A comparison of schedules combining fractionated hyperthermia and irradiation in mice.

A comparison was made of three study arms delivering localized fractionated hyperthermia followed by irradiation for two weeks. The treatment results demonstrated 18-week survival and NED survival to be 35 per cent (7/20) and 30 per cent (6/20) respectively for heat and irradiation 5 days per week, 57.9 per cent (11/19) and 52.6 per cent (10/19) for combined treatment 3 days per week and 27.8 per cent (5/18) for heat 3 days per week and irradiation 5 days per week. It is felt that thermotolerance will account for the lack of difference between 24 h and 48 h irradiation schedules when irradiation is given daily. Irradiation fraction size, however, is suggested as a moderating variable as well.

Suppression of tumor growth and enhancement of immune status with high levels of dietary vitamin B6 in BALB/c mice.

Effects of dietary vitamin B6 at levels ranging from deficiency to megadoses on the development of herpes simplex virus type 2-transformed (H238) cell-induced tumors and on in vitro responses relating to cell-mediated immunity were examined. Male BALB/cByJ mice (n = 260), 5 weeks of age, were fed 20% casein diets containing pyridoxine (PN) at 0.2, 1.2 for the control diet, 7.7, or 74.3 mg/kg diet for 4-11 weeks. After 4 weeks of dietary treatment, 120 of the mice received an injection of H238 cells; mice without H238 injection served as controls. At 4, 8, and 11 weeks, animals from each group were euthanized and blood and spleen samples obtained. Mice fed 0.2 mg PN developed mild deficiency symptoms and gained significantly less weight than those fed 1.2-, 7.7-, and 74.3-mg PN diets. Thirteen to 16 days after tumor cell injection, primary tumor incidence was lowest in mice fed 74.3 mg PN; later, incidence among groups was similar. Mice fed 1.2 mg PN had the largest primary tumor volume, the highest incidence of lung metastases, and the greatest number of metastatic nodules per animal at 7 weeks post injection. Overall, lower tumor volumes were found in animals fed 7.7 and 74.3 mg PN (14 and 32% less than the tumor volume for those fed 1.2 mg PN, respectively); mice fed 0.2 mg PN had the lowest tumor volume. Blood and spleen lymphoproliferative response to stimulation by phytohemagglutinin or concanavalin A generally tended to be higher in mice fed 7.7 and 74.3 mg PN as compared to that in animals fed either 0.2 or 1.2 mg PN. However, decreased mitogen-stimulated responsiveness was observed in all animals with progressive tumor growth. Tumor growth also resulted in splenomegaly and increased thymic atrophy. Significant negative relationships between tumor volume and tumor pyridoxal 5-phosphate (PLP) concentrations were observed for 1.2-, 7.7-, and 74.3-mg PN diet groups. These data suggest that high dietary intake of vitamin B6 may have suppressed tumor development by either immune enhancement or PLP growth regulation of this tumor.

Hyperthermia and radiation in vivo: effect of 2-deoxy-D-glucose.

Since hypoxic cells rely heavily on glucose metabolism for energy, 2-deoxy-D-glucose (2-DG), an inhibitor of anaerobic glycolysis, would be expected to increase tumor cell killing by heat and thus enhance the effect of concurrent radiation. In order to test this hypothesis two types of BALB/c mouse tumors, one induced by subcutaneous injection of 10(6) herpes virus Type 2-transformed (H238) cells and the other by injection of 1.6 X 10(5) 1,2-dimethylhydrazine-transformed (#51) cells in the right thigh, were subjected to radiation, 2-DG, and heat used singly and in various combinations. Control mice were injected with saline. Three to four weeks after inoculation the mice were assigned to one of eight treatment groups (28 mice/group) so that average tumor volume/group before treatment would be equivalent. A single 2000 rad dose of radiation 3 hr prior to heat and 2-DG injected intraperitoneally at 1 g/kg 30 min before heating were given to some of the groups. Localized heat at 43.5 +/- 0.1 degrees C for 30 min, when used, was administered by means of a water bath. Rectal temperatures were kept below 39 degrees C, whereas intratumor temperatures reached a maximum of 42 degrees C. After treatment, tumor volume, mouse weight, and mortality were noted twice a week for four weeks. In both tumor models, mice receiving radiation plus heat, and radiation plus heat plus 2-DG, had significantly smaller tumors over the entire 4 to 28 day range after treatment than saline-injected control mice. In addition, in the H238 tumor model, addition of 2-DG to treatment with radiation and heat resulted in significantly smaller tumors at 25 days. 2-DG alone or in combination with heat (without radiation) resulted in significantly smaller H238 cell-induced tumors at day 28 post-treatment when compared to the saline controls. The H238 tumor-bearing mice experienced a significant (4.7%) loss in total body weight after heating. It could be that heating trauma produced dehydration and possibly also decreased caloric intake to an extent which could be measured in weight loss. This observation, however, was not made in the heated mice in the #51 tumor model.

Modification of spontaneous mammary tumors in mice fed different sources of protein, fat and carbohydrate.

The effects of different sources of dietary protein (milk, soy, wheat, fish and beef), fat (corn oil and butter), and carbohydrate (dextrin and sucrose) on the development of spontaneous mammary tumors in virgin female C3H/HeJ mice were investigated. Weanling mice were randomly divided (28 mice/group) and fed ad libitum one of 14 equicaloric diets containing either 11% or 33% protein and 5% or 30% fat or a standard mouse feed for approximately 2 years. Beginning at 6 months of age, tumor incidence, non-specific deaths, individual weights and amount of food consumed were monitored. Variations in tumor incidence were most pronounced when the mice fed different sources of protein (at a high level) were compared. The mice fed the low fat diets containing either low milk protein (high carbohydrate) or high fish protein generally exhibited the lowest tumor incidence and highest percent survival. High weight gain was correlated with early tumor appearance, but not with tumor incidence later in the experiment. The mice fed a low fat diet containing low milk protein were tumor-free significantly longer than mice fed the diets containing fish or beef. The only groups with 100% tumor incidence by 120 weeks of age were those fed diets containing sucrose (table sugar) or a high fat level.