Search results for "Factor receptor"
showing 10 items of 350 documents
Echovirus 1 internalization negatively regulates epidermal growth factor receptor downregulation
2017
We have demonstrated previously that the human picornavirus Echovirus 1 (EV1) triggers an infectious internalization pathway that follows closely, but seems to stay separate, from the epidermal growth factor receptor (EGFR) pathway triggered by epidermal growth factor (EGF). Here, we confirmed by using live and confocal microscopy that EGFR and EV1 vesicles are following intimately each other but are distinct entities with different degradation kinetics. We show here that despite being sorted to different pathways and located in distinct endosomes, EV1 inhibits EGFR downregulation. Simultaneous treatment with EV1 and EGF led to an accumulation of EGFR in cytoplasmic endosomes, which was evi…
MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation
2019
Mesenchymal stromal cells (hMSCs) display a pleiotropic function in bone regeneration. The signaling involved in osteoblast commitment is still not completely understood, and that determines the failure of current therapies being used. In our recent studies, we identified two miRNAs as regulators of hMSCs osteoblast differentiation driving hypoxia signaling and cytoskeletal reorganization. Other signalings involved in this process are epithelial to mesenchymal transition (EMT) and epidermal growth factor receptor (EGFR) signalings through the regulation of Yes-associated protein (YAP)/PDZ-binding motif (TAZ) expression. In the current study, we investigated the role of miR-33a family as a (…
Molecular Subtypes, Metastatic Pattern and Patient Age in Breast Cancer: An Analysis of Italian Network of Cancer Registries (AIRTUM) Data
2021
Breast cancer stage at diagnosis, patient age and molecular tumor subtype influence disease progression. The aim of this study was to analyze the relationships between these factors and survival in breast cancer patients among the Italian population using data from the AIRTUM national database. We enrolled women with primary breast cancer from 17 population-based cancer registries. Patients were subdivided into older (>69 years), middle (50–69 years) and younger age groups (<50 years) and their primary tumors categorized into four molecular subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. There were 8831 patients diagnosed betwe…
Targeting a Targeted Drug: An Approach Toward Hypoxia-Activatable Tyrosine Kinase Inhibitor Prodrugs
2016
Tyrosine kinase inhibitors (TKIs), which have revolutionized cancer therapy over the past 15 years, are limited in their clinical application due to serious side effects. Therefore, we converted two approved TKIs (sunitinib and erlotinib) into 2-nitroimidazole-based hypoxia-activatable prodrugs. Kinetics studies showed very different stabilities over 24 h; however, fast reductive activation via E. coli nitroreductase could be confirmed for both panels. The anticancer activity and signaling inhibition of the compounds against various human cancer cell lines were evaluated in cell culture. These data, together with molecular docking simulations, revealed distinct differences in the impact of …
Inhibition of Delta-like 4 mediated signaling induces abortion in mice due to deregulation of decidual angiogenesis.
2013
Objective: To explore whether the Dll4/Notch1 pathway plays a key role in regulating the vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) driven decidual angiogenesis and related pregnancy through induction of a tip/stalk phenotype. Methods: Progesterone-replaced ovariectomized pregnant mice received a single injection of YW152F (Dll4 blocking antibody, BAb) or placebo at embryonic day (E) 4.5. Animals were sacrificed at different time points; blood and uterus were collected for further analysis. Number of embryos and implantation site, uteri weight, and serum progesterone levels were assessed. Alterations in the tip/stalk phenotype were determined by quantitative immunofl…
Amphiregulin activates human hepatic stellate cells and is upregulated in non alcoholic steatohepatitis
2015
AbstractAmphiregulin (AR) involvement in liver fibrogenesis and hepatic stellate cells (HSC) regulation is under study. Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular cancer (HCC). Our aim was to investigate ex vivo the effect of AR on human primary HSC (hHSC) and verify in vivo the relevance of AR in NAFLD fibrogenesis. hHSC isolated from healthy liver segments were analyzed for expression of AR and its activator, TNF-α converting enzyme (TACE). AR induction of hHSC proliferation and matrix production was estimated in the presence of antagonists. AR involvement in fibrogenesis was also ass…
Getting the Fat out of Met and Fas
2008
Lack of Fas antagonism by Met in human fatty liver disease. Zou C, Ma J, Wang X, Guo L, Zhu Z, Stoops J, Eaker AE, Johnson CJ, Strom S, Michalopoulos GK, DeFrances MC, Zarnegar R. Hepatocytes in fatty livers are hypersensitive to apoptosis and undergo escalated apoptotic activity via death receptor-mediated pathways, particularly that of Fas–FasL, causing hepatic injury that can eventually proceed to cirrhosis and end-stage liver disease. Here we report that the hepatocyte growth factor receptor, Met, plays an important part in preventing Fas-mediated apoptosis of hepatocytes by sequestering Fas. We also show that Fas antagonism by Met is abrogated in human fatty liver disease (FLD). Throug…
Genetic basis of dental agenesis - molecular genetics patterning clinical dentistry
2013
Tooth agenesis is one of the most common congenital malformations in humans. Hypodontia can either occur as an isolated condition (non-syndromic hypodontia) or can be associated with a syndrome (syndromic hypodontia), highlighting the heterogeneity of the condition. Though much progress has been made to identify the developmental basis of tooth formation, knowledge of the etiological basis of inherited tooth loss is still lacking. To date, the mutation spectra of non-syndromic form of familial and sporadic tooth agenesis in humans have revealed defects in various such genes that encode transcription factors, MSX1 and PAX9 or genes that code for a protein involved in canonical Wnt signaling …
The role of insulin-like growth factor II in the malignant transformation of rat liver oval cells
1997
Oval cells are small nonparenchymal epithelial cells that first appear in the periportal areas of the liver and thereafter invade the whole parenchyma when mice or rats are exposed to a variety of chemical carcinogens. In the present study we have analyzed the expression of insulin-like growth factor II (IGF II) in the recently established oval cell line OC/CDE 22 and its malignantly transformed counterpart (the M22 cells) and the biological consequences of the constitutive expression of IGF II in oval cells. OC/CDE 22 cells do not express the above-mentioned growth factor, whereas the M22 cells do and addition of a neutralizing anti-IGF II antibody to M22 cells resulted in an almost comple…
Insulin-like growth factors in chick embryo retina during development.
1996
Evidence exists supporting an important role for insulin-like growth factors (IGFs) during fetal growth. In the present report we performed studies to define whether developing chick retina contains IGFs and whether IGFs play a role in the growth of this tissue. We have shown that both IGF-I and IGF-II are present in chick embryo retina throughout development (7th-18th day). The highest values, when expressed as ng/g of tissue, were found in the youngest retinas studied (7th-9th day) and at 16th-18th day of development. During whole development the content of IGF-II was about two to three times higher than that ascertained for IGF-I. The tissue also contains cell-surface binding for IGFs. H…