Immune modulatory potentials of antineoplaston A-10 in breast cancer patients

Antineoplastons are naturally occurring cytodifferentiating agents. Chemica lly, they are medium and small sized peptides, amino acid derivatives and o rganic acids, which exist in blood, tissues and urine. Antineoplaston A-10 (3-phenylacetylamino-2,6-piperidinedione) is the first chemically identifie d antineoplaston. Previously we have shown a strong inverse association of urinary antineoplaston A-10 with breast cancer. This study is designed to e valuate neutrophil apoptosis in patients with breast cancer at time of diag nosis and to correlate urinary antineoplaston A-10 levels with neutrophil a poptosis and to describe the direct effect of A-10 in vitro on neutrophil a poptosis in breast cancer patients. The participants were patients with a h istologically confirmed diagnosis of breast cancer. Only those cases withou t previous treatment for breast cancer were included. Neutrophil apoptosis was assessed in breast cancer patients both morphologically and by DNA frag mentation and studied relative to healthy controls. Antineoplaston A-10 was measured using high performance liquid chromatography in urine samples col lected from the patients. Urine samples from normal women served as control s. Direct effect of antineoplaston A-10 on neutrophil apoptosis was tested in vitro after adding A-10 at a concentration of 10 ng/ml to the cellular s uspensions of breast cancer patients. Non-treated samples served as control s. Significantly higher neutrophil apoptosis levels were detected among pat ients with breast cancer with a P value <0.001, Urinary antineoplaston A-10 level is significantly negatively correlated with high apoptosis levels (P < 0.0001). In vitro, antineoplaston A-10 was found to inhibit significantl y the neutrophil apoptosis with a P value (0.0001. These findings confirm t he presence of immune defects among patients with breast cancer and such re sults should stimulate the development of new strategies to induce and augm ent immunity for the treatment of breast cancer. Antineoplaston A-10 may pr ovide rational basis for designing trials to employ its immune modulatory p otentials as adjuvant therapy in breast cancer patients, (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.