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A few clinical investigations suggest that while primary breast cancer surgical removal favorably modifies the natural history for some patients, it may also hasten the metastatic development for others. The concepts underlying this disease paradigm, i.e. tumor homeostasis, tumor dormancy and surgery-driven enhancement of metastasis development, have a long(More)
Fluoropyrimidines induce cytotoxicity, in part, by inhibiting the proliferation-coordinated enzyme thymidylate synthase (TS), which is essential for DNA synthesis. Tumor TS levels are clinically predictive of post-surgical tumor recurrence and of response to fluoropyrimidine chemotherapy. Fluoropyrimidine drug toxicity and efficacy each vary reproducibly in(More)
We studied the relative RNA expression of clock genes throughout one 24-hour period in biopsies obtained from the oral mucosa and skin from eight healthy diurnally active male study participants. We found that the human clock genes hClock, hTim, hPer1, hCry1, and hBmal1 are expressed in oral mucosa and skin, with a circadian profile consistent with that(More)
In a retrospective study of 44 premenopausal women who underwent resection of a primary breast cancer and were followed for 5 to 12 years, disease recurrence and metastasis were more frequent and more rapid in women who had been operated upon during the perimenstrual period (days 0-6 and 21-36 of the menstrual cycle). By multivariate analysis, the time of(More)
Cisplatin-based therapy results in a cumulative anemia that is disproportionate to the effects on other blood cells. The severity of this treatment-induced anemia and the resultant transfusion requirement in cancer patients correlate with cisplatin-induced renal tubular dysfunction. Observed/expected serum erythropoietin (EPO) ratios decline with(More)
Animal studies have indicated that the time of administration of adriamycin and cisplatin, two widely used anticancer drugs, has a profound effect on their toxicity. This effect in cancer chemotherapy was studied in 31 patients with advanced ovarian cancer. Patients received at least eight monthly courses of adriamycin that were followed 12 hours later by(More)
Circadian rhythms of DNA synthesis and cellular proliferation in the gastrointestinal mucosa have been well documented in animal models. This investigation was designed to determine whether similar rhythms could be demonstrated in the human rectal epithelium: 24 studies were performed in 16 healthy men under fasting (n = 14) and fed (n = 10) conditions.(More)
To explain bimodal relapse patterns observed in breast cancer data, we have proposed that metastatic breast cancer growth commonly includes periods of temporary dormancy at both the single cell phase and the avascular micrometastasis phase. The half-lives of these states are 1 and 2 years respectively. We also suggested that surgery to remove the primary(More)