Journal of the National Cancer Institute
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J. Natl. Cancer Inst. · Oct 2000
Role of alpha1 acid glycoprotein in the in vivo resistance of human BCR-ABL(+) leukemic cells to the abl inhibitor STI571.
Chronic myeloid leukemia is caused by a chromosomal translocation that results in an oncogenic fusion protein, Bcr-Abl. Bcr-Abl is a tyrosine kinase whose activity is inhibited by the antineoplastic drug STI571. This drug can cure mice given an injection of human leukemic cells, but treatment ultimately fails in animals that have large tumors when treatment is initiated. We created a mouse model to explore the mechanism of resistance in vivo. METHODS Nude mice were injected with KU812 Bcr-Abl(+) human leukemic cells. After 1 day (no evident tumors), 8 days, or 15 days (tumors >1 g), mice were treated with STI571 (160 mg/kg every 8 hours). Cells recovered from relapsing animals were used for in vitro experiments. Statistical tests were two-sided. ⋯ AGP in the plasma of relapsed animals binds to STI571, preventing this compound from inhibiting the Bcr/Abl tyrosine kinase. Molecules such as erythromycin that compete with STI571 for binding to AGP may enhance the therapeutic potential of this drug.
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J. Natl. Cancer Inst. · Oct 2000
Health outcomes after prostatectomy or radiotherapy for prostate cancer: results from the Prostate Cancer Outcomes Study.
Radical prostatectomy and external beam radiotherapy are the two major therapeutic options for treating clinically localized prostate cancer. Because survival is often favorable regardless of therapy, treatment decisions may depend on other therapy-specific health outcomes. In this study, we compared the effects of two treatments on urinary, bowel, and sexual functions and on general health-related quality-of-life outcomes over a 2-year period following initial treatment. ⋯ There are important differences in urinary, bowel, and sexual functions over 2 years after different treatments for clinically localized prostate cancer. In contrast to previous reports, these outcome differences reflect treatment delivered to a heterogeneous group of patients in diverse health care settings. These results provide comprehensive and representative information about long-term treatment complications to help guide and inform patients and clinicians about prostate cancer treatment decisions.