Search results for "Suppressor"
showing 10 items of 532 documents
Cytotoxicity of cucurbitacin E from Citrullus colocynthis against multidrug-resistant cancer cells
2019
Abstract Background Cucurbitacin E (CuE) is an oxygenated tetracyclic triterpenoid isolated from the fruits of Citrullus colocynthis (L.) Schrad. Purpose This study outlines CuE's cytotoxic activity against drug-resistant tumor cell lines. Three members of ABC transporters superfamily, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and ABCB5 were investigated, whose overexpression in tumors is tightly linked to multidrug resistance. Further factors of drug resistance studied were the tumor suppressor TP53 and the epidermal growth factor receptor (EGFR). Methods Cytotoxicity assays (resazurin assays) were used to investigate the activity of Citrullus colocynthis and CuE towar…
TP53 and p16INK4A, but not H-KI-Ras, are involved in tumorigenesis and progression of pleomorphic adenomas.
2006
The putative role of TP53 and p16INK4A tumor suppressor genes and Ras oncogenes in the development and progression of salivary gland neoplasias was studied in 28 cases of pleomorphic adenomas (PA), 4 cases of cystic adenocarcinomas, and 1 case of carcinoma ex-PA. Genetic and epigenetic alterations in the above genes were analyzed by Polymerase Chain Reaction/Single Strand Conformational Polymorphism (PCR/SSCP) and sequencing and by Methylation Specific-PCR (MS-PCR). Mutations in TP53 were found in 14% (4/28) of PAs and in 60% (3/5) of carcinomas. Mutations in H-Ras and K-Ras were identified in4%(1/28) and7% (2/28) of PAs, respectively. Only 20% (1/5) of carcinomas screened displayed mutatio…
Research in practice: Regulatory T cells - targets for therapeutic approaches?
2010
• regulatory T cells • tolerance • signal transduction • autoimmunity • allergies • cancer Summary Regulatory T cells (Tregs) are essential for induction and maintenance of immunological tolerance. They contribute to prevention of autoimmunity by control and modulation of immune responses. The prevalence of autoimmune diseases, chronic infections, cancer and allergies has markedly increased in the last decades. In additions the treatment of these disorders is often unsatisfactory so that improvements are needed. This has stimulated intensive research in the biology of Tregs. Recent studies revealed that naturally occurring CD4 + CD25 + Tregs (nTregs) and induced Tregs (iTregs) are critical …
CAF-like state in primary skin fibroblasts with constitutional BRCA1 epimutation sheds new light on tumor suppressor deficiency-related changes in he…
2016
Constitutive epimutations of tumor suppressor genes are increasingly considered as cancer predisposing factors equally to sequence mutations. In light of the emerging role of the microenvironment for cancer predisposition, initiation, and progression, we aimed to characterize the consequences of a BRCA1 epimutation in cells of mesenchymal origin. We performed a comprehensive molecular and cellular comparison of primary dermal fibroblasts taken from a monozygous twin pair discordant for recurrent cancers and BRCA1 epimutation, whose exceptional clinical case we previously reported in this journal. Comparative transcriptome analysis identified differential expression of extracellular matrix-r…
A recurrent TP63 mutation causing EEC3 and Rapp–Hodgkin syndromes
2016
The ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3; OMIM #604292), the Rapp-Hodgkin syndrome (RHS), and various other syndromes are caused by mutations in the TP63 gene, which encodes a p53-like transcription factor. Here, we report on a woman aged 37 years and her daughter aged 3 years with the previously reported c.1028G>A (p.Arg343Gln) mutation in exon 8 of TP63. The mother lacked ectrodactyly, indicating a diagnosis of RHS, whereas the girl presented with all three major features (ectrodactyly, ectodermal dysplasia, clefting) and different minor features (including small and brittle nails, and recurrent conjunctivitis believed to be because of stenotic and blo…
Congenital undifferentiated sarcoma associated to BCOR-CCNB3 gene fusion
2017
Small round cell sarcomas are aggressive bone and soft tissue tumors that predominantly affect children and young adults. A new group of sarcomas with a recurrent BCOR-CCNB3 gene fusion has been recently identified in previously unclassifiable small round cell sarcomas. BCOR-CCNB3 sarcomas share clinical and pathologic similarities with Ewing sarcoma, but show a stronger male predilection and less aggressiveness, as well as distinct gene expression profiling and pangenomic SNP array analyses. We report the unusual case of a congenital BCOR-CCNB3 retroperitoneal sarcoma in a female born at 34th gestational week, which was diagnosed in necropsy after 21hours of life. Immunohistochemical analy…
A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine
2018
ObjectiveTo describe a large series of BIN1 patients, in which a novel founder mutation in the Roma population of southern Spain has been identified.MethodsPatients diagnosed with centronuclear myopathy (CNM) at 5 major reference centers for neuromuscular disease in Spain (n = 53) were screened for BIN1 mutations. Clinical, histologic, radiologic, and genetic features were analyzed.ResultsEighteen patients from 13 families carried the p.Arg234Cys variant; 16 of them were homozygous for it and 2 had compound heterozygous p.Arg234Cys/p.Arg145Cys mutations. Both BIN1 variants have only been identified in Roma, causing 100% of CNM in this ethnic group in our cohort. The haplotype analysis confi…
Havep53 gene mutations and protein expression a different biological significance in colorectal cancer?
2002
p53 alterations are considered the most common genetic events in many types of neoplasms, including colorectal carcinoma (CRC). These alterations include mutations of the gene and/or overexpression of the protein. The aim of our study was to assess whether in 160 patients undergoing resective surgery for primary operable CRC there was an association between p53 mutations and protein over-expression and between these and other biological variables, such as cell DNA content (DNA-ploidy) and S-phase fraction (SPF), and the traditional clinicopathological variables. p53 mutations, identified by PCR-SSCP-sequencing analysis, were found in 68/160 patients (43%) and positive staining for p53 prote…
MDM2 and CDKN1A gene polymorphisms and risk of Kaposi's sarcoma in African and Caucasian patients
2010
A single-nucleotide polymorphism in the MDM2 promoter (SNP309; rs2279744) causes elevated transcription of this major negative regulator of p53 in several cancer types. We investigated MDM2 SNP309 and CDKN1A (p21/Waf1/Cip1) codon 31 (rs1801270) polymorphisms in 86 cases of cutaneous Kaposi's sarcoma (KS) from African and Caucasian patients, and 210 healthy controls. A significant increase of the MDM2 SNP309 T/G genotype was observed among classic KS cases (odds ratio 2.38, 95% confidence interval 1.0-5.5). Frequencies of CDKN1A codon 31 genotypes were not significantly different between cases and controls. The results suggest that the MDM2 SNP309 G allele may act as a susceptibility gene fo…
Molecular analysis of the 9p21 locus and p53 genes in Ewing family tumors.
2001
The EWS-ETS rearrangements, and their respective fusion gene products, are specifically associated with histopathologically Ewing family tumors (EFT). These translocations are implicated in generating malignant transformation of EFT, but the presence of additional genetic alterations must be considered in the pathogenesis of such tumors. We analyzed 26 samples (biopsies and/or nude mice xenotransplants) collected from 19 patients with an EFT to determine whether molecular and cytogenetic alterations of the G(1)/S checkpoint genes are implicated in the pathogenesis of EFT. We found inactivating p53 mutations in three (16%) cases, which correlated with a loss of p21(WAF1/Cip1) expression and …