The global incidence of metabolic syndrome (MetS) is dramatically increasing. Considerable interest has been devoted to the relationship between MetS and prostate cancer (PCa) risk. However, few studies have examined the association between MetS and PCa progression. This retrospective study consisted of 1016 patients with PCa who received radical prostatectomy. The association between MetS and pathological features was evaluated using logistic regression analysis. Compared with patients without MetS, those with MetS indicated an increased risk of prostatectomy Gleason score (GS) ≥8 (odds ratio [OR] =1.670, 95% confidence interval (CI) 1.096–2.545, P= 0.017), and a 1.5-fold increased risk of pT3–4 disease (OR = 1.583, 95% CI 1.106–2.266, P= 0.012). The presence of MetS was an independent predictor of lymph node involvement (OR = 1.751, 95% CI 1.038–2.955, P= 0.036). Furthermore, as the number of MetS components accumulated, the risk of a GS ≥ 8 increased. The present study indicates a significant association between MetS and advanced PCa. The results need to be evaluated in large-scale prospective cohorts.
Objective: Adrenocortical carcinoma (ACC) is a rare but aggressive malignant cancer that has been attracting growing attention over recent decades. This study aims to integrate protein interaction networks with gene expression profiles to identify potential biomarkers with prognostic value in silico. Methods: Three microarray data sets were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) according to the normalization annotation information. Enrichment analyses were utilized to describe biological functions. A protein–protein interaction network (PPI) of the DEGs was developed, and the modules were analyzed using STRING and Cytoscape. LASSO Cox regression was used to identify independent prognostic factors. The Kaplan–Meier method for the integrated expression score was applied to analyze survival outcomes. A receiver operating characteristic (ROC) curve was constructed with area under curve (AUC) analysis to determine the diagnostic ability of the candidate biomarkers. Results: A total of 150 DEGs and 24 significant hub genes with functional enrichment were identified as candidate prognostic biomarkers. LASSO Cox regression suggested that ZWINT, PRC1, CDKN3, CDK1 and CCNA2 were independent prognostic factors in ACC. In multivariate Cox analysis, the integrated expression scores of the modules showed statistical significance in predicting disease-free survival (DFS, P=0.019) and overall survival (OS, P<0.001). Meanwhile, ROC curves were generated to validate the ability of the Cox model to predict prognosis. The AUC index for the integrated genes scores was 0.861 (P<0.0001). Conclusion: In conclusion, the present study identifies DEGs and hub genes that may be involved in poor prognosis and early recurrence of ACC. The expression levels of ZWINT, PRC1, CDKN3, CDK1 and CCNA2 are of high prognostic value, and may help us understand better the underlying carcinogenesis or progression of ACC. Further studies are required to elucidate molecular pathogenesis and alteration in signaling pathways for these genes in ACC.
To explore the effectiveness and significance of whether electrical acupuncture stimulation combining with pelvic floor muscle therapy (PFMT) can improve the recovery of urinary continence.A total of 109 patients took part in the study of novel combination treatment for urinary continence from September 2008 to September 2009. Patients were divided into study group (n = 40) and control group (n = 69). The patients in study group received electrical acupuncture stimulation therapy combined with PFMT one week after removal the catheter. The patients in control group performed PFMT as the only treatment for post prostatectomy incontinence. The patients were followed up closely, with their clinical characteristics recorded, questionnaires of ICI-Q-SF filled up, and all the data for statistical analysis collected.There was a significant difference between the study group and the control group in the urinary control curve (P = 0.029). The difference of continence probability between these two groups became greater from 4 weeks after surgery, and the difference reached the peak at 6 weeks (P = 0.023). Then the difference became smaller, and there was no difference at 16 weeks after surgery. ICI-Q-SF questionnaires showed the same results.Electrical acupuncture stimulation therapy combining with PFMT can improve the recovery of patients' urinary continence after radical prostatectomy.
PBRM1 is a novel tumor suppressor gene that can inhibit cancer cell proliferation and predict the outcome of renal cell carcinoma (RCC), but its biological role needs further elucidation. We examined expression of the PBRM1 gene in RCC cell lines and the effect of PBRM1 on cell proliferation and cell cycle in RCC ACHN cells. Microarray processing and analysis was used to explore novel pathways involved in tumorigenesis related to PBRM1 knockdown. PBRM1 was expressed at high levels in RCC ACHN cells and lentivirus-mediated PBRM1 knockdown in these cells caused an increase in the proportion of cells in S phase of the cell cycle and promoted in vitro proliferation and migration. In vivo experiments showed that downregulation of PBRM1 promoted tumorigenesis in nude mice. In pathway gene chip analysis, the chemokine/chemokine receptor interaction pathway showed the greatest difference in gene expression upon PBRM1 knockdown. Protein levels of IL6ST and CCL2 were increased, whereas levels of interleukin (IL)-8, IL-6, and CXCL2 were decreased, in knockdown cells. Re-expression of IL-8 in PBRM1 knockdown ACHN cells could significantly decrease cell proliferation/migration and induced cell arrest in the G2/M phase. These findings indicate that PBRM1 alters cell cycle progression and inhibits proliferation and migration of ACHN cells through the chemokine/chemokine receptor pathway.
Background The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Abnormally increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and thus contribute to cancer risk. Methodology/Principal Findings In a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped six potentially functional SNPs of mTOR (rs2536 T>C, rs1883965 G>A, rs1034528 G>C, rs17036508 T>C, rs3806317 A>G, and rs2295080 T>G) and assessed their associations with risk of PCa by using logistic regression analysis. Conclusions/Significances In the single-locus analysis, we found a significantly increased risk of PCa associated with mTOR rs2536 CT/CC and rs1034528 CG/CC genotypes [adjusted OR = 1.42 (1.13–1.78), P = 0.003 and 1.29 (1.07–1.55), P = 0.007), respectively], compared with their common homozygous genotypes, whereas mTOR rs2295080 GT/GG genotypes were associated with a decreased risk of PCa [adjusted OR = 0.76 (0.64–0.92), P = 0.003], compared with wild-type TT genotypes. In the combined analysis of the six SNPs, we found that individuals carrying two or more adverse genotypes had an increased risk of PCa [adjusted OR = 1.24 (1.04–1.47), P = 0.016], compared with individuals carrying less than two adverse genotypes. In the multiple dimension reduction analysis, body mass index (BMI) was the best one-factor model with the highest CVC (100%) and the lowest prediction error (42.7%) among all seven factors. The model including an interaction among BMI, rs17036508, and rs2536 was the best three-factor model with the highest CVC (100%) and the lowest prediction error of 41.9%. These findings suggested that mTOR SNPs may contribute to the risk of PCa in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies.
4594 Background: In a phase I study, intravesical camrelizumab (at a maximum tolerated dose [MTD] of 200 mg) was well tolerated by patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC). This phase II trial aimed to assess the efficacy and safety of intravesical camrelizumab at the established phase I MTD. Methods: Patients with histologically confirmed BCG-unresponsive high-risk NMIBC, who were ineligible for or declined radical cystectomy, received intravesical camrelizumab at a dose of 200 mg every week for up to 6 weeks as the induction course. Subsequently, the maintenance therapy started with 200 mg administered every 3 weeks and continued until reaching the maximum treatment duration of 2 years or in the event of disease progression or unacceptable toxicity. The primary endpoint was the 3-month event-free survival (EFS) rate. The secondary endpoints included 6-month EFS rate, 1-year EFS rate, recurrence-free survival (RFS), progression-free survival (PFS), and safety. Biomarker exploration included PD-L1 expression and protein sequencing. Results: Between June 2021, and December 2023, 14 patients were enrolled and received at least one dose of camrelizumab, all of whom were included in the safety analysis.At a median follow-up of 23.1 months (IQR 15.8-28.6), the median EFS was 12.68 months (95% CI 6.31-NE), with a 3-month EFS rate of 92.3% (95%CI 77.8-100), a 6-month EFS rate of 75.5% (95%CI 51.4-99.7) and a 12-month EFS rate of 50.3% (95%CI 22.1-78.6). Both median RFS and PFS was 12.68 months (95% CI 6.31-NE). Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 2 (14.3%) patients, one with urinary tract infection and the other with vertebrobasilar insufficiency. Serious TEAEs occurred in one (7.1%) patient. No deaths were reported. PD-L1 expression was not related to treatment efficacy. Protein sequencing revealed a total of 296 proteins with differential expression between responsive and unresponsive patients. Analysis using Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway demonstrated that the responsive group was associated with activated biological processes, including T cell receptor signaling pathway, alpha-beta T cell activation, and adaptive immune response. Conclusions: Intravesical camrelizumab demonstrated promising anti-tumor activity and acceptable tolerance in patients with BCG-unresponsive NMIBC who either declined or were ineligible for radical cystectomy. This suggests its potential as an effective non-surgical and topical treatment option for this specific population. The efficacy was attributed to enhanced immune pathway activation. Clinical trial information: NCT04706598 .
To explore the feasibility and efficacy of docetaxel plus prednisone for Chinese population with metastatic castration refractory prostate cancer (mCRPC).A total of 228 patients recruited from 15 centers were randomized to receive 10 cycles of D3P arm (docetaxel: 75 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily) or M3P arm (mitoxantrone: 12 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily). Primary end point was overall survival, and secondary end points were events progression-free survival (PFS), response rate, response duration. Quality of life (QoL) was also assessed in both treatment groups.The median overall survival was 21.88 months in D3P arm and 13.67 months in M3P arm (P = 0.0011, hazard ratio = 0.63, 95% confidence interval, 0.46-0.86). Subgroup analysis was consistent with the results of overall analysis. Events progression-free survival (pain, PSA, tumor and disease) were significantly improved in D3P arm compared with M3P arm. PSA response rate was 35.11% for patients treated by D3P arm and 19.39% for M3P arm (P = 0.0155). Pain response rate was higher in D3P arm (61.11%, P = 0.0011) than in M3P (23.08%) arm. No statistical differences were found between D3P arm and M3P arm for QoL, tumor response rate and response duration of PSA and pain. The tolerability and overall safety of D3P arm were generally comparable to that of M3P arm.Compared with M3P arm, D3P arm significantly prolonged overall survival for the Chinese patients with mCRPC and improved the response rate for PSA and pain.clinicaltrials.gov NCT00436839.
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