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V Chiarugi

Publications and source records attributed to V Chiarugi.

60 records · Page 4Linked to original sources
PubMedDate not supplied

Association between vitamin D receptor gene polymorphism and nephrolithiasis.

AIMS: To study the distribution of vitamin D receptor (VDR) gene alleles in hypercalciuric and nonhypercalciuric nephrolithiasis patients, hypothesizing that distinct biochemical parameters would be associated with different VDR genotypes. METHODS: 12 hypercalciuric, 15 normocalciuric nephrolithiasis patients, and 150 healthy subjects were recruited. The individual genetic pattern for VDR was evaluated by DNA extraction followed by polymerase chain reaction amplification of the VDR gene and digestion with the restriction enzyme BsmI. RESULTS: In the hypercalciuric group, Bb patients represented 50% (6/12); bb patients 33% (4/12), and BB cases were 16% (2/12). The VDR frequency distribution was not statistically different in hypercalciuric patients and controls (Bb 72%; bb 16%; BB 12%). In the nonhypercalciuric group, the prevalence of the bb genotype (7/15; 47%) was thrice the percentage of control subjects, while the percentage of BB patients was similar to that of the control group (2/15; 13%). Patients with the bb haplotype exhibited a higher daily urinary calcium excretion. Among hypercalciuric patients, after a calcium-restricted diet, bb patients showed a 39% reduction in daily urinary calcium excretion in comparison with a nonsignificant 13% reduction observed in BB subjects (p = 0.004). CONCLUSIONS: The effects of VDR gene polymorphism on calcium metabolism contribute to the understanding of the pathogenesis of urinary calculi.

Adult↗
PubMedDate not supplied

Role of p53 mutations in the radiosensitivity status of tumor cells.

Wild-type p53 is involved in cellular response to DNA damage including cell cycle control, DNA repair and activation of apoptosis. Accumulation of p53 protein following DNA damage may initiate the apoptotic process, resulting in cell death. DNA damage induced by radiation is an example of apoptotic stimulus involving p53. Regulation of apoptosis by p53 can occur through transcriptional regulation of pro-apoptotic (e.g. bax) and anti-apoptotic (e.g. bel-2) factors. Although wild-type p53 usually sensitizes cells to radiation therapy, p53 mutations have a variable effect on radiation response. For example p53 mutations in bone or breast tumors have been found to be associated with resistance to chemotherapeutic drugs or ionizing radiation. Mutated p53 has has been reported to increase sensitivity to radiation and drugs in colorectal and bladder tumors. The present brief commentary tries to find an explanation at molecular level of these conflicting results.

Genes, p53↗
PubMedDate not supplied

Role of three cancer "master genes" p53, bcl2 and c-myc on the apoptotic process.

We review some of the most recent developments concerning three genes involved in human cancer: p53, bcl2 and c-myc. Recent data have demonstrated that the bcl2 gene protects tumor cells from apoptosis induced by a variety of agents, including ionizing radiation, and is thus related to resistance to DNA-damaging therapeutic agents. The p53 tumor suppressor gene, however, has been related with growth arrest, apoptosis and thus with selective sensitivity to the killing effects of ionizing radiation and DNA-damaging drugs. This functional antagonism between the two genes was recently substantiated in molecular terms by demonstration of reciprocal down-regulation due to the presence of a p53-dependent transcription silencer in the untranslated region of the bcl2 gene. Growth arrest in the G1 phase of the cell cycle and induction of apoptosis are two distinct and dissectable functions of p53: bcl2 is able to antagonize the induction of apoptosis by p53, but not the growth arrest in G1. However, coexpression of bcl2 and of the oncogene c-myc efficiently antagonizes effects of p53 on G1 arrest and apoptosis, thus suggesting a cooperation between the two oncogenes. In addition, c-myc disrupts other functions of genetic control in the early G1 phase of the cell cycle including the expression of D1 cyclin. We believe that knowledge of the functional/molecular interactions between these three genes involved in human cancer is a fundamental prerequisite to improve the knowledge on prognosis and to design innovative therapeutic approaches.

Animals↗