Experiments with mammalian tumor isolates.
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The adoptive transfer of tumor-infiltrating lymphocytes (TIL) expanded in interleukin-2 (IL-2) to mice bearing micrometastases from various types of tumors showed that TIL are 50 to 100 times more effective in their therapeutic potency than are lymphokine-activated killer (LAK) cells. Therefore the use of TIL was explored for the treatment of mice with large pulmonary and hepatic metastatic tumors that do not respond to LAK cell therapy. Although treatment of animals with TIL alone or cyclophosphamide alone had little impact, these two modalities together mediated the elimination of large metastatic cancer deposits in the liver and lung. The combination of TIL and cyclophosphamide was further potentiated by the simultaneous administration of IL-2. With the combination of cyclophosphamide, TIL, and IL-2, 100% of mice (n = 12) bearing the MC-38 colon adenocarcinoma were cured of advanced hepatic metastases, and up to 50% of mice were cured of advanced pulmonary metastases. Techniques have been developed to isolate TIL from human tumors. These experiments provide a rationale for the use of TIL in the treatment of humans with advanced cancer.
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Serum haptoglobin (Hp) levels were determined periodically in mice treated with the carcinogen 7, 12-dimethylbenz[a]anthracene (DMBA). The magnitude and duration of the Hp response to tumors induced by DMBA were dependent on the tumor type; lymphocytic lymphomas elicted a minimal response, whereas mice bearing mammary carcinomas and stomach squamous cell carcinomas had high Hp levels which remained elevated throughout most of the period of tumor development. In the majority of mice with mammary carcinomas, the initial rise in serum Hp coincided fairly closely with the first appearance of palpable masses. Some variation in the magnitude of the Hp response was observed between individual mice bearing chemically-induced tumors of similar histological types.
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The anti-caries effects of water fluoridation are well-established. The non-dental tissue effects of fluoride in drinking water, either naturally occurring or as an additive, have been too poorly studied to permit definitive conclusions to be drawn. Claims have been made that fluoride results in an increased occurrence of malignancies, particularly osteogenic sarcoma. Experimental rat data have not resolved this issue, and epidemiologic studies are equally unclear. Initial claims that fluoride offers protection against atherosclerosis remain viable, but here too, much more directed research is needed. Early studies suggested that a water fluoride content greater than 1 ppm resulted in a lower prevalence of osteoporotic fractures. Recent epidemiologic data seriously question this conclusion and raise the possibility that even this relatively low level may increase the prevalence of osteoporotic hip fractures. Other elements, including calcium and magnesium, also vary in amount as water fluoride content varies, and it has proved difficult to distinguish the independent effects of the various nutrients in water from each other. Therapeutic use of fluoride has been largely restricted to studies of its effect on the osteoporotic study, this important issue remains unresolved. This review provides an overview of these issues, focusing on the uncertainties alluded to, and attempting to develop strategies for future research.
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