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Background: Prostate cancer (PCa) is one of the most common malignancies of the urinary system. Cuproptosis, a newly discovered form of cell death. The relationship between cuproptosis-related long non-coding RNAs (ClncRNAs) related to PCa and prognosis remains unclear. This study aimed to explore the clinical significance of novel ClncRNAs in the prognostic assessment of PCa. Methods: ClncRNAs and differentially expressed mRNAs linked to these ClncRNAs were identified using Pearson's correlation and differential expression analyses. A prognostic signature (risk score) comprising three ClncRNAs was established based on multivariable Cox regression analysis. The predictive performance of this ClncRNAs signature was validated using receiver operating characteristic curves and nomograms. Finally, further in vitro cell experiments were conducted for validation, including quantitative polymerase chain reaction (qPCR), western blot (WB), cell proliferation assays, cell migration assays, cell invasion assays, apoptosis, and cell cycle analysis. Results: We constructed a prognostic signature of ClncRNAs for PCa comprising three key differentially expressed ClncRNAs(AC010896-1, AC016394-2, and SNHG9). Multivariable Cox regression analysis indicated that clinical staging and risk scores of the ClncRNAs signature were independent prognostic factors for PCa. Compared to other clinical features, the ClncRNAs signature exhibited higher diagnostic efficiency and performed well in predicting the 1-, 3-, and 5-year progression-free intervals (PFIs) for PCa. Notably, in terms of immune activity, PCa patients with high-risk scores exhibited higher tumor mutational burden (TMB) levels, while their Tumor Immune Dysfunction and Exclusion (TIDE) scores were lower than those of PCa patients with low-risk scores. Additionally, in vitro cellular functional experiments, we knocked down SNHG9 that is the most significantly differentially expressed ClncRNA among the three key ClncRNAs. SNHG9 knockdown resulted in a significant increase in G1 phase cells and a decrease in S and G2 phases, indicating inhibition of DNA synthesis and cell cycle progression. Colony formation assays showed reduced clonogenic ability, with fewer and smaller colonies. Western blot analysis revealed the upregulation of the key cuproptosis-related mRNAs FDX1 and DLST. These findings suggested that SNHG9 promotes PCa cell proliferation, migration, and invasion. Conclusion: Building on the three ClncRNAs, we identified a novel prognostic signature of PCa. The ClncRNA SNHG9 can promote PCa cell proliferation, migration, and invasion. [ABSTRACT FROM AUTHOR]

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Simple Summary: Available studies suggest that radiomics and machine learning applied to PSMA-radioligand avid primary prostate carcinoma have potential to serve as an alternative for non-invasive Gleason score characterization, for the prediction of biochemical recurrence and to differentiate benign from malignant increased tracer uptake. However, prior to their implementation in clinical practice, additional, clinically relevant studies performed according to recently published guidelines and checklists, offering full transparency, including large enough datasets as well as external validation, are mandatory. Positron emission tomography (PET) using radiolabeled prostate-specific membrane antigen targeting PET-imaging agents has been increasingly used over the past decade for imaging and directing prostate carcinoma treatment. Here, we summarize the available literature data on radiomics and machine learning using these imaging agents in prostate carcinoma. Gleason scores derived from biopsy and after resection are discordant in a large number of prostate carcinoma patients. Available studies suggest that radiomics and machine learning applied to PSMA-radioligand avid primary prostate carcinoma might be better performing than biopsy-based Gleason-scoring and could serve as an alternative for non-invasive GS characterization. Furthermore, it may allow for the prediction of biochemical recurrence with a net benefit for clinical utilization. Machine learning based on PET/CT radiomics features was also shown to be able to differentiate benign from malignant increased tracer uptake on PSMA-targeting radioligand PET/CT examinations, thus paving the way for a fully automated image reading in nuclear medicine. As for prediction to treatment outcome following 177Lu-PSMA therapy and overall survival, a limited number of studies have reported promising results on radiomics and machine learning applied to PSMA-targeting radioligand PET/CT images for this purpose. Its added value to clinical parameters warrants further exploration in larger datasets of patients. [ABSTRACT FROM AUTHOR]

Assessing the perioperative, oncological, and functional results of robotic-assisted radical prostatectomy (RARP) versus three-dimensional laparoscopic radical prostatectomy (3D LRP), a comprehensive exploration of the Cochrane Library, PubMed, EMBASE, and Web of Science databases was carried out until July 2024. The combined results were evaluated by utilizing the weighted mean differences (WMDs) and odds ratios (ORs) through the application of Stata version 18, where data were gathered and scrutinized. In addition, sensitivity analyses were performed to ensure the robustness of our findings. In the meta-analysis we conducted, four studies were incorporated in total, which comprised two randomized controlled trials, one study that was retrospective and another that was prospective. The findings revealed that RARP was associated with a significantly reduced estimated blood loss (EBL) (WMD − 31.04, 95%CI − 54.57, − 7.51; p = 0.01) compared to 3D LRP. Nonetheless, there were no notable statistical variances seen between the two groups regarding operative time (OT), nerve-sparing rates, positive surgical margin (PSM) rates, biochemical recurrence (BCR) rates, or the restoration of urinary continence and potency 3 or 6 months after the surgery. In conclusion, our comprehensive meta-analysis has offered a detailed contrast between the results of RARP and 3D LRP in the treatment of prostate cancer. The findings highlight a considerable decrease in projected blood loss linked with RARP, yet no notable variances were detected between the two methods regarding other perioperative, oncological, and functional results. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is one of the most prevalent malignancies affecting males; however, the role of inflammatory activity in the pathogenesis of this disease is not yet fully elucidated. Although inflammation is recognized as being closely associated with the onset and progression of PCa, the specific causal relationships between individual inflammatory factors and the disease require further clarification. Methods: Mendelian randomization (MR) methodologies can mitigate bias by utilizing whole-genome sequencing data, leveraging specific genetic variants to assess causal relationships between a given exposure and an outcome of interest. This research employed an MR approach to investigate the association between inflammatory cytokines and PCa. Results: In total, 44 inflammatory cytokines were evaluated in a large GWAS dataset to enable the drawing of robust conclusions. Elevated circulating Creactive protein (CRP) and prostaglandin E2 (PGE-2) levels were related to greater PCa risk. The reverse Mendelian randomization (MR) study indicates a causal relationship between prostate cancer and stem cell factor (SCF) (P=0.025). Conclusion: CRP and PGE-2 play crucial roles in the regulation of PCa development. Moreover, PCa may have an impact on SCF levels. Further research is imperative to elucidate whether these biomarkers can be effectively utilized to prevent or treat PCa. [ABSTRACT FROM AUTHOR]

This study aimed to compare toxicities, prostate volume and dosimetry, between patients who underwent intensity-modulated radiation therapy (IMRT) combined with ≥3 months of neoadjuvant androgen deprivation therapy (NADT) and those without NADT for prostate cancer. In total, 449 patients with intermediate- and high-risk prostate cancer received 78 Gy IMRT in 39 fractions, of which 129 were treated without any ADT (non-ADT group) and 320 with NADT ≥3 months (NADT group). Adverse events and dose-volume indices were compared between the two groups retrospectively. The NADT group had a lower rate of acute grade 2 gastrointestinal (GI) toxicities (17% vs 25%, P  = 0.063) and late grade 2 GI toxicities (P  = 0.055), including a significantly lower rate of late grade 2 rectal hemorrhage (P  = 0.033), compared with the non-ADT group. There were no cases of late grade 3 or higher GI toxicities. The average volume of the prostate in the NADT group was 38% smaller than that in the non-ADT group (43.7 vs 27.0 cm3, P  < 0.001). Bladder V40Gy and V50Gy, and rectum V40Gy, V50Gy, V60Gy and V70Gy were significantly smaller in the NADT group. In the NADT group, no significant difference was observed in adverse events or dosimetry between the subgroups with NADT ≥12 and <12 months. Acute and late rectal toxicities were reduced by NADT within ≥3 months in accordance with reduced prostate volume and improved rectal dosimetry. This suggests a merit of administering neoadjuvant ADT ≥3 months for reducing rectal toxicities. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic value of prostate imaging-reporting and data system (mpMRI) version 2.0 with classical parameters for prostate cancer detection in gray zone patients with ultrasonography-guided prostate biopsy as a reference point. Materials and Methods: With the retrospective nature of the study, 438 biopsy-naïve patients in the gray zone with pre-biopsy mpMRI were reviewed. Ultrasonography-guided transrectal prostate biopsy was the reference point. Diagnostic performance of classical parameters compared with mpMRI results for prostate carcinoma and clinically significant prostate carcinoma. Results: The overall cancer detection rate was 30%. Prostate-specific antigen density, free/total prostate-specific antigen ratio, prostate volume, suspicious digital rectal examination, and mpMRI score >3 were independent predictors of clinically significant prostate carcinoma. Prostate-specific antigen density followed by free/total prostate-specific antigen ratio had the largest area under the curve values compared with mpMRI score >3 for prostate carcinoma and clinically significant prostate carcinoma. Conclusion: Classical parameters, prostate-specific antigen density, and f/t prostate-specific antigen ratio were still critical to deciding prostate biopsy in gray zone patients, in whom ultrasonography-guided transrectal prostate biopsy was used as a reference point. In centers where targeted fusion biopsies were unavailable, pre-biopsy mpMRI still had some benefits. However, biopsy decisions should be made according to each patient’s individual characteristics.

Objective To observe the expression changes of serum exosome long non-coding RNA HOXA-AS3 (lncRNA HOXA-AS3) and microRNA 29a (miR-29a) in patients with prostate cancer (PCa), and to analyze their relationships with clinical characteristics and prognosis of patients. Methods Totally 115 PCa patients (observation group) and 115 healthy individuals (control group) undergoing physical examinations at the same time were enrolled. The expression levels of lncRNA-HOXA-AS3 and miR- 29a in serum exosomes were detected by qRT-PCR. The correlation between the two indicators and their relationships with the clinical features of patients were analyzed by Pearson correlation analysis. The observation group was divided into the high lncRNA-HOXA-AS3 expression group (56 cases) and low lncRNAHOXA-AS3 expression group (59 cases) according to the mean relative expression of lncRNA-HOXA-AS3, and divided into the high miR-29a expression group (58 cases) and low miR-29a expression group (57 cases) according to the mean relative expression of miR-29a. The survival curves were drawn by Kaplan-Meier method, and the survival rates of high expression group and low expression group were compared by Log-rank test. The risk factors for poor prognosis of PCa patients were analyzed by Cox regression analysis. Results Compared with the control group, the relative expression level of serum exosome lncRNA-HOXA-AS3 in the observation group increased, while the relative expression level of miR-29a decreased (both P<0. 05). The expression of lncRNA-HOXA-AS3 and miR-29a in the serum exosomes of the observation group was negatively correlated (r=–0. 689，P<0. 05). The expression of lncRNA-HOXA-AS3 and miR-29a in serum exosomes was related to Gleason score, T stage, and lymph node metastasis in PCa patients (all P<0. 05). Compared with patients with low expression of lncRNA-HOXA-AS3, patients with high expression of lncRNA-HOXA-AS3 had a lower survival rate (P<0. 05)； compared with those with high expression of miR-29a, patients with low expression of miR29a had a lower survival rate (P<0. 05). Univariate and multivariate analysis showed that lncRNA-HOXA-AS3 and miR29a were independent risk factors for poor prognosis in patients with PCa (P<0. 05). Conclusions The expression of lncRNA-HOXA-AS3 in the serum exosomes of PCa patients increases, while the expression of miR-29a is down-regulated, and the two expression levels are negatively correlated. Both indicators are related to the patient's Gleason score, T stage, and lymph node metastasis. Patients with high expression of lncRNA-HOXA-AS3 and low expression of miR-29a have a low survival rate. The lncRNA-HOXA-AS3 and miR-29a are independent risk factors for poor prognosis in PCa patients. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic value of prostate imaging-reporting and data system (mpMRI) version 2.0 with classical parameters for prostate cancer detection in gray zone patients with ultrasonography-guided prostate biopsy as a reference point. Materials and Methods: With the retrospective nature of the study, 438 biopsy-naïve patients in the gray zone with pre-biopsy mpMRI were reviewed. Ultrasonography-guided transrectal prostate biopsy was the reference point. Diagnostic performance of classical parameters compared with mpMRI results for prostate carcinoma and clinically significant prostate carcinoma. Results: The overall cancer detection rate was 30%. Prostate-specific antigen density, free/total prostate-specific antigen ratio, prostate volume, suspicious digital rectal examination, and mpMRI score >3 were independent predictors of clinically significant prostate carcinoma. Prostatespecific antigen density followed by free/total prostate-specific antigen ratio had the largest area under the curve values compared with mpMRI score >3 for prostate carcinoma and clinically significant prostate carcinoma. Conclusion: Classical parameters, prostate-specific antigen density, and f/t prostate-specific antigen ratio were still critical to deciding prostate biopsy in gray zone patients, in whom ultrasonography-guided transrectal prostate biopsy was used as a reference point. In centers where targeted fusion biopsies were unavailable, pre-biopsy mpMRI still had some benefits. However, biopsy decisions should be made according to each patient's individual characteristics. [ABSTRACT FROM AUTHOR]

Canine urothelial carcinoma (UC) and prostate carcinoma (PC) frequently exhibit the BRAFV595E mutation, akin to the BRAFV600E mutation common in various human cancers. Since the initial discovery of the BRAF mutation in canine cancers in 2015, PCR has been the standard method for its detection in both liquid and tissue biopsies. Considering the similarity between the canine BRAFV595E and human BRAFV600E mutations, we hypothesized that immunohistochemistry (IHC) using a BRAFV600E‐specific antibody could effectively identify the canine mutant BRAFV595E protein. We tested 122 canine UC (bladder n = 108, urethra n = 14), 21 PC, and benign tissue using IHC and performed digital droplet PCR (ddPCR) on all 122 UC and on 14 IHC positive PC cases. The results from ddPCR and IHC were concordant in 99% (135/136) of the tumours. Using IHC, BRAFV595E was detected in 72/122 (59%) UC and 14/21 (65%) PC. Staining of all benign bladder and prostate tissues was negative. If present, mutant BRAF staining was homogenous, with rare intratumour heterogeneity in three (4%) cases of UC. Additionally, the BRAFV595E mutation was more prevalent in tumours with urothelial morphology, and less common in glandular PC or UC with divergent differentiation. This study establishes that BRAFV600‐specific IHC is a reliable and accurate method for detecting the mutant BRAFV595E protein in canine UC and PC. Moreover, the use of IHC, especially with tissue microarrays, provides a cost‐efficient test for large‐scale screening of canine cancers for the presence of BRAF mutations. This advancement paves the way for further research to define the prognostic and predictive role of this tumour marker in dogs and use IHC to stratify dogs for the treatment with BRAF inhibitors. [ABSTRACT FROM AUTHOR]

Interstitial high-dose-rate brachytherapy (HDR-BT) is an effective therapy modality for patients with localized prostate carcinoma. The objectives of the study were to optimise the therapy regime variables using two models: response surface methodology (RSM) and artificial neural network (ANN). Thirty-one studies with 5651 patients were included (2078 patients presented as low-risk, 3077 patients with intermediate-risk, and 496 patients with high-risk). A comparison of these therapy schedules was carried out using an effective biologically effective dose (BED ef) that was calculated assuming the number of treatment days and dose (D) per day. The modelling and optimization of therapy parameters (BED ef and risk level) in order to obtain the maximum biochemical free survival (BFS) were carried out by the RSM and ANN models. An optimal treatment schedule (BFS = 97%) for patients presented with low-risk biochemical recurrence would be D = 26 Gy applied in one application, 2 fractions at least 6 h apart, within an overall treatment time of 1 day (BED ef = 251 Gy) by the RSM and ANN model. For patients presented with intermediate- or high-risk an optimal treatment regime (BFS = 94% and 90%, respectively) would be D = 38 Gy applied in one application, 4 fractions at least 6 h apart, with an overall treatment time of 2 days (BED ef = 279 Gy) by the RSM and ANN models. The RSM and ANN models determine almost the same optimal values for the set of predicted therapy parameters that make a feasible selection of an optimal treatment regime. • HDR-BT is an effective therapy modality for patients with localised prostate carcinoma. • Optimisation of HDR-BT regime variables was carried out by the RSM and ANN models. • The RSM and ANN models determined almost the same optimal values. [ABSTRACT FROM AUTHOR]

BackgroundProstate cancer (PCa) is one of the most common malignancies of the urinary system. Cuproptosis, a newly discovered form of cell death. The relationship between cuproptosis-related long non-coding RNAs (ClncRNAs) related to PCa and prognosis remains unclear. This study aimed to explore the clinical significance of novel ClncRNAs in the prognostic assessment of PCa.MethodsClncRNAs and differentially expressed mRNAs linked to these ClncRNAs were identified using Pearson’s correlation and differential expression analyses. A prognostic signature (risk score) comprising three ClncRNAs was established based on multivariable Cox regression analysis. The predictive performance of this ClncRNAs signature was validated using receiver operating characteristic curves and nomograms. Finally, further in vitro cell experiments were conducted for validation, including quantitative polymerase chain reaction (qPCR), western blot (WB), cell proliferation assays, cell migration assays, cell invasion assays, apoptosis, and cell cycle analysis.ResultsWe constructed a prognostic signature of ClncRNAs for PCa comprising three key differentially expressed ClncRNAs(AC010896-1, AC016394-2, and SNHG9). Multivariable Cox regression analysis indicated that clinical staging and risk scores of the ClncRNAs signature were independent prognostic factors for PCa. Compared to other clinical features, the ClncRNAs signature exhibited higher diagnostic efficiency and performed well in predicting the 1-, 3-, and 5-year progression-free intervals (PFIs) for PCa. Notably, in terms of immune activity, PCa patients with high-risk scores exhibited higher tumor mutational burden (TMB) levels, while their Tumor Immune Dysfunction and Exclusion (TIDE) scores were lower than those of PCa patients with low-risk scores. Additionally, in vitro cellular functional experiments, we knocked down SNHG9 that is the most significantly differentially expressed ClncRNA among the three key ClncRNAs. SNHG9 knockdown resulted in a significant increase in G1 phase cells and a decrease in S and G2 phases, indicating inhibition of DNA synthesis and cell cycle progression. Colony formation assays showed reduced clonogenic ability, with fewer and smaller colonies. Western blot analysis revealed the upregulation of the key cuproptosis-related mRNAs FDX1 and DLST. These findings suggested that SNHG9 promotes PCa cell proliferation, migration, and invasion.ConclusionBuilding on the three ClncRNAs, we identified a novel prognostic signature of PCa. The ClncRNA SNHG9 can promote PCa cell proliferation, migration, and invasion.

Abstract Several studies have shown an association between prostate carcinoma (PCa) and Epstein-Barr virus (EBV); however, none of the studies so far have identified the histopathological and genetic markers of cancer aggressiveness associated with EBV in PCa tissues. In this study, we used previously characterized EBV-PCR-positive (n = 39) and EBV-negative (n = 60) PCa tissues to perform an IHC-based assessment of key histopathological and molecular markers of PCa aggressiveness (EMT markers, AR expression, perineural invasion, and lymphocytic infiltration characterization). Additionally, we investigated the differential expression of key oncogenes, EMT-associated genes, and PCa-specific oncomiRs, in EBV-positive and -negative tissues, using the qPCR array. Finally, survival benefit analysis was also performed in EBV-positive and EBV-negative PCa patients. The EBV-positive PCa exhibited a higher percentage (80%) of perineural invasion (PNI) compared to EBV-negative PCa (67.3%) samples. Similarly, a higher lymphocytic infiltration was observed in EBV-LMP1-positive PCa samples. The subset characterization of T and B cell lymphocytic infiltration showed a trend of higher intratumoral and tumor stromal lymphocytic infiltration in EBV-negative tissues compared with EBV-positive tissues. The logistic regression analysis showed that EBV-positive status was associated with decreased odds (OR = 0.07; p-value

Abstract Leontodon hispidulus Boiss is a wild annual plant growing in Egypt. The present study aims for the first time, to evaluate the phytochemical profile of the main secondary metabolites of the optimized ethanolic extract of the plant using Quadrupole Time-of-Flight Liquid chromatography-mass spectrometry and Gas chromatography-mass spectrometry. It also aims to assess the anticancer activity of its different fractions against the prostate carcinoma cell line. Moreover, an in-silico docking study was performed using the Hexokinase-two enzyme. LC-qToF-MS analysis revealed the tentative identification of 36 phenolic compounds including the glycosides of (luteolin, quercetin, kaempferol, apigenin, isorhamnetin, and daidzein), coumarines (esculin, esculetin, and daphnetin), and phenolic acids (chlorogenic, caffeic, quinic, P-coumaric, and rosmarinic). GC–MS/MS analysis revealed the presence of 18 compounds where palmitic acid, myristic acid, alpha-amyrin, and beta-amyrin were the major ones. The cytotoxic activity results revealed that methylene chloride and ethyl acetate fractions showed the highest cytotoxic activity against the PC3 cell line, with IC50 values of 19, and 19.6 μg/ml, respectively. Interestingly, the docking study demonstrated that apigenin-7-O-glucoside, luteolin-7-O-glucoside, kaempferol-3-O-glucuronide, quercetin-4′-O-glucoside, esculin, rosmarinic acid, chlorogenic acid, and α-amyrin exhibited high affinity to the selected target, HEK-2 enzyme.

Several studies have shown an association between prostate carcinoma (PCa) and Epstein-Barr virus (EBV); however, none of the studies so far have identified the histopathological and genetic markers of cancer aggressiveness associated with EBV in PCa tissues. In this study, we used previously characterized EBV-PCR-positive (n = 39) and EBV-negative (n = 60) PCa tissues to perform an IHC-based assessment of key histopathological and molecular markers of PCa aggressiveness (EMT markers, AR expression, perineural invasion, and lymphocytic infiltration characterization). Additionally, we investigated the differential expression of key oncogenes, EMT-associated genes, and PCa-specific oncomiRs, in EBV-positive and -negative tissues, using the qPCR array. Finally, survival benefit analysis was also performed in EBV-positive and EBV-negative PCa patients. The EBV-positive PCa exhibited a higher percentage (80%) of perineural invasion (PNI) compared to EBV-negative PCa (67.3%) samples. Similarly, a higher lymphocytic infiltration was observed in EBV-LMP1-positive PCa samples. The subset characterization of T and B cell lymphocytic infiltration showed a trend of higher intratumoral and tumor stromal lymphocytic infiltration in EBV-negative tissues compared with EBV-positive tissues. The logistic regression analysis showed that EBV-positive status was associated with decreased odds (OR = 0.07; p-value < 0.019) of CD3 intratumoral lymphocytic infiltration in PCa tissues. The analysis of IHC-based expression patterns of EMT markers showed comparable expression of all EMT markers, except vimentin, which showed higher expression in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Furthermore, gene expression analysis showed a statistically significant difference (p < 0.05) in the expression of CDH1, AR, CHEK-2, CDKN-1B, and CDC-20 and oncomiRs miR-126, miR-152-3p, miR-452, miR-145-3p, miR-196a, miR-183-3p, and miR-146b in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Overall, the survival proportion was comparable in both groups. The presence of EBV in the PCa tissues results in an increased expression of certain oncogenes, oncomiRs, and EMT marker (vimentin) and a decrease in CD3 ITL, which may be associated with the aggressive forms of PCa. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationships between blood lipids and the risk of recurrence after radical prostatectomy (RP). Methods Totally 161 prostate cancer patients undergoing RP were enrolled, including 68 cases of medium-low prognosis risk and 93 cases of high prognosis risk. After a follow-up period of 3 years, biochemical recurrence was observed in 45 patients while no biochemical recurrence occurred in 116 patients. The general data, laboratory examination results, Gleason score and clinical stage of the subjects were collected. A comparison of the collected data was made between the medium-low risk group and the high-risk group, as well as between the biochemical recurrence group and the non-recurrence group. Indexes with statistically significant differences were included in the multivariate Logistic regression model to identify the risk factors associated with high prognosis risk and biochemical recurrence. Results Compared with the medium-low risk group, the high-risk group exhibited a higher abnormal rate of HDL-C and an elevated level of Lp (a)（both P<0. 05). Multivariate Logistic regression analysis revealed that abnormal HDL-C level was a high risk factor for prognosis of patients after RP (P<0. 05). The abnormal rates of HDL-C and Lp (a), the levels of Lp (a) and PSA, the proportions of Gleason score ≥8 and clinical stage ≥T2c were higher in the recurrence group than in the non-recurrence group (all P<0. 05). Multivariate Logistic regression analysis showed that high-grade clinical stage (≥T2c), elevated PSA level and abnormal Lp (a) level were risk factors for recurrence in patients undergoing RP (all P< 0. 05). Conclusions The abnormal serum HDL-C and Lp (a) are associated with the high prognosis risk and biochemi⁃ cal recurrence in patients undergoing RP. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of long chain non-coding RNA (lncR) HOXA-AS3 and microRNA29a (miR-29a) on apoptosis and autophagy of prostate cancer (PCa) cells. Methods Human PCa cells (DU-145, LNCaP, C4-2B) and human normal prostate cells RWPE-1 were cultured in vitro, and RT-qPCR was used to detect the relative expression of lncR-HOXA-AS3 and miR-29a in the cells. Dual luciferase reporter assay was used to verify the targeted regulatory relationship between lncR-HOXA-AS3 and miR-29a. LNCaP cells in the logarithmic growth phase were divided into the si-NC group, si-HOXA-AS3 group, si-HOXA-AS3+anti-miR-NC group and si-HOXA-AS3+ anti-miR-29a group. Si-NC, si-HOXA-AS3, si-HOXA-AS3+anti-miR-NC, si-HOXA-AS3+ anti-miR-29a were transfected into LNCaP cells of the above groups by liposome transfection. The expression changes of lncR-HOXA-AS3 and miR-29a in each group were detected by RT-qPCR, and the apoptosis of cells in each group was detected by flow cytometry, and the expression levels of apoptosis-related proteins Caspase-3, autophagy related proteins LC3II, LC3I and Beclin 1 in each group were detected by Western blotting. Results Compared with the normal prostate cells, the expression of lncR-HOXA-AS3 significantly increased (P<0. 05), while the expression of miR-29a significantly decreased in human PCa cells (P<0. 05) . Dual luciferase reporter genes showed that lncR-HOXA-AS3 inhibited luciferase activity by targeting miR-29a (P<0. 05) . Compared with the si-NC group, the lncR-HOXA-AS3 expression of LNCaP cells decreased, and the miR-29a expression increased (both P<0. 05), the apoptosis rate significantly increased (P<0. 05), and the protein expression levels of Caspase-3, LC3II/LC3I and Beclin 1 significantly increased in the si-HOXA-AS3 group (all P<0. 05) . Compared with the si-HOXAAS3+anti-miR-NC group, the expression of miR-29a significantly decreased (P<0. 05), the apoptosis rate significantly decreased (P<0. 05), and the expression levels of Caspase-3, LC3II/LC3I, and Beclin 1 proteins significantly decreased in the si-HOXA-AS3+anti-miR-29a group (all P<0. 05) . Conclusion Inhibiting lncR-HOXA-AS3 can target and regulate the miR-29a gene to promote apoptosis and autophagy in PCa cells. [ABSTRACT FROM AUTHOR]

Multiple diseases and disorders are connected with occupational and environmental exposure risk. It is also well-established that chemicals and chemical mixtures have an influence on the immune cells of humans. This is an important field of research that has been pursued extensively in relation to autoimmune illnesses, allergy/asthma, and lung cancer, but Prostate Carcinoma has received rare reports. Chronic chemical exposure is known to produce inflammation, which is one of the most prominent characteristics of all malignancies. Changes in the ratio of pro-inflammatory to anti-inflammatory molecules are thought to be a key factor in the emergence of inflammation. Prostate gland cells express the pro-inflammatory cytokine interleukin-18 (IL-18), which is a major facilitator of immunological responses. Conversely, interleukin-10 (IL-10) is an anti-inflammatory cytokine that is linked to immune responses and inhibits the development of an inflammatory environment. Our goal is to investigate the inflammatory status of IL-18 (pro-) and IL-10 (anti-) in a variety of occupationally exposed populations in patients with Benign Prostate Hyperplasia (BPH) and patients with Prostate Carcinoma. The present study was conducted with 664 subjects, comprising 285 Prostate Carcinoma patients, 94 BPH patients and 285 controls. The subjects of BPH and Prostate Carcinoma were screened and confirmed on the basis of Prostate Serum Antigen (PSA) and pathological biopsy. All subjects were categorized as per their occupational exposure into various groups. The pro-inflammatory and anti-inflammatory Interleukins (IL-18 and IL-10) and serum PSA levels were analysed by using corresponding quantitative ELISA kits. The results showed that as compared to control participants, the serum PSA levels were higher in the Prostate Carcinoma and BPH groups. When mean levels of IL-18 were compared between various occupational groups, Tanners (tanning industry), Agriculture, and Ordnance workers had significantly higher levels (P < 0.05) of IL-18 than sedentary workers. The pro-inflammatory cytokine (IL-18) levels were also found to be aggravated in Prostate Carcinoma compared to BPH and controls. According to the findings of the current study, the levels of inflammatory cytokines (IL-18 and IL-10) in various occupational groups of BPH, Prostate Carcinoma, and controls were altered. Long-term occupational exposure may have a negative influence on inflammation levels and the immune system; therefore, preventative measures should be explored for improved health. [ABSTRACT FROM AUTHOR]

Decision-making after a diagnosis of prostate cancer is based on many determining factors, one of the most important is undoubtedly the histological grade. The Gleason grading system for prostate carcinoma is the dominant method used worldwide in research and daily practice. To determine the relationship between tumor grade in needle biopsy samples and after a prostatectomy, the results of 33 patients who underwent both procedures in a hospital in the interior of Paraná were compared; using the Gleason classification modified by the International Society of Urological Pathology (ISUP). Differences were observed between biopsy and prostatectomy for primary Gleason pattern, secondary pattern and score. As evidenced by the overclassification variable and mainly by the subclassification of the pathological stage, showing the difficulties of using the Gleason pattern as the only prognostic and therapeutic decision factor. Gleason correlations were identical in 57.6% of cases, 33.4% differed by just one Gleason score grade, 6% differed by two or more score grades. The Gleason score of radical prostatectomy samples was higher than that of needle biopsy in 33.4% of cases and lower than that of biopsy in 9% of cases. [ABSTRACT FROM AUTHOR]

Leontodon hispidulus Boiss is a wild annual plant growing in Egypt. The present study aims for the first time, to evaluate the phytochemical profile of the main secondary metabolites of the optimized ethanolic extract of the plant using Quadrupole Time-of-Flight Liquid chromatography-mass spectrometry and Gas chromatography-mass spectrometry. It also aims to assess the anticancer activity of its different fractions against the prostate carcinoma cell line. Moreover, an in-silico docking study was performed using the Hexokinase-two enzyme. LC-qToF-MS analysis revealed the tentative identification of 36 phenolic compounds including the glycosides of (luteolin, quercetin, kaempferol, apigenin, isorhamnetin, and daidzein), coumarines (esculin, esculetin, and daphnetin), and phenolic acids (chlorogenic, caffeic, quinic, P-coumaric, and rosmarinic). GC–MS/MS analysis revealed the presence of 18 compounds where palmitic acid, myristic acid, alpha-amyrin, and beta-amyrin were the major ones. The cytotoxic activity results revealed that methylene chloride and ethyl acetate fractions showed the highest cytotoxic activity against the PC3 cell line, with IC50 values of 19, and 19.6 μg/ml, respectively. Interestingly, the docking study demonstrated that apigenin-7-O-glucoside, luteolin-7-O-glucoside, kaempferol-3-O-glucuronide, quercetin-4′-O-glucoside, esculin, rosmarinic acid, chlorogenic acid, and α-amyrin exhibited high affinity to the selected target, HEK-2 enzyme. [ABSTRACT FROM AUTHOR]

177Lu-PSMA is a novel therapy in patients with metastatic castration-resistant prostate carcinoma (mCRPC). The radiolabeled drug is administered intravenously, usually in 4–6 cycles, in which β‑radiation induces intracellular DNA damage and cell death of PSMA-expressing prostate cancer cells. The γ‑decay of the radionuclide can be used for imaging and dosimetry. An international phase III study showed that end stage mCRPC patients that received 177Lu-PSMA had a survival benefit (15.3 vs. 11.3 months; p < 0.001). Moreover, several studies suggest that ~25% of these heavily pre-treated patients respond better and likely have a longer survival benefit. The most important side effects are: grade I–II fatigue (~40%) and xerostomia (~40%), which are mostly transient. Grade III–IV CTCAE hematologic toxicity (thrombocytopenia, leukopenia) was seen in ~8% of patients. Recently, the American Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the drug for patients with end stage prostate cancer. Currently, there are several studies investigating if patients in an earlier stage of the disease, metastatic hormone-sensitive or hormone-naïf, can also benefit from therapy with 177Lu-PSMA. [ABSTRACT FROM AUTHOR]

For prostate cancer, the role of elective nodal irradiation (ENI) for cN0 or pN0 patients has been under discussion for years. Considering the recent publications of randomized controlled trials, the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO) aimed to discuss and summarize the current literature. Modern trials have been recently published for both treatment-naïve patients (POP-RT trial) and patients after surgery (SPPORT trial). Although there are more reliable data to date, we identified several limitations currently complicating the definitions of general recommendations. For patients with cN0 (conventional or PSMA-PET staging) undergoing definitive radiotherapy, only men with high-risk factors for nodal involvement (e.g., cT3a, GS ≥ 8, PSA ≥ 20 ng/ml) seem to benefit from ENI. For biochemical relapse in the postoperative situation (pN0) and no PSMA imaging, ENI may be added to patients with risk factors according to the SPPORT trial (e.g., GS ≥ 8; PSA > 0.7 ng/ml). If PSMA-PET/CT is negative, ENI may be offered for selected men with high-risk factors as an individual treatment approach. [ABSTRACT FROM AUTHOR]

Background: A simultaneous integrated boost (SIB) may result in increased out-of-field (DOOF) and photoneutron (HPN) doses in volumetric modulated arc therapy (VMAT) for prostate cancer (PCA). This work therefore aimed to compare DOOF and HPN in flattened (FLAT) and flattening filter-free (FFF) 6‑MV and 10-MV VMAT treatment plans with and without SIB. Methods: Eight groups of 30 VMAT plans for PCA with 6 MV or 10 MV, with or without FF and with uniform (2 Gy) or SIB target dose (2.5/3.0 Gy) prescriptions (CONV, SIB), were generated. All 240 plans were delivered on a slab-phantom and compared with respect to measured DOOF and HPN in 61.8 cm distance from the isocenter. The 6‑ and 10-MV flattened VMAT plans with conventional fractionation (6- and 10-MV FLAT CONV) served as standard reference groups. Doses were analyzed as a function of delivered monitor units (MU) and weighted equivalent square field size Aeq. Pearson's correlation coefficients between the presented quantities were determined. Results: The SIB plans resulted in decreased HPN over an entire prostate RT treatment course (10-MV SIB vs. CONV −38.2%). Omission of the flattening filter yielded less HPN (10-MV CONV −17.2%; 10-MV SIB −22.5%). The SIB decreased DOOF likewise by 39% for all given scenarios, while the FFF mode reduced DOOF on average by 60%. A strong Pearson correlation was found between MU and HPN (r > 0.9) as well as DOOF (0.7 < r < 0.9). Conclusion: For a complete treatment, SIB reduces both photoneutron and OOF doses to almost the same extent as FFF deliveries. It is recommended to apply moderately hypofractionated 6‑MV SIB FFF-VMAT when considering photoneutron or OOF doses. [ABSTRACT FROM AUTHOR]

Introduction: Rarely solitary sternum metastases are addressed by resection. Two additional cases are presented as they are interesting because of their long-term follow-up. Case Presentation: Case 1: A renal cell carcinoma was treated by transabdominal nephrectomy at age 64. Right iliac bone and sternum metastases were diagnosed 7 months later and treated by internal hemipelvectomy followed by sternum metastasectomy 6 weeks after the internal hemipelvectomy. At 12-year follow-up, the patient appears disease free. Case 2: Prostate cancer was treated by prostatectomy at age 67. A subsequent solitary sternum metastasis was resected 10 years later for persistent PSA-activity despite repeated radiotherapy. The patient remains asymptomatic for 3 years now. Conclusion: Resection of sternum metastases may have curative potential and should be considered in tumours known to be rather resistant to chemo- and/or radiotherapy.

In the pre-prostate specific antigen era, patients with prostate cancer (PC) commonly presented with symptoms. Currently, most PC are diagnosed at an asymptomatic stage with abnormal digital rectal examination or raised prostate specific antigen. In rare cases, PC may infiltrate the rectum and cause symptoms mimicking rectal cancer. It is difficult to differentiate between the two based on clinical features alone. We here report our experience in managing an 86-year-old male, with no significant personal pathological history, who presented with diarrhea and occasional rectal bleeding without any lower urinary tract symptoms. Investigations concluded to a PC invading the rectum and the patient was referred to urology department. [ABSTRACT FROM AUTHOR]

Background and purpose: Prostate cancer is the most prevalent non-cutaneous malignancy in men. The Gleason grading system is an important prognostic factor in prostatic carcinoma. Nowadays, identifying biomarkers indicating high-risk patients and targeted therapy is considered. The CD38 is a membranous glycoprotein involved in adenosine generation, and in this way, it plays a role in tumorigenesis and progression of various tumors. Therefore, this study aimed to evaluate the relationship between CD38 expression and Gleason score in prostatic carcinoma. Materials and methods: In this cross-sectional retrospective study, 85 paraffin blocks from prostatic carcinoma tissue samples were immunohistochemically stained by CD38 monoclonal antibody. The percentage of CD38 expression in tumor cells was determined, and its relation with primary and secondary Gleason grade and total Gleason score in evaluated samples was analyzed by SPSS (version 16). Results: The mean of evaluated patients’ age was 70.67 ± 8.84 years, and 40% were in the range of 71-80 years. The mean of CD38 expression percentage in prostatic carcinoma tumor cells was %49.18 ± 16.58 and in the range of 8%-84%. A significant reverse relationship was found between CD38 expression percentage with primary Gleason grade (P

Abstract Background One of the most prevalent malignancies among males is prostate carcinoma (PCa). For the diagnosis of PCa, multiparametric magnetic resonance imaging (mpMRI) constitutes by far the most accurate imaging technique. The PI-RADS v2.1 indications for dynamic contrast enhanced (DCE) sequence include identifying PI-RADS score 3 lesions, as clinically significant prostate carcinoma, aiding evaluation of examinations having poor quality of T2 as well as diffusion weighted imaging (DWI), and helping readers having relatively reduced expertise. Most articles don't provide outcomes pertaining to these indications, which weakens their conclusions. All MRI scans, even those with low quality T2 or DWI, were included in our study. Additionally, special emphasis on assessing peripheral zone lesions was made. Our objective was to assess the diagnostic accuracy of the various mpMRI pulse sequences, including the T2 sequence, diffusion and apparent diffusion coefficient (ADC) sequences, both T2 and diffusion sequences (biparametric (bp) MRI), DCE sequence, and the entire examination (mpMRI), in the diagnosis of PCa in the peripheral as well as the transitional zone using PI-RADS version 2.1 scoring system, once when malignant lesions are considered as those having PI-RADS scores 4 and 5 and once when PI-RADS categories 3, 4 and 5 were regarded as malignant. Results In the assessment of peripheral zone lesions, when PI-RADS categories 3, 4, and 5 were considered malignant, both bpMRI and mpMRI showed similar sensitivity (94.29%) and diagnostic accuracy (77.78%) while when considering scores 4 and 5 malignant, mpMRI demonstrated increased diagnostic accuracy and sensitivity but lower specificity (sensitivity was 82.86%/60%, specificity was 80%/100%, and diagnostic accuracy was 82.22%/68.89% for mpMRI/bpMRI test comparaison). Both bpMRI and mpMRI had similar sensitivity (95.83%) and diagnostic accuracy (71.05%) when PI-RADS categories 3, 4, and 5 were regarded as malignant; however, mpMRI demonstrated better diagnostic accuracy and sensitivity considering scores 4 and 5 malignant (sensitivity was 77.08% for mpMRI compared to 60.42% for bpMRI and diagnostic accuracy was 82.89% for mpMRI compared to 75% for bpMRI). Conclusions Both bpMRI and mpMRI demonstrated similar diagnostic accuracy when PI-RADS categories 3, 4, and 5 were taken into account as malignant while mpMRI had higher diagnostic accuracy considering categories 4 and 5 malignant.

Purpose: Investigation of Microtubuli-associated Protein 2 (MAP2) expression and its clinical relevance in prostate cancer. Material and Methods: MAP2 expression was immunohistochemically analysed on radical prostatectomy specimens using whole block sections (n = 107) and tissue microarrays (TMA; n = 310). The staining intensity was evaluated for carcinoma, benign tissue and prostatic intraepithelial neoplasia. Expression data were correlated with clinicopathological parameters and biochemical recurrence-free survival. Additionally, MAP2 protein expression was quantitatively analysed in the serum of histologically confirmed prostate carcinoma patients and the control group using a commercial enzyme-linked immunosorbent assay. Results: MAP2 staining was significantly stronger in neoplastic tissue than in non-neoplastic prostatic glands, both in whole block sections (p < 0.01) and in TMA sections (p < 0.05). TMA data revealed significantly stronger MAP2 staining in high-grade tumors. Survival analysis showed a significant correlation between strong MAP2 staining in carcinoma and shortened biochemical recurrence-free survival after prostatectomy (p < 0.001). Multivariate Cox regression analysis confirmed MAP2 as an independent predictor for an unfavourable course. Mean MAP2 serum levels for non-PCA vs. PCA patients differed significantly (non-PCA = 164.7 pg/ml vs. PCA = 242.5 pg/ml, p < 0.001). Conclusion: The present data support MAP2 as a novel biomarker in PCA specimens. MAP2 is correlated with tumor grade and MAP2 high-expressing PCA is associated with an increased risk of biochemical recurrence after radical prostatectomy. Future studies are necessary to evaluate MAP2 as a valuable immunohistochemical biomarker in preoperative PCA diagnostic procedures, in particular with regard to treatment modalities. [ABSTRACT FROM AUTHOR]

The interdisciplinary possibilities inherent in nuclear medicine offer an opportunity for the patient-centered development of radioactive pharmaceuticals based on specific research questions. This approach provides radiopharmaceutical manufacturers with a robust scientific foundation on which to navigate the regulatory requirements for drug approval laid down by the law. A vivid illustration of this interdisciplinary cooperation has been the development of a Zr-89-labeled PSMA ligand where reliable results have been obtained across various domains, including chemistry, radiochemistry, biochemistry, and preclinical research. This comprehensive process extended to feasibility studies conducted with carefully selected patients from a single nuclear medicine clinic. The approach demonstrates how far close collaboration between different disciplines within nuclear medicine can further the move towards patient-oriented radiopharmaceutical treatments while simultaneously meeting regulatory demands. With such a strategy, innovative radiopharmaceutical solutions can be brought to the market more swiftly and efficiently, in line with the needs of patients. [ABSTRACT FROM AUTHOR]

Introduction: Rarely solitary sternum metastases are addressed by resection. Two additional cases are presented as they are interesting because of their long-term follow-up. Case Presentation: Case 1: A renal cell carcinoma was treated by transabdominal nephrectomy at age 64. Right iliac bone and sternum metastases were diagnosed 7 months later and treated by internal hemipelvectomy followed by sternum metastasectomy 6 weeks after the internal hemipelvectomy. At 12-year follow-up, the patient appears disease free. Case 2: Prostate cancer was treated by prostatectomy at age 67. A subsequent solitary sternum metastasis was resected 10 years later for persistent PSA-activity despite repeated radiotherapy. The patient remains asymptomatic for 3 years now. Conclusion: Resection of sternum metastases may have curative potential and should be considered in tumours known to be rather resistant to chemo- and/or radiotherapy. [ABSTRACT FROM AUTHOR]

Background: One of the most prevalent malignancies among males is prostate carcinoma (PCa). For the diagnosis of PCa, multiparametric magnetic resonance imaging (mpMRI) constitutes by far the most accurate imaging technique. The PI-RADS v2.1 indications for dynamic contrast enhanced (DCE) sequence include identifying PI-RADS score 3 lesions, as clinically significant prostate carcinoma, aiding evaluation of examinations having poor quality of T2 as well as diffusion weighted imaging (DWI), and helping readers having relatively reduced expertise. Most articles don't provide outcomes pertaining to these indications, which weakens their conclusions. All MRI scans, even those with low quality T2 or DWI, were included in our study. Additionally, special emphasis on assessing peripheral zone lesions was made. Our objective was to assess the diagnostic accuracy of the various mpMRI pulse sequences, including the T2 sequence, diffusion and apparent diffusion coefficient (ADC) sequences, both T2 and diffusion sequences (biparametric (bp) MRI), DCE sequence, and the entire examination (mpMRI), in the diagnosis of PCa in the peripheral as well as the transitional zone using PI-RADS version 2.1 scoring system, once when malignant lesions are considered as those having PI-RADS scores 4 and 5 and once when PI-RADS categories 3, 4 and 5 were regarded as malignant. Results: In the assessment of peripheral zone lesions, when PI-RADS categories 3, 4, and 5 were considered malignant, both bpMRI and mpMRI showed similar sensitivity (94.29%) and diagnostic accuracy (77.78%) while when considering scores 4 and 5 malignant, mpMRI demonstrated increased diagnostic accuracy and sensitivity but lower specificity (sensitivity was 82.86%/60%, specificity was 80%/100%, and diagnostic accuracy was 82.22%/68.89% for mpMRI/bpMRI test comparaison). Both bpMRI and mpMRI had similar sensitivity (95.83%) and diagnostic accuracy (71.05%) when PI-RADS categories 3, 4, and 5 were regarded as malignant; however, mpMRI demonstrated better diagnostic accuracy and sensitivity considering scores 4 and 5 malignant (sensitivity was 77.08% for mpMRI compared to 60.42% for bpMRI and diagnostic accuracy was 82.89% for mpMRI compared to 75% for bpMRI). Conclusions: Both bpMRI and mpMRI demonstrated similar diagnostic accuracy when PI-RADS categories 3, 4, and 5 were taken into account as malignant while mpMRI had higher diagnostic accuracy considering categories 4 and 5 malignant. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) protein tyrosine kinases co-expressed in various cancers such as ovarian, breast, colon, and prostate subtypes. Herein, new TAK-285 derivatives (9a–h) were synthesised, characterised, and biologically evaluated as dual EGFR/HER2 inhibitors. Compound 9f exhibited IC50 values of 2.3 nM over EGFR and 234 nM over HER2, which is 38-fold of staurosporine and 10-fold of TAK-285 over EGFR. Compound 9f also showed high selectivity profile when tested over a small kinase panel. Compounds 9a–h showed IC50 values in the range of 1.0–7.3 nM and 0.8–2.8 nM against PC3 and 22RV1 prostate carcinoma cell lines, respectively. Cell cycle analysis, apoptotic induction, molecular docking, dynamics, and MM-GBSA studies confirmed the plausible mechanism(s) of compound 9f as a potent EGFR/HER2 dual inhibitor with an effective antiproliferative action against prostate carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this research is to evaluate the compatibility of the pathological grading of prostate carcinoma in transrectal biopsy sample (TRUS), Gleason scores 3 + 3 = 6, and a palpable nodule in digital rectal examination (DRE) with radical prostatectomy samples in patients with prostate cancer. Methods: Sixty-one patients with prostate cancer were included. Transrectal biopsy of the prostate and Gleason score were recorded in the histopathological report of the radical prostatectomy sample independently for each patient. Results: The mean ± standard deviation of PSA level in patients was 8.52 ± 2.23. The average prostate volume was 46.0 ± 12.17 ml. The average density of PSA was 20.06 ± 7.74 ml. The results revealed that 36% of the people after surgery had similar pathology compared to the score before surgery (Gleason score 3 + 3 = 6) while 64% had non-homogeneous reporting (Gleason score 3 + 4 = 7 and other results). The study showed that low prostate volume before surgery was associated with a higher Gleason score after surgery. Although there was no significant relationship between PSA level above 10 before surgery and higher Gleason scores after surgery, there was a statistically significant relationship between PSA density above 15% and higher Gleason scores after surgery (P < 0.001). PSA density was a strong predictor for postoperative Gleason score (P = 0.004). Conclusion: The high level of PSA density before surgery increased the risk of higher Gleason scores after surgery by 95.99%. Over 64% of the individuals had inconsistency in tumor upgrading, and the palpable firm nodule in the DRE should not be ignored. [ABSTRACT FROM AUTHOR]

Background and purpose: Prostate cancer is the second cause of cancer-related death in men. Early diagnosis and identification of prognostic factors help to predict clinical outcome and select the most effective treatment protocol in each patient. The relationship between CD117 expression and various tumor prognoses has been identified and there is evidence for the role of this marker in prostate cancer pathogenesis. So, the aim of this study was to evaluate CD117 marker expression in prostate benign hyperplasia and adenocarcinoma, and to find its association with Gleason grade. Materials and methods: In this cross-sectional study, paraffin blocks of tissue samples obtained from 85 patients with prostatic benign hyperplasia and 78 patients with prostatic adenocarcinoma, who referred to Shahid Mostafa Khomeini hospital during 2018 to 2021, were immunohistochemically stained by anti-CD117 antibody. Membranous and cytoplasmic staining in more than 10% of epithelial tumor cells was considered as positive result. Results: Positive CD117 expression was found in 27.1% of prostatic benign hyperplasia and 50% of prostatic adenocarcinoma samples showed a statistically significant difference (P=0.003). There was no significant relationship between CD117 status expression and primary Gleason grade in prostatic adenocarcinoma samples (P=0.166); however, secondary Gleason grade and total Gleason score had a significant relationship with CD117 expression status (P=0.002 and P=0.017, respectively). Conclusion: CD117 expression was higher in prostatic carcinoma compared to benign prostatic hyperplasia and its higher expression was associated with higher Gleason grade as one of the most important prognostic factors in prostatic carcinoma

Abstract Background Prostate cancer (PCa) is the most common malignancy diagnosed in men. Immune checkpoint blockade (ICB) alone showed disappointing results in PCa. It is partly due to the formation of immunosuppressive tumor microenvironment (TME) could not be reversed effectively by ICB alone. Methods We used PCa cell lines to evaluate the combined effects of CN133 and anti-PD-1 in the subcutaneous and osseous PCa mice models, as well as the underlying mechanisms. Results We found that CN133 could reduce the infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and CN133 combination with anti-PD-1 could augment antitumor effects in the subcutaneous PCa of allograft models. However, anti-PD-1 combination with CN133 failed to elicit an anti-tumor response to the bone metastatic PCa mice. Mechanistically, CN133 could inhibit the infiltration of PMN-MDSCs in the TME of soft tissues by downregulation gene expression of PMN-MDSC recruitment but not change the gene expression involved in PMN-MDSC activation in the CN133 and anti-PD-1 co-treatment group relative to the anti-PD-1 alone in the bone metastatic mice model. Conclusions Taken together, our work firstly demonstrated that combination of CN133 with anti-PD-1 therapy may increase the therapeutic efficacy to PCa by reactivation of the positive immune microenvironment in the TME of soft tissue PCa.

Hybrid MRI linear accelerators (MR-Linac) might enable individualized online adaptation of radiotherapy using quantitative MRI sequences as diffusion-weighted imaging (DWI). The purpose of this study was to investigate the dynamics of lesion apparent diffusion coefficient (ADC) in patients with prostate cancer undergoing MR-guided radiation therapy (MRgRT) on a 1.5T MR-Linac. The ADC values at a diagnostic 3T MRI scanner were used as the reference standard.

Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) protein tyrosine kinases co-expressed in various cancers such as ovarian, breast, colon, and prostate subtypes. Herein, new TAK-285 derivatives (9a–h) were synthesised, characterised, and biologically evaluated as dual EGFR/HER2 inhibitors. Compound 9f exhibited IC50 values of 2.3 nM over EGFR and 234 nM over HER2, which is 38-fold of staurosporine and 10-fold of TAK-285 over EGFR. Compound 9f also showed high selectivity profile when tested over a small kinase panel. Compounds 9a–h showed IC50 values in the range of 1.0–7.3 nM and 0.8–2.8 nM against PC3 and 22RV1 prostate carcinoma cell lines, respectively. Cell cycle analysis, apoptotic induction, molecular docking, dynamics, and MM-GBSA studies confirmed the plausible mechanism(s) of compound 9f as a potent EGFR/HER2 dual inhibitor with an effective antiproliferative action against prostate carcinoma.

Background and purpose: Prostate cancer is the second cause of cancer-related death in men. Early diagnosis and identification of prognostic factors help to predict clinical outcome and select the most effective treatment protocol in each patient. The relationship between CD117 expression and various tumor prognoses has been identified and there is evidence for the role of this marker in prostate cancer pathogenesis. So, the aim of this study was to evaluate CD117 marker expression in prostate benign hyperplasia and adenocarcinoma, and to find its association with Gleason grade. Materials and methods: In this cross-sectional study, paraffin blocks of tissue samples obtained from 85 patients with prostatic benign hyperplasia and 78 patients with prostatic adenocarcinoma, who referred to Shahid Mostafa Khomeini hospital during 2018 to 2021, were immunohistochemically stained by anti-CD117 antibody. Membranous and cytoplasmic staining in more than 10% of epithelial tumor cells was considered as positive result. Results: Positive CD117 expression was found in 27.1% of prostatic benign hyperplasia and 50% of prostatic adenocarcinoma samples showed a statistically significant difference (P=0.003). There was no significant relationship between CD117 status expression and primary Gleason grade in prostatic adenocarcinoma samples (P=0.166); however, secondary Gleason grade and total Gleason score had a significant relationship with CD117 expression status (P=0.002 and P=0.017, respectively). Conclusion: CD117 expression was higher in prostatic carcinoma compared to benign prostatic hyperplasia and its higher expression was associated with higher Gleason grade as one of the most important prognostic factors in prostatic carcinoma. [ABSTRACT FROM AUTHOR]

In patients with prostate cancer, Prostate-specific Membrane Antigen Reporting and Data System version 2.0 provides a structured reporting system for prostate-specific membrane antigen imaging that guides scan interpretation by optimized lesion-level characterization and can potentially assist in clinical decision-making. Prostate-specific Membrane Antigen Reporting and Data System (PSMA-RADS) was introduced for standardized reporting, and PSMA-RADS version 1.0 allows classification of lesions based on their likelihood of representing a site of prostate cancer on PSMA-targeted positron emission tomography (PET). In recent years, this system has extensively been investigated. Increasing evidence has accumulated that the different categories reflect their actual meanings, such as true positivity in PSMA-RADS 4 and 5 lesions. Interobserver agreement studies demonstrated high concordance among a broad spectrum of 68Ga- or 18F-labeled, PSMA-directed radiotracers, even for less experienced readers. Moreover, this system has also been applied to challenging clinical scenarios and to assist in clinical decision-making, for example, to avoid overtreatment in oligometastatic disease. Nonetheless, with an increasing use of PSMA-RADS 1.0, this framework has shown not only benefits, but also limitations, for example, for follow-up assessment of locally treated lesions. Thus, we aimed to update the PSMA-RADS framework to include a refined set of categories in order to optimize lesion-level characterization and best assist in clinical decision-making (PSMA-RADS version 2.0). [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is the most common malignancy diagnosed in men. Immune checkpoint blockade (ICB) alone showed disappointing results in PCa. It is partly due to the formation of immunosuppressive tumor microenvironment (TME) could not be reversed effectively by ICB alone. Methods: We used PCa cell lines to evaluate the combined effects of CN133 and anti-PD-1 in the subcutaneous and osseous PCa mice models, as well as the underlying mechanisms. Results: We found that CN133 could reduce the infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and CN133 combination with anti-PD-1 could augment antitumor effects in the subcutaneous PCa of allograft models. However, anti-PD-1 combination with CN133 failed to elicit an anti-tumor response to the bone metastatic PCa mice. Mechanistically, CN133 could inhibit the infiltration of PMN-MDSCs in the TME of soft tissues by downregulation gene expression of PMN-MDSC recruitment but not change the gene expression involved in PMN-MDSC activation in the CN133 and anti-PD-1 co-treatment group relative to the anti-PD-1 alone in the bone metastatic mice model. Conclusions: Taken together, our work firstly demonstrated that combination of CN133 with anti-PD-1 therapy may increase the therapeutic efficacy to PCa by reactivation of the positive immune microenvironment in the TME of soft tissue PCa. [ABSTRACT FROM AUTHOR]

We describe the 18F-fluorodeoxyglucose positron emission tomography/contrast enhanced computed tomography (FDG PET/CECT) images of a 63-year-old male who complained of back pain and was suspected of multiple myeloma based on magnetic resonance imaging. PET/CECT suggested the FDG avid lesion involving prostate, accompanied by multiple lytic skeletal lesions with no evidence to suggest other possible primary site. A bone marrow biopsy suggested a metastatic adenocarcinoma of primary prostatic origin. Post anti-androgen therapy follow-up FDG PET/CT revealed reductions in the metabolic activities and soft tissue components of most of the metastatic skeletal lesions. These images highlight the possible indication of FDG PET/CT in evaluation of prostatic malignancy in era of 68Ga-PSMA. [ABSTRACT FROM AUTHOR]

The patient is a 68-year-old male. Although his PSA was found to be within the normal range by his local doctor, he was referred to our clinic for close examination and treatment because of irregular prostate margins and stony hardness of the prostate. PSA was low at 0.068 and CEA was high at 123.7. A prostate biopsy was performed, and a diagnosis of prostatic mucinous gland carcinoma was made. MRI showed an invasion of the bladder, but the CT scan showed no distant metastasis, so a diagnosis of cT4N0M0 was made. As a treatment, he underwent total pelvic exenteration. Histopathology revealed bladder wall invasion and prominent mucus production, and a positive urethral segment. Postoperatively, the CEA decreased to normal, but an MRI scan at 7 months postoperatively showed local recurrence in the left penile corpus cavernosum, and so total penile resection was performed. Subsequently, a CT scan 10 months postoperatively revealed multiple lung metastases and the patient was started on Docetaxel. After 13 courses of treatment, the patient developed side effects and the drug was withdrawn. Forty-eigh months after surgery, the patient was restarted on Docetaxel due to progression of the disease. Subsequently, the patient was switched to Cabazitaxel due to the presence of elevated CEA and continued on Cabazitaxel for 6 months with no evidence of metastatic enlargement. The patient had a relatively good prognosis for mucinous adenocarcinoma of the prostate, with a 4-year follow-up after distant metastasis was observed. We herein report a case of prostate mucinous adenocarcinoma treated with surgery and a taxane-based anticancer agent. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the diagnostic accuracy of MRI in diagnosis of prostatic carcinoma in patients with raised PSA levels keeping histopathology as gold standard. MATERIALS AND METHODS: This cross-sectional validation study was conducted in department of Radiology, KRL Hospital Islamabad, which is equipped with PHILIPS MULTIVA 1.5 TESLA MRI machine after taking permission from The Hospital Ethical Committee for six months from 01-02-20 till 01-08-20. A total of 121 patients were selected with raised PSA levels, who later on underwent MRI with different sequences including T1WI, T2WI, DWI, and dynamic contrast enhanced sequences after giving I/V contrast followed by biopsy and histopathology. Data was collected on a proforma and later on analyzed on SPSS Version 16 while the results were analyzed by descriptive and inferential statistics. RESULTS: Out of 121 patients with mean age 51. 23 years with the standard deviation of - 8.57. Out of 121 patients, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of MRI for the diagnosis of prostate carcinoma by taking histopathology as gold standard was found to be 92.3%, 82.7%, 94.4%, 77.4% and 90% respectively. CONCLUSION: It is concluded that magnetic resonance imaging is a highly sensitive, specific and rapid method for diagnosing prostate cancer which has potential to complement the current reference standard of histopathology and increase its overall sensitivity. [ABSTRACT FROM AUTHOR]

Radical prostatectomy (RP) constitutes the primary treatment option for patients with clinically localized, biopsy-proven prostate cancer that requires local treatment with curative intent. Accurate reporting of radical prostatectomy specimens is required to guide further risk stratification and management of patients. Hence, for the handling and reporting of RP specimens, a standardized protocol should be followed. Many general pathologists may not be well-versed with the guidelines for the handling of radical prostatectomy specimens. This article discusses a detailed approach to grossing techniques, including specimen description, fixation requirements, gross cut-up, and reporting of the grade and stage of RP specimens. This will enable the pathologist to aid in multidisciplinary management. [ABSTRACT FROM AUTHOR]

Active surveillance (AS), radical prostatectomy (RP), and radical radiotherapy (RT) are the three options for localized prostate cancer. Only a few studies have been conducted in developing countries or in centers in their initial learning curve that predict the outcomes of RARP. Therefore, this study aimed to present data from a novice center; how we started and progressed, and to compare our results with the rest of the world. This is a retrospective analysis to study the outcomes following robot-assisted radical prostatectomy and to identify the predictors of quadrifecta outcomes, i.e., the patients who were continent, did not have complications, were biochemical recurrence free with at least 1 year of follow-up and had negative surgical margins. In our data, we excluded the erectile function as one of the parameters as the majority of our patients were not sexually active or did not want to discuss this parameter. Seventy-two patients were included in this study, and 50 (69.4%) of these achieved the quadrifecta outcomes. Of all the factors, studied, seven factors were statistically significantly different between Group I (quadrifecta achieved) and Group II (quadrifecta not achieved), namely, BMI, co-morbidities like CAD, COPD, ASA grade, pre-op D'Amico risk stratification groups, clinical staging, positive lymph-node status, and hospital stay. With this study, we reported outcomes of RARP in a newly established robotic center and the results were fairly comparable with the well-developed center in India and abroad, emphasizing the short learning curve, and so, the requirement of establishing more robotic surgery centers in developing as well as developed countries. [ABSTRACT FROM AUTHOR]

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Introduction: Cell-cell communication is an important process in healthy tissue but also gains enhanced attention regarding pathological tissue. To date, the tumor microenvironment is gradually brought into focus when studying tumorigenesis. In the prostate gland, stromal and epithelial cells greatly interact to maintain homeostasis or tissue integrity. This study focuses on an indirect communication via soluble factors. Methods: To investigate the cell-cell interaction via soluble factors, the prostate carcinoma cell line LNCaP and the stromal primary cells p21 were co-cultured without direct contact and RNA was isolated at defined time points. Differences in gene expression were finally analyzed by RNA sequencing. Results: RNA sequencing revealed a time-depending differential expression profile. Selected factors were subsequently characterized at molecular level and analyzed in human prostate tissue of different developmental stages as well as pathology. GALNT14 was one of the highest induced co-culture-specific genes in LNCaP cells. Detection in healthy tissue and BPH revealed an agedependent decrease in GALNT14 expression. Moreover, in prostate carcinoma, GALNT14 expression heavily varied independent of the Gleason score. Conclusion: Overall, this work provides a basis for further studies related to paracrine stromal-epithelial interaction in prostate carcinoma and highlights the importance of GALNT14. [ABSTRACT FROM AUTHOR]