The incidence of prostate cancer has been increasing worldwide in recent years. The GLOBOCAN project showed that prostate cancer was the second most frequently diagnosed cancer and the fifth leading ...cause of cancer mortality among men worldwide in 2012. This trend has been growing even in Asian countries, where the incidence had previously been low. However, the accuracy of data about incidence and mortality as a result of prostate cancer in some Asian countries is limited. The cause of this increasing trend is multifactorial. One possible explanation is changes in lifestyles due to more Westernized diets. The incidence is also statistically biased by the wide implementation of early detection systems and the accuracy of national cancer registration systems, which are still immature in most Asian countries. Mortality rate decreases in Australia, New Zealand and Japan since the 1990s are possibly due to the improvements in treatment and/or early detection efforts employed. However, this rate is increasing in the majority of other Asian countries. Studies of latent and incidental prostate cancer provide less biased information. The prevalence of latent and incidental prostate cancer in contemporary Japan and Korea is similar to those in Western countries, suggesting the influence of lifestyle changes on carcinogenesis. Many studies reported evidence of both congenital and acquired risk factors for carcinogenesis of prostate cancer. Recent changes in the acquired risk factors might be associated with the increasing occurrence of prostate cancer in Asian countries. This trend could continue, especially in developing Asian countries.
Extracellular vesicles (EVs) are small lipid membrane vesicles that are secreted from almost all kinds of cells into the extracellular space. EVs are widely accepted to be involved in various ...cellular processes; in particular, EVs derived from cancer cells have been reported to play important roles in modifying the tumor microenvironment and promoting tumor progression. In addition, EVs derived from cancer cells encapsulate various kinds of tumor-specific molecules, such as proteins and RNAs, which contribute to cancer malignancy. Therefore, the unveiling of the precise mechanism of intercellular communication via EVs in cancer patients will provide a novel strategy for cancer treatment. Furthermore, a focus on the contents of EVs could promote the use of EVs in body fluids as clinically useful diagnostic and prognostic biomarkers. In this review, we summarize the current research knowledge on EVs as biomarkers and therapeutic targets and discuss their potential clinical applications.
Bladder cancer is the 9th leading cause of cancer death worldwide. The major problem in bladder cancer is primarily the high recurrence rate after drug treatment and resection. Although conventional ...screening methods, such as cystoscopy, urinary cytology and ultrasound sonography, have become widely used in clinical settings, the diagnostic performance of these modalities is unsatisfactory due to low accuracy or high invasiveness. Because circulating micro RNA (miRNA) profiles have recently been reported as an attractive tool for liquid biopsy in cancer screening, here, we performed global miRNA profiling of 392 serum samples of bladder cancer patients with 100 non‐cancer samples and 480 samples of other types of cancer as controls. We randomly classified the bladder cancer and control samples into 2 cohorts, a training set (N = 486) and a validation set (N = 486). By comparing both controls, we identified specific miRNA, such as miR‐6087, for diagnosing bladder cancer in the training and validation sets. Furthermore, we found that a combination of 7 miRNA (7‐miRNA panel: miR‐6087, miR‐6724‐5p, miR‐3960, miR‐1343‐5p, miR‐1185‐1‐3p, miR‐6831‐5p and miR‐4695‐5p) could discriminate bladder cancer from non‐cancer and other types of tumors with the highest accuracy (AUC: .97; sensitivity: 95%; specificity: 87%). The diagnostic accuracy was high, regardless of the stage and grade of bladder cancer. Our data demonstrated that the 7‐miRNA panel could be a biomarker for the specific and early detection of bladder cancer.
The present study selected 7 miRNA expression levels among bladder cancer, non‐cancer and other cancer samples. A diagnostic index was calculated and plotted in the dot plot among 12 different cancers. An index score ≥0 indicated the presence of bladder cancer and an index score <0 indicated the absence of bladder cancer.
Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with next-generation androgen receptor inhibitors. However, direct comparative data are not ...available to inform treatment decisions and/or guideline recommendations. Therefore, we performed network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or metastasis-free and/or prostate-specific antigen (PSA) progression-free survival (OS/MFS/PSA-PFS) and/or adverse events (AEs) in nmCRPC patients were considered eligible. Three studies (
n
= 4117) met our eligibility criteria. Formal network meta-analyses were conducted. For MFS, apalutamide, darolutamide, and enzalutamide were significantly more effective than placebo, and apalutamide emerged as the best option (
P
score: 0.8809). Apalutamide hazard ratio (HR): 0.85, 95% credible interval (CrI): 0.77–0.94 and enzalutamide (HR: 0.86, 95% CrI: 0.78–0.95) were both significantly more effective than darolutamide. For PSA-PFS, all three agents were statistically superior to placebo, and apalutamide emerged as the likely preferred option (
P
score: 1.000). Apalutamide (HR: 0.71, 95% CrI: 0.69–0.74) and enzalutamide (HR: 0.76, 95% CrI: 0.74–0.79) were both significantly more effective than darolutamide. For AEs (including all AEs, grade 3 or grade 4 AEs, grade 5 AEs, and discontinuation rates), darolutamide was the likely best option. Apalutamide and enzalutamide appear to be more efficacious agents for therapy of nmCRPC, while darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials.
Renal angiomyolipoma (AML) is the most common benign tumor of the kidney. It consists of blood vessels, smooth muscle and fat components in varying proportions. AML is divided into the sporadic type ...and tuberous sclerosis complex (TSC)-associated type. TSC-associated AML develops at a younger age and tends to exhibit a much faster growth rate over time than sporadic AML. AMLs are classified as classic AML, fat-poor AML and epithelioid AML. Epithelioid AML, though rare, shows aggressive behavior leading to distant metastasis and mortality. TSC-associated AML is more likely to have an epithelioid component than sporadic AML. Active surveillance is the suggested management for small AML. Clinical intervention is mainly indicated when there is a substantial risk of rupture. Minimally invasive therapies, including partial nephrectomy, transcatheter arterial embolization, and mammalian target of rapamycin (mTOR) inhibitor treatment are employed for patients who require treatment. An updated algorithm for the management of AML is herein described. According to this algorithm, treatment intervention is recommended for TSC-associated AML >3 cm, even in asymptomatic cases. In cases with asymptomatic sporadic AML >4 cm in size or with an intra-tumoral aneurysm of >5 mm, treatment, including transcatheter arterial embolization or partial nephrectomy, is advised. The major complication of AML is intra-tumoral or retroperitoneal hemorrhage due to rupture that may be serious and life threatening. Thus, correct diagnosis, proper observation, and appropriate treatment are very important in the management of renal AML.
Range shifts of mountain organisms toward higher elevations in response to global warming may result in spatial mismatches between plants and their pollinators. Here, we aimed to examine whether ...bumblebee diversity decreases in a high‐altitude zone, and whether it parallels a decrease in the altitudinal diversity of bumblebee‐visited plants. We surveyed the alpha diversities of flower‐visiting bumblebees and bumblebee‐visited plants along an altitudinal gradient on a Japanese high mountain. Then, we examined whether the alpha diversities of bumblebees and bumblebee‐visited plants could be explained by altitude, or by other factors such as season, surveyed area and flower abundance. We found that a model including only altitude best explained bumblebee diversity, and that flower abundance and plant diversity had considerable value in explaining bumblebee diversity. In contrast, none of the studied factors explained plant diversity. Bumblebee diversity was minimal in the high‐altitude zone (1,900–2,600 m a.s.l.), where the only dominant bumblebee species, Bombus beaticola, visited many species of flowering plants. In contrast, five to seven bumblebee species were distributed in the low‐ (700–1,300 m a.s.l.) and middle‐ (1,300–1,900 m a.s.l.) altitude zones. These results show that plant–pollinator mutualism in high‐altitude zone of a Japanese mountain is asymmetric: many bee‐pollinated plants rely almost exclusively on one bumblebee species (B. beaticola) for pollination. Monitoring future changes in the distribution and abundance of B. beaticola is indispensable for the conservation of alpine plant in Japan.
We aimed to examine whether bumblebee diversity decreases in high–altitude zone, and whether it parallels altitudinal diversity decrease of bumblebee–visited plants. We show that the model including only altitude best explained bumblebee diversity, which decreases in high–altitude zone, and in contrast, no appropriate factors including altitude explained plant diversity. These results show that plant–pollinator mutualism in high–altitude zone of Japanese mountain is asymmetric: many bee‐pollinated plants rely almost exclusively on one bumblebee species (B. beaticola) for pollination there.
Purpose
To assess the prognostic value of alkaline phosphatase in patients with hormone-sensitive prostate cancer.
Methods
A systematic review and meta-analysis was performed using the PUBMED, Web of ...Science, Cochrane Library, and Scopus in April 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared hormone-sensitive prostate cancer patients with high vs. low alkaline phosphatase to determine its predictive value for overall survival, cancer-specific survival, and progression-free survival. We performed a formal meta-analysis of these outcomes.
Results
42 articles with 7938 patients were included in the systematic review and 28 studies with 5849 patients for the qualitative assessment. High alkaline phosphatase was associated with worse overall survival (pooled HR 1.72; 95% CI 1.37−2.14) and progression-free survival (pooled HR 1.30; 95% CI 1.10−1.54). In subgroup analyses of patients with “high-volume” and “low-volume”, alkaline phosphatase was associated with the overall survival (pooled HR 1.41; 95% CI 1.21−1.64 and pooled HR 1.64; 95% CI, 1.06−2.52, respectively).
Conclusions
In this meta-analysis, elevated serum levels of alkaline phosphatase were associated with an increased risk of overall mortality and disease progression in patients with hormone-sensitive prostate cancer. In contrast, those were not associated with an increased risk of cancer-specific mortality. Alkaline phosphatase was independently associated with overall survival in both patients with “high-volume” and “low-volume” hormone-sensitive prostate cancer. Alkaline phosphatase may be useful for being integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision making process.
Introduction and hypothesis
We investigated the effects of locally administered human multilineage-differentiating stress enduring (Muse) cells, nontumorigenic pluripotent-like endogenous stem cells, ...on bladder tissues, function, and nociceptive behavior in a chemically induced Hunner-type interstitial cystitis (HIC)-like rat model without immunosuppressant.
Methods
Chemical cystitis was induced by intravesical instillation of 0.2 N hydrochloride (HCl) for 15 min in female F344 rats. SSEA-3
+
Muse cells, SSEA-3
−
non-Muse cells or Hanks' balanced salt solution (HBSS; vehicle) were injected into the anterior and posterior bladder wall at each 1×10
4
cells/10 μl 6 h after HCl application. The sham group received HBSS without HCl instillation. Urinary frequency was assessed using metabolic cages, cystometrograms, nociceptive behavior, and histological analysis of the bladder and L6 spinal cord.
Results
Increases in urinary frequency and decreases in bladder capacity compared with the sham group were observed in the vehicle and non-Muse groups, but not in the Muse group, at 1 week. Significant increases in nociceptive behavior compared with the sham group and the expression of TNFα in the bladder and c-Fos in the bilateral dorsal horns of L6 spinal cord were also observed in the vehicle and non-Muse groups, whereas these changes were not seen in the Muse group at 1 week. Histological analysis exhibited a higher proportion of injected Muse cells remaining in the urothelial basal layer and lamina propria of the bladder than non-Muse cells until 4 weeks.
Conclusions
Muse cell therapy could be a promising modality for treating HIC.
The incidence of prostate cancer (PC) has been increasing in Asian countries, where it was previously low. Although the adoption of a Westernized lifestyle is a possible explanation, the incidence is ...statistically biased due to the increase in prostate-specific antigen (PSA) screening and the accuracy of national cancer registration systems. Studies on latent PC provide less biased information. This review included studies evaluating latent PC in several countries after excluding studies using random or single-section evaluations and those that did not mention section thickness. The findings showed that latent PC prevalence has been stable since 1950 in Western countries, but has increased over time in Asian countries. Latent PC in Asian men has increased in both prevalence and number of high-grade cases. Racial differences between Caucasian and Asian men may explain the tumor location of latent PC. In conclusion, the recent increase in latent PC in Asian men is consistent with an increase in clinical PC. Evidence suggests that this increase is caused not only by the increase in PSA screening, but also by the adoption of a more Westernized lifestyle. Autopsy findings suggest the need to reconsider the definition of clinically insignificant PC.
The high false-positive rate of prostate-specific antigen (PSA) may lead to unnecessary prostate biopsies. Therefore, the United States Preventive Services Task Force recommends that decisions ...regarding PSA-based screening of prostate cancer should be made with caution in men ages 55-69 years, and that men ≥70 years should not undergo PSA screening. Here, we investigated the potential of serum miRNAs as an accurate diagnostic method in patients with suspected prostate cancer.
Serum samples of 809 patients with prostate cancer, 241 negative prostate biopsies, and 500 patients with other cancer types were obtained from the National Cancer Center, Japan. Forty-one healthy control samples were obtained from two other hospitals in Japan. Comprehensive microarray analysis was performed for all samples. Samples were divided into three sets. Candidate miRNAs for prostate cancer detection were identified in the discovery set (
= 123). A diagnostic model was constructed using combinations of candidate miRNAs in the training set (
= 484). The performance of the diagnostic model was evaluated in the validation set (
= 484).
In the discovery set, 18 candidate miRNAs were identified. A robust diagnostic model was constructed using the combination of two miRNAs (miR-17-3p and miR-1185-2-3p) in the training set. High diagnostic performance with a sensitivity of 90% and a specificity of 90% was achieved in the validation set regardless of the Gleason score and clinical tumor-node-metastasis stage.
The model developed in this study may help improve the diagnosis of prostate cancer and reduce the number of unnecessary prostate biopsies.
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