Animal studies on antioxidants.

The wealth of existing epidemiologic evidence suggests that antioxidant intake limits the clinical expression of coronary artery disease. Because the oxidative modification of low-density lipoprotein is an important event in atherogenesis, it has been attractive to speculate that antioxidants act by limiting low-density lipoprotein orientation and, as a consequence, atherosclerotic lesion development. Early studies on animals also suggested that a number of structurally distinct antioxidant compounds could limit the extent of lesion development in animal models of atherosclerosis. More recently, however, secure evidence linking the antioxidant protection of low-density lipoprotein with a reduction in atherosclerosis has been elusive. This discrepancy may be explained by emerging evidence demonstrating that antioxidants may prove beneficial through tissue-specific effects that are not strictly related to the antioxidant protection of low-density lipoprotein.

13-cis-retinoic acid with alpha-2a-interferon enhances radiation cytotoxicity in head and neck squamous cell carcinoma in vitro.

The treatment of locally advanced squamous cell carcinomas of the head and neck presents a challenge for oncologists. Radiation therapy alone fails to control many of these tumors. Chemotherapy added to radiation therapy has not clearly demonstrated an improvement in survival in the majority of trials reported to date. In this study, we have evaluated whether IFN-alpha-2a and/or 13-cis-retinoic acid (RA) enhance radiation cytotoxicity in a head and neck squamous cell carcinoma cell line (FaDu). Using a clonogenic cell survival assay, IFN-alpha-2a (1000 units/ml) or RA (1 microM) alone did not significantly enhance radiation cytotoxicity. The combination of the two agents, however, significantly increased the cytotoxicity of radiation against FaDu cells. The calculated survival fraction at 2 Gy was decreased from 0.649 with radiation alone to 0.477 when combined with the other two agents (P = 0.016), and the MID was decreased from 3.318 to 2.499 Gy (P = 0.028). A Phase I clinical trial to combine IFN-alpha-2a and/or RA in patients with unresectable head and neck cancer has been initiated.