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

Androgen deprivation is the mainstay of therapy for prostate cancer. LHRH agonists are an essential part of this form of treatment and may be employed as the only endocrine manipulation, or in combination with antiandrogens, i.e., maximal androgen blockade. In patients with bone metastases, maximal androgen blockade prolongs life for 3-6 months. The patient with minimal metastatic spread, however, may benefit much longer from this combination. In addition to being used permanently, maximal androgen blockade may be given intermittently. In locally advanced prostate cancer, LH-RH analogues, alone or together with antiandrogens, are presently being studied in conjunction with radical surgery or definitive irradiation. Whether such a neoadjuvant or adjuvant use postpones the time to progression has not yet been decided. The patient with lymph node metastases seems to benefit from early androgen deprivation in conjunction with radical prostatectomy, if the primary tumor is diploid.
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PMID:The combination of LH-RH analogues with other treatment modalities in prostate cancer. 1062 90

BACKGROUND: Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in men in the United States. It is estimated that over 300,000 men will have been diagnosed with prostate cancer in 1996, and more than 40,000 will have died of this disease. METHODS: The authors combined their experience with a review of the literature on management of this disease to examine the effectiveness of treatments for both localized and metastatic prostate cancer. RESULTS: Surgery and radiation therapy are potentially curative modalities for cancer still limited to the gland. Androgen ablation therapy results in stabilization or regression of metastatic disease in most instances but is not curative. Some new approaches are described for patients with hormone-refractory prostate cancer. CONCLUSIONS: Newer tumor-biology-based combinations are promising in the treatment of hormone-refractory prostate cancer, but their effect on patient survival needs to be evaluated in larger clinical trials.
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PMID:Hormonal and Chemotherapeutic Systemic Therapy for Metastatic Prostate Cancer. 1076 7

Androgen deprivation has been the standard treatment for advanced prostate cancer. With the development of antiandrogen drugs, combination hormonal therapy achieving "total androgen blockade" has been demonstrated to be superior to monotherapy for patients with low-tumor-burden metastatic disease. Combination therapy is now being used more aggressively in locally advanced disease, with phase II studies suggesting benefit as measured by prolonged disease-free survival. Phase III randomized, controlled trials currently are being conducted.
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PMID:Hormonal Therapy for Prostate Cancer: When to Use It. 1088 94

Androgen suppressive maneuvers still represent the gold standard for prostate cancer patients. However, they are associated with side effects (fatigue, sexual impotence, hot flushes, anemia, anxiety, depression and osteoporosis) all of which have a negative impact on quality of life. Nonsteroidal antiandrogens compete with dihydrotestosterone for the linkage of its own receptors. These compounds are commonly used in combination with suppressive maneuvers. However, there is a growing experience with them as monotherapy, based on the possibility to spare gonadal function and therefore prevent the effects related to its suppression. Many studies have demonstrated the feasibility and safety of this approach, which can represent a valuable alternative to suppressive maneuvers for patients wishing to retain sexual function, especially for those without distant metastases. Unfortunately, none of the comparative studies performed so far had the power to detect the equivalence between monotherapy and castration.
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PMID:Hormone therapy of prostate cancer: is there a role for antiandrogen monotherapy? 1093 69

In prostate cancer, the development of skeletal metastases is associated with a significant increase in morbidity, mainly because of severe bone pain, which eventually becomes refractory to conventional analgesia. Androgen ablation is the treatment of choice, but the majority of patients relapse within 2 to 3 years from initiation of treatment. After failure of hormone therapy, external-beam irradiation therapy is effective in the palliation of pain, but radionuclides represent an attractive and cost-effective alternative. Strontium 89 is currently the most commonly used radionuclide in the palliative management of prostate cancer metastatic to the skeleton. The rationale for the use of bisphosphonates in metastatic prostate cancer is not immediately obvious, given the predominantly osteoblastic nature of the metastatic process. The clinical use of these agents rests on a number of basic and clinical observations that provide ample evidence that, in prostate cancer, the metastatic process is associated with increased bone resorption. Evidence regarding the beneficial effects of bisphosphonates in reducing morbidity from metastatic prostate cancer is reasonably solid, although the choice of optimal bisphosphonate, mode of administration, dose, and duration of treatment must be determined in large, controlled studies before their widespread clinical use can be advocated. Available therapeutic modalities that use either radionuclides or bisphosphonates can effectively and safely be used in the palliative management of metastatic prostate cancer. Neither radionuclides nor bisphosphonates have been shown to prolong survival, but the potential of both agents to beneficially alter the metastatic process in prostate cancer is intriguing.
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PMID:The palliative management of skeletal metastases in prostate cancer: use of bone-seeking radionuclides and bisphosphonates. 1120 Feb 6

In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.
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PMID:Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prostatic epithelial cells. 1132 27

Androgen plays a critical role in the promotion and growth of prostate cancer. Androgen ablation has an expanding role in prostate cancer treatment and is now used to improve the efficacy of radiation therapy in addition to its role in treatment of metastatic disease. Here we show that androgen interferes with induction of prostate cancer cell death induced by a variety of stimuli. The effect of androgen on cell death occurs predominantly by interference with caspase activation and the inhibition of caspase cleavage in both the extrinsic and intrinsic cell death pathways. Androgen inhibited apoptosis induced by both tumor necrosis factor alpha (TNF-alpha) and by Fas activation with or without concomitant irradiation. An antiapoptotic effect was seen in the presence of R1881, dihydrotestosterone, and also 17beta-estradiol within 24 h of death induction. Sustained inhibition of apoptosis at 72 h was seen only with R1881, dihydrotestosterone, cyproterone acetate, and hydroxyflutamide. Androgen treatment inhibited activation of caspases-8, -7, and -9 by TNF-alpha +/- irradiation. Androgen attenuated BAX expression and blocked appearance of the proapoptotic p18 fragment of BAX. Androgen also abrogated BID cleavage induced by TNF-alpha + irradiation that contributed to a decrease in cytochrome c egress from mitochondria induced by TNF-alpha +/- irradiation. There was also decreased mitochondrial depolarization in response to TNF-alpha + irradiation. Production of the proapoptotic lipid metabolite ceramide was not affected by androgen, but androgen acted downstream from ceramide generation because R1881 blocked cell-death induction by bacterial sphingomyelinase. Inhibition of phosphoinositol-3-kinase activity by wortmannin induced apoptosis that was also blocked by androgen, but there was no effect on protein levels or phosphorylation of AKT, indicating that R1881 did not interact with survival signaling of phosphoinositol-3-kinase. Lastly, androgen inhibited activation of nuclear factor-kappaB during death induction, but the effect of androgen on cell death was not mediated by interference with the nuclear factor-kappaB pathway. The data suggest that androgen induced blockade of caspase activation in both intrinsic and extrinsic cell death pathways and thereby was able to protect prostate cancer cells from apoptosis induced by diverse stimuli.
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PMID:Androgen blocks apoptosis of hormone-dependent prostate cancer cells. 1145 15

Hormonal treatment is a androgenoprive therapy. Adjuvant treatment after radical prostatectomy or radiotherapy seems to have no survival benefit. Neoadjuvant hormonal treatment before local therapy has no proven survival benefit. Hormonal treatment in metastatic disease can be initiated immediately, deferred or intermittent. Androgen-deprivation is performed by castration or LHRH-analoga and/or anti-androgens. Maximal androgen-deprivation has significant more side effect and is of only limited survival bebefit for a subgroup of patients. The onset of hormonal treatment is under discussion. An increase of PSA (> 25 ng/ml) and/or occurrence of symptoms is an indication for hormonal treatment. Intermittent androgen-deprivation is under investigation as a new concept.
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PMID:[Hormone therapy of locally advanced and metastatic prostate carcinoma]. 1167 17

Prostate cancer is one of the most common malignancies and a leading cause of cancer-related death in men worldwide. In the majority of cases, prostate cancer metastases to the skeleton, in which case cancer-related bone pain becomes a major cause of morbidity. Androgen ablation is the treatment of choice for securing regression of skeletal metastases in the majority of cases. Intermittent androgen ablation is an attractive alternative, aimed at minimising adverse effects of hormone deprivation but also potentially delaying hormone-refractoriness. The development of hormone-refractoriness is heralded by a significant increase in morbidity largely because of escalating bone pain caused by the progression of the metastatic process. Skillful use of analgesics is initially successful but eventually fails to control symptoms. Localised metastases are best treated with local radiotherapy that is rapidly effective. Over the last few years, it has become clear that therapeutic modalities using bone-seeking radionuclides or bisphosphonates have been effective in the palliation of prostate cancer-related bone pain, although not affecting survival. The main limiting factor with the use of radionuclides is bone marrow suppression, also a feature of the very late stages of prostate cancer. Bisphosphonates do not carry this disadvantage. Results of large double-blind, placebo-controlled studies should be awaited, however, before advocating the widespread use of these agents in the management of patients with prostate cancer and skeletal metastases.
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PMID:Strategies for management of prostate cancer-related bone pain. 1188 45

Osteoporosis and other body composition changes are important complications of androgen deprivation therapy (ADT) for prostate cancer. Bilateral orchiectomy and gonadotropin-releasing hormone agonist treatment decrease bone mineral density and increase fracture risk. Other factors including diet and lifestyle may contribute tobone loss in men with prostate cancer. Estrogens play an important role in male bone metabolism. Androgen deprivation therapy with estrogens probably causes less bone loss than bilateral orchiectomy or gonadotropin-releasing hormone agonist treatment. Bicalutamide monotherapy increases serum estrogen levels and may also spare bone. Lifestyle modification including smoking cessation, moderation of alcohol use, and regular weight bearing exercise are recommended to decrease treatment-related bone loss. Supplemental calcium and vitamin D are also recommended. Pamidronate (Aredia), an intravenous bisphosphonate, prevents bone loss during ADT. Other bisphosphonates are probably effective but have not been studied in hypogonadal men. Androgen deprivation therapy increases fat mass and decreases muscle mass. These body composition changes may contribute to treatment-related decreases in physical capacity and quality of life.
Cancer Metastasis Rev 2002
PMID:Osteoporosis and other adverse body composition changes during androgen deprivation therapy for prostate cancer. 1246 55


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