Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin (IL)-6 may play possible roles in the proliferation and metastasis of cancer cells, in the development of osteolysis and humoral hypercalcemia, and in the regulation of estrogen production in breast cancer tissues. IL-6 is also suggested to be a cachectic factor in cancer patients. A decrease in serum IL-6 levels induced by medroxyprogesterone acetate (MPA) has been reported to correlate with a reversion of body weight loss in patients with advanced breast cancer. To elucidate the mechanisms of action of the anti-cachectic effect of MPA its effects on IL-6 secretion from the KPL-4 cell line, the first human breast cancer cell line to secrete IL-6 and to induce cachexia, were explored. It has been suggested that an inhibitory effect of MPA on IL-6 secretion from breast cancer cells causes the anti-cachectic effect of MPA. Our other studies have revealed that 5'-fluorouridine (5'-DFUR) inhibits the growth of KPL-4 tumors and decreases IL-6 levels in both serum and tumor tissues. Decreasing serum IL-6 levels resulted in alleviation of body weight loss. Docetaxel increased IL-6 levels in both serum and KPL-4 tumors, but combined treatment with docetaxel and 5'-DFUR resulted not only in a potent antitumor effect but also in a drastic decrease of serum IL-6 levels. In the present paper the possible roles of IL-6 in the development and progression of breast cancer are reviewed, and the regulatory mechanisms of IL-6 secretion from breast cancer cells and the possible clinical implications of decreasing IL-6 secretion by therapeutic agents are discussed.
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PMID:Regulation of interleukin-6 secretion from breast cancer cells and its clinical implications. 1102 83

Although the antineoplastic activity of calcitriol in prostate cancer has been known for many years, the agent's use in oncology has been prevented because of the occurrence of hypercalcemia with daily administration. High-dose pulse administration of calcitriol has the potential to improve the therapeutic index of calcitriol. Results of a phase II study of calcitriol and docetaxel (Taxotere(R)) suggest that this combination may have utility in androgen-independent prostate cancer (AIPC). DN-101, a high-dose (15 mug) formulation of calcitriol suitable for use in oncology, is now being tested in a randomized trial (AIPC Study of Calcitriol Enhancing Taxotere). This formulation of calcitriol could become an important new tool for improving the efficacy of docetaxel in the treatment of AIPC and would join the ranks of other nuclear receptor ligands in cancer treatment. Investigations of DN-101 in the treatment of a broad range of tumor types and in combination with a variety of agents are an exciting new area of research.
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PMID:A New Formulation of Calcitriol (DN-101) for High-Dose Pulse Administration in Prostate Cancer Therapy. 1698 49

Docetaxel is becoming standard therapy for androgen-independent prostate cancer (AIPC), and investigational agents are being added to docetaxel to assess potential additive effects and synergy. Although one of these agents, calcitriol, has repeatedly demonstrated antiproliferative properties against cancer of the prostate, breast, colon, and lung, the antineoplastic activity of calcitriol requires superphysiologic levels. Unfortunately, chronic exposure to superphysiologic levels of calcitriol causes hypercalcemia and resulting toxicity. Therefore, a host of analogues of calcitriol have been investigated for antineoplastic function, including intermittent dose-intense calcitriol, or DN-101. Because of encouraging results from phase II studies of DN-101 combined with docetaxel, the ASCENT (AIPC Study of Calcitriol Enhancement of Taxotere) phase II trial investigated docetaxel plus DN-101 versus docetaxel plus placebo in 250 men with metastatic AIPC and an abnormal baseline prostate-specific antigen (PSA) level. Although the ASCENT trial did not achieve its primary endpoint for increased PSA response, there was a significant trend in PSA response rate in the DN-101 arm. DN-101 in combination with docetaxel seems to improve overall survival and, interestingly, has a favorable safety profile compared with docetaxel alone. The DN-101/docetaxel combination is currently being studied in a much larger international trial, ASCENT-2.
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PMID:Recent Progress in the Treatment of Advanced Prostate Cancer With Intermittent Dose-Intense Calcitriol (DN-101). 1739 66