Potential utility of antineoplaston A-10 levels in breast cancer☆
Introduction
Investigation for the presence of physiologically or pathologically active peptides in urine has been going on for the past 100 years. Biologically active polypeptides have been isolated from urine, which have demonstrated hormone like activity or regulation of biologic function. Examples of biologically active peptides isolated from urine include growth factors, pituitary hormones and kinins [1], [2]. Bruzynski's earliest studies described methods for the isolation and quantitative measurement of peptides from the blood of human with renal diseases, heart diseases and obesity. Effects of peptides from human urine on cancer cells were later tested for their capacity to inhibit tumor cell growth. Early reports of an effect of these fractions on cancer cells in vitro appeared in 1973 and 1976 [3], [4]. The active principles were therefore named antineoplastons. Two types of antineoplastic compounds were found, the first consisted of strongly acidic peptides acted specifically on different kinds of tumor cells while the other type had both neutral and slightly acidic properties and displayed a broad spectrum activity. The later preparations were designed antineoplaston A and further separated into fractions A-1, A-2, A-3, A-4 and A-5 that were reported to have low cytotoxicity. A-10 was the active component present in the urinary antineoplastons and it was identified as 3-phenylacetyl amino-2,6-pepridinedione [5], [6]. Therefore, urine is a convenient and economic source for isolation of biologically active peptides. The overall objective of our program is the identification of antineoplaston A-10 present in human urine under normal and pathological conditions and determination of its potential utility as a predictive test for women who are at high risk of developing breast cancer.
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Subjects
The participants were 31 women between 30 and 67 years of age who had histologically confirmed diagnosis of breast cancer. Only those cases without previous treatment for breast cancer were included in the study. The tumor stage was classified following the International Union Against Cancer/TNM staging system [7]. All of the 17 age-matched controls had no history of cancer or any other breast disease.
Purification, detection and determination of A-10
Urine (25 ml) was purified by Amberlite XAD-2 resin by washing with water (100 ml×2), 100 ml
Results
The study included 31 patients with histologically confirmed diagnosis of breast cancer. Mean age was 41.5 years range (30–67 years). Five were stage I, ten stage IIa, nine stage IIIa and seven stage IV.
As shown in Fig. 1, significantly lower antineoplaston A-10 level has been detected among breast cancer patients relative to their healthy controls with a P value <0.001 (Student t-test). No other significant relations as regards age, histologic grade or stage of the disease were observed in
Discussion
The evaluation of tumor markers has not been shown to be of benefit in the pre-operative evaluation of breast cancer patients [9]. Although carcinoembryonic antigen (CEA) may be useful in monitoring response to therapy, it is infrequently elevated in primary breast cancer [10]. The marker that has caused the most interest is CA 15-3.
CA 15-3 is elevated in only 20% of women with primary breast cancer but elevations between 61 and 84% have been recorded for women with metastatic breast lesions,
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These data were presented at the second UICC Cancer Management Meeting, Antwerp-Belgium, April 14–18, 1999.