Trends of Prostate Cancer Morbidity in Low-Incidence Countries from 1990-2019.

BACKGROUND: Our study was designed to elucidate the morbidity trends of prostate cancer in low-incidence countries. METHODS: Data on prostate cancer were extracted from the 2019 Global Burden of Disease study. A cluster analysis of growth rates stratified by age was conducted, and correlation analyses were performed between age-standardized incidence rates (ASIR), estimated annual percent change (EAPC), and socio-demographic index (SDI). RESULTS: Among 35 low-incidence countries for prostate cancer, predominantly located in Asia and North Africa, the SDI ranged from low to high-middle levels. Higher SDI regions exhibited considerably higher ASIR. With the exception of Kyrgyzstan, Kiribati, and Samoa that experienced a decrease in ASIR, the remaining 32 countries displayed an upward morbidity trend since 1990, with all their EAPCs exceeding the global average. In addition, men ages 90 years and above consistently exhibited the highest ASIR for prostate cancer. The most notable growth rate of ASIR was observed in individuals ages 20 to 44 years. CONCLUSIONS: Overall, low-incidence countries generally witnessed an increase in prostate cancer morbidity, albeit at levels lower than those seen in Western countries. Individuals ages 90 years and above consistently maintained the highest ASIR since 1990. Notably, more substantial increase of ASIR in younger age was also observed in low-incidence countries. IMPACT: This study offers a comprehensive overview of prostate cancer morbidity in low-incidence countries worldwide from 1990 to 2019. Future research should delve into the associations between incidence, clinical stages, PSA screening, environmental factors, lifestyle, and genetic risk in these low-incidence countries.

The Impact of Nutrient Supply on Prostate Cancer Risk Worldwide.

We aim to explore the association between nutrient supply and the incidence of prostate cancer globally. We utilized national nutrient supply data from the Food and Agriculture Organization of the United Nations for 150 countries, including the average supply of total protein (APS), animal protein (AAPS), fat (AFS), animal protein/total protein ratio (ATR), and share of dietary energy supply derived from cereals, roots, and tubers (CR). Prostate cancer incidence data were sourced from the Global Burden Disease 2019 (GBD2019). Correlation, regression analyses, and subgroup analysis were conducted. Our findings imply that incidence of prostate cancer is significantly correlated to APS (ρ = 0.394, p < 0.01), AAPS (ρ = 0.560, p < 0.01), AFS (ρ = 0.522, p < 0.01), ATR (ρ = 0.592, p < 0.01), and CR (ρ = -0.667, p < 0.01). After adjusting for confounders, regression analysis showed linear relationships between the AAPS (ß = 0.605, p = 0.006), ATR (ß = 70.76, p = 0.005), CR (ß = -1.4451, p < 0.01), and age-standardized incidence rates (ASIRs) of prostate cancer, while no association was observed with APS (ß = 0.030, p = 0.483) or AFS (ß = 0.237, p = 0.405). Subgroup analysis suggested that dietary supply indicators were associated with ASIR in middle, middle-high, and high SDI, but not in countries with low and middle-low SDI. In summary, prostate cancer rates globally correlate significantly with AAPS, ATR, and CR, but not with APS and AFS. When considering the SDI of countries, the relationship is generally more pronounced in economically advanced nations, but not evident in low and middle-low SDI countries.

Different predictive values of microvessel density for biochemical recurrence among different PCa populations: A systematic review and meta-analysis.

BACKGROUND: Several studies have explored the relationship between intratumoral microvessel density (MVD) and the risk of postoperative biochemical recurrence (BCR) in prostate cancer (PCa), although the results are contradictory. Therefore, we conducted a meta-analysis to investigate the effect of MVD on BCR in PCa. METHOD: We searched PubMed, MEDLINE, Science Direct/Elsevier, the Cochrane Library, CNKI, and EMBase databases from inception through January 2022, with no year or language restrictions, and used NOS guidelines to evaluate the quality of the 19 eligible studies. The derived hazard ratio (HR) and 95% confidence interval (95%CI) were used to assess each endpoint. Data synthesis was performed with RevMan to assess the prognostic value of MVD in PCa and its heterogeneity, while the publication bias was examined using STATA 16.0. RESULTS: Our meta-analysis included 19 articles (4 for T1-2, 6 for T1-3, and 9 for T1-4) on postoperative biochemical recurrence of PCa, among which, 3933 patients were pooled. The predictive ability of intratumoral MVD for different stages of PCa on BCR was T1-2 (HR, 2.46; 95% CI, 1.08-5.58; p = 0.03; I2  = 83%), T1-3 (HR, 2.38, 95% CI, 1.41-4.01; p = 0.001; I2  = 82%), T1-4 (HR, 1.61; 95% CI, 1.19-2.19; p = 0.002; I2  = 61%).The subgroup analyses based on European and immunohistochemical antibody none-factor VII were consistent with primary one. Sensitivity analysis excluding those studies judged to be at high risk of bias in T1-2 showed a HR of 2.99[1.70,5.27] (I2  = 38%, p = 0.0001), demonstrating the robustness of risk estimates of MVD for the assessment of biochemical recurrence. CONCLUSION: Microvessel density is a predictor of BCR among patients with PCa, and earlier T stage PCa with a stronger MVD is associated with BCR. Further studies are needed to investigate neoangiogenesis in different T stages of PCa and whether MVD will be of benefit to the EAU-recommended tool for biochemical recurrence risk assessment.

Prognostic Utility of the Modified Glasgow Prognostic Score in Urothelial Carcinoma: Outcomes from a Pooled Analysis.

Background: Many studies explored the prognostic value of the modified Glasgow Prognostic Score (mGPS) in urothelial carcinoma (UC), but the results are controversial. This study aimed to quantify the relationship between pretreatment mGPS and survival in patients with UC. Methods: A systematic literature search was conducted using Embase, PubMed, and Web of Science to identify eligible studies published before August 2022. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the association between pretreatment mGPS and the prognosis of UC. Results: Thirteen eligible studies involving 12,524 patients were included. A high mGPS was significantly associated with poor overall survival (mGPS 1/0: HR = 1.33, 95% CI 1.12−1.58, p = 0.001; mGPS 2/0: HR = 2.02, 95% CI 1.43−2.84, p < 0.0001), progression-free survival (mGPS 1/0: HR = 1.26, 95% CI 1.03−1.53, p = 0.021; mGPS 2/0: HR = 1.76, 95% CI 1.12−2.77, p = 0.013), recurrence-free survival (mGPS 1/0: HR = 1.36, 95% CI 1.18−1.56, p < 0.0001; mGPS 2/0: HR = 1.70, 95% CI 1.44−2.000, p < 0.0001), and cancer-specific survival (mGPS 2/0: HR = 1.81, 95% CI 1.30−2.52, p < 0.0001). A subgroup analysis of OS also yielded similar results. Conclusions: Evidence suggests that high pretreatment mGPS in UC is closely related to poor survival. Pre-treatment mGPS is a powerful independent prognostic factor in patients with UC.

The Prognostic and Clinicopathological Significance of Systemic Immune-Inflammation Index in Bladder Cancer.

Background: Systemic immune-inflammation index (SII) has recently emerged as a biomarker for the prognosis of a variety of malignant tumors. However, the role of SII in bladder cancer (BC) remains unclear. To this end, we performed a pooled analysis to investigate the prognostic value of preoperative SII in patients with BC. Methods: A comprehensive search of electronic databases (PubMed/Medline, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials) was conducted to determine the eligible studies that were published until January 2022. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association between preoperative SII and the prognosis and clinicopathological characteristics of BC. Results: Ten studies with 7,087 patients were included in this analysis. SII was observed to be correlated with inferior overall survival (HR = 1.22, 95% CI 1.04-1.44, p = 0.013), cancer-specific survival (HR = 1.68, 95% CI 1.14-2.47, p = 0.009), and recurrence-free survival (HR = 1.29, 95% CI 1.03-1.61, p = 0.027). An increased preoperative SII was also associated with poor tumor differentiation, higher tumor stage, presence of lymph node involvement, and tumor size ≥3 cm (all p < 0.05). Conclusions: An elevated preoperative SII is significantly associated with worse survival outcomes and adverse pathological features in patients with BC. Hence, SII may serve as a strong independent prognostic predictor for patients with BC after surgery.

Aloperine Exerts Antitumor Effects on Bladder Cancer in vitro.

BACKGROUND: Human bladder cancer is the most common malignant tumor of the urinary system and one of the 10 most common tumors of the whole body. Although most patients with bladder cancer exhibit a good prognosis with standard treatment, effective therapies for patients with a recurrent or advanced bladder cancer are unavailable. Therefore, highly effective drugs to treat such patients need to be developed. Aloperine (ALO), a natural compound isolated from Sophora alopecuroides, has antitumor properties. However, the role of ALO in human bladder cancer remains unclear. METHODS: In the present study, MTT was used to detect the cytotoxic effect of ALO on human BC cell line EJ and human urothelium cell line SV-HUC-1cells. Meanwhile, in order to investigate the effects of ALO on the proliferation, apoptosis, migration, and invasion of BC EJ cells and its mechanism by Cell Counting Kit-8 (CCK-8) assay, immunofluorescence, Hoechst 33342 staining, wound scratch assay, transwell migration and invasion assay, Western blot analysis. RESULTS: ALO can inhibit the proliferation and invasion of human bladder cancer EJ cells, and is low-toxic to human urothelium cells. Moreover, it can promote cellular apoptosis in vitro. Further analysis demonstrated the involvement of Caspase-dependent apoptosis following ALO treatment. ALO also downregulated the protein expression levels of Ras, p-Raf1 and p-Erk1/2. CONCLUSION: ALO is a potential drug for human bladder cancer therapy.

Lefty-1 inhibits renal epithelial-mesenchymal transition by antagonizing the TGF-ß/Smad signaling pathway.

Epithelial-mesenchymal transition (EMT) is a biological process in which tubular epithelial cells lose their phenotypes, and new mesenchymal feature are obtained. In particular, type II EMT possibly contributes to renal tissue fibrogenesis. Recent studies indicate that Lefty-1, a novel member of the TGF-ß superfamily with pleiotropical and biological regulation characteristics on TGF-ß and other signaling pathways, is considered to have potential fibrotic effects. However, its role in EMT, which is often a long-term consequence of renal tubulointerstitial fibrosis, remains unknown. In this study, we found that Lefty-1 alleviates EMT induction through antagonizing TGF-ß/Smad pathway in vivo and in vitro. In unilateral ureteral obstruction (UUO) model mice, administration of adenovirus-mediated overexpression of Lefty-1 (Ad-Lefty-1) significantly reduced TGF-ß1/Smad expression and alleviated the phenotypic transition of epithelial cells to mesenchymal cells and extracellular matrix (ECM) accumulation. In high glucose-induced rat renal tubular duct epithelial cell line (NRK-52E), EMT and ECM synthesis were alleviated with Lefty-1 treatment, which significantly inhibited TGF-ß1/Smad pathway activation in UUO mice and high glucose-treated NRK-52E cells. Thus, Lefty-1 can alleviate EMT and renal interstitial fibrosis in vivo and in vitro through antagonizing the TGF-ß/Smad pathway, and Lefty-1 might have a potential novel therapeutic effect on fibrotic kidney diseases.

Influence of ABCB1 (1236C > T, 2677G > T and 3435C > T) polymorphisms on the transport ability of P-gp-mediated sunitinib in Caco-2 cell line.

P-glycoprotein (P-gp), encoded by ABCB1 gene, participants in the transmembrane transport of multiple anticancer drugs. The aim of the current research was to observe in vitro the impacts of ABCB1 (1236 C > T, 2677G > T, and 3435C > T) polymorphisms on the efflux activity of P-gp-mediated sunitinib.Stable recombinant colonic adenocarcinoma cell (Caco-2) systems transfected with ABCB1 wild-type allele and variant alleles (1236 T, 2677T and 3435T) were constructed. The resistance of each cell line to sunitinib was assessed by cell counting kit-8 (CCK8) assay. The effects of ABCB1 (1236 C > T, 2677G > T and 3435C > T) polymorphisms on the intracellular accumulation and transepithelial permeability of sunitinib were also investigated.The recombinant cell lines transfected with ABCB1 variant alleles (1236 T, 2677T, and 3435T) showed higher resistance to sunitinib compared to cells transfecting with ABCB1 wild-type allele (p < .05). The intracellular accumulation of sunitinib was significantly decreased in the three types of recombinant cell lines overexpressing ABCB1 variant alleles in comparison of their wild-type cell lines (p < .05). The transepithelial permeability of sunitinib in recombinant cell systems in transfected with variant alleles was significantly increased compared with cells overexpressing ABCB1 wild-type allele. The P-gp activity in recombinant variant cells is stronger when mediated transport of sunitinib than wild-type counterpart. P-gp encoded by ABCB1 (1236 T, 2677T, and 3435T) variant alleles may be more efficient to transport sunitinib than wild-type allele. Our observation suggests that ABCB1 (1236 C > T, 2677G > T, and 3435C > T) polymorphisms affect the transport ability of P-gp-mediated sunitinib.Collectively, ABCB1 polymorphisms may alter the P-gp-mediated sunitinib sensitivity via regulating drug transport.

[Mechanism in growth inhibition of quercetin on human bladder cancer cell line].

To investigate the inhibitory mechanism of quercetin on growth of human bladder cancer cell line(BIU-87). BIU-87 cells were cultured in vitro, and co-cultured with varying concentrations of quercetin, and the anti-proliferative activity was determined by CCK-8 assay. Apoptosis of quercetin-induced BIU-87 cells and cell cycle were determined by flow cytometry analysis. Expressions of Bal-2 and Bal-xL, and related proteins in TAK1/JNK signal pathway were measured using Western blot analysis. After treatment with quercetin for 24 h and 48 h, the proliferation of BIU-87 cells was significantly suppressed in a dose-dependent manner according to CCK-8 assay(P<0.05). The flow cytometry analysis indicated that each group of quercetin leads to a significant higher percentage of apoptosis of BIU-87 cells than control group after treatment with quercetin for 24 h and 48 h; In G0/G1 period, cells reduced, while the amount of cells in G2/M period increased, and cells in S period remained the same amount. Expressions of Bal-2, Bal-xL, p-TAK1, p-MKK4/7, p-JNK decreased in BIU-87 cells after treatment with quercetin. Quercetin could inhibit the proliferation and promote the apoptosis of BIU-87 cells. The mechanism may be correlated with the inhibition of TAK1/JNK signaling pathway, which led to the further decrease in expressions of Bal-2 and Bal-xL.

Left-right determination factor is down-regulated in fibrotic renal tissue of human hydronephrosis.

OBJECTIVE: • To compare the expressions of common fibrosis-relevant genes in hydronephrosis-induced fibrotic renal tissues and normal human renal tissues, thereby providing insights into the cellular and molecular mechanisms of renal fibrosis resulting from hydronephrosis. PATIENTS AND METHODS: • A total of 12 extensively fibrotic renal tissue samples from patients with hydronephrosis (H-group) and six normal renal tissue samples from patients who underwent nephrectomy for renal cell carcinoma (N-group), along with their clinical data, were collected at Renmin Hospital of Wuhan University in China between October 2005 and August 2007. • These tissue samples were compared for their transforming growth factor-ß (TGF-ß)/bone morphogenetic protein (BMP) pathway-related gene profiles using a real-time polymerase chain reaction (PCR) microarray. • Subsequently, reverse transcriptase-PCR assays were used to validate the expression changes of left-right determination factor (LEFTY), a gene of interest, at the mRNA level. • The different expression of LEFTY at the protein level was confirmed by western blotting and immunohistochemistry assays. RESULTS: • The results showed that 49 genes were differently expressed in fibrotic renal tissues relative to normal control tissues. Among these genes, 25 were up-regulated and 24 were down-regulated. • LEFTY-B, one of the most markedly altered genes, was down-regulated 13.55-fold compared with N-group tissues. • RT-PCR showed that the LEFTY-A (6.05-fold down-regulated, P < 0.001) and LEFTY-B (12.5-fold down-regulated, P < 0.001) genes, two members of the LEFTY family in human tissues, were both significantly down-regulated in H-group tissues. • Similarly, down-regulations of LEFTY-A (0.25-fold vs N-group, P < 0.001) and LEFTY-B (0.20-fold vs N-group, P < 0.001) proteins were detected by western blotting (P < 0.001). • Immunohistochemical staining showed different distributions of LEFTY in the two tissue samples, and quantitative image analyses confirmed that LEFTY protein expression was lower in H-group tissues than in N-group tissues (P < 0.001). CONCLUSIONS: • The gene and protein expressions of LEFTY were found to be down-regulated in extensively fibrotic renal tissues induced by hydronephrosis. • LEFTY may represent an ideal candidate for a therapeutic target for renal fibrosis.