Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orchiectomy and estrogens have been used for over 50 years in the treatment of advanced prostatic cancer. Although orchiectomy is a simple procedure, it may cause psychological stress. Oral estrogen therapy is as effective as orchiectomy in terms of cancer inhibitory effect, but its acceptance as primary hormonal treatment is overshadowed by an increased risk of cardiovascular complications. Parenteral estrogen, polyestradiol phosphate (PEP), is effective, but also associated with cardiovascular complications, although to a lesser extent. During the last 20 years, well tolerated luteinizing hormone releasing hormone (LHRH) analogues have been replacing orchiectomy and estrogens. Efforts have been made to increase the efficacy of the treatment by adding antiandrogens to LHRH analogues and also to orchiectomy (combined androgen blockade, CAB). However, the efficacy of LHRH analogues and CAB has not proved to be superior to that of simple orchiectomy and, moreover, they are expensive treatment modalities. Orchiectomy and LHRH analogues are associated with negative effects on bone mass and may cause osteoporosis, whereas PEP treatment has an opposite effect. Parenteral polyestradiol phosphate is still a cheap potential treatment for advanced prostatic cancer, but further studies should be conducted to establish its future role, e.g. combining acetylsalicylic acid to prevent cardiovascular complications.
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PMID:The role of parenteral polyestradiol phosphate in the treatment of advanced prostatic cancer on the threshold of the new millennium. 1023 Jun 77

Prostate cancer screening and intervention remain controversial, despite significant strides in the detection and treatment of this common malignancy. False-positive results from the test for prostate specific antigen (PSA) lead to unnecessary workups and biopsies, as well as psychological stress for patients. Radial prostatectomy remains the most effective treatment for organ-confined cancer, yet many patients opt for the opt for the organ-sparing advantage of radiation therapy. Others may opt for unproven interventions such as cryoablation. Recently-developed tools designed for use with PSA testing are helping to improve screening accuracy in the lower tier of serum total PSA (2.5 to 10.0 ng/mL).
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PMID:Refined testing and targeted therapy lead new fight against prostate cancer. Interview by Wayne Kuznar. 1049 27

This paper gives an overview of our own studies and the literature on the biosynthesis and metabolism of estrogens in elderly men, the estrogen action in the male, and the clinical usefulness of estrogen therapy, including the phytoestrogens. Finally, the paper includes a short review of our knowledge of xenoestrogens and men's sexual health. A strong estrogen-deficient status is seen in male patients with mutations of the estrogen receptors or in cases of deviations of the aromatase gene. On the other hand, there are no clear age-dependent changes in estrogen secretion. But, in men with disorders of glucose metabolism and also of increased body mass index, the serum estrogen concentrations are significantly elevated. There are also strong positive correlations between serum estrogen levels and bone density, including prevalence of fractures and mood in men. New fields of interest are natural fatty esters of endogenous estrogens, e.g. lipoprotein-associated estrogens, and the role and clinical significance of tissue-specific, local estrogen biosynthesis (e.g. different promoters of the aromatase gene). Exogenous estrogen treatment is focused today on patients with normal testosterone and low levels of circulating estrogens documented on several occasions and with clinical symptoms of hormone deficiency; male-to-female transsexuals; and selected patients with prostate cancer. Some clinical studies show the benefits of estrogen treatment on some cardiovascular parameters and for treating selected signs of mental stress. An indirect estrogen replacement can occur if dehydroepiandrosterone is given orally to men. The clinical usefulness of dissociated estrogens, including non-feminizing estrogens and selective estrogen receptor modulators, is still an open question. The beneficial action of phytoestrogens in lowering the clinical symptoms of benign prostatic hyperplasia is well documented. Finally, the question about the definitive influence of so-called endocrine disruptors (xenoestrogens) on sexual functions in men is also discussed.
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PMID:Is there a role for estrogens in the maintenance of men's health? 1263 73

Androgen deprivation therapy for prostate cancer is associated with several complications, including loss of libido, hot flashes, night sweats, psychological stress, osteoporosis, anemia, fatigue, loss of muscle mass, glucose intolerance, and changes in lipid profile. The natural history of prostate cancer while on such therapy is the attainment of an incurable androgen-independent state. Early diagnosis by prostate-specific antigen screening, longer life expectancies, and a penchant for immediate therapy pose a problem where clinicians have to balance the potential benefits of early hormonal therapy with the risks of development of these metabolic and psychological complications. Intermittent androgen deprivation offers clinicians a prospect to improve quality of life in patients with prostate cancer by harmonizing the benefits of androgen ablation with a reduction in treatment-related side effects and expenditure. In this review we discuss the challenges and opportunities of this mode of therapy and shed light on some of the underlying molecular mechanisms.
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PMID:Intermittent androgen deprivation therapy for prostate cancer. 1516 84

We investigate the association between psychological stress and breast cancer and, as oestrogen may provide a common mechanism, the association between stress and prostate cancer. A prospective study of 991 women and 5743 men employed in Scotland in the 1970s provided data. Risk exposure was measured by questionnaire and physical examination, routine data collection provided cancer outcomes over the subsequent 30 years. There was weak evidence of elevated incidences in those reporting moderate (breast cancer: hazard ratio [HR] 2.16, 95% CI 1.00-4.71; prostate cancer: HR 1.65, 95% CI 1.20-2.27) and high stress (breast cancer: HR 1.92, 95% CI 0.81-4.55; prostate cancer: HR 1.35, 95% CI 0.87-2.10) compared to those reporting low stress. These estimates are adjusted for socioeconomic circumstances and health-related behaviours. With no dose-response relationship and no established mechanism linking stress with breast and prostate cancer, confounding is the parsimonious explanation of these findings.
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PMID:The role of self-reported stress in the development of breast cancer and prostate cancer: a prospective cohort study of employed males and females with 30 years of follow-up. 1733 53

The population of Leningrad suffered from severe starvation, cold and psychological stress during the siege in World War II in 1941-1944. We investigated the long-term effects of the siege on cancer mortality in 3,901 men and 1,429 women, born between 1910 and 1940. All study subjects were residents of St. Petersburg, formerly Leningrad, between 1975 and 1982. One third of them had experienced the siege as children, adolescents or young adults (age range, 1-31 years at the peak of starvation in 1941-1942). Associations of siege exposure with risk of death from cancer were studied using a multivariable Cox regression, stratified by gender and period of birth, adjusted for age, smoking, alcohol and social characteristics, from 1975 to 1977 (men) and 1980 to 1982, respectively (women), until the end of 2005. Women who were 10-18 years old at the peak of starvation were taller as adults (age-adjusted difference, 1.7 cm; 95% CI, 0.5-3.0) and had a higher risk of dying from breast cancer compared with unexposed women born during the same period (age-adjusted HR, 9.9; 95% CI, 1.1-86.5). Mortality from prostate cancer was nonsignificantly higher in exposed men. The experience of severe starvation and stress during childhood and adolescence may have long-term effects on cancer in surviving men and women.
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PMID:Cancer mortality in women and men who survived the siege of Leningrad (1941-1944). 1904 20

Prostate cancer patients often have increased levels of psychological stress or anxiety, but the molecular mechanisms underlying the interaction between psychological stress and prostate cancer as well as therapy resistance have been rarely studied and remain poorly understood. Recent reports show that stress inhibits apoptosis in prostate cancer cells via epinephrine/beta2 adrenergic receptor/PKA/BAD pathway. In this study, we used experimental data on the signaling pathways that control BAD phosphorylation to build a dynamic network model of apoptosis regulation in prostate cancer cells. We then compared the predictive power of two different models with or without the role of Mcl-1, which justified the role of Mcl-1 stabilization in anti-apoptotic effects of emotional stress. Based on the selected model, we examined and quantitatively evaluated the induction of apoptosis by drug combination therapies. We predicted that the combination of PI3K inhibitor LY294002 and inhibition of BAD phosphorylation at S112 would produce the best synergistic effect among 8 interventions examined. Experimental validation confirmed the effectiveness of our predictive model. Moreover, we found that epinephrine signaling changes the synergism pattern and decreases efficacy of combination therapy. The molecular mechanisms responsible for therapeutic resistance and the switch in synergism were explored by analyzing a network model of signaling pathways affected by psychological stress. These results provide insights into the mechanisms of psychological stress signaling in therapy-resistant cancer, and indicate the potential benefit of reducing psychological stress in designing more effective therapies for prostate cancer patients.
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PMID:Systems modeling of anti-apoptotic pathways in prostate cancer: psychological stress triggers a synergism pattern switch in drug combination therapy. 2433 59