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Biomedical subjects

M Ciomei

Publications and source records attributed to M Ciomei.

23 records · Page 2Linked to original sources
PubMed1984

Structural alterations of pathologically or physiologically modified DNA.

We have studied the alterations of DNA conformation in in vitro depurinated or methylated topological isomers of the plasmid pAT 153. Depurination by heat/acid treatment or alkylation by methyl methanesulfonate (pathological modifications) result in DNA unwinding detected as a reduction in the degree of supercoiling of DNA topoisomers as measured by the alteration of electrophoretic mobility on agarose gel. On the contrary, in vitro enzymic methylation at the C-5 position of cytosine (physiological modification) does not measurably alter the tertiary structure of the circular substrates. From the average number of modified sites needed to remove one superhelical twist from each single topoisomer of a population of partially relaxed DNA molecules, we have calculated an unwinding angle smaller than -3.4 degree per methylated purine and of approximately -12.0 degree per apurinic site. These results, together with previously reported values of unwinding by pyrimidine dimers, suggest a possible mechanism of recognition of damaged sites by repair mechanisms that are not single-damage specific.

Apurinic Acid↗
PubMedDate not supplied

Effects of topoisomerase II inhibitors on gastric cancer cells characterized by different genetic lesions.

Gastric cancer is poorly-responsive to widely used antitumour drugs, the efficacy of which is thought to be related to the capacity of triggering apoptosis. This process requires a series of gene products including a functional p53 protein. We tested the effects of two DNA topoisomerase II poisons, etoposide and doxorubicin, on gastric cancer cell lines with different genetic lesions. We characterised MKN74 and MKN28 cells for p53 gene status and for the expression of p53 and p21 proteins, as well as of topoisomerase II alpha and beta isoforms. After drug treatments, the cells were analysed for drug cytotoxicity, colony forming ability, cell cycle distribution and presence of apoptotic features. Our findings demonstrated that both etoposide and doxorubicin have a potent anti-proliferative effect on gastric cancer cells. Cell death kinetics was different in the two cell lines, MKN74 cells being more sensitive than MKN28 to the drugs. MKN74 cells, although harboring a wt p53 gene, were unable to undergo a massive apoptosis following etoposide treatment. The response of this cell line might be related to the topoisomerase II beta isozyme, the expression of which proved to be undetectable.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

In vitro and in vivo activity of alkylating bombesin receptor antagonists on small cell lung carcinoma.

Bombesin (BN) and bombesin-like peptides are autocrine growth factors for small cell lung carcinoma (SCLC). BN receptor antagonists can therefore find clinical application in the treatment of this highly malignant disease. Six peptides belonging to a new class of alkylating BN analogues have been selected according to their characteristics evidenced on Swiss 3T3 fibroblasts: high binding affinity to BN receptor, relevant inhibition (> 60%) of the proliferative stimulus induced by BN, long-lasting effect and specificity for BN receptor. The six peptides were able to bind BN receptors on SCLC cells and to inhibit the growth of two SCLC cell lines: NCI-H69 and NCI-N592. Conversely, they did not inhibit the growth of tumor cell lines devoid of BN receptors. Two of them were tested in vivo on N592 cells transplanted into nude mice. The peptide carrying a Cab [p-bis(2 chloroethyl)aminobenzoyl] moiety proved to be completely inactive. The second peptide, with a Melphalan moiety (Mel), showed a moderate activity (33-45% of tumor growth inhibition) without any toxicity. The low solubility of this compound prevented the use of the higher doses in vivo.

3T3 Cells↗