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Many different genetic alterations, as well as complex epigenetic interactions, are the basis of the genesis and progression of prostate cancer (CaP). This is the reason why until now the molecular pathways related to development of this cancer were only partly known, and even less those that determine aggressive or indolent tumour behaviour. MicroRNAs (miRNAs) represent a class of about 22 nucleotides long, small non-coding RNAs, which are involved in gene expression regulation at the post-transcriptional level. MiRNAs play a crucial role in regulating several biological functions and preserving homeostasis, as they carry out a wide modulatory activity on various molecular signalling pathways. MiRNA genes are placed in cancer-related genomic regions or in fragile sites, and they have been proven to be involved in the main steps of carcinogenesis as oncogenes or oncosuppressors in many types of cancer, including CaP. We performed a narrative review to describe the relationship between miRNAs and the crucial steps of development and progression of CaP. The aims of this study were to improve the knowledge regarding the mechanisms underlying miRNA expression and their target genes, and to contribute to understanding the relationship between miRNA expression profiles and CaP. [ABSTRACT FROM AUTHOR]

Purpose: Currently, bladder cancer (BC) surveillance consists of periodic white light cystoscopy and urinary cytology (UC). However, both diagnostic tools have limitations. Therefore, to improve the management of recurrent BC, novel, innovative diagnostic tests are needed. The primary aim of this study was to determine the diagnostic performance of Bladder EpiCheck (BE) and photodynamic diagnosis (PDD) guided cystoscopy in the surveillance of high-risk BC. A secondary aim was to compare Bladder EpiCheck (BE) and PDD-guided cystoscopy findings with whose of UC to design a diagnostic algorithm that facilitates clinical decision making. PATIENTS AND METHODS: This was a prospective, blinded, single-arm, single-visit cohort study. All patients were under surveillance for high-risk non-muscle-invasive bladder cancer, and underwent cystoscopy with PDD and a BE test. Those who received a histological diagnosis were used as a reference population. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of BE, PDD-guided cystoscopy, and UC for identifying biopsy-confirmed BC lesions. The diagnostic power of the test was assessed by determining the area under the curve (AUC).Results: Forty patients were enrolled. For BE, the AUC was 0.95, and BC recurrence was detected at a sensitivity of 100% and specificity of 90.9%. For PDD, the AUC was 0.51, with a sensitivity and specificity of 61% and 41%, respectively. BE was combined with UC to create a decision-making algorithm capable of reducing the number of follow-up cystoscopies needed.Conclusion: BE is a very accurate diagnostic tool that has the potential to be useful in the surveillance of high-risk BC patients. Especially when combined with UC, it may be used to reduce the number of cystoscopies needed throughout follow-up. Conversely, the use of PDD as a diagnostic tool in such patients should be reconsidered. However, due to the small sample size of this study, a larger prospective clinical trial should be performed to confirm findings. [ABSTRACT FROM AUTHOR]

Background: Nowadays, the intravesical Bacillus Calmette-Guérin (BCG) instillation is the method of choice for the postsurgical treatment of high-grade nonmuscle-invasive bladder cancer , to reduce both recurrence rate and risk of progression. BCG is hypothesized to correct the immune system disequilibrium occurring during carcinogenesis, through an immunostimulation with detrimental effects for tumoral cells. Inflammation plays a crucial role in tumor progression. The deregulation of inflammasomes upon carcinogenesis underlines its importance both in physiologic and pathologic human conditions. Nucleotide oligomerization domain-like receptors (NLRs) are key components of this molecular platform and the increase in expression of some members of nucleotide oligomerization domain-like receptors family (NLRP3, NLRP4, NLRP9, and NLR family apoptosis inhibitory protein [NAIP]) in urothelial carcinoma was already demonstrated in our previous work. The first aim of the present work was to estimate whether these inflammasome-related genes show alterations during BCG instillations. The expression levels of NLRP3, NLRP4, NLRP9, and NAIP were assessed in the urine sediments from patients, which underwent surgery for superficial high-grade bladder cancer and further subjected to serial BCG instillations. The eventual association between NLR expression and recurrence was also evaluated. The expression of CK20 mRNA as confirmed marker of bladder cancer was also assayed.Methods: Urine were sampled from patients harboring high-grade superficial bladder cancer and treated postsurgically with weekly BCG instillations for 6 weeks (induction cycle, I). Urine sediments were processed and resulting RNA was reverse transcribed and used for amplification by real-time PCR.Results: After surgery, CK20 levels decreased significantly whereas NLRP4 and NLRP9 genes showed an increase. NLRP3 and NAIP remained substantially unmodified. CK20 mRNA decreased at the end of the induction cycle. NLRP3 did not show relevant modifications. The expression levels of NLRP4 and NLRP9 decreased significantly after 2 BCG administrations and remained substantially downregulated during the whole induction cycle. CK20 was higher in recurrence cases before BCG administration compared to the recurrence-free group, while no significant difference after BCG therapy was recorded. NLRP4 and NLRP9 were higher in patients with recurrence before BCG administration.Conclusions: The study underlines the importance of NLRP4 and NLRP9 in urothelial carcinoma and if these preliminary data will be confirmed in larger cohort studies, the assessment of NLRP4 and NLRP9 expression levels could help to predict the BCG failure, playing a relevant role in decision making for early radical surgery. [ABSTRACT FROM AUTHOR]

Background: Inflammation plays a crucial role in different stages of cancer development and has long been associated with various types of cancer. Strong associations between dysregulated inflammasome activity and human heritable and acquired inflammatory diseases highlight the importance of this pathway in the immune response. The inflammasome is a large complex of NOD-like receptors called NLRs and drives growth and progression of different tumors. The aim of the present study was the characterization of some NLR genes, NLRP3, NLRP4, NLRP9, and NAIP, in urine sediment of patients with bladder cancer. Cytokeratin 20 and survivin were used as confirmed markers of bladder cancer.Basic Procedures: For this study, 3 groups of subjects were considered: patients harboring bladder cancer, subjects affected by bladder inflammation (CTR1), and healthy subjects (CTR0). Total RNA was extracted from urine sediments and resulting complementary DNA was used for amplification by real-time polymerase chain reaction. Results were stratified according to tumor stage, grade, and risk of progression and recurrence.Main Findings: The expression of cytokeratin 20 was always significantly higher in patients with bladder cancer when compared with that in both the tumor-free groups. NLRP3, NLRP4, NLRP9, and NAIP were overexpressed in patients with BCa when compared with that in CTR0. Stratification according to tumor stage, grade, and risk of recurrence and progression showed NLRP up-regulations in patients with early-stage cancer. NAIP was overexpressed in high-risk patients in comparison to CTR0 and in high-grade patients compared with CTR0 and CTR1.Principal Conclusions: These data are relevant to demonstrate the role of inflammasome in urothelial carcinoma, making NLR genes in urine sediment potential candidates for bladder cancer diagnosis. [ABSTRACT FROM AUTHOR]

Objective: 3D models are increasingly used as additional preoperative tools for renal surgery. We aim to evaluate the impact of 3D renal models in the assessment of PADUA, RENAL, Contact Surface Area (CSA) and Arterial Based Complexity (ABC) for the prediction of complications after Robot assisted Partial Nephrectomy (RAPN).Methods and Materials: Overall, 57 patients with T1 and 1 patient with T2 renal mass referred to RAPN, were prospectively enrolled. 3D virtual modelling was obtained from 2D computed tomography (CT). Two radiologists recorded PADUA2D, RENAL2D, CSA2D and ABC2D by evaluation of 2D images; two bioengineers recorded PADUA3D, RENAL3D, CSA3D and ABC3D by evaluation of the 3D model, using MeshMixer software. To evaluate the concordance between 2D and 3D nephrometry scores, Cohen's j coefficient was calculated. Receiver-operating characteristic (ROC) curves were generated to evaluate the accuracy of 3D and 2D nephrometry scores to predict overall complications. Finally, the impact of 3D model on clamping approach during RAPN was compared to 2D imaging.Results: PADUA3D, RENAL3D, CSA3D and ABC3D scores had a significant different distribution compared to PADUA2D, RENAL2D, CSA2D and ABC2D (all p≤0.03). 2D nephrometry scores may be unchanged, reduced or increased after assessment by 3D models: CSA3D, PADUA3D, RENAL3D and ABC3D were reduced in14%, 26%, 29% and 16% and increased in 16%, 36%, 38% and 29% of cases, respectively. At ROC curve analysis, PADUA3D, RENAL3D and ABC3D showed were significantly better accuracy to predict complications compared to PADUA2D, RENAL2D and ABC2D. PADUA3D (OR: 1.66), RENAL3D (OR: 1.69) and ABC3D (OR: 2.44) revealed a significant correlation with postoperative complications (all P ≤0.03).Conclusion: Nephrometry scores calculated via 3D models predict complications after RAPN with higher accuracy than conventional 2D imaging. [ABSTRACT FROM AUTHOR]