Caffeine induces metformin anticancer effect on fibrosarcoma in hamsters.

OBJECTIVE: We investigated the effect of metformin and caffeine on fibrosarcoma in hamsters. MATERIALS AND METHODS: 32 Syrian golden hamsters of both sexes, weighing approximately 100 g, were randomly allocated to 3 experimental and 2 control groups, with a minimum of 6 animals per group. 2 x 106 BHK-21/C13 cells in 1 ml were injected subcutaneously into the animals' back in 4 groups. The first experimental group started peroral treatment with metformin 500 mg/kg daily, the second with caffeine 100 mg/kg daily and the third with a combination of metformin 500 mg/kg and caffeine 100 mg/kg daily, via a gastric probe 3 days before tumor inoculation. After 2 weeks, when the tumors were approximately 2 cm in the control group, all animals were sacrificed. The blood was collected for glucose and other analyses. The tumors were excised and weighed and their diameters were measured. The tumor samples were pathohistologically (HE) and immunohistochemically (Ki-67, CD 31, COX IV, GLUT-1, iNOS) assessed and the main organs toxicologically analyzed, including the control animals that had received metformin and caffeine. Tumor volume was determined using the formula LxS2/2, where L was the longest and S the shortest diameter. Ki-67-positive cells in the tumor samples were quantified. Images were taken and processed by software UTHSCSA Image Tools for Windows Version 3.00. Statistical significances were determined by the Student's t-test. RESULTS: The combination of metformin and caffeine inhibited fibrosarcoma growth in hamsters without toxicity. CONCLUSIONS: Administration of metformin with caffeine might be an effective and safe approach in novel nontoxic adjuvant anticancer treatment.

Effect of metformin on fibrosarcoma in hamsters.

OBJECTIVE: We investigated the effect of metformin on an in vivo solid tumor model of fibrosarcoma in hamsters. MATERIALS AND METHODS: 33 Syrian golden hamsters of both sexes, weighing approximately 100 g, were randomly allocated to 3 experimental and 2 control groups. 2 x 106 BHK-21/C13 cells in 1 ml were injected subcutaneously into the animals' back in 4 groups. The first experimental group (7 animals) started peroral treatment with metformin 500 mg/kg daily via a gastric probe 7 days before tumor inoculation, the second (8 animals) 3 days before inoculation and the third (6 animals) immediately after inoculation. After 2 weeks, when the tumors were approximately 2-3 cm in the control group with tumors (6 hamsters), all animals were sacrificed. The blood was collected for glucose and other analyses. The tumors were excised and weighed and their diameters were measured. The tumor samples were histologically assessed and the main organs toxicologically analyzed, including 6 control animals that had received metformin without tumor inoculation. Tumor volume was determined using the formula Lx S2/2, where L was the longest and S the shortest diameter. Ki-67-positive cells in the tumor samples were quantified; images were taken and processed by software UTHSCSA Image Tools for Windows Version 3.00. Statistical significances of differences in tumor weight, volume, number of Ki-67-positive cells and other parameters were determined by the Student´s t-test. RESULTS: Metformin inhibited fibrosarcoma growth in hamsters without toxicity. The seven-day pretreatment was important for the statistically significant effect. CONCLUSIONS: Administration of metformin as an anti-tumor drug might be an effective and safe therapeutic approach in novel non-toxic therapies for human sarcomas.

Prostaglandin E2, trace elements and levels of oxidative processes in spontaneous miscarriages.

OBJECTIVE: We investigated the significance of prostaglandin (PG)E2, trace elements level, pro-oxidative and antioxidative parameters changes in spontaneous miscarriages. PATIENTS AND METHODS: In the 125 first trimester pregnancies, 35 with complete spontaneous abortion (group S), 40 with missed abortion (M) and 50 healthy (H), PGE2 plasma concentrations were analysed by commercial ELISA kits, plasma trace elements colorimetrically, lipid peroxidation and the antioxidative enzyme activities in hemolysate by commercial sets. Student's t-test and ANOVA were applied. RESULTS: Average PGE2 plasma concentration in the group H was higher than in S and M (p < 0.05). The higher average plasma Cu concentration, glutathione peroxidase and catalase contents were in the group H than in groups S and M (p < 0.01). Significantly lower value of lipid peroxidation was in the group H than in the groups S and M (p < 0.01). The lowest superoxide dismutase (SOD) content was in the group H and the highest in group S (p < 0.01). CONCLUSIONS: In patients with abortions significantly lower levels of plasma PGE2, plasma Cu and anti-oxidative enzymes, except SOD, and significantly higher level of lipid peroxidation products than in healthy pregnancies may be important for miscarriage etiology and prevention.