Immunohistochemical and histomorphological analysis of rat mammary tumors after simvastatin treatment.

The results of experimental studies have indicated the pleiotropic effects of statins in organism, e.g. the influence on cell cycle, apoptosis or angiogenesis. In this study, the effects of simvastatin on selected parameters of apoptosis and proliferation in chemocarcinogen-induced mammary tumorigenesis in female rats were determined. Simvastatin was administered dietary at a dose of 18 mg/kg and highly effective dose of 180 mg/kg the entire experiment (18 weeks). At autopsy mammary tumors were removed and prepared for immunohistochemical and histomorphological analysis. In treated animals (simvastatin 180 mg/kg), significant decrease by 12% in Bcl-2 protein expression and non-significant decrease by 27% of Ki67 protein expression in tumor cells compared to tumor cells in control animals were observed after semiquantitative evaluation. Morphometrical analysis has shown significant proapototic shift in Bcl-2/Bax ratio in tumor cells. In high grade control carcinoma cells, the expression of Ki67 increased by 37% (non-significantly) in comparison with control low grade carcinomas. A histomorphological analysis of malignant tumors has revealed a shift from high grade to low grade carcinomas after simvastatin treatment. The noticeable decrease of mammary tumor frequency and incidence in rats after simvastatin treatment was accompanied with antiapoptotic Blc-2 protein decrease and proapoptotic Bax protein increase in this experiment.

Melatonin enhanced bexarotene efficacy in experimental mammary carcinogenesis.

The aim of this paper was to test lower, safe bexarotene dose administered alone and in combination with melatonin to improve its efficacy. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea in female Sprague-Dawley rats, administered in two doses intraperitoneally between 42.-54. postnatal days and chemoprevention was initiated 7 days prior to first N-methyl-N-nitrosourea injection and lasted 15 weeks. Bexarotene, particularly in combination with melatonin decreased mammary tumor incidence and frequency with a shift from poorly to well differentiated carcinomas. Bexarotene alleviated glycaemia and liver/heart muscle glycogen concentration decreased as well as liver/thymus malondialdehyde increased in comparison with control group. The combination of bexarotene and melatonin is therefore beneficial in preventive-curative model of experimental mammary carcinogenesis and may be applied in oncological practice as such.

Antineoplastic effects of simvastatin in experimental breast cancer.

BACKGROUNDS: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have proven therapeutic and preventive effects on cardiovascular diseases. Preclinical evidence demonstrates tumor-suppressive effects of statins in several human neoplasias, including breast cancer. MATERIALS AND METHODS: In this study, antineoplastic effects of simvastatin in chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. The drug was dietary administered at two concentrations--18 mg/kg (SIMVA 18) and 180 mg/kg (SIMVA 180). RESULTS: Basic parameters of experimental carcinogenesis after long-term simvastatin treatment in animals were assessed. In the SIMVA 180 group, simvastatin significantly suppressed tumour frequency by 80.5% and tumour incidence by 58.5% in comparison to the controls. Higher dose simvastatin non-significantly decreased the mean tumor volume by 23.5%, as well as non-significantly lengthened the latency period by 14.5 days compared to the control animals. Simvastatin, administered at a lower dose did not change parameters of mammary carcinogenesis in comparison to the control group. Simvastatin in both treated groups significantly decreased serum levels of triacylglycerols and VLDL-cholesterol in comparison to the control animals. Compared to the controls, a significant increase in food intake by the animals was recorded in the SIMVA 18 and SIMVA 180 groups. No significant differences in the final body weight gain between the simvastatin-administered and the control group were found. CONCLUSION: This study represents the first report of simvastatin use in experimental mammary carcinogenesis in vivo.

[Analysis of the effect of 2 criteria in the creation of age groups on the value spread of selected somatic parameters]. / Analýza vplyvu dvoch kritérií tvorby vekových skupín na rozptyly hodnôt vybraných somatických parametrov.

In the paper we present the results from the statistic analysis of the effect of two age-group creation criterions (1-st criterion--f.e. the 7 years old--from 6,500 to 7,499 years, 2-nd criterion--f.e. the 7 years old--from 7,000 to 7,999) on value dispersion of somatic characteristics chosen. We analyzed the body weight and body height in the set consists of 846 Gypsy children from 7 to 13 years of age. The dispersions of individual values of parameters followed for both criterions were tested by F-test, average values by un-pair Student's t-test. We found that the both criterions have no effect on value dispersion of evaluated somatic characteristics, except of two cases. Further, average values of testing parameters by criterion No. 1 are somewhat lower in comparison with those by criterion No. 2. Statistically significant differences are however incidental and rare. We suggest that in the case of population studies concerning with body growth and development it is possible to compare the sets with different age-group creation criterions.

[Bone age of preschool children in Eastern Slovakia]. / Kostný vek predskolských detí z východného Slovenska.

The authors present the results of evaluation of the skeletal maturation in 579 children aged 1-5 years. Bone maturation was evaluated, based on skeletal age, by the Tanner-Whitehouse II method (Tanner et al., 1975). It was found that girls up to the age of three years had lower and in the more advanced age groups higher values of skeletal age than boys. Boys were retarded as regards skeletal age in relation to chronological age on average by 0.28 years and girls by 0.25 years.

[Comparison of physical growth in school-children living in children's residential facilities and in families with emphasis on the gypsy ethnic group]. / Porovnanie telesného rastu skolských detí z detských domovov a rodín so zameraním na rómske etnikum.

The authors investigated the growth of 1208 gipsy and non-gipsy children living with their families and in childrens homes. They revealed that gipsy children from childrens homes were shorter, lighter and had a smaller chest circumference as compared with gipsy children living with their families. This applied only to younger school children. Somatic development caught up in boys at the age of 11-12 years and in girls approximately 1-2 years sooner. The values of the body mass index in boys declined with age. In girls this decline was found only up to the age of 11 to 12 years. Non-gipsy children from childrens homes were smaller than non-gipsy children according to Slovak standards (Lipková et al.; 5); this was particularly marked in boys. The authors found also that the somatic development of gipsy children from childrens homes oscillates between the somatic development of non-gipsy children according to the Slovak standards and the somatic development of gipsy children from families but only during later school age.

[Bone age of preschool-age children in the Eastern Slovakia Region]. / Kostný vek predskolských detí z Východoslovenského kraja.

In a group of 579 children the bone age was assessed by the Tanner-White house II method. It was revealed that girls up to the age of three years have lower values of bone age than boys who are ahead in subsequent age groups. Boys lagged behind as regards bone age in relation to chronological age by 0.4 years and girls by 0.3 years.

[Body growth in low birth weight premature children up to 5 years of age]. / Telesný rast nedonosených detí s nízkou pôrodnou hmotnost'ou do 5 rokov.

Investigation of the growth in 488 premature infants born with a low birth weight, compared with infants born in term with a birth weight above 2,500 g at the age of 1-5 years. Body weight, height, head circumference and chest circumference were assessed as well as Quetelet-Kaup-Gould and Quetelet-Bouchard index. It was found that premature infants are retarded in the above parameters, as compared with mature infants, still at the life of live years.