/STAT3 signaling mechanism.
2008
Macrophages play key roles in obesity-associated pathophysiology, including inflammation, atherosclerosis, and cancer, and processes that affect the survival-death balance of macrophages may have an important impact on obesity-related diseases. Adipocytes and other cells secrete a protein called extracellular nicotinamide phosphoribosyltransferase (eNampt; also known as pre-B cell colony enhancing factor or visfatin), and plasma levels of eNampt increase in obesity. Herein we tested the hypothesis that eNampt could promote cell survival in macrophages subjected to endoplasmic reticulum (ER) stress, a process associated with obesity and obesity-associated diseases. We show that eNampt potent…
Expression pattern of Notch1, 2 and 3 and Jagged1 and 2 in lymphoid and stromal thymus components: distinct ligand–receptor interactions in intrathym…
1999
The suggested role of Notch1 or its mutants in thymocyte differentiation and T cell tumorigenesis raises the question of how the different members of the Notch family influence distinct steps in T cell development and the role played by Notch ligands in the thymus. We report here that different Notch receptor-ligand partnerships may occur inside the thymus, as we observed differential expression of Notch1, 2 and 3 receptors, their ligands Jagged1 and 2, and downstream intracellular effectors hairy and Enhancer of Split homolog 1 (HES-1) and hairy and Enhancer of Split homolog 5 (HES-5), depending on ontogenetic stage and thymic cell populations. Indeed, while Jagged2 is expressed in both st…
Creating a conditional mutation of Wnt-1 by antisense transgenesis provides evidence that Wnt-1 is not essential for spermatogenesis.
1993
We have used mice transgenic for an antisense construct for Wnt-1 to study the role of this gene in post-meiotic sperm development. The human PGK-2 promoter provided levels of Wnt-1 antisense mRNA in testes in 5 transgenic lines greatly in excess of Wnt-1 mRNA concentrations, and Wnt-1 mRNA levels were greatly decreased in the lines, by 98% in three of them. There was a general correlation between copy number of the insert, levels of antisense RNA, and decreases in mRNA. There was little effect of the antisense transgene on fertility or testicular histology suggesting that normal levels of Wnt-1 transcript are not essential for spermatogenesis.
Complement Activation in Peritoneal Dialysis–Induced Arteriolopathy
2017
Cardiovascular disease (CVD) is the leading cause of increased mortality in patients with CKD and is further aggravated by peritoneal dialysis (PD). Children are devoid of preexisting CVD and provide unique insight into specific uremia- and PD-induced pathomechanisms of CVD. We obtained peritoneal specimens from children with stage 5 CKD at time of PD catheter insertion (CKD5 group), children with established PD (PD group), and age-matched nonuremic controls (n=6/group). We microdissected omental arterioles from tissue layers not directly exposed to PD fluid and used adjacent sections of four arterioles per patient for transcriptomic and proteomic analyses. Findings were validated in omenta…
Muscle protein synthesis, mTORC1/MAPK/Hippo signaling, and capillary density are altered by blocking of myostatin and activins
2012
Loss of muscle mass and function occurs in various diseases. Myostatin blocking can attenuate muscle loss, but downstream signaling is not well known. Therefore, to elucidate associated signaling pathways, we used the soluble activin receptor IIb (sActRIIB-Fc) to block myostatin and activins in mice. Within 2 wk, the treatment rapidly increased muscle size as expected but decreased capillary density per area. sActRIIB-Fc increased muscle protein synthesis 1–2 days after the treatment correlating with enhanced mTORC1 signaling (phosphorylated rpS6 and S6K1, r = 0.8). Concurrently, increased REDD1 and eIF2Bε protein contents and phosphorylation of 4E-BP1 and AMPK was observed. In contrast, pr…
UNC-52/perlecan affects gonadal leader cell migrations in C. elegans hermaphrodites through alterations in growth factor signaling.
2003
0012-1606 doi: DOI: 10.1016/S0012-1606(03)00014-9; The unc-52 gene of Claenorhabditis elegans encodes a homologue of the basement membrane heparan sulfate proteoglycan perlecan. Viable alleles reduce the abundance of UNC-52 in late larval stages and increase the frequency of distal tip cell (DTC) migration defects caused by mutations disrupting the UNC-6/netrin guidance system. These unc-52 alleles do not cause circumferential DTC migration defects in an otherwise wild-type genetic background. The effects of unc-52 mutations on DTC migrations are distinct from effects on myofilament organization and can be partially suppressed by mutations in several genes encoding growth factor-like molecu…
TRTH-08. HIGH GRADE NEUROEPITHELIAL TUMOR OF THE CENTRAL NERVOUS SYSTEM WITH BCOR ALTERATION IS SENSITIVE TO IGF1R INHIBITION
2017
High grade neuroepithelial tumor of the central nervous system with BCOR alteration (CNS HGNET-BCOR) is a recently described new tumor entity which was formerly diagnosed with diverse histological diagnoses, for example as ependymoma. This tumor predominantly affects children and has a dismal prognosis. No standard therapies for this entity exist so far. Recently we described the activation of the Sonic hedgehog (SHH) and the WNT signaling pathway in this tumor and described a primary cell culture (PhKh1) isolated from a skull metastasis of a seven years old patient. We also detected a high expression of IGF2, which is known to be required for SHH signaling in medulloblastoma. IGF2 signals …
CONSERVED CELLULAR AND MOLECULAR MECHANISMS IN DEVELOPMENT
2002
This review discusses examples of conserved cellular and molecular mechansims in development, including the pathway of signal transduction between the photoreceptors R8 and R7 in Drosophila, which is compared to vulval induction in Caenorhabditis elegans. The Wg pathway in Drosophila is compared, first, to the Wnt pathway in dorsal mesoderm specification in Xenopus: second, to the same pathway in sea urchins; third, to the equivalent in the mom cascade of C. elegans; and finally, to parts of the equivalent pathway in Dictyostelium discoideum. The conserved expression of some hox genes in vertebrate limb buds and in the heads or tails of several invertebrate and vertebrate embryos is also il…
Expression profile of components of the β-catenin destruction complex in oral dysplasia and oral cancer
2021
Background Oral cancer represents the sixth most common cancer in the world and is associated with 40-50% survival at 5 years. Within oral malignancies, oral squamous cell carcinoma (OSCC) is commonly preceded by potentially malignant lesions, which, according to histopathological criteria, are referred to as oral dysplasia and their diagnosis are associated with higher rates of malignant transformation towards cancer. We recently reported that aberrant activation of the Wnt/β‑catenin pathway is due to overexpression of Wnt ligands in oral dysplasia. However, the expression of other regulators of this pathway, namely components of the β-catenin destruction complex has not been explored in o…