p53 gene mutations and codon 72 polymorphism in ovarian carcinoma patients from Serbia.

PURPOSE: Ovarian cancer is the leading cause of death from gynecological malignancies. The early stages of this disease are asymptomatic and more than 75% of the cases are diagnosed with regional or distant metastases. p53 gene is frequently mutated in some histological subtypes of ovarian carcinomas. The role of p53 mutations and polymorphic variant of codon 72 in the prognosis of disease is still unclear. The aim of this study was to determine the frequency of p53 mutations and polymorphic variants of codon 72 among ovarian carcinoma patients and to correlate them with clinicopathological characteristics of disease. METHODS: 54 ovarian carcinoma patients were included in the study. DNA was isolated from tumor tissue by the salting- out method. p53 mutations in exons 4-8 were detected by PCR-SSCP (polymerase chain reaction - single-stranded conformational polymorphism) electrophoresis. Codon 72 polymorphism was assessed by RFLP (restriction fragment-length polymorphism) method. RESULTS: p53 mutations were present in 11 out of 54 patients (20.4%). Twenty-four patients (44.4%) exhibited Arg/ Arg, 24 patients (44.4%) Arg/Pro and 6 patients (11.2%) Pro/ Pro genotype of 72 codon polymorphism. Correlations between p53 mutations and various clinicopathological characteristics were not found. However, we observed that the frequency of Pro/Pro genotype was increasing with higher histological grade as well as in advanced compared to localized disease, but without statistical significance. Distribution of p53 gene mutations between Pro/Pro genotype and Arg/Pro plus Arg/Arg genotypes was not statistically significant. CONCLUSION: Our study suggests that Pro/Pro genotype of 72 codon polymorphism could be an independent prognostic marker in ovarian carcinomas.

Applicational possibilities of linear and non-linear (polynomial) regression and analysis of variance. III. Stability determination of pharmaceutical preparations: stability of diclofenac-sodium in Diclofen injections.

This paper presents the application of the regression analysis program and the program for comparing linear regressions (modified method for one-way, analysis of variance), writtens in BASIC program language, for instance, determination of content of Diclofenac-Sodium (active ingredient in DIKLOFEN injections, ampules á 75 mg/3 ml). Stability testing of Diclofenac-Sodium was done by isothermic method of accelerated aging at 4 different temperatures (30 degrees, 40 degrees, 50 degrees and 60 degrees C) as a function of time (4 different duration of treatment: (0-155, 0-145, 0-74 and 0-44 days). The decrease in stability (decrease in the mean value of the content of Diclofenac-Sodium (in %), at different temperatures as a function of time, is possible to describe by, linear dependance. According to the value for regression equation values, the times are assessed in which the content of Diclofenac-Sodium (in %) will decrease by 10%, of the initial value. The times are follows at 30 degrees C 761.02 days, at 40 degrees C 397.26 days, at 50 degrees C 201.96 days and at 60 degrees C 58.85 days. The estimated times (in days) in which the mean value for Diclofenac-Sodium content (in %) will by 10% of the initial values, as a junction of time, are most suitably described by 3rd order parabola. Based on the parameter values which describe the 3rd order parabola, the time was estimated in which Diclofenac-Sodium content mean value (in %) will fall by 10% of the initial one at average ambient temperatures of 20 degrees C and 25 degrees C. The times are: 1409.47 days (20 degrees C) and 1042.39 days (25 degrees C). Based on the value for Fischer's coefficien (F), the comparison of trenf of Diclofenac-Sodium content (in %) shows that, under the influence of different temperatures as a function of time, among them, depending on temperature value, there is: statistically very significant difference (P << .05) at 50 degrees C and lower toward 60 degrees C, i.e. statistically probably significant difference (P > 0.01) at 40 degrees C and lower towards 50 degrees C and there is no statistically significance difference (P >> 0.05) at 30 degrees C towards 40 degrees C.