Search

To determine the effect of age on susceptibility to azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation and its underlying mechanism, young and old mice were injected with AOM weekly for 4 or 5 weeks and euthanized 5 or 6 weeks later. Given the same (12 or 15) mg/kg body weight dose of AOM, old mice had significantly more ACF than young mice. However, given the same total dose of AOM (to avoid confounding effect of higher dose to heavier old mice), at a low total dose (1.5 mg) there was no age difference, but at higher total doses (1.8 and 2.2 mg) young mice had significantly more ACF than old mice. These results indicate that the age-related susceptibility to AOM differs depending on whether administration of the carcinogen is based on weight or total dose. These age differences are not due to variations in cyclooxygenase-2 expression, cell proliferation, or AOM hydroxylase activity.

Vitamin E, part of the body's primary lipid-soluble defense against free radicals and reactive oxygen molecules, has been suggested to reduce the risk for some cancers. However, the role of vitamin E in the etiology and prevention of colon cancer, especially in the highest risk group, the aged, is not clear. Thus, this study was conducted to elucidate the effect of vitamin E supplementation on susceptibility to colon cancer by examining azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation, a surrogate biomarker of colon cancer. Young (3-4 mo) and old (19-20 mo) C57BL/6JNIA mice were fed either a control diet (30 mg dl-[alpha]-tocopheryl acetate/kg diet) or a vitamin E-supplemented diet (500 mg dl-[alpha]-tocopheryl acetate/kg diet) for 16 wk. After 6 wk of dietary supplementation, young and old mice were injected with saline or AOM weekly for 5 wk to receive the same total dose of AOM (2.2 mg) and killed 10 wk after the first AOM injection. Vitamin E supplementation had no effect on the number of AOM-induced ACF in young or old mice. In addition, vitamin E supplementation did not have an effect on splenocyte interferon-[gamma], interluekin-6 and tumor necrosis factor-[alpha] levels, natural killer cell killing activity or colonic cell proliferation in young or old mice. Thus, [alpha]-tocopherol does not seem to affect the initiation and early promotion stages of AOM-induced colon carcinogenesis in young or old mice. Whether vitamin E supplementation might be effective in reducing AOM-induced colon tumors is unclear. KEY WORDS: * vitamin E * colon cancer * aberrant crypt foci * mice

Aging is associated with a decline in the immune response in mammals. Conjugated linoleic acid (CLA) has been suggested to have immunoenhancing properties. We examined the influence of dietary CLA on the immune response of young and old mice. Forty young (4 mo) and 40 old (22 mo) mice consumed ad libitum diets containing 0 or 1 g CLA/100 g for 8 wk. Splenocytes from half of the mice were isolated to evaluate proliferation to concanavalin A (Con A) (0.5, 1.5, 5.0 mg/L) and phytohemagglutinin A (PHA) (5, 20, 40 mg/L) and lipopolysaccharide (LPS) (5, 15, 30 mg/L), natural killer cell (NK) activity and prostaglandin (PG)[E.sub.2] and interleukin (IL)-2 production. The remaining mice were used to evaluate in vivo delayed-type hypersensitivity (DTH) skin response. There was a significant decline due to age in response to all three mitogens tested (P < 0.05). CLA supplementation significantly increased all CLA isomers measured in hepatic neutral lipids and phospholipids (P < 0.05). Young mice fed 1% CLA had greater splenocyte proliferation in response to Con A (0.5 and 5.0 mg/L) and PHA (40 mg/L) (P < 0.05) than young mice fed control diet. Old mice fed 1 g CLA/100 g had significantly higher proliferative response to optimal concentrations of Con A (1.5 mg/L) (P < 0.001) than the mice fed the control diet. Old mice fed the control diet had significantly lower splenocyte IL-2 production than the young mice (P < 0.005). CLA-supplemented young mice had significantly higher splenocyte IL-2 production than those fed the control diet (P < 0.05). CLA had no effect on NK cell activity, PG[E.sub.2] production or DTH in young or old mice. Further studies are needed to determine the mechanism of CLA-induced enhancement of IL-2 production and T cell proliferation. KEY WORDS: conjugated linoleic acid; mice; immune response; age

A study was conducted to identify the effect of vitamin E supplementation on macrophage PGE2 synthesis in young and old mice. Macrophages from old mice that were stimulated with lipopolysaccharide produced more PGE2 than those from young mice. Vitamin E supplementation reversed the increased production in old mice but had no significant effect in those of the young mice. Cyclooxygenase activity was higher in old than in young mice at all intervals.

Decline in immune response is a well-documented age-associated biological change. Protein-bound polysaccharides (PSP) are biological response modifiers and have been shown to have immunoenhancing and antitumor effects. This study was conducted to examine the effect of dietary supplementation with PSP-containing extract derived from mycelia of Coriolus versicolor on in vitro and in vivo indices of immune function of young and old mice. Young (5 mo) and old (23 mo) C57BL/6NIA mice were fed purified diets containing 0, 0.1, 0.5 or 1.0% PSP for 1 mo at which time indices of immune function were measured. PSP supplementation had no significant effect on mitogenic response to concanavalin A (Con A), phytohemagglutinin (PHA) or lipopolysaccharide (LPS), or on production of interleukin (IL)-1, IL-2, IL-4 and prostaglandin [E.sub.2] (PG[E.sub.2]). Of the in vivo indices of immune function tested, old mice fed 1.0% PSP had significantly higher delayed-type hypersensitivity (DTH) response than those fed 0% PSP. No significant effect of PSP was observed on the DTH response of young mice. The antibody response to sheep red blood cells was not significantly influenced by PSP in young or old mice. These results suggest that PSP-containing extract from mycelia of Coriolus versicolor might have a modest immunoenhancing effect in aged mice, but not in young mice. KEY WORDS: mice biological response modifier protein-bound polysaccharide immune response aging

This study compared the effect of vitamin E on the course of influenza infection with that of other antioxidants. (In a previous study we showed that short-term vitamin E supplementation significantly decreased pulmonary viral titer in influenza-infected old mice). Eighteen-month-old C57BL/6NCrlBR mice were fed one of the following semisynthetic diets for 6 months: control, vitamin E supplemented, glutathione supplemented, vitamin E and glutathione supplemented, melatonin supplemented, or strawberry extract supplemented. After influenza virus challenge, mice fed vitamin E-supplemented diet had significantly lower pulmonary viral titers compared to those fed the control diet ([10.sup.2.6] vs [10.sup.4.0],p [is less than] .05) and were able to maintain their body weight after infection (1.8 [+ or -] 0.9 g weight loss/5 days postinfection in vitamin E group vs 6.8 [+ or -] 1.4 g weight loss/5 days postinfection in control group, p [is less than] .05). Other antioxidants did not have a significant effect on viral titer or weight loss. There was a significant inverse correlation of weight loss with food intake (r = -.96, p [is less than] .01), indicating that the observed weight changes were mainly due to decreased food intake. Pulmonary interleukin (IL)-6, IL-1[Beta], and tumor necrosis factor (TNF)-[Alpha] levels increased significantly postinfection. The vitamin E group had lower lung IL-6 and TNF-a levels following infection compared to the control group. In addition, there was a significant positive correlation between weight loss and lung IL-6 (r = .77, p [is less than] .01) and TNF-[Alpha] (r = .68, p [is less than] .01) levels. Because IL-6 and TNF-[Alpha] have been shown to contribute to the anorexic effect of infectious agents, the prevention of weight loss by vitamin E might be due to its reduced production of IL-6 and TNF-a following infection. Thus, among the antioxidants tested, only vitamin E was effective in reducing pulmonary viral titers and preventing an influenza-mediated decrease in food intake and weight loss. Other dietary antioxidant supplementations that reduced one or more measures of oxidative stress (4-hydroxynonenal, malondialdehyde, and hydrogen peroxide) did not have an effect on viral titer, which suggests that, in addition to its antioxidant activity, other mechanisms might be involved in vitamin E's beneficial effect on lowering viral titer and preventing weight loss.

Background: Serum vitamin B12 levels have been proposed as one of the survival prediction factors, although no survival analysis in metastatic cancer patients has been conducted yet. This study examined whether serum vitamin B12 levels could be a prognostic factor in metastatic cancer patients. Methods: Data from a retrospective chart review were used to perform Kaplan-Meier and multivariate analyses of the Cox proportional hazards. Subgroup analysis was performed on patients without a liver lesion (hepatocellular carcinoma or liver metastasis). Results: A total of 523 patients were included. The median survival time was 1.8 months (mo) in the high B12 group (>911 pg/mL) and 5.1 mo in the normal B12 group (211–911 pg/mL) (p < 0.001). In patients without a liver lesion, the median survival times were 2.1 and 6.1 mo in the high and normal B12 groups, respectively (p < 0.001). Multivariate analysis revealed that serum vitamin B12 level was an independent prognostic factor for overall survival (hazard ratio [HR]: 1.62; 95% confidence interval [CI]: 1.34–1.96, p < 0.001). Conclusion: Serum vitamin B12 level can be used to predict survival time in metastatic cancer patients. Further large-scale cohort studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]