Biomedical subjects

M Chiara

Publications and source records attributed to M Chiara.

7 recordsLinked to original sources

PubMed2005

Mycophenolate mofetil and roscovitine decrease cyclin expression and increase p27(kip1) expression in anti Thy1 mesangial proliferative nephritis.

The response of mesangial cells to a phlogistic challenge includes cell proliferation and mesangial matrix expansion. Cell proliferation is a highly regulated process which includes enhancing factors such as cyclins, cyclin dependent kinases, and inhibitory proteins, such as p27(kip1). The aim of the study was to evaluate the effects of Mycophenolate mofetil (MMF), and roscovitine (R), on the cell cycle regulatory system when administered in the florid phase of the experimental model of mesangial proliferative nephritis induced by the anti Thy-1 antigen monoclonal antibody. Three days after nephritis induction, different groups were given MMF and R. Rats treated with MMF or R showed a slight decrease in mesangial proliferation and matrix expansion. Samples of cortical tissue were tested by 'real time' RT-PCR in order to study gene expression of cyclins B, D1, D2, D3, E, and the cyclin inhibitor p27(kip1). Localization of mRNA was evaluated by in situ hybridization. Real time RT-PCR analysis showed a significant decrease in cyclins B, D1, D2, and D3 in rats treated with either MMF or R as compared to controls. Both MMF and R treatment induced a significant increase in p27(kip1) mRNA expression. In situ hybridization showed a mesangial-endothelial expression pattern in glomeruli. The number of labelled cells per glomerulus, the number of positive glomeruli in each examined slide as well as cyclin D2 and D3 signal intensity was significantly lower in rats treated with MMF or R as compared to controls, whereas MMF or R treatment up-regulated p27(kip1) mRNA expression. Immunohistochemical evaluation of p27(kip1) aimed to examine the influence of MMF or R on protein expression confirmed up-regulation.

Animals↗

PubMed1997

Fasting during promotion, but not during initiation, enhances the growth of methylnitrosourea-induced mammary tumours.

The purpose of this work was to investigate the effect of fasting on the induction and growth of chemically-induced mammary carcinogenesis. Female Sprague-Dawley rats were given methylnitrosourea (MNU) i.p. (50 mg/kg) at 50 days of age; a group of rats were exposed to 4 day fasting followed by 1 day of refeeding before the administration of the carcinogen, while another group was exposed to three cycles of 3 days fasting in 10 days, beginning 1 week after MNU injection. Fasting enhanced the development of mammary tumours only in rats fasted after carcinogen damage, while it did not affect the induction of tumours in rats fasted before MNU, if compared with full-fed controls. The enhanced growth of mammary tumours sustained by fasting during promotion was observed in the cervical-thoracic region. In addition, exposure to fasting made rats susceptible to the development of MNU-induced extra-mammary cancers. Different from the preventive effect of caloric restriction on tumor development, these data demonstrate that fasting affects the promotion phase of carcinogenesis by enhancing the growth of MNU-induced mammary tumours.

Adenocarcinoma↗

PubMed1996

Phosphatidylethanolamine N-methyltransferase 2 and CTP-phosphocholine cytidylyltransferase expressions are related with protein kinase C isozymes in developmental liver growth.

PEMT and CT activities were reciprocally regulated during the perinatal period. Consistently, PEMT2 expression was undetectable before birth when CT was highly expressed. Surprisingly, PEMT2 was relatively highly expressed at birth when the cell division and CT expression were still high. During development liver cell growth was associated with enhanced levels in the activity of beta, zeta and, particularly, alpha PKC. The activity of delta PKC was lower in foetal, higher in the newborn and again slightly lower than adult liver 10 days after birth. These data show that CT expression and alpha, beta and zeta PKC activities are positively, whereas PEMT2 expression and delta PKC activity are negatively associated with the liver cell division during development.

Animals↗

PubMedDate not supplied

Fasting/refeeding enhances the development of mammary tumors induced by methylnitrosourea in the rat.

The effect of fasting/refeeding on MNU-induced mammary carcinogenesis was investigated. Female Sprague-Dawley rats were given i.p. a single dose of MNU (50 mg/Kg body weight) and beginning 1 week after MNU administration were exposed to 3 cycles of 3 days fasting followed by refeeding (10 days). Rats were palpated twice a week and killed when tumor diameter was about 2 cm. Tumors palpated were registered by location. The exposure to fasting/refeeding after initiation increased the total number of mammary tumors about 2-fold compared to full-fed control group. In addition, fasted rats developed about 3-fold mammary tumors in the cervical-thoracic gland chains versus the abdominal-inguinal gland chains, while no difference in tumor distribution was observed in controls. The present study reports that fasting/refeeding enhances the development of MNU-induced mammary tumors.

Animals↗

PubMedDate not supplied

The delay in rat liver regeneration by choline is associated to alteration in c-myc expression.

Previous data of our laboratory showed that female rats regenerated earlier than males and choline shifted the female growth pattern toward that of males. We investigated if the effect of choline on the liver compensatory growth was associated to a modulation of the expression and methylation pattern of an early cell cycle dependent proto-oncogene, c-myc. The peak of DNA synthesis was 22 h after 2/3 partial hepatectomy in female regenerating liver, while it was delayed to 30 h when female rats received choline for 3 weeks before liver surgery. Partial hepatectomy induced the expression of c-myc that was already maximal at 1 h. Choline reduced the c-myc expression and it shifted the maximum increase at 2 h. The methylation pattern of c-myc was studied with the Hpa II restriction enzyme. The delay in c-myc expression was not due to hypermethylation of the gene.

Animals↗

PubMedDate not supplied

Choline feeding depresses the phospholipase C activity in the regenerating liver of female rats.

The administration of an excess of choline for 3 weeks is able to delay the proliferative response to partial hepatectomy (PH) in female rats. Choline feeding can affect the phospholipid composition of cell membranes and, as a consequence, the transduction of the mitogenic signals. On these bases, we studied the turnover of phosphatidylinositol-4,5-biphosphate (PIP2) in the regenerating liver of female rats. The hydrolysis of PIP2 is catalysed by a specific phospholipase C (PL-C) and it generates the second messenger molecules, namely diacylglycerol and inositol-1,4,5-triphosphate (IP3). Our results showed that the administration of an excess of choline to females was able to reduce the PL-C activity and the membrane IP3 content in the quiescent liver. Both parameters remained lower than controls during liver regeneration, even if they were higher 1 and 2 h after PH in comparison with the quiescent liver, in choline-fed females. These data suggest that the delay in the liver regeneration by choline is due, at least in part, to the alteration in the pathway of PIP2 turnover for the transduction of mitogenic signals.

Animals↗

PubMedDate not supplied

Fasting/refeeding enhances the crypt multiplicity in rat colon carcinogenesis induced by azoxymethane.

Aberrant crypt foci (ACF) are putative preneoplastic lesions of colon cancer which are being utilized currently as a biological end point to evaluate the induction and modulation of colon carcinogenesis. In rodents, caloric restriction reduces carcinogen-induced colon cancer incidence. The present study was designed to investigate the effect of fasting followed by refeeding on the development of ACF. Male Fisher 344 rats were fasted for 4 days and they were given a single injection of azoxymethane (AOM) at the dose of 20 mg/kg body weight on the first day of refeeding, and killed 3 months later. Controls were fed ad libitum and received the same dose of AOM. The number and crypt multiplicity (number of crypts/focus) of ACF were measured on the medial colon. No effect of fasting/refeeding was observed in the total number of foci/medial colon. On the contrary, rats fasted for 4 days and refed developed foci with higher number of crypts than fed controls. Our results are of particular interest because the crypt multiplicity, rather than the number of foci, is a consistent predictor of tumor incidence. As a consequence these data suggest a possible role of fasting/refeeding in enhancing the colon tumor outcome.

Animals↗