Search results for " signaling."

Self-organised symmetry breaking in zebrafish reveals feedback from morphogenesis to pattern formation

2019

A fundamental question in developmental biology is how the early embryo breaks initial symmetry to establish the spatial coordinate system later important for the organisation of the embryonic body plan. In zebrafish, this is thought to depend on the inheritance of maternal mRNAs [1–3], cortical rotation to generate a dorsal pole of beta-catenin activity [4–8] and the release of Nodal signals from the yolk syncytial layer (YSL) [9–12]. Recent work aggregating mouse embryonic stem cells has shown that symmetry breaking can occur in the absence of extra-embryonic tissue [19,20]. To test whether this is also true in zebrafish, we separated embryonic cells from the yolk and allowed them to deve…

Paternal uniparental disomy chromosome 14-like syndrome due a maternal de novo 160 kb deletion at the 14q32.2 region not encompassing the IG- and the…

2015

The human chromosome 14q32 carries a cluster of imprinted genes which include the paternally expressed genes (PEGs) DLK1 and RTL1, as well as the maternally expressed genes (MEGs) MEG3, RTL1as, and MEG8. PEGs and MEGs expression at the 14q32.2-imprinted region are regulated by two differentially methylated regions (DMRs): the IG-DMR and the MEG3-DMR, which are respectively methylated on the paternal and unmethylated on the maternal chromosome 14 in most cells. Genetic and epigenetic abnormalities affecting these imprinted gene clusters result in two different phenotypes currently known as maternal upd(14) syndrome and paternal upd(14) syndrome. However, only few patients carrying a maternal…

Development of polypeptide-based therapeutics for the treatment of castration resistant prostate cancer

2019

El cáncer de próstata (CaP) es el segundo cáncer más frecuente en los hombres. Los estudios han establecido el gen de fusión (T2E) compuesto por TMPRSS2 (serina proteasa dependiente de andrógenos) y ERG (factor de transcripción de la familia ETS) como un biomarcador potencial de CaP. La progresión en el CaP incluye tanto el receptor de andrógenos (AR) como el receptor del factor de crecimiento de insulina 1 (IGF-1R), y el tratamiento con un anticuerpo anti-IGF-1R (AVE1642) ha demostrado un gran potencial en el tratamiento de los pacientes con CaP T2E-positivos. Por ello, el desarrollo de terapias personalizadas basadas en polímeros terapéuticos puede favorecer el tratamiento de CaP para un …

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…