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G Voutsinas

Publications and source records attributed to G Voutsinas.

12 recordsLinked to original sources
PubMed2005

Tenascin-C protein expression and mRNA splice variants in thyroid carcinoma.

Tenascin-C (Tn-C) is a matricellular protein involved in the initial and intermediate stages of cell adhesion. The present study is the first undertaken to comparatively investigate Tn-C in neoplastic, non-neoplastic thyroid lesions and normal thyroid tissues. Forty-eight thyroid specimens were studied immunohistochemically using a monoclonal antibody against Tn-C. Immunohistochemistry was supplemented by RT-PCR analysis of the two Tn-C mRNA splice variants in 13 thyroid cancer cell lines. Normal and non-neoplastic tissues were devoid of Tn-C, as well as follicular neoplasms, Huerthle-cell and anaplastic carcinomas. Most papillary carcinomas showed a focally intensive extracellular staining, localized in the connective tissue stroma, whereas most medullary carcinomas showed a staining in the connective tissue but also in intracellular location mainly. RT-PCR analysis detected Tn-C mRNA in all thyroid cancer cell lines with prevalence of the large splice variant in all but the medullary line, characterized by a higher Tn-Csmall:Tn-Clarge ratio. In conclusion, Tn-C re-expression has been observed in papillary and medullary thyroid carcinomas with different staining patterns accompanied by the prevalence of different mRNA splice variants in cell cultures. It seems possible that Tn-C is rather synthesized by tumor cells than by activated stromal cells.

Adolescent↗
PubMed2004

Mononucleotide markers of microsatellite instability in carcinomas of the urinary bladder.

AIMS: To determine the presence of microsatellite instability (MSI) and to assess the expression of the human mismatch repair (MMR) gene products hMLH1 and hMSH2 in primary transitional cell carcinomas (TCCs) of the urinary bladder in relation to clinico-pathological parameters. METHODS: Seventy-two cases of primary TCC were screened for the presence of alterations in MSI markers by molecular techniques and evaluated immunohistochemically for the expression of hMLH1 and hMSH2 proteins. Clinical data were available in 70 cases. The percentage of MSI rose to 16.6%. RESULTS: Reduced (<20%) hMLH1 expression was closely related to the presence of MSI (p=0.0004). Neither MMR proteins nor MSI was associated with grade, stage, papillary status. Clinical outcome analysed as a function of MSI did not show significant differences in terms of both disease-free and overall survival. Reduced hMLH1 expression was a significant predictor of shorter disease-free survival in univariate and multivariate analysis. CONCLUSIONS: The presence of MSI is not related to classical clinico-pathological parameters in TCCs, nor does it appear to be of prognostic significance. hMLH1 was an important indicator for recurrence.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Bladder cancer mortality in the Epirus district population (Greece).

OBJECTIVE: To describe the pattern of bladder cancer mortality in the Epirus district population (North-Western Greece) and to establish some relationships with cigarette smoking. PATIENTS AND METHODS: Mortality rates of bladder cancer in the Epirus district population were analysed according to the official data from the Department of Statistics of the University Hospital of Ioannina during the last decade (January 1990-January 2000). Age standardization of death rates was done by the direct method, using the world population as a standard. Fisher's test was used as a significance test for linear regression coefficient in time trend analysis of mortality. RESULTS: The average annual standardized mortality rates from bladder cancer during the study period were 5.23 per 100,000 population (96% Confidence Interval--Cl 4.02-5.63) in males and 1.63 per 100,000 population (96% Confidence Interval--CI 1.18-1.96) in females. Significantly increasing trends of the rates were observed in males (y = 2.421 + 0.231x; p < 0.01), but not in females (y = 1.263 + 0.027x: p > 0.05). The greatest increase in age - specific rates in males was observed in the age group of 70 and more years (y = 25.602 + 3.673x; p < 0.01). In females, all age--specific rates except for the group 60-69 years showed significantly increasing tendency. The increasing tendency of bladder cancer mortality is followed by the rise of per capita cigarette consumption among the Epirus district population. CONCLUSION: Further studies are needed for the explanation of the irregularities in the age-specific rates.

Adolescent↗
PubMed2001

Mutagenesis, apoptosis, basic relation to carcinogenic models.

Cancer arises from an accumulation of mutations as well as changes in the expression pattern of genes mainly involved in cell cycle regulation, DNA repair and apoptosis, which promote clonal selection of cells with an increasingly malignant phenotype. Although a single mutant gene may not be able to redirect the growth program of a normal cell, the multiplicity of downstream targets of a deregulated molecule and the extensive cross-talk between biochemical pathways suggest that cellular context and genotype are of great importance in cancer initiation, while gene activation and inactivation events may not be independent. Complex exposure patterns affecting molecular targets exhibiting multiple intracellular interactions add a significant percentage of uncertainty when assessing cancer risk.

Apoptosis↗
PubMed1998

Specific recombinogenic activity of a new polyene antibiotic.

A new antibiotic from Streptomyces sp., tetrapol A159, active against various fungi, a promising compound for the control of plant diseases, was studied for its genotoxic effects. It was produced at the Institute of Microbiological Preparations for Agriculture, Sofia, Bulgaria. The chemical was tested in three different test systems: a bacterial system, the Ames test for point mutations, the micronucleus test in bone marrow cells of rats for chromosomal aberrations and the fungal system of Aspergillus nidulans for mitotic recombination and aneuploidy. No increase in histidine revertants was observed in any of the TA100, TA98, TA1535 and TA1537 strains of Salmonella at concentrations ranging from 1 to 4000 mg/plate. The results were also negative in the micronucleus test of bone marrow cells at concentrations from 124 to 600 mg/kg b.w., whereas a statistically significant threefold increase of mitotic crossovers was found in Aspergillus, at concentrations from 0.5 to 2.5 mg/ml.

Animals↗
PubMed1997

The effect of environmental aneuploidy-inducing agents on the microtubule architecture of mitotic meristematic root cells in Hordeum vulgare.

Microtubules are the prime components involved in chromosomal segregation, their functional accuracy ensuring maintenance of the normal karyotype in the progeny. Chemically-induced disruption of microtubules during mitosis can lead to aneuploidy. In this study, seven environmental chemicals, i.e. cadmium chloride (CD), econazole nitrate (EZ), benomyl (BM), thiabendazole (TB), griseofulvin (GF), thimerosal (TM) and hydroquinone (HQ), were tested for their ability to induce microtubule disruption in mitotic meristematic root cells of the higher plant Hordeum vulgare, with the use of anti-tubulin indirect immunofluorescence microscopy. All chemicals tested in this study, with the exception of TB and HQ, produced modifications in the morphology of microtubule organization and reduced the fidelity of the spindle apparatus in Hordeum vulgare.

Aneuploidy↗
PubMed1994

Antimutagenicity of three isomers of aminobenzoic acid in Salmonella typhimurium.

The m-, o- and p-isomers of aminobenzoic acid (ABA) repressed the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Salmonella typhimurium TA100. Their antimutagenic potency was in the order of o-ABA > m-ABA > p-ABA. The mechanism of this antimutagenicity is ascribed mainly to the decomposition of MNNG induced by the aminobenzoic acid isomers outside or within the bacterial cells. The inhibition of plant cell peroxidases and bacterial acetyltransferases that are required for the plant activation of 2-aminofluorene (2-AF) to mutagenic product(s) may participate in the repression of 2-AF mutagenesis by the aminobenzoic acids in S. typhimurium strain YG1024. The aminobenzoic acid isomers exhibited no inhibitory effects towards the direct-acting agent 2-acetoxy-2-acetylaminofluorene, the stable diacetylated metabolic product of 2-AF.

Acetoxyacetylaminofluorene↗
PubMed1993

Comparative study on the mutagenicity of three structurally related substituted aniline mustards in the Salmonella/microsome assay.

The ortho, meta and para isomers of N,N-bis(2-chloroethyl)aminocinnamic acid were tested for their ability to mutate Salmonella typhimurium strains in the Salmonella/microsome mutagenicity test. The aim of the work was to establish a structure-activity relationship between these three isomers. The drugs were found to induce base-pair substitutions, causing dose-dependent increases in his+ revertants, in strains TA100 and TA1535. The study showed that the position of the substituent groups influenced the mutagenic activity of the compounds. The ortho isomer exhibited a poorer mutagenic effect than meta and this was found to be a weaker mutagen than para. The presence of metabolic activation enzymes in the test system induced a further increase in his+ revertants, in strains TA100 and TA1535, which is consistent with the findings for melphalan, a cancer chemotherapeutic agent with a chemical structure similar to that of the isomers tested.

Aniline Mustard↗
PubMed1993

Mutagenicity of four homo-aza-steroidal esters of m-N,N-bis(2-chloroethyl)aminocinnamic acid in the Ames test.

Four new chemicals, the homo-aza-steroidal esters of m-N,N-bis(2-chloroethyl)aminocinnamic acid, originaly synthesized to be used as antineoplastic agents, were tested for their mutagenic activity in the Ames test. 3 beta-Hydroxy-13 alpha-amino-13,17-seco-5-androsten-17-oic-13,17- lactam ester (ACALE3) and 3 alpha-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam ester of m-N,N-bis(2-chloroethyl)aminocinnamic acid (ACALE4) were found to induce base-pair substitutions, causing dose-dependent increases in his+ revertants in strains TA100 and TA1535, while no dose-dependent relations were established when 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam ester (ACALE1) and 17 beta-hydroxy-3-aza-A-homo-4 alpha-androsten-4-one ester of m-N,N-bis(2-chloroethyl)aminocinnamic acid (ACALE2) were tested. The presence of metabolic activation enzymes in the test system had no effect in his+ revertants in strains TA100 and TA1535. The chemicals tested although having the same alkylating moiety and a similar chemical structure exhibited different mutagenic activities.

Androstanes↗
PubMed1993

Mutagenic activity of the antitumour agent homo-aza-steroidal ester of p-N,N-bis(2-chloroethyl)aminophenoxyacetic acid (NSC 294859) in the Salmonella/microsome assay.

The mutagenic activity of the new antitumour agent 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam- p-N,N-bis(2-chloroethyl)aminophenoxyacetate (NSC 294859) was studied in the Salmonella/microsome assay. It was found to induce base pair substitutions, causing dose-dependent increases in his+ revertants in strains TA100 and TA1535. The alkylating moiety, p-N,N-bis(2-chloroethyl)-aminophenoxyacetic acid, was shown to be less effective than the parent compound, while the modified steroid moiety, 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam, showed no mutagenic effect in all strains used. The presence of metabolic activation enzymes in the test system induced a further increase in his+ revertants in strains TA100 and TA1535, in both the parent compound and the alkylating moiety of the parent compound, while it had no effect in the case of the steroidal lactam.

Androstanes↗
PubMedDate not supplied

A comparison of genomic structures and expression patterns of two closely related flanking genes in a critical lung cancer region at 3p21.3.

In the search for a tumour suppressor gene in the 3p21.3 region we isolated two genes, RBM5 and RBM6. Gene RBM5 maps to the region which is homozygously deleted in the small cell lung cancer cell line GLC20; RBM6 crosses the telomeric breakpoint of this deletion. Sequence comparison revealed that at the amino acid level both genes show 30% identity. They contain two zinc finger motifs, a bipartite nuclear signal and two RNA binding motifs, suggesting that the proteins for which RBM5 and RBM6 are coding have a DNA/RNA binding function and are located in the nucleus. Northern and Southern analysis did not reveal any abnormalities. By SSCP analysis of 16 lung cancer cell lines we found only in RBM5 a single presumably neutral mutation. By RT-PCR we demonstrated the existence of two alternative splice variants of RBM6, one including and one excluding exon 5, in both normal lung tissue and lung cancer cell lines. Exclusion of exon 5 results in a frameshift which would cause a truncated protein of 520 amino acids instead of 1123 amino acids. In normal lung tissue, the relative amount of the shorter transcript was much greater than that in the lung tumour cell lines, which raises the question whether some tumour suppressor function may be attributed to the derived shorter protein.

Alternative Splicing↗