Showing papers by "Michael S. Gordon published in 1999"

Immunological Effects of Interleukin 12 Administered by Bolus Intravenous Injection to Patients with Cancer

Abstract: The immunological effects of recombinant human interleukin 12 (rhIL-12) administration were examined during the conduct of a Phase I clinical trial. Forty patients with advanced cancer received bolus i.v. injections of rhIL-12 in doses ranging between 3 and 1000 ng/kg. Dose-dependent increases in serum IFN-γ levels were seen during rhIL-12 therapy. Significant lymphopenia was observed 24 h after single i.v. injections of rhIL-12 at each dose level. The degree of lymphopenia was dose dependent, and a plateau effect was seen with rhIL-12 doses of 100 ng/kg and higher. Lymphocyte counts reached nadir levels at approximately 10 h after rhIL-12 injection and returned to baseline within 14 days postinjection. Rebound lymphocytosis, as seen after interleukin 2 therapy, was not observed after recovery from rhIL-12-induced lymphopenia. rhIL-12-induced lymphopenia involved all major lymphocyte subsets, although natural killer (NK) cell numbers were the most profoundly affected, and CD4 T-cell numbers were the least affected. CD2, LFA-1, and CD56 were transiently up-regulated on the surface of NK cells exposed to rhIL-12 in vivo . Peripheral blood mononuclear cells obtained from cancer patients before rhIL-12 therapy exhibited defective NK cell cytotoxicity and T-cell-proliferative responses. Peripheral blood mononuclear cells obtained after lymphocyte recovery following the administration of a single 500 ng/kg dose of rhIL-12 displayed augmented NK cell cytolytic activity in four of four patients tested and enhanced T-cell proliferation in three of four patients tested. These studies confirm that doses of rhIL-12 resulting in significant immunological activity can be administered with acceptable toxicity to cancer patients. Furthermore, rhIL-12 therapy can reverse defects in NK cell and T-cell function that are associated with advanced cancer in humans.

The effect of tea consumption on oxidative stress in smokers and nonsmokers.

Abstract: While the anticarcinogenic effects of tea in animal models have been reported by several groups, human epidemiological studies examining tea consumption and cancer prevention have produced equivocal results. The beneficial properties of tea to human health may be related to the antioxidant properties of tea components. However, little evidence has been provided that tea consumption can either increase the antioxidant capacity or decrease oxidative stress in humans. In the present study, the effects of tea treatment (green tea) on biomarkers of oxidative stress were investigated in smokers and nonsmokers in two volunteer study groups (one in China and the other in United States). Green tea consumption in both study groups decreased oxidative DNA damage (8-OHdG in white blood cells and urine), lipid peroxidation (MDA in urine), and free radical generation (2, 3-DHBA in urine) in smokers. Nonsmokers (US study group) also exhibited a decrease in overall oxidative stress.