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Lower urinary tract symptoms (LUTS) and hematuria are common symptoms in men with neoplasms, mainly affecting the elderly population. Prostatic arterial embolization (PAE) is a minimally invasive procedure that has shown promising results in managing LUTS and massive intractable prostatic hematuria in patients with benign prostatic hyperplasia (BPH) and prostate cancer (PCa). A few studies, however, have provided valuable insights into the durability and efficacy of PAE focusing on the long-term effectiveness, quality of life, and cancer-specific control of hemostasis and urinary symptoms. As a result of concomitant cardiovascular conditions, these patients often take anticoagulants or antithrombotics, which can worsen their hematuria and clinical status. Transurethral resection of the prostate (TURP) is considered a very high-risk procedure, even without massive bleeding, and requires discontinuation of vitamin K antagonists and antiplatelet therapies. Such patients usually have their surgery postponed, and PAE should be considered a safe alternative treatment. We aimed to report a narrative review from 1976 to June 2023 of the current state of PAE for massive and intractable hematuria, highlighting recent developments in this technique, including prospective cohort studies, and focusing on long-term outcome, safety, and complication management of patients with prostatic neoplasms who develop significant hemorrhagic symptoms. Additionally, we present a case report and a simple algorithm for treating intractable bleeding in a 92-year-old man with PCa and massive hematuria.
The PTEN tumor suppressor gene is frequently inactivated in human prostate cancer. Using Osr1 (odd skipped related 1)-Cre mice, we generated a novel conditional Pten knockout mouse strain, Pten(LoxP):Osr1-Cre. Conditional biallelic and monoallelic Pten knockout mice were viable. Deletion of Pten expression was detected in the prostate of Pten(LoxP/LoxP):Osr1-Cre mice as early as 2 weeks of age. Intriguingly, Pten(LoxP/LoxP):Osr1-Cre mice develop high-grade prostatic intraepithelial neoplasms (PINs) with high penetrance as early as one-month of age, and locally invasive prostatic tumors after 12-months of age. Pten(LoxP/+):Osr1-Cre mice show only mild oncogenic changes after 8-weeks of age. Castration of Pten(LoxP/LoxP):Osr1-Cre mice shows no significant regression of prostate tumors, although a shift of androgen receptor (AR) staining from the nuclei to cytoplasm is observed in Pten null tumor cells of castrated mice. Enhanced Akt activity is observed in Pten null tumor cells of castrated Pten(LoxP/LoxP):Osr1-Cre. This study provides a novel mouse model that can be used to investigate a primary role of Pten in initiating oncogenic transformation in the prostate and to examine other genetic and epigenetic changes that are required for tumor progression in the mouse prostate.
Prostate is a male sex-accessory organ. The prostatic epithelia consist primarily of basal and luminal cells that differentiate from embryonic urogenital sinus epithelia. Prostate tumors are believed to originate in the basal and luminal cells. However, factors that promote normal epithelial differentiation have not been well elucidated, particularly for bone morphogenetic protein (Bmp) signaling. This study shows that Bmp signaling prominently increases during prostatic differentiation in the luminal epithelia, which is monitored by the expression of phosphorylated Smad1/5/8. To elucidate the mechanism of epithelial differentiation and the function of Bmp signaling during prostatic development, conditional male mutant mouse analysis for the epithelial-specific Bmp receptor 1a (Bmpr1a) was performed. We demonstrate that Bmp signaling is indispensable for luminal cell maturation, which regulates basal cell proliferation. Expression of the prostatic epithelial regulatory gene Nkx3.1 was significantly reduced in the Bmpr1a mutants. These results indicate that Bmp signaling is a key factor for prostatic epithelial differentiation, possibly by controlling the prostatic regulatory gene Nkx3.1.
Genitourinary (GU) cancers are among the most prevalent neoplasms in the world, with bladder cancers constituting 3% of global cancer diagnoses. However, several pathogenetic mechanisms remain controversial and unclear. Claudins, for example, have been shown to play a significant role in several cancers of the human body. Their role in GU cancers has not been extensively studied. Aberrant expression of claudins -1, -2, -3, -4, -7, and -11 has been expressed in urothelial cell carcinomas. In prostate cancers, altered levels of claudins -1, -2, -3, -4, and -5 have been reported. Furthermore, the levels of claudins -1, -2, -3, -4, -6, -7, -8, and -10 have been studied in renal cell carcinomas. Specifically, claudins -7 and -8 have proven especially useful in differentiating between chromophobe renal cell carcinomas and oncocytomas. Several of these claudins also correlate with clinicopathologic parameters and prognosis in GU cancers. Although mechanisms underpinning aberrant expression of claudins in GU cancers are unclear, epigenetic changes, tumor necrosis factor-ɑ, and the p63 protein have been implicated. Claudins also provide therapeutic value through tailored immunotherapy via molecular subtyping and providing therapeutic targets, which have shown positive outcomes in preclinical studies. In this review, we aim to summarize the literature describing aberrant expression of claudins in urothelial, prostatic, and renal cell carcinomas. Then, we describe the mechanisms underlying these changes and the therapeutic value of claudins. Understanding the scope of claudins in GU cancers paves the way for several diagnostic, prognostic, and therapeutic innovations.
The transcription factor LMO2 is involved in vascular and hematopoietic development and hematolymphoid neoplasia. We have demonstrated that LMO2 is expressed nearly ubiquitously in native and neoplastic vasculature, including lymphatics. LMO2 reactivity is otherwise virtually absent in nonhematolymphoid tissues except in breast myoepithelium, prostatic basal cells, and secretory phase endometrial glands. Vasculature is LMO2- in adult and fetal heart, brain of older adults, hepatic sinusoids, and hepatocellular carcinoma. LMO2 is uniformly expressed in benign vascular and lymphatic neoplasms and in most malignant vascular neoplasms with the exception of epithelioid vascular neoplasms of pleura and bone. Among nonvascular neoplasms, LMO2 reactivity is present in giant cell tumor of tendon sheath, juvenile xanthogranuloma, a subset of gastrointestinal stromal tumors, small round blue cell tumors, and myoepithelial-derived neoplasms. The restricted expression pattern, nuclear localization, and crisp staining of LMO2 in paraffin blocks make it an attractive candidate for the diagnostic immunohistochemistry laboratory.
Prostate cancer is the most commonly diagnosed cancer among men in the Western world. Although localized disease can be effectively treated with established surgical and radiopharmaceutical treatments options, the prognosis of castration-resistant advanced prostate cancer is still disappointing. The objective of this study was to review the role of angiogenesis in prostate cancer and to investigate the effectiveness of anti-angiogenic therapies. A literature search of clinical trials testing the efficacy of anti-angiogenic therapy in prostate cancer was performed using Pubmed. Surrogate markers of angiogenic activity (microvessel density and vascular endothelial growth factor A (VEGF-A) expression) were found to be associated with tumor grade, metastasis, and prognosis. Six randomizedstudies were included in this review: two phase II trials on localized and hormone-sensitive disease (n = 60 and 99 patients) and four phase III trials on castration-resistant refractory disease (n = 873 to 1224 patients). Although the phase II trials showed improved relapse-free survival and stabilisation of the disease, the phase III trials found increased toxicity and no significant improvement in overall survival. Although angiogenesis appears to have an important role in prostate cancer, the results of anti-angiogenic therapy in castration-resistant refractory disease have hitherto been disappointing. There are various possible explanations for this lack of efficacy in castration-resistant refractory disease: redundancy of angiogenic pathways, molecular heterogeneity of the disease, loss of tumor suppressor protein phosphatase and tensin homolog (PTEN) expression as well as various VEGF-A splicing isoforms with pro- and anti-angiogenic activity. A better understanding of the molecular mechanisms of angiogenesis may help to develop effective anti-angiogenic therapy in prostate cancer.
Purpose: A recent meta-analysis in patients with non-small cell lung cancer showed no difference between whole-body magnetic resonance imaging (WBMRI) and positron emission tomography/computed tomography (PET/CT), but no such study is available for prostate cancer (PCa). This study aimed to compare WBMRI and PET/CT for bone metastasis detection in patients with PCa. Materials and Methods: PubMed, Embase, and the Cochrane library were searched for papers published up to April 2020. The population was the patients with untreated prostate cancer diagnosed by WBMRI or PET/CT. The outcomes were the true positive and negative and false positive and negative rates for WBMRI and PET/CT. The summarized sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratios (DOR) were calculated with their 95% confidence intervals (CIs). Results: Four prospective and one retrospective study are included (657 patients). Significant differences are observed between WBMRI and PET/CT for sensitivity (WBMRI/PET/CT: 0.896; 95% CI: 0.813-0.987; P = 0.025) and NLR (WBMRI/PET/CT: 2.38; 95% CI: 1.13-5.01; P = 0.023), but not for specificity (WBMRI/PET/CT: 0.939; 95% CI: 0.855-1.031; P = 0.184) and PLR (WBMRI/PET/CT: 0.42; 95% CI: 0.08-2.22; P = 0.305). WBMRI has a similar a DOR compared with PET/CT (WBMRI/PET/CT: 0.13; 95% CI: 0.02-1.11; P = 0.062). The summary area under the receiver operating characteristic curves for WBMRI is 0.88 (standard error: 0.032) and 0.98 (standard error: 0.013) for PET/CT for diagnosing bone metastases in PCa. Conclusion: PET/CT presents a higher sensitivity and NLR for the bone metastasis detection from PCa, whereas no differences are found for specificity and PLR, compared with WBMRI.
After radical prostatectomy (RP) or radiotherapy (RT) for prostate cancer, erectile dysfunction (ED) is the main complication next to urinary incontinence, affecting quality of life. The pathophysiology of ED after these treatments is believed to include neuropraxia causing reduced oxygenation and structural changes of the tissue in the corpora cavernosa. Next to the option of sparing the nerves during RP, research has been focusing on methods for penile rehabilitation after RP and RT, since it occurs often, even after nerve-sparing techniques were used. In animal studies, the use of phosphodiesterase type 5 inhibitors (PDE5i) after cavernous nerve damage is supported, but results in human studies are contradictory. Non-medical treatment options such as vacuum device therapy, hyperbaric oxygen therapy, yoga, aerobic, or pelvic floor training may be helpful, but evidence is scarce. Clear guidelines for penile rehabilitation are not yet available. However, care and support for ED after RP and RT is highly demanded by a large group of patients, so measures have to be taken even though the evidence is not strong yet. In this systematic review, an overview of the literature for penile rehabilitation and treatment options for ED after RP and RT is provided, using only randomized controlled trials (RCT).
Previous studies regarding the relationship between legume intake and risk of prostate cancer have reported inconsistent results. We conducted a meta-analysis of prospective cohort studies to summarize evidence on this association. A systematic literature search of articles published through June 2016 was performed using PubMed and Web of Science databases. The combined relative risk (RR) with its 95% confidence interval (CI) for the highest versus the lowest intake of legumes was calculated with a random-effects model. Dose-response meta-analysis was also performed for the studies that provided at least three levels of legume consumption. Ten articles (eight cohorts) reporting 281,034 individuals and 10,234 incident cases were identified. The individuals with high consumption of legumes compared with the reference group experienced a significantly reduced risk for developing prostate cancer (RR: 0.85 [95% CI 0.75-0.96], P = 0.010). Moderate heterogeneity of RRs was observed across these studies (P = 0.064 for heterogeneity, I2 = 45.8 %). Dose-response meta-analysis indicated that the risk of prostate cancer reduced by 3.7% (95% CI 1.5%-5.8%) for each 20 grams per day increment of legume intake. In conclusion, the results from this meta-analysis suggest that a high intake of legumes is associated with a low incidence of prostate cancer.
Platelet to lymphocyte ratio (PLR) is a candidate prognostic marker for metastatic castration-resistant prostate cancer patients receiving abiraterone acetate and evidence demonstrates that a high PLR is associated with poor survival. More studies are required to verify current findings and establish a definite cutoff point.
At present, the application of tumor reduction surgery in oligometastatic prostate cancer has aroused extensive discussion among urologists, but clinicians have not reached a consensus on this issue. The purpose of this study was to evaluate the effect of cytoreductive surgery for patients with oligometastatic prostate cancer by meta-analysis.
Growing evidence suggests serum C-reactive protein (CRP) can serve as a prognostic marker in urological cancers. However, some studies yield contradictory results. Our objective was to determine the relationship between baseline serum CRP and survival outcome in urological cancers. We searched PubMed and EMBASE databases until October 2014 without language restrictions. 44 independent studies investigating the association between baseline serum CRP and cancer-specific survival (CSS) or overall survival (OS) were selected. High CRP yielded a worse survival in renal cell carcinoma, prostate cancer, bladder cancer, and upper urinary tract urothelial carcinoma. Combined results of meta-analyses indicated that CRP was a prognostic factor in urological cancers (CSS: p < 0.01; OS: p < 0.01). Subgroup analyses confirmed the significant association between CRP and prognosis, regardless of race and cutoff value of CRP. Specifically, prognostic impact of CRP was also noted in patients with localized RCC treated with nephrectomy (CSS: p < 0.01) and metastatic RCC treated with molecular-targeted therapy (OS: p < 0.01). In conclusion, serum CRP is an independent prognostic factor in urological cancers and risk stratification by serum CRP level could be helpful for prognostic assessment.
The objective of this study is to compare health-related quality of life (QOL) outcomes between radical prostatectomy (RP) and external beam radiation therapy (EBRT) for localized prostate cancer. PubMed, EMBASE, the Cochrane Library and Web of Science (to July 2017) were searched. Pooled analysis of each domain-specific score was calculated in relevant studies, and its change with follow-up time was explored by sub-group analysis. A total of six studies containing 4423 patients were included. Men underwent RP was associated with worse urinary and sexual domain score than EBRT (standardized mean difference (SMD) = -0.59, -0.58; 95% confidence interval (CI) = -0.73 to -0.45, -0.72 to -0.44). In contrast, EBRT group had lower bowel domain score than RP group (SMD = 0.42, 95% CI = 0.33 to 0.52). The sub-group analysis revealed the most severe urinary and sexual QOL in RP as well as bowel QOL in EBRT group all happened in the first month post operation. The different performance of two treatments in three QOL domains diminished afterwards. Health-related QOL should be considered comprehensively when planning follow-up for men after RP or EBRT for localized prostate cancer.
Prostate cancer (PC) is the second most commonly diagnosed cancer in males. 68Ga-PSMA PET/CT, a non-invasive diagnostic tool to evaluate PC with prostate-specific membrane antigen (PSMA) expression, has emerged as a more accurate alternative to assess disease staging. We aimed to identify predictors of positive 68Ga-PSMA PET and the accuracy of this technique.
Prostate cancer disproportionately affects men of African descent and it is estimated that Africa will bear the highest disease burden in the next decade. Underlying genomic factors may contribute to prostate cancer disparities; however, it is unclear whether Africa has prioritised genomics research toward addressing these disparities. A Pubmed review was performed of publications spanning a 15-year period, with specific focus on prostate cancer genomics research that included samples from Africa and investigators in Africa. Data are presented on research publications from Africa relative to similar publications from different geographical regions, and more specifically, the extent of disparities and the contributions to prostate cancer knowledge as a result of genomics research that included African samples and African institutions. Limited publication output may reflect the infrastructure and funding challenges in Africa. Widespread cooperation should be fostered by sharing capacity and leveraging existing expertise to address the growing cancer burden facing the continent.
This review of the literature aims to study potential associations between high consumption of milk and/or dairy products and prostate cancer (PC). Literature is scarce, yet there is a direct relationship between mTORC1 activation and PC; several ingredients in milk/dairy products, when in high concentrations, increase signaling of the mTORC1 pathway. However, there are no studies showing an unequivocal relationship between milk products PC initiation and/or progression. Three different reviews were conducted with articles published in the last 5 years: (M1) PC and intake of dairy products, taking into account the possible mTORC1signaling mechanism; (M2) Intake of milk products and incidence/promotion of PC; (M3) mTORC1 activation signaling pathway, levels of IGF-1 and PC; (M4) mTORC pathway and dairy products. Of the 32 reviews identified, only 21 met the inclusion criteria and were analyzed. There is little scientific evidence that directly link the three factors: incidence/promotion of PC, intake of dairy products and PC, and PC and increased mTORC1 signaling. Persistent hyper-activation of mTORC1 is associated with PC promotion. The activity of exosomal mRNA in cellular communication may lead to different impacts of different types of milk and whether or not mammalian milks will have their own characteristics within each species. Based on this review of the literature, it is possible to establish a relationship between the consumption of milk products and the progression of PC; we also found a possible association with PC initiation, hence it is likely that the intake of dairy products should be reduced or minimized in mens' diet.
To overview the diagnostic accuracy of SelectMDx for the detection of clinically significant prostate cancer and to review sources of methodologic variability. Four electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library were searched for eligible studies investigating the diagnostic value of SelectMDx compared with the gold standard. The pooled sensitivity, specificity, and positive and negative predictive values were calculated. Included studies were assessed according to the Standards for Quality Assessment of Diagnostic Accuracy Studies 2 tool. The review identified 14 relevant publications with 2579 patients. All reports constituted phase 1 biomarker studies. Pooled analysis of findings found an area under the receiver operating characteristic analysis curve of 70% [95% CI, 66%-74%], a sensitivity of 81% [95% CI, 69%-89%], and a specificity of 52% [95% CI, 41%-63%]. The positive likelihood ratio was 1.68, and the negative predictive value is 0.37. Factors that may influence variability in test results included the breath collection method, the patient's physiologic condition, the test environment, and the method of analysis. Considerable heterogeneity was observed among the studies owing to the difference in the sample size. SelectMDx appears to have moderate to good diagnostic accuracy in differentiating patients with clinically significant prostate cancer from people at high risk of developing prostate cancer. Higher-quality clinical studies assessing the diagnostic accuracy of SelectMDx for clinically significant cancer are still needed.
It is widely thought that statins have huge therapeutic potential against prostate cancer (PCA). This study aimed to investigate the effect of statin exposure on PCA incidence and prognosis. PubMed, Web of Science, Embase, and Cochrane databases were searched for observational studies on the association between statin exposure and PCA from inception until July 2022. The primary endpoints were the incidence of PCA and the survival rate. A total of 21 studies were included in this meta-analysis. The pooled estimates showed that exposure to hydrophilic statins was not associated with the incidence of PCA (odds ratio [OR]=0.94, 95% CI=0.88-1.01, P =0.075), while the incidence of PCA was significantly decreased in populations exposed to lipophilic statins compared with the nonexposed group (OR=0.94, 95% CI=0.90-0.98, P =0.001), mainly in Western countries (OR=0.94, 95% CI=0.91-0.98, P =0.006). Subgroup analysis showed that simvastatin (OR=0.83, 95% CI=0.71-0.97, P =0.016) effectively reduced the incidence of PCA. The prognosis of PCA in patients exposed to both hydrophilic (hazard ratio [HR]=0.57, 95% CI=0.49-0.66, P <0.001) and lipophilic (HR=0.65, 95% CI=0.58-0.73, P <0.001) statins were better than in the nonexposed group, and this improvement was more significant in the East than in Western countries. This study demonstrates that statins can reduce the incidence of PCA and improve prognosis, and are affected by population region and statin properties (hydrophilic and lipophilic).
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