ABSTRACT
Antineoplastons are naturally occurring cytodifferentiating agents. Chemically, they are medium and small sized peptides, amino acid derivatives and organic acids, which exist in blood, tissues and urine. Antineoplaston A-10 (3-phenylacetylamino-2,6-piperidinedione) is the first chemically identified antineoplaston. Previously we have shown a strong inverse association of urinary antineoplaston A-10 with breast cancer. This study is designed to evaluate neutrophil apoptosis in patients with breast cancer at time of diagnosis and to correlate urinary antineoplaston A-10 levels with neutrophil apoptosis and to describe the direct effect of A-10 in vitro on neutrophil apoptosis in breast cancer patients. The participants were patients with a histologically confirmed diagnosis of breast cancer. Only those cases without previous treatment for breast cancer were included. Neutrophil apoptosis was assessed in breast cancer patients both morphologically and by DNA fragmentation and studied relative to healthy controls. Antineoplaston A-10 was measured using high performance liquid chromatography in urine samples collected from the patients. Urine samples from normal women served as controls. 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 suspensions of breast cancer patients. Non-treated samples served as controls. Significantly higher neutrophil apoptosis levels were detected among patients 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 significantly the neutrophil apoptosis with a P value <0.0001. These findings confirm the presence of immune defects among patients with breast cancer and such results should stimulate the development of new strategies to induce and augment immunity for the treatment of breast cancer. Antineoplaston A-10 may provide rational basis for designing trials to employ its immune modulatory potentials as adjuvant therapy in breast cancer patients.
