Clinical trials in cancer prevention.

Research in cancer prevention can be divided into laboratory research, epidemiologic research, and clinical trials. When results from laboratory and/or epidemiologic research support the possibility of clinical cancer prevention, these leads should be subjected to study in clinical trials. If clinical trials produce positive results, wide application of these results to the relevant segments of the general population should then be emphasized. Why are clinical trials needed in cancer prevention? There are several considerations: epidemiologic studies may lack specificity, that is, the ability to reach conclusions that apply to only one specific factor; the predictive value of animal models based on laboratory studies is not entirely known; clinical trials quantitate the level of participant acceptance of the intervention; and clinical trials address the issues of risk/benefit ratios. Over the last 3 years, the National Cancer Institute has supported the development of a program of clinical trials in cancer prevention. The aim of these studies includes the reversal of precursor lesions, prevention of progression from a precursor state to overt malignancy, reduction in the incidence of malignancy, reduction in cancer mortality, and reduction in overall mortality. Interventions under study include a diet with less than 20% of calories from fat, and the administration of single agents or combinations of agents, including beta carotene, vitamin A, 13-cis-retinoic acid, vitamins C, E, and B12, and folacin.

Possible adverse health effects of vitamin C and ascorbic acid.

Consensus from individual studies and several review articles is that consumption of supplemental vitamin C leads to no significant adverse health effects to humans in general. Individuals who have a history of kidney stone formation and those who experience iron overload should exercise caution before using supplemental vitamin C. Occasionally, individuals experience diarrhea or mild nausea. There is also the possibility that vitamin C taken simultaneously with other drugs may contribute to adverse health effects and that its interference in clinical laboratory tests will mask diagnosis of disease. Few controlled clinical trials exist that conclusively demonstrate the adverse health effects that humans may experience with supplemental vitamin C usage, and before definite conclusions can be made of the health hazards to humans, more clinical trials are required.

Isolation and characterization of a cloned cell line R3327H-G8-A1 derived from the dunning R3327H rat adenocarcinoma.

A cloned cell line (R3327H-G8-A1) has been isolated from the Dunning R3327H adenocarcinoma. Light and electron microscopic studies showed that the cell line possessed features common to secretory epithelial cells. These cells, which grow in monolayer culture, produced s.c. hind flank tumors when inoculated inoculated into Copenhagen X Fischer F1 rats.l Chromosomal karyotype analysis confirmed that the cell line is distinctly that of the Rattus norvegicus genus and species. The cells specifically bind testosterone and dexamethasone with equilibrium dissociation constants (Kd) of 0.49 and 0.8 nM, respectively. The numbers of saturable binding sites per cell are 10,000 for testosterone and 60,000 for dexamethasone. The cells also have 5 alpha-reductase activity. These properties are characteristic of the prostate and of the Dunning tumor from which the cells are derived. Cell growth in vitro was stimulated by androgens and inhibited by glucocorticoids at concentrations of 10(-8) M. An int riguing finding was that estradiol and progestins dramatically stimulated growth in the apparent absence of receptors for these hormones. Finally, comparisons between the G8-A1 cells and the tumor induced by the G8-A1 clone and a second generation of cells from this G8-A1-induced tumor showed that the cloned cells retained their properties following passaging in the animal.

Dunning adenocarcinoma in tissue culture: isolation of a cloned cell line, R3327H-G8-A1.

A cloned cell line, R3327H-G8-A1, was isolated from an explant of the well differentiated androgen dependent Dunning R3327H adenocarcinoma. Preliminary characterization of this cell line indicates that it is epithelial-like, and that it synthesizes and secretes large quantities of acid phosphatase. The cells bind testosterone in a saturable manner with an equilibrium dissociation constant of 0.5 nM and with a capacity of 5000 sites/cell. When these cells were injected subcutaneously into the hind flank of Copenhagen-Fischer rats, or into the dorsal or ventral lobes of the prostate, large tumors were produced 3 months following administration, thus demonstrating the tumorigenicity of the cells.

Methods for ligand-receptor assays in clinical chemistry.

This is intended to be a practical review for the clinical chemist of the laboratory procedures most commonly used to quantitate hormone receptors in various cellular fractions. These procedures include use of charcoal adsorption and hydroxylapatite for intracellular receptors and of centrifugation and filtration for membrane receptors. We discuss the use of the Scatchard analysis to establish the steroid-receptor affinity and the quantity of steroid-receptor binding sites. Both pre- and post-labeled sucrose density gradient methods are outlined. One section is devoted to the direct and indirect methods used in nuclear "exchange" assays. Basic theory underlying each assay is presented, but, more importantly, we assess the advantages and disadvantages of each procedure. On the basis of this information, one may decide which assay is best suited for a particular laboratory and (or) specimen.