Biomedical subjects

D Di Simone

Publications and source records attributed to D Di Simone.

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↗

PubMed2003

Dehydroepiandrosterone reduces expression and activity of BACE in NT2 neurons exposed to oxidative stress.

Recently, we showed that oxidative stress activates the expression and activity of the beta-site AbetaPP-cleaving enzyme (BACE), an aspartyl protease responsible for the beta-secretase cleavage of AbetaPP. The identification of compounds able to prevent the induction of this event is an important goal of therapeutic strategies for Alzheimer's disease (AD). Dehydroepiandrosterone (DHEA) is an adrenal steroid that improves a variety of functions in the central nervous system. Moreover, a series of evidence suggests that DHEA displays antioxidant properties in different experimental models. In the present paper we show that pretreatment with DHEA is able to rescue the increase of mRNA expression, protein levels, and activity of BACE, produced by oxidative stress in NT2 neurons. BACE, being the enzyme that initiates the production of Abeta, is a drug target for AD. Our results imply that DHEA administration may slow down the AD pathological process, lowering Abeta accumulation.

Amyloid Precursor Protein Secretases↗

PubMed1995

Evaluation of resistance index of several anticancer agents on parental and resistant P-388 cell lines.

Multidrug resistance is frequently detected in haematological malignancies and in acute leukaemias with a poor prognosis. In the last few years, several reports seem to suggest that the new anthracycline derivative idarubicin and the anthraquinone mitoxantrone have some advantages in the management of untreated or relapsed acute leukaemias compared with older anthracyclines. This could be due to a different interaction of these drugs with multidrug resistance. To evaluate this possibility, we compared the activity of doxorubicin (DOXO), epirubicin (EPI), idarubicin (IDA) and mitoxantrone (MITO) on a murine, multidrug resistant, leukaemic cell line (P-388/Dx) cultured in vitro. ID50 of IDA and MITO was in the ng range whereas that of DOXO and EPI was in the microgram(s) range. Moreover, IDA has a resistance index of 50 whereas DOXO has one of 250. Verapamil is able to almost completely abolish the resistance to IDA. Efflux experiments confirm that verapamil increases IDA intracellular concentration. IDA and MITO appear to be less involved in multidrug resistance than older anthracyclines.

Animals↗

PubMed1995

GST-pi and P-170 co-expression in multiple myeloma.

Bone marrow samples from 40 patients affected by multiple myeloma either treated or untreated were examined for expression of glutathione-S-transferase pi (GST-pi), P-glycoprotein and the protein product of ras oncogenes family, p-21, on plasma cells, by immunocytochemical detection. 72% of evaluated samples were positive for P-170 and 82% for GST-pi without any correlation with clinical or prognostic parameters. A significant relationship between GST-pi expression and P-170 positivity was found and co-expression was observed in 91% of evaluated samples. Expression of P-170 and GST-pi was found both in treated and untreated patients. However, patients evaluated before and after therapy showed an increase in the percentage of plasma cells positive for GST-pi or P-170 or both. Expression of p-21 was not associated with these mechanisms of drug resistance. These data suggest that different resistance mechanisms are present in multiple myeloma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Glutathione-S-transferase activity and multidrug resistance phenotype in chronic lymphocytic leukemia: do they have any clinical relevance?

BACKGROUND: Lymphocytes from patients affected by B-cell chronic lymphocytic leukemia (B-CLL) have frequently been shown to be positive for the multidrug resistance (MDR) phenotype. However, this phenotype does not seem to be responsible for the resistance to alkylating agents usually employed in the management of CLL. METHODS: Lymphocytes from 42 patients were evaluated by flow cytometry for P-170 expression and by spectrophotometry for glutathione-S-transferase (GST) activity. RESULTS: Our findings show that GST is not related to any clinical parameter but is increased in treated patients. Conversely, 85% of patients were positive for P-170 and this was related to the percentage of CD5/CD19-positive lymphocytes. CD5/CD19-negative patients were also negative for P-170. MDR was not related to any clinical parameter evaluated nor to GST activity in lymphocytes. CONCLUSIONS: MDR is constitutively expressed in B-cell chronic lymphocytic leukemia and seems to be related to a CD5/CD19 B-CLL phenotype. The increase of GST activity in treated patients is statistically significant (p < 0.005).

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

c-Jun and GST-pi expression in human plasma cells.

Bone marrow samples from 33 patients affected by MM and MGUS, and 8 patients not affected by lymphoproliferative diseases were studied for expression of c-Jun (a component of the transcription factor AP-1) and glutathione-S-transferase pi (GST-pi) using immunocytochemical methods. A high and frequent expression of these two proteins was found both in MM and MGUS patients (31/33 patients positive for c-Jun and 29/33 patients positive for GST-pi) and in controls not affected by monoclonal gammopathy (7/8 patients positive for both c-Jun and GST-pi). No statistically significant correlation was found between c-Jun- and GST-pi-positive plasma cells. The expression of these two proteins was not related to clinical or laboratory data. Our results seem to confirm a possible role of the transcriptional complex AP-1 in activating GST-pi promoter in human plasma cells.

Aged↗

PubMedDate not supplied

c-Ha-ras transfection and expression of MDR-related genes in MCF-10A human breast cell line.

BACKGROUND: We studied the relationship between ras transfection and the drug resistance phenotype in the MCF-10A cell line (a non-transformed immortalized human breast epithelial cell line). MATERIALS AND METHODS: Parental (MCF-10A) and c-Ha-ras transfected (MCF-10A H) cell lines were tested for resistance to Doxorubicin, Maphosphamide and Cisplatinum, by evaluating the inhibition of [3H]-thymidine incorporation. Cells were also examined for the expression of different resistance mechanisms by immunocytochemical and RT-PCR methods. RESULTS: ras-transfected cells were much more resistant to Cis-platinum than parental ones. GST-pi the GST isoenzyme frequently involved in human cancers) increased only in transfected cells. No expression of any other resistance mechanisms (MDR, MRP, LRP) was found by immunocytochemistry either in parental or in transfected cells; nevertheless, the more sensitive RT-PCR tests detected mrp products in parental and in transfected cells: gene expression levels were low and equivalent in both cell lines. CONCLUSIONS: ras transfection can induce resistance to Cis-platinum by increasing GST-pi expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗