The small intestine (SI) of vertebrates exhibits low tumorigenesis and rarely supports metastatic growth from distant tumors. Many theories have been proposed to address this phenomenon, but none has been consistently supported. One candidate mechanism is that the vast immunologic compartment of the SI provides a heightened level of tumor immunosurveillance. Consistent with this, we have identified a molecule of low abundance from bovine SI that has the hallmarks of a potent immunostimulant and may be associated with the natural suppression of cancer in the intestinal tract. The protein originates from an endemic gut protozoan, Eimeria spp., and is homologous to the antigen 3-1E previously isolated from the avian apicomplexan E. acervulina. We show here that it is a very potent stimulator of IL-12 release from dendritic cells, upregulates inflammatory modulators in vivo (IL-12, MCP-1, IL-6, TNF-␣ and INF-␥) and has antitumor properties in mice. In addition, it is synergistic in vitro with anti-CD40 antibody, IFN-␥, IL-4 and GM-CSF; is active across species barriers in vivo; and has no observable toxicity. Based on these activities, we speculate that it is an inducer of protozoan-targeted innate immunity, which may explain its potential benefit to the intestinal tract and potency as an agent in cancer immunotherapy.

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Cross-generational effects (grandmother effects) associated with epigenetic imprinting, environmental exposures, and lifestyle choices are beginning to be explored by various investigators. The possibility that low-level background radiation can be a driver of such effects has been suggested previously and is explored further in this study. Age-period-cohort analysis was performed on United States (US), United Kingdom (UK), and Australian (AU) female breast cancer mortality of the twentieth century, as well as on UK female total cancer mortality, to extract the high-frequency oscillations in the birth cohort time series. US fetal and infant congenital mortality were examined to extend the birth cohorts to modern times. A approximately 17-year cycle was detected in all birth cohort series, which spanned approximately 180 years from 1820 to 2000. This suggests a global, environmental cause. To mimic previous work in examining a possible link to cosmic radiation, the 17- to 18-year cycles of the cosmogenic nuclide (14)C, the sunspot double-cycle, neutron monitors, and a compilation of ground-based magnetic field observations were examined in the birth cohort and germ cell cohort time frames. Evidence is presented that optimal alignments with extraterrestrial oscillations occur in the time frame of the germ-cell cohort, one generation before the birth cohorts. Furthermore, the alignment is optimized by accounting for the changes in the maternal age distribution over time. These findings have potential importance to the mechanisms of disease as well as species adaptation and evolution.