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DNA topoisomerases, nuclear enzymes that regulate DNA topology, are recognized as the primary targets of effective anti-tumor drugs. These enzymes may also have a role in the repair of DNA damage induced by alkylating agents and platinum compounds; therefore, their expression may be a determinant of tumor response to chemotherapy. Our study was undertaken in an attempt to establish a correlation between the enzyme expression and response of ovarian cancer to cisplatin-based chemotherapy. The expression of topoisomerase I, II alpha and II beta genes was assessed by RNase protection assay in tumor specimens obtained from 37 untreated patients with advanced epithelial ovarian cancer at initial surgery and from 13 pre-treated patients at subsequent laparotomy. The expression levels were compared with those found in 5 specimens from benign ovarian tissue and 5 specimens from normal ovarian tissue. The expression levels in untreated patients were used to establish a correlation with response to high-dose cisplatin therapy. A significant intertumor variability of mRNA expression was noted for all the genes examined. However, a comparison of median values indicated a remarkable increase of expression in malignant tumors over benign or normal tissues only for topoisomerase II alpha. This change is not related to alterations or amplification of topoisomerase II alpha gene. Interestingly, a correlation was found between tumor response to chemotherapy and the expression level of the isoform alpha (but not of topoisomerase II beta and topoisomerase I). The observed correlation suggests a contribution of the enzyme in determining tumor sensitivity. Alternatively, increased expression levels of the alpha isoenzyme gene in responsive tumors might reflect higher fractions of proliferating tumor cells that may be more drug-sensitive than resting cells.

Chronic hepatitis in children seems to have a better prognosis than in adults, with a discrete trend to spontaneous remission. Actually biopsy and liver enzymes are mandatory for a correct follow up of the disease, while few authors are interested in the assessment of growth and nutritional status. We think that an auxological approach is one of the main points in every chronic disease of the pediatric age, chiefly when some anabolic step might be affected. Our first result in a cross sectional study of growth and nutritional status in a selected group of untreated HBsAg+ chronic hepatitis children are as follows. According to enzyme values in the range of 16-171 UI/1 SGOT all patients are growing very well with a good-discrete nutritional status. Though anthropometric proteic nutritional status (muscle circumference) was in the range of normal distribution, we were able to show a moderate correlation between SGOT and muscle circumference (r = -0,50). Our impression is that some patients with a worse hepatic damage can be exposed at risk of proteic malnutrition which is a negative element in the prognosis of every chronic disease. Anthropometric auxology can detect degrees of proteic malnutrition, and can follow its development. So we recommend routine auxological assessment in all pediatric patients with chronic hepatitis.