Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A metastatic ovarian lipid cell tumor was treated with BV-CAP chemotherapy following cytoreductive surgery and VAC chemotherapy for persistent disease found at second-look laparotomy before disease progression was noted. Serum Dihydrotestosterone (DHT) levels correlated with disease status during all phases of treatment, as did serum testosterone (T) to a lesser degree. Measurement of these two hormones may provide additional useful information on the response of patients with subclinical metastatic disease to post-operative therapy.
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PMID:Treatment of metastatic lipid cell tumor of the ovary with BV-CAP and VAC chemotherapy, using serum testosterone and dihydrotestosterone as tumor markers. 246 68

Dihydrotestosterone (DHT) concentration, a marker for biochemical differentiation and possible clonal origin of prostate tumors, was measured in cancer present in lymph nodes (LN) from patients with untreated metastatic prostate cancer and compared to levels in untreated primary prostate cancer. The mean DHT of 2.23 ng/g in LN (S.E. = 0.28, N = 22) was significantly less (P less than .001) than the mean DHT of 4.8 ng/g in primary cancer (S.E. = 0.52, N = 20). Since primary prostate cancer may be admixed with stromal tissue, while lymph node represents pure epithelial cell tumor, we chose for this comparison only the 20 prostate cancer tissues that were judged by our pathologist to contain 90% or more epithelial cell tumor. Using this selection criteria, we found that prostate stroma, which has an average DHT concentration 1.18 times higher than prostate epithelia, would have an insignificant effect on primary prostate tumor DHT concentration. These data suggest that the decreased DHT in prostate tumor cells present in LN metastases may be a marker for a clone of cells with metastatic potential. These findings are consistent with previous reports from this laboratory indicating that DHT concentration less than 2.4 ng/g in primary prostate cancer is a predictor of a reduced disease-free interval following androgen blockade in advanced prostate cancer.
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PMID:Comparison of dihydrotestosterone levels in prostatic cancer metastases and primary prostate cancer. 279 34

Analogous to the impact of anti-estrogen therapy in breast cancer, anti-androgen therapy may have a greater impact on the castrate male with non-metastatic disease. The use of castration or a LHRH drug alone, does not appear to adequately suppress intra-prostatic DHT (Dihydrotestosterone) levels. Normal prostate elements appear to be more efficient than metastatic elements at converting DHT precursors to active DHT. Thus, blocking this step may be more critical for clinically localized disease. Laverdiere et al. reported a 2 year positive (+) biopsy rate of 65% with XRT alone compared to 28% when 3 months of NHT preceded radiotherapy, but 5% if NHT was continued for a total of 10.5 months of combined androgen blockade (CAB). Bolla et al. incorporated one month of NHT prior to XRT followed by 3 years of an LHRH drug. An improvement in local control, disease free survival and overall survival of nearly 20% was noted at 5 years. Thus far, these important studies demonstrate that a survival benefit may require long term adjuvant hormonal therapy. There is a need for further studies to define the optimal timing and duration of CAB and the role of XRT. Long term data recently provided by the Radiation Therapy Oncology Group (RTOG) may provide insights into criteria for defining which patients are likely to benefit the most from long term CAB.
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PMID:Current status of androgen suppression and radiotherapy for patients with prostate cancer. 1041 97

The high morbidity and mortality associated with prostate cancer (PCa) result from its tendency to metastasize to bone where it produces predominantly osteoblastic lesions. The Wnt signaling pathway plays an important role in embryogenesis, tumorigenesis, osteoblast development, and bone formation. Androgen signaling via the androgen receptor (AR) is critical in both PCa and bone cell growth. We examined the effects of androgens on cell growth and Wnt signaling in the AR-positive MDA-PCa-2b cell line and MC3T3 preosteoblasts, grown alone and in coculture. We show that the potent androgen dihydrotestosterone increases AR expression and transcriptional activity only in the preosteoblasts. Although dihydrotestosterone induced an 80% increase in PCa cell growth when the cells were grown alone, dihydrotestosterone had a more significant effect on MDA-PCa-2b cell proliferation (3.2-fold increase) when the PCa cells were cocultured with preosteoblasts. Dihydrotestosterone addition to preosteoblasts promoted Wnt-dependent transcriptional reporter activity associated with GSK3beta(S-9) phosphorylation and accumulation of nuclear beta-catenin as well as elevated Runx2 expression. In addition, the increased proliferation of PCa cells in coculture with MC3T3 cells in response to dihydrotestosterone was abrogated by the addition of either exogenous DKK-1 or sFRP-1 protein, two naturally occurring Wnt antagonists. Finally, we show that the paracrine growth-promoting effect of androgens is limited to MDA-PCa-2b cells. These data imply that Wnt signaling is involved in the androgen-regulated crosstalk between preosteoblasts and PCa cells and suggest that androgens may stimulate growth of some prostate tumor cells indirectly, via up-regulation of Wnt signaling in bone cells.
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PMID:Androgen-induced Wnt signaling in preosteoblasts promotes the growth of MDA-PCa-2b human prostate cancer cells. 1757 41