Protein-protein interaction network analysis applied to DNA copy number profiling suggests new perspectives on the aetiology of Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare disease, characterised by the aplasia of vagina and uterus in women with a 46,XX karyotype. Most cases are sporadic, but familial recurrence has also been described. Herein, we investigated an Italian cohort of 36 unrelated MRKH patients to explore the presence of pathogenic copy number variations (CNVs) by array-CGH and MLPA assays.

MiR-200c sensitizes Olaparib-resistant ovarian cancer cells by targeting Neuropilin 1.

Background: Ovarian cancer (OC) is the most lethal gynecological malignancy and the second leading cause of cancer-related death in women. Treatment with PARP inhibitors (PARPi), such as Olaparib, has been recently introduced for OC patients, but resistance may occur and underlying mechanisms are still poorly understood. The aim of this study is to identify target genes within the tumor cells that might cause resistance to Olaparib.

PARP inhibitors affect growth, survival and radiation susceptibility of human alveolar and embryonal rhabdomyosarcoma cell lines.

Purpose: PARP inhibitors (PARPi) are used in a wide range of human solid tumours but a limited evidence is reported in rhabdomyosarcoma (RMS), the most frequent childhood soft-tissue sarcoma. The cellular and molecular effects of Olaparib, a specific PARP1/2 inhibitor, and AZD2461, a newly synthesized PARP1/2/3 inhibitor, were assessed in alveolar and embryonal RMS cells both as single-agent and in combination with ionizing radiation (IR).

Methods: Cell viability was monitored by trypan blue exclusion dye assays.

Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis.

Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps.

Autophagy activation is required for myofibroblast differentiation during healing of oral mucosa.

Aim: It is known that periodontal tissues heal faster that skin, and gingiva in particular heal without scar formation. The mechanisms regulating this behaviour are still unclear. The aim of our work was to compare wound healing in oral mucosa and gingiva, investigating the role of α-smooth muscle actin (αSMA)-expressing myofibroblasts and autophagy.

Autologous in vitro cultured vaginal tissue for vaginoplasty in women with Mayer-Rokitansky-Küster-Hauser syndrome: anatomic and functional results.

Study Objective: To present the procedure and the results of a technique in which in vitro autologous cell cultures were used for the canal lining in patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) subjected to vaginoplasty with a modified Abbè-McIndoe technique. MRKHS is a rare anomaly characterized by vaginal agenesis with variable müllerian duct abnormalities. The Abbè-McIndoe procedure is 1 of the most frequent surgical treatments adopted in these women.

Characterization of human vaginal mucosa cells for autologous in vitro cultured vaginal tissue transplantation in patients with MRKH syndrome.

Mayer-Rokitansky-Küster-Hauser (MRKH) is a rare syndrome characterized by congenital aplasia of the uterus and vagina. The most common procedure used for surgical reconstruction of the neovagina is the McIndoe vaginoplasty, which consists in creation of a vaginal canal covered with a full-thickness skin graft. Here we characterized the autologous in vitro cultured vaginal tissue proposed as alternative material in our developed modified McIndoe vaginoplasty in order to underlie its importance in autologous total vaginal replacement.

Topical KGF treatment as a therapeutic strategy for vaginal atrophy in a model of ovariectomized mice.

One of the most frequent complaints for post-menopausal women is vaginal atrophy, because of reduction in circulating oestrogens. Treatments based on local oestrogen administration have been questioned as topic oestrogens can reach the bloodstream, thus leading to consider their safety as controversial, especially for patients with a history of breast or endometrial cancers. Recently, growth factors have been shown to interact with the oestrogen pathway, but the mechanisms still need to be fully clarified.

Potential prognostic and diagnostic application of a novel monoclonal antibody against keratinocyte growth factor receptor.

KGFR is involved in the pathogenesis of several human cancers. In this study, we generated and characterized a monoclonal antibody specific to KGFR (SC-101 mAb) and evaluated its potential use in basic research and as a diagnostic and prognostic tool. The specificity and biological activity of the SC-101 mAb were evaluated by Western blotting, immunofluorescence, and immunoprecipitation analyses on various cell lines.

Gene expression profile of patients with Mayer-Rokitansky-Küster-Hauser syndrome: new insights into the potential role of developmental pathways.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a rare disease characterized by congenital aplasia of uterus and vagina. Although many studies have investigated several candidate genes, up to now none of them seem to be responsible for the aetiology of the syndrome. In our study, we identified differences in gene expression profile of in vitro cultured vaginal tissue of MRHKS patients using whole-genome microarray analysis.

Fibroblast growth factor receptor-2 expression in thyroid tumor progression: potential diagnostic application.

Fibroblast growth factor receptor-2 (FGFR-2) plays an important role in tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation, but the role of this receptor has not been yet clarified. Therefore, we decided to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in different histological thyroid variants such as hyperplasia, follicular adenoma and papillary carcinoma.

TNFα modulates Fibroblast Growth Factor Receptor 2 gene expression through the pRB/E2F1 pathway: identification of a non-canonical E2F binding motif.

Interactions between epithelium and mesenchyme during wound healing are not fully understood, but Fibroblast Growth Factors (FGFs) and their receptors FGFRs are recognized as key elements. FGFR2 gene encodes for two splicing transcript variants, FGFR2-IIIb or Keratinocyte Growth Factor Receptor (KGFR) and FGFR2-IIIc, which differ for tissue localization and ligand specificity. Proinflammatory cytokines play an essential role in the regulation of epithelial-mesenchymal interactions, and have been indicated to stimulate FGFs production.