Search results for "Oncogene"
showing 10 items of 1005 documents
Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations : Results from a Multi-institutional European Retrospective Study
2022
[Purpose] The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9–mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopathologic variables with survival was evaluated in a large multi-institutional European cohort.
OPLA scaffold, collagen I, and horse serum induce a higher degree of myogenic differentiation of adult rat cardiac stem cells
2009
In the last few years, a major goal of cardiac research has been to drive stem cell differentiation to replace damaged myocardium. Several research groups have attempted to differentiate potential cardiac stem cells (CSCs) using bi- or three-dimensional systems supplemented with growth factors or molecules acting as differentiating substances. We hypothesize that these systems failed to induce a complete differentiation because they lacked an architectural space. In the present study, we isolated a pool of small proliferating and fibroblast-like cells from adult rat myocardium. The phenotype of these cells was assessed and the characterized cells were cultured in a collagen I/OPLA scaffold …
THE ROLE OF PSYCHOLOGICAL ASPECTS IN ONCOGENETIC COUNSELLING
2010
Background: As result of the recent developments in DNA testing and the knowledge that cancer can be hereditary, it is now possible to offer genetic counselling to people within identified “cancer families”, and to inform them about their assumed increased risk for developing cancer. The aim of this study was to test the role of psychological aspect in oncogenetic counselling. The primary purpose of the research was to evaluate the difference between Anxiety Trait and Anxiety State in subjects going to oncogenetic counselling. The secondary aim was to explore the relationships between alexithymia, personality trait, coping style, psychological distress, in subjects attending genetic counsel…
The mitotic kinase Aurora-A promotes distant metastases by inducing epithelial-to-mesenchymal transition in ERα+ breast cancer cells
2013
In this study, we demonstrate that constitutive activation of Raf-1 oncogenic signaling induces stabilization and accumulation of Aurora-A mitotic kinase that ultimately drives the transition from an epithelial to a highly invasive mesenchymal phenotype in estrogen receptor α-positive (ERα(+)) breast cancer cells. The transition from an epithelial- to a mesenchymal-like phenotype was characterized by reduced expression of ERα, HER-2/Neu overexpression and loss of CD24 surface receptor (CD24(-/low)). Importantly, expression of key epithelial-to-mesenchymal transition (EMT) markers and upregulation of the stemness gene SOX2 was linked to acquisition of stem cell-like properties such as the ab…
RNAi mediated acute depletion of Retinoblastoma protein (pRb) promotes aneuploidy in human primary cells via micronuclei formation
2009
BACKGROUND: Changes in chromosome number or structure as well as supernumerary centrosomes and multipolar mitoses are commonly observed in human tumors. Thus, centrosome amplification and mitotic checkpoint dysfunctions are believed possible causes of chromosomal instability. The Retinoblastoma tumor suppressor (RB) participates in the regulation of synchrony between DNA synthesis and centrosome duplication and it is involved in transcription regulation of some mitotic genes. Primary human fibroblasts were transfected transiently with short interfering RNA (siRNA) specific for human pRb to investigate the effects of pRb acute loss on chromosomal stability. RESULTS: Acutely pRb-depleted fibr…
TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies
2009
AIM: To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors, in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand (TRAIL), on overcoming TRAIL resistance in hepatocellular carcinoma (HCC) and to study the efficacy of agonistic TRAIL antibodies, as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS: Surface expression of TRAIL receptors (TRAIL-R1-4) and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting, respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNA…
What links BRAF to the heart function? new insights from the cardiotoxicity of BRAF inhibitors in cancer treatment
2015
The RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolonga…
Sarcophytolide: a new neuroprotective compound from the soft coral Sarcophyton glaucum
1998
Abstract Bioactivity-guided fractionation of an alcohol extract of the soft coral Sarcophyton glaucum collected from the intertidal areas and the fringing coral reefs near Hurghada, Red Sea, Egypt resulted in the isolation of a new lactone cembrane diterpene, sarcophytolide. The structure of this compound was deduced from its spectroscopic data and by comparison of the spectral data with those of known closely related cembrane-type compounds. In antimicrobial assays, the isolated compound exhibited a good activity towards Staphylococcus aureus, Pseudomonas aeruginosa , and Saccharomyces cerevisiae. Sarcophytolide was found to display a strong cytoprotective effect against glutamate-induced …
Antiproliferative properties and g-quadruplex-binding of symmetrical naphtho[1,2-b:8,7-b’]dithiophene derivatives
2021
Background: G-quadruplex (G4) forming sequences are recurrent in telomeres and promoter regions of several protooncogenes. In normal cells, the transient arrangements of DNA in G-tetrads may regulate replication, transcription, and translation processes. Tumors are characterized by uncontrolled cell growth and tissue invasiveness and some of them are possibly mediated by gene expression involving G-quadruplexes. The stabilization of G-quadruplex sequences with small molecules is considered a promising strategy in anticancer targeted therapy. Methods: Molecular virtual screening allowed us identifying novel symmetric bifunctionalized naphtho[1,2-b:8,7-b’]dithiophene ligands as interesting ca…
Interplay of three G‑quadruplex units in the KIT promoter
2019
The proto-oncogene KIT encodes for a tyrosine kinase receptor, which is a clinically validated target for treating gastrointestinal stromal tumors. The KIT promoter contains a G-rich domain within a relatively long sequence potentially able to form three adjacent G-quadruplex (G4) units, namely, K2, SP, and K1. These G4 domains have been studied mainly as single quadruplex units derived from short truncated sequences and are currently considered promising targets for anticancer drugs, alternatively to the encoded protein. Nevertheless, the information reported so far does not contemplate the interplay between those neighboring G4s in the context of the whole promoter, possibly thwarting dru…