Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma

Lessons Learned

• Melatonin did not increase the efficacy of systemic chemotherapy in melanoma.
• Metformin did not increase the efficacy of systemic chemotherapy in melanoma.

     

Body weight is not always a good predictor of longevity in mice

There have been some observations that low body weight and a low level of some hormones (e.g. IGF-1) during the first half of life are predictors of longer life in mice. However, contradictions in the available data on the biomarkers of aging and predictors of longevity have shown that the research in these fields has become a controversial pursuit. In our study we addressed the following questions: (i) Can particular physiological parameters (body weight, food intake, estrus function, body temperature, incidence of chromosome aberrations in bone marrow cells) measured at the age of 3 and 12 months be a predictor of longevity and the rate of tumor development in five strains of mice? (ii) Can a heavy body weight at the age of 3 and 12 months be a predictor of longevity and high tumor risk in five strains of mice? Mice of five strains-CBA, SHR, SAMR, SAMP and transgenic HER-2/neu (FVB/N)-were under observation from the age of 2-3 months until natural death. Body weight and temperature, food consumption, and estrous cycle were longitudinally studied in all animals. Tumors discovered at autopsy were studied morphologically. We calculated the life span's parameters (mean, maximum, mortality rate, mortality rate doubling time) as well as their correlation with other parameters studied. The longest living CBA mice have the lowest body weight at the ages of 3 and 12 months, the lowest food consumption, body temperature, incidence of chromosome aberrations and spontaneous tumor incidence. In comparison with all other mouse strains they also have the latest disturbances in estrus function and highest body weight gain. The shortest living transgenic HER-2/neu mice have the lowest weight at the ages of 12 months, the lowest body weight gain, maximal body temperature, the most rapid disturbances in estrus function and the highest incidence of chromosome aberrations and tumor incidence in comparison to all other mouse strains. Our findings have shown that heavier body weight at the age of 12 months is a predictor of longevity in female CBA and SAMP mice but not in SHR, SAMR and HER-2/neu mice. Excessive body weight at the ages of 3 or 12 months is not a predictor of increased tumor risk in the strains studied. In general, the existence and direction of a significant correlation between body weight and life span depends upon the animals' age and genotype.     

Effect of age on dose-response relationship in carcinogenesis induced by single administration of N-nitrosomethylurea in female rats

Summary Female rats aged 3 months and 15 months each received a single i.v. administration of N-nitrosomethylurea (NMU) at one of three doses: 10, 20, and 50 mg/kg. The rats exposed to NMU at the age of 3 months developed neoplasms of all sites examined, including mammary carcinomas and tumors of the kidney, ovaries and colon, the incidence varying with the carcinogen dose. The incidence of malignant neoplasms in old animals did not depend on NMU dose. In contrast to young animals, the old ones showed a higher frequency of tumors of the corpus and cervix uteri following exposure to NMU, and a lower frequency of mammary and intestinal adenocarcinomas and tumors of the ovary and kidney. Comparison of the present experimental results with the data on DNA alkylation, synthesis and O ⁶-methylguanine repair obtained previously on the same model suggests a leading role of age-related proliferative activity changes occurring in the target tissues in the mechanism of age in modifying the effect on carcinogenesis. The analysis of data on the dose dependance of the carcinogenic effect of NMU within the framework of a multistage model suggests age-related accumulation, in different tissues, of cells occasionally lesioned and in the late stages of becoming malignant.     

Expression of peripheral benzodiazepine receptor, PCNA, and caspase-3 in cells of skin melanoma and squamous cell Carcinoma

The intensity of cell proliferation and apoptosis and expression peripheral benzodiazepine receptor were studied in skin biopsy specimens from patients with squamous cell carcinoma and melanoma of the skin. Sharp inhibition of apoptosis and changes in the levels of cell proliferation in tumor cells were paralleled by decreased expression of peripheral benzodiazepine receptor. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 7, pp. 87–89, July, 2007     

Early Resistance to experimental plague in animals immunized with recombinant plague vaccine

The protective properties of recombinantSalmonella minnesota R595/pFS1 strain soon after immunization (1–3 days) are studied in a model of experimental mouse plague. Unlike the commercial EV strainYersinia pestis vaccine produced at the Saratov Anti-Plague Institute (Mikrob Research-Manufacturing Conglomerate), the experimental recombinant p preparation affords a high level of protection from the 1st day postvaccination, and surpasses the commercial preparation in such parameters as LD₅₀, mean survival time, and percentage of survivors. By the 21st day the protective indexes of both preparations are comparable. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny,Vol. 119, N ^o 1, pp. 54–57, January, 1995 Presented by A. A. Vorob'ev, Member of the Russian Academy of Medical Sciences     

Polyphenolic drug composition based on benzenepolycarboxylic acids (BP-C3) increases life span and inhibits spontaneous tumorigenesis in female SHR mice

Effects of long-term application of novel polyphenolic composition BP-C3, containing polyphenolic benzenepolycarboxylic acids, vitamins and minerals on some biomarkers of aging, life span and spontaneous tumorigenesis has been studied in female SHR mice. Administration of BP-C3 with drinking water (0.005%) did not exert any toxic effect (did not have effect on general condition of animals, weight dynamics and consumption of food), postponed age-related switch-off of estrous function, caused slight reduction of body temperature. An increased survival was observed in mice treated with BP-C3 (p=0.00164, log rank test). BP-C3 increased mean lifespan – by 8.4%, lifespan of the last 10% of animals – by 12.4%, and life span of tumor-free mice – by 11.6%. A tendency in ability of BP-C3 to inhibit development of spontaneous tumors in mice was detected, though it did not reach the level of statistical significance (p=0.166, log rank test). The number of malignant mammary tumors was 1.5 times less and total number of tumors of various localizations was 1.6 times less in BP-C3 treated animals. Multiple tumors were registered in 8% of mice in the control group and no cases – in BP-C3 treated group. Thus, BP-C3 demonstrated some anti-carcinogenic and a pronounced geroprotective activity.     

Effect of vilon on biological age and lifespan in mice

Subcutaneous administration of vilon (Lys-Glu) to female CBA mice starting from the 6th month of life increased physical activity and endurance, decreased body temperature, prolonged the lifespan, and prevented the development of spontaneous neoplasms. Vilon had no effect on age-related changes of estrous function and free radical processes. Long-term administration of vilon caused no unfavourable effects on animal development. The obtained results show safety of chronic vilon administration and allow to use this preparation for geroprotection and prophylaxis of age pathology. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 88–91, July, 2000