Serum interleukin-6 levels in metastatic renal cell cancer: correlation with survival but not an independent prognostic indicator.
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Biomedical subjects
Publications and source records attributed to W M Stadler.
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A total of 25 patients with metastatic renal cancer were treated on a phase II protocol with 5 days of continuous-infusion fluorodeoxyuridine (FUDR), (0.1 mg/kg daily) together with high-dose oral leucovorin (100 mg 4 h) and daily x6 high-dose interferon-alpha 2b (30 x 10(6) IU/m2). Despite the good performance status of the patients and the inclusion of 14 previously untreated patients in the cohort, no response was observed among the 20 evaluable patients. Toxicities included high fever, moderate anemia, transient leukopenia, transient and mild elevations of transaminases, and moderate to severe nausea, vomiting, diarrhea, and mucositis. There were also two episodes each of confusion, fluid retention, and pancreatitis and one episode of increased creatinine levels. During the study three deaths occurred, two of which were possibly therapy-related. Despite previous reports of activity of FUDR in metastatic renal cancer, the present regimen cannot be recommended.
Prostate cancers account for 43% of all cancers diagnosed in American men. It is estimated that in 1996, 317,000 new cases of prostate cancer were diagnosed and 41,000 men died of the disease. The challenge of treating prostate cancer lies in accurately distinguishing those histologically-localized cancers which will complete metastatic progression from those that will remain indolent. At this time, we lack appropriate histological markers to make such distinctions, therefore, it is often difficult to accurately predict the clinical course of an individual patient's disease. There is growing evidence that a critical event in the progression of a tumor cell from a non-metastatic to metastatic phenotype is the loss of function of metastasis-suppressor genes. These genes specifically suppress the ability of a cell to metastasize. Work from several groups has demonstrated that human chromosomes 8, 10, 11 and 17 encode prostate cancer metastasis suppressor activities. As a result of these efforts the first prostate cancer metastasis-suppressor gene, KAI1, was identified and mapped to the p11-2 region of chromosome 11. In subsequent studies, an additional gene encoded by the same region, CD44 was also determined to have metastasis-suppressor activity. Recent studies have shown a correlation between decreased expression of KAI1 and CD44 and an increased malignant potential of prostate cancers. It is anticipated that the identification of other metastasis suppressor genes may allow for the development of diagnostic markers useful in the clinical substaging of individual tumors. This manuscript is intended to present our perspective on the importance of these genes in the understanding of prostate cancer progression. More importantly, we present new findings from our laboratory's effort to identify the metastasis-suppressor genes encoded by human chromosome 17. Specifically we report the strategy currently being used to evaluate a series of candidate genes and the approach being utilized to pinpoint the metastasis-suppressor region on human chromosome 17.