Search results for "Signaling."

Cytotoxicity of the indole alkaloid reserpine from Rauwolfia serpentina against drug-resistant tumor cells.

2015

Abstract Background: The antihypertensive reserpine is an indole alkaloid from Rauwolfia serpentina and exerts also profound activity against cancer cells in vitro and in vivo. The present investigation was undertaken to investigate possible modes of action to explain its activity toward drug-resistant tumor cells. Material and methods: Sensitive and drug-resistant tumor cell lines overexpressing P-glycoprotein (ABCB1/MDR1), breast cancer resistance protein (ABCG2/BCRP), mutation-activated epidermal growth factor receptor (EGFR), wild-type and p53-knockout cells as well as the NCI panel of cell lines from different tumor origin were analyzed. Reserpine's cytotoxicity was investigated by res…

STEM CELLS AND COLON CANCER

2012

The current concept of tumorigenesis suggests that cancers arise and are “driven” by cells with stem cell-like properties, known as cancer stem cells (CSCs), which share many functional and molecular features with normal stem cells. Self-renewal key pathways (e.g., Wnt, Notch, and Hedgehog) are tightly regulated in normal stem cells, but are impaired in CSCs. For instance, active Wnt pathway plays a crucial role in colon cancer pathophysiology, where deregulation of the adenomatous polyposis coli (APC) gene, a negative regulator of Wnt signaling, represents one of the earliest alterations in the multistep process of colon carcinogenesis, causing early adenoma formation. Normal colon stem ce…

Adhesion Molecules in Kidney Diseases

2010

TCTN3 Mutations Cause Mohr-Majewski Syndrome

2012

Orofaciodigital syndromes (OFDSs) consist of a group of heterogeneous disorders characterized by abnormalities in the oral cavity, face, and digits and associated phenotypic abnormalities that lead to the delineation of 13 OFDS subtypes. Here, by a combined approach of homozygozity mapping and exome ciliary sequencing, we identified truncating TCTN3 mutations as the cause of an extreme form of OFD associated with bone dysplasia, tibial defect, cystic kidneys, and brain anomalies (OFD IV, Mohr-Majewski syndrome). Analysis of 184 individuals with various ciliopathies (OFD, Meckel, Joubert, and short rib polydactyly syndromes) led us to identify four additional truncating TCTN3 mutations in un…

CD4+CD25+ Regulatory T Cells and TGF-Beta in Mucosal Inflammation

2008

Transforming growth factor-beta (TGF-beta) is an anti-inflammatory cytokine which plays a key role in the maintenance of the immune system homeostasis. Indeed the abrogation of the TGF-beta signaling in immune cells leads to autoimmunity and inflammation in several organs including the gut. TGF-beta acts at multiple levels to maintain the immune system in check. However, TGF-beta has been recently shown to play a key role in the peripheral generation and function of CD4+CD25+ regulatory T cells, a subset of suppressive lymphocytes involved in the control of effector T cell activation and proliferation. Consistently abrogation of Tregs maturation as observed in different systems leads to a p…

Topical application of the Wnt/β-catenin activator methyl vanillate increases hair count and hair mass index in women with androgenetic alopecia

2016

Activation of the WNT/β-catenin pathway has emerged as a potential therapeutic target in androgenetic alopecia (AGA). Methyl vanillate (MV) - a safe plant-derived ingredient - has been recently shown to activate the WNT/β-catenin signaling. Objectives Two distinct substudies were conducted. First, we designed a 6-month, uncontrolled, open-label clinical study to investigate whether topically applied MV may increase hair count and hair mass index (HMI) in female AGA. Second, we conducted a molecular study on the effect of MV on WNT10B mRNA expression in scalp biopsies of women with AGA. A total of 20 Caucasian women (age range: 25-57 years) with AGA (Sinclair grade 1-2) were included. The re…

Inhibition of tumor cell proliferation in human uterine leiomyomas by vitamin D via Wnt/β-catenin pathway.

2018

To assess the effect of vitamin D (VitD) on human uterine leiomyomas through Wnt/β-catenin pathway inhibition, apoptosis induction, and cell growth arrest.A prospective study comparing leiomyoma vs. myometrium tissues. Paired design study comparing human uterine leiomyoma primary (HULP) cells treated with or without VitD.University hospital.Human uterine leiomyoma and myometrium were collected from women (aged 35-52 years) without hormonal treatment.Samples were collected from women undergoing surgery due to symptomatic uterine leiomyoma pathology.Uterine leiomyoma and myometrium tissues were analyzed by western blot (WB) to determine proliferation, Wnt/β-catenin, and apoptosis pathways. HU…

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&gt;…

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,…