Search results for " signaling."
showing 10 items of 1032 documents
Circulating Apelin is increased in patients with type 1 or type 2 diabetes and is associated with better glycaemic control
2013
SummaryContext Apelin is an adipokine expressed in several tissues and it appears to be involved in energy metabolism. Objective The aim of this study was to determine serum apelin levels in a large cohort of patients with type 1 and type 2 diabetes and control subjects and to correlate the results with glycaemic control. Design and Participants One hundred and thirty patients with type 1 diabetes, 98 patients with type 2 diabetes and 162 controls were enrolled in the study. Apelin levels were measured by enzyme-linked immunosorbent assay. Results Serum apelin levels were significantly higher in type 1 and type 2 diabetic patients than in controls (P < 0·0001). Serum apelin levels were high…
Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence…
2011
Abstract Background Several polymorphisms of genes involved in the immunological recognition of Helicobacter pylori and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding Angiotensin converting enzyme (ACE), Nod-like receptor 1 (NOD1), Toll-like receptor 4 (TLR4) and FAS/FASL. Methods Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. ACE I/D (rs4646994), NOD1 796G>…
Evidence for altered adipocyte function in polycystic ovary syndrome.
2005
Background: Adipocytokines are produced by adipose tissue and have been thought to be related to insulin resistance and other health consequences. We measured leptin, adiponectin, and resistin simultaneously in women with polycystic ovary syndrome (PCOS) and age- and weight-matched controls. Our hypothesis was that these simultaneous measurements would help determine whether adipocytokine secretion is abnormal in PCOS independent of body mass and whether these levels are related to insulin resistance as well as other hormonal changes. Methods: Fifty-two women with PCOS and 45 normal ovulatory women who were age- and weight-matched were studied. Blood was obtained for adipocytokines (leptin,…
Vitamin D as an effective treatment in human uterine leiomyomas independent of mediator complex subunit 12 mutation.
2021
Objective To study whether vitamin D (VitD) inhibits cell proliferation and Wnt/β-catenin and transforming growth factor−β (TGFβ) signaling pathways in uterine leiomyomas independent of mediator complex subunit 12 (MED12) mutation status. Design Prospective study comparing leiomyoma vs. myometrial tissues and human uterine leiomyoma primary (HULP) cells treated with or without VitD and analyzed by MED12 mutation status. Setting Hospital and university laboratories. Patient(s) Women with uterine leiomyoma without any treatment (n = 37). Intervention(s) Uterine leiomyoma and myometrium samples were collected from women undergoing surgery because of symptomatic leiomyoma pathology. Main Outcom…
Bone marrowVEGFCexpression is associated with multilineage dysplasia and several prognostic markers in adult acute myeloid leukemia, but not with sur…
2018
Vascular endothelial growth factor C (VEGFC) stimulates leukemia cell proliferation and survival, and promotes angiogenesis. We studied VEGFC expression in bone marrow samples from 353 adult acute myeloid leukemia (AML) patients and its relationship with several clinical, cytogenetic, and molecular variables. We also studied the expression of 84 genes involved in VEGF signaling in 24 patients. We found that VEGFC expression was higher in AML patients with myelodysplasia-related changes (AML-MRC) than in patients with non-AML-MRC. We also found an association between VEGFC expression and the patient cytogenetic risk group, with those with a worse prognosis having higher VEGFC expression leve…
Hypoxic macrophages impair autophagy in epithelial cells through Wnt1: relevance in IBD.
2014
A defective induction of epithelial autophagy may have a role in the pathogenesis of inflammatory bowel diseases. This process is regulated mainly by extracellular factors such as nutrients and growth factors and is highly induced by diverse situations of stress. We hypothesized that epithelial autophagy is regulated by the immune response that in turn is modulated by local hypoxia and inflammatory signals present in the inflamed mucosa. Our results reveal that HIF-1 alpha and Wnt1 were co-localized with CD68 in cells of the mucosa of IBD patients. We have observed increased protein levels of beta-catenin, phosphorylated mTOR, and p62 and decreased expression of LC3II in colonic epithelial …
Migration of renal tumor cells depends on dephosphorylation of Shc by PTEN.
2011
The tumor suppressor PTEN is a phosphatase using FAK and Shc as direct substrates, and Akt as a key effector via PIP3. PTEN regulates cell migration and may influence metastases. We quantified PTEN in 135 clear cell renal cell carcinomas (ccRCC) by Western blot analysis and found statistically significant lower PTEN expression in patients who died, usually caused by metastases, within 5 years after surgery, compared to those surviving this time period. In athymic mice, PTEN transfected 786-O cells were injected into the tail vein and metastatic load of the lungs was quantified. We observed a strongly reduced metastatic load after PTEN transfection. For analyses of the PTEN activities, trans…
Temsirolimus for the treatment of mantle cell lymphoma.
2010
Although recent progress has been made in the treatment of mantle cell lymphoma (MCL) the majority of patients experience relapse and ultimately die of their disease. The translocation t(11;14) is a prerequisite for the diagnosis of MCL and results in overexpression of cyclin D1. Its protein translation is controlled by mTOR, a key element of the PI3K/Akt pathway, and mTOR constitutes an attractive therapeutic target. Temsirolimus, a specific inhibitor of mTOR, has been evaluated in two Phase II trials in patients with relapsed MCL, and promising response rates up to 40% were found. Subsequently, a randomized Phase III trial was initiated, in which superiority in remission induction and pro…
Neddylation inhibition ameliorates steatosis in NAFLD by boosting hepatic fatty acid oxidation via the DEPTOR-mTOR axis
2021
Objective Neddylation is a druggable and reversible ubiquitin-like post-translational modification upregulated in many diseases, including liver fibrosis, hepatocellular carcinoma, and more recently, non-alcoholic fatty liver disease (NAFLD). Herein, we propose to address the effects of neddylation inhibition and the underlying mechanisms in pre-clinical models of NAFLD. Methods Hepatic neddylation measured by immunohistochemical analysis and NEDD8 serum levels measured by ELISA assay were evaluated in NAFLD clinical and pre-clinical samples. The effects of neddylation inhibition by using a pharmacological small inhibitor, MLN4924, or molecular approaches were assessed in isolated mouse hep…
Sequential transcriptome analysis of human liver cancer indicates late stage acquisition of malignant traits
2014
Background & Aims Human hepatocarcinogenesis is as a multi-step process starting from dysplastic lesions to early carcinomas (eHCC) that ultimately progress to HCC (pHCC). However, the sequential molecular alterations driving malignant transformation of the pre-neoplastic lesions are not clearly defined. This lack of information represents a major challenge in the clinical management of patients at risk. Methods We applied next-generation transcriptome sequencing to tumor-free surrounding liver (n=7), low- (n=4) and high-grade (n=9) dysplastic lesions, eHCC (n=5) and pHCC (n=3) from 8 HCC patients with hepatitis B infection. Integrative analyses of genetic and transcriptomic changes were pe…