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)

This summary of the American Cancer Society Prostate Cancer Survivorship Care Guidelines targets primary care physicians who coordinate care of prostate cancer survivors with subspecialists. Prostate cancer survivors should undergo prostate-specific antigen screening every six to 12 months and digital rectal examination annually. Surveillance of patients who choose watchful waiting for their prostate cancer should be conducted by a subspecialist. Any hematuria or rectal bleeding must be thoroughly evaluated. Prostate cancer survivors should be screened regularly for urinary incontinence and sexual dysfunction. Patients with predominant urge incontinence symptoms, which can occur after surgical and radiation treatments, may benefit from an anticholinergic agent. If there is difficulty with bladder emptying, a trial of an alpha blocker may be considered. A phosphodiesterase type 5 inhibitor can effectively treat sexual dysfunction following treatment for prostate cancer. Osteoporosis screening should occur before initiation of androgen deprivation therapy, and patients treated with androgen deprivation therapy should be monitored for anemia, metabolic syndrome, and vasomotor symptoms. Healthy lifestyle choices should be encouraged, including weight management, regular physical activity, proper nutrition, and smoking cessation. Primary care physicians should be vigilant for psychosocial distress, including depression, among prostate cancer survivors, as well as the potential impact of this distress on patients' family members and partners.
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PMID:Primary Care of the Prostate Cancer Survivor. 2717 54

Cancer stem cells (CSC) are critical for initiation, metastasis, and relapse of cancers, however, the underlying mechanism governing stemness of CSC remains unknown. Herein, we have investigated the roles of phosphodiesterase 5 (PDE5) in stemness of prostate cancer cells. Both PDE5 and WW domain-containing transcription regulator protein-1 (TAZ), a core effector of Hippo pathway, are highly expressed in the PC3-derived cancer stem cells (PCSC). Either TAZ knockdown or inhibition of PDE5 activity attenuated colony formation, altered expression patterns of stem cell markers, and enhanced cisplatin cytotoxicity, resulting in attenuation of stemness in PCSC. In addition, inhibition of PDE5 activity by its specific inhibitors activates cGMP-dependent protein kinase G (PKG), which in turn induces MST/LATS kinases, resulting in cytosolic degradation of TAZ and activation of Hippo pathway. Accordingly, knockdown of TAZ almost completely abolished PDE5 inhibitor-induced attenuation in stemness in cultured PCSC, whereas knockdown of TAZ not only abolished PDE5 inhibitor-induced attenuation in stemness but also facilitated PDE5 inhibitor-induced trans-differentiation in PCSC xenografts. Together, the present study has uncovered that PDE/cGMP/PKG signal targets to Hippo/TAZ pathway in maintaining stemness of PCSC, and suggested that PDE5 inhibitors in combination with chemotherapeutic agents could effectively prevent initiation, metastasis, and relapse of prostate cancer.
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PMID:Phosphodiesterase 5/protein kinase G signal governs stemness of prostate cancer stem cells through Hippo pathway. 2717 30

Despite advances in technical and surgical approaches, erectile dysfunction (ED) remains the most common complication among prostate cancer survivors, adversely impacting quality of life. This article analyzes the concept and rationale of ED rehabilitation programs in prostate cancer patients. Emphasis is placed on the pathophysiology of ED after diagnosis and treatment of prostate cancer to understand the efficacy of rehabilitation programs in clinical practice. Available evidence shows that ED is a transient complication following prostate biopsy and cancer diagnosis, with no evidence to support rehabilitation programs in these patients. A small increase in ED and in the use of phosphodiesterase type 5 (PDE5) inhibitors was reported in patients under active surveillance. Patients should be advised that active surveillance is unlikely to severely affect erectile function, but clinically significant changes in sexual function are possible. Focal therapy could be an intermediate option for patients demanding treatment/refusing active surveillance and invested in maintaining sexual activity. Unlike radical prostatectomy, there is no support for PDE5 inhibitor use to prevent ED after highly conformal external radiotherapy or low-dose rate brachytherapy. Despite progress in the understanding of the pathophysiologic mechanisms responsible for ED in prostate cancer patients, the success rates of rehabilitation programs remain low in clinical practice. Alternative strategies to prevent ED appear warranted, with attention toward neuromodulation, nerve grafting, nerve preservation, stem cell therapy, investigation of neuroprotective interventions, and further refinements of radiotherapy dosing and delivery methods.
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PMID:Penile Rehabilitation Strategies Among Prostate Cancer Survivors. 2722 41

As the radical prostatectomy (RP) for the patient diagnosed as localized prostate cancer has been increasing, erectile dysfunction (ED) associated with RP is increased and ED after RP is a significant risk factor to reduce the quality of life for the patient after RP. Therefore, the treatment concept called penile rehabilitation was introduced and phosphodiesterase type 5 inhibitor (PDE5I) is used widely for the prostate cancer patient after RP. Generally PDE5I is considered as safe and effective drug for the prostate cancer patient after RP. Recently, a report against the general opinion that PDE5I use is safe in the patient with prostate cancer was reported and the analysis of 5-yr biochemical recurrence-free survival after RP between the PDE5I users and non-PDE5I users after bilateral nerve sparing RP showed decreased 5-yr biochemical recurrence-free survival in the PDE5I users. In addition, a longitudinal cohort study reported that sildenafil, a kind of PDE5I, use might be associated with the development of melanoma and this result suggested the possibility of adverse effect of PDE5I on some kinds of cancers as well as prostate cancer. Moreover, the studies to evaluate the influence of nitric oxide (NO) and guanosine monophosphate (cGMP) signaling pathway associated with PDE5 showed both cancer reduction and cancer development. Therefore, the role of NO and cGMP signaling pathway in cancer was reviewed based on the previous studies and suggested the necessity of further clinical studies concerning about the safety of PDE5I in prostate cancer.
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PMID:Let's rethinking about the safety of phosphodiesterase type 5 inhibitor in the patients with erectile dysfunction after radical prostatectomy. 2741 7

In the current era of the early diagnosis of prostate cancer (PCa) and the development of minimally invasive surgical techniques, erectile dysfunction (ED) represents an important issue, with up to 68% of patients who undergo radical prostatectomy (RP) complaining of postoperative erectile function (EF) impairment. In this context, it is crucial to comprehensively consider all factors possibly associated with the prevention of post-RP ED throughout the entire clinical management of PCa patients. A careful assessment of both oncological and functional baseline characteristics should be carried out for each patient preoperatively. Baseline EF, together with age and the overall burden of comorbidities, has been strongly associated with the chance of post-RP EF recovery. With this goal in mind, internationally validated psychometric instruments are preferable for ensuring proper baseline EF evaluations, and questionnaires should be administered at the proper time before surgery. Careful preoperative counselling is also required, both to respect the patient's wishes and to avoid false expectations regarding eventual recovery of baseline EF. The advent of robotic surgery has led to improvements in the knowledge of prostate surgical anatomy, as reflected by the formal redefinition of nerve-sparing techniques. Overall, comparative studies have shown significantly better EF outcomes for robotic RP than for open techniques, although data from prospective trials have not always been consistent. Preclinical data and several prospective randomized trials have demonstrated the value of treating patients with oral phosphodiesterase 5 inhibitors (PDE5is) after surgery, with the concomitant potential benefit of early re-oxygenation of the erectile tissue, which appears to be crucial for avoiding the eventual penile structural changes that are associated with postoperative neuropraxia and ultimately result in severe ED. For patients who do not properly respond to PDE5is, proper counselling regarding intracavernous treatment should be considered, along with the further possibility of surgical treatment for ED involving the implantation of a penile prosthesis.
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PMID:Postprostatectomy Erectile Dysfunction: A Review. 2757 91

Erectile dysfunction (ED) is the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. It is common, affecting at least 12 million U.S. men. The five-question International Index of Erectile Function allows rapid clinical assessment of ED. The condition can be caused by vascular, neurologic, psychological, and hormonal factors. Common conditions related to ED include diabetes mellitus, hypertension, hyperlipidemia, obesity, testosterone deficiency, and prostate cancer treatment. Performance anxiety and relationship issues are common psychological causes. Medications and substance use can cause or exacerbate ED; antidepressants and tobacco use are the most common. ED is associated with an increased risk of cardiovascular disease, particularly in men with metabolic syndrome. Tobacco cessation, regular exercise, weight loss, and improved control of diabetes, hypertension, and hyperlipidemia are recommended initial lifestyle interventions. Oral phosphodiesterase-5 inhibitors are the firstline treatments for ED. Second-line treatments include alprostadil and vacuum devices. Surgically implanted penile prostheses are an option when other treatments have been ineffective. Counseling is recommended for men with psychogenic ED.
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PMID:Erectile Dysfunction. 2792 75

Erectile dysfunction (ED) is a worldwide commonly reported condition; epidemiological data showed a prevalence ranging from 2.3 to 53.4% within different population subsets. In this context, the advent of phosphodiesterase type 5 inhibitors (PDE5is) in the second mid of 1990s has deeply changed the treatment scenario of this bothersome condition. Being user-friendly compounds with an excellent overall safety profile, PDE5is emerged as the first-line treatment for ED, thus overcoming topical alprostadil and intracavernous injections (ICIs). However, available data on treatment-utilization patterns and medical prescriptions of PDE5is showed a range of as wide as 22-78% of patients reporting to purchase PDE5is even without a proper medical prescription. Moreover, an increase in the recreational use of PDE5is among young men has been observed in the last decades, with a worrisome diffusion of potential health-risky behaviours associated with this habit. Indeed, treatment of ED should carefully follow internationally based clinical guidelines to avoid inappropriate drug prescriptions, which may eventually expose treated patients to drug-related side effects. Thereof, a careful assessment of the so-called modifiable and reversible ED risk factors along with a patient-tailored screening for potential contraindications to the treatment itself should be performed in every case. Lastly, although conclusive data still lack, the potential association between life-risky PDE5is side effects (i.e. cardiovascular adverse events, melanoma skin cancer and worsening of prostate cancer outcomes) should be carefully taken into account when counselling patients for ED treatment.
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PMID:Medical treatment of erectile dysfunction: too many medical prescriptions? 2870 3

Low dose rate brachytherapy (LDR-Br) with radioactive isotopes is a curative treatment and has shown to be comparable for the management of localized prostate cancer (PCa) to more conventional treatments such as radical prostatectomy or external beam radiotherapy, but with fewer side effects. The aim of this study is to show the global, specific and biochemical recurrence-free survival in 193 patients undergoing low dose rate Brachytherapy with permanent implants with iodine 125 and analyze the quality of life impact. 193 patients with localized PCa were consecutively treated over a period of 10 years (2005-2015). All of them were followed up on levels of prostate specific antigen (PSA) and 68 of them completed a quality of life survey. The average age was 62.8 years and the average PSA was 6.4 ng/dl at the time of Br. 29.5% of patients were classified as intermediate risk, with a Gleason score sum of 7 and/or a PSA between 10 and 20 ng/dl. Mean follow-up was 64.2 months; overall, specific and biochemical recurrence-free survival were 92.8%, 99.0% and 90.2% respectively. The most significant changes in the quality of life recorded were urinary incontinence, urinary and bowel irritative symptoms, in the first 6 months after brachytherapy. Sexual function shows significant changes but all with favorable response using phosphodiesterase inhibitors. This series of patients with PCa shows similar biochemical free survival rates BFSR in low risk patients to external beam radiotherapy and radical prostatectomy, but better BFSR in intermediate risk patients. The impact in the quality of life was significant in urinary incontinence, urinary irritate symptoms, and sexual function, but they were transitory with the exception of sexual function.
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PMID:[Low dose rate brachytherapy in low and middle risk prostate cancer: Results and impact on quality of life with 5 year follow up.] 2920 61

Penile erection is a neurovascular event and neurologic or vascular disturbances are major causes of erectile dysfunction (ED). Radical prostatectomy for prostate cancer not only induces cavernous nerve injury (CNI) but also results in cavernous angiopathy, which is responsible for poor responsiveness to oral phosphodiesterase-5 inhibitors. Dickkopf2 (DKK2) is known as a Wnt signaling antagonist and is reported to promote mature and stable blood vessel formation. Here, we demonstrated in CNI mice that overexpression of DKK2 by administering DKK2 protein or by using DKK2-Tg mice successfully restored erectile function: this recovery was accompanied by enhanced neural regeneration through the secretion of neurotrophic factors, and restoration of cavernous endothelial cell and pericyte content. DKK2 protein also promoted neurite outgrowth in an ex vivo major pelvic ganglion culture experiment and enhanced tube formation in primary cultured mouse cavernous endothelial cells and pericytes co-culture system in vitro. In light of critical role of neuropathy and angiopathy in the pathogenesis of radical prostatectomy-induced ED, reprogramming of damaged erectile tissue toward neurovascular repair by use of a DKK2 therapeutic protein may represent viable treatment option for this condition.
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PMID:Dickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury. 2925 7

Recent studies have examined the impact of phosphodiesterase type 5 inhibitors (PDE5-Is) use on the risk of prostate cancer, and biochemical recurrence (BCR) in prostate cancer patients, but the results were inconsistent. A meta-analysis was conducted to assess the associations with all published studies. Databases (PubMed, Web of Science and MEDLINE) were retrieved to identify relevant studies which explored the impact of PDE5-Is use on the risk of prostate cancer, and BCR in prostate cancer patients. The summary results along with 95% confidence intervals (CIs) were calculated. Nine articles were eligible for the inclusion criteria. The pooled analysis showed that PDE5-Is use was not related to the increased risk of prostate cancer (odds ratio (OR), 0.71; 95% CI, 0.40-1.29). Moreover, PDE5-Is use was not linked to BCR risk in prostate cancer patients with erectile dysfunction (ED) following radical prostatectomy or radiation therapy (relative risk (RR), 1.09; 95% CI, 0.89-1.34). The heterogeneity test suggested moderate heterogeneity across studies. PDE5-Is use does not influence the risk of prostate cancer, and BCR in prostate cancer patients. More well-designed studies are warranted to confirm the findings of our analyses.
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PMID:Effect of phosphodiesterase type 5 inhibitors on prostate cancer risk and biochemical recurrence after prostate cancer treatment: A systematic review and meta-analysis. 3044 68


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