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Carcinoma prostate (CaP) is second most common cancer and sixth leading cause of cancer-related mortality among men worldwide. Prostate-specific antigen (sr. PSA) levels are prostate specific, not cancer specific. Therefore, finding non-invasive novel markers that can detect clinically significant CaP for preventing unnecessary biopsies is needed. Relation between host inflammatory responses and tumour has been increasingly recognized in various carcinomas. Many follow-up studies used neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with sr. PSA level for CaP detection in India. The present study explored the use of these biomarkers in predicting CaP in patients with lower urinary tract symptoms (LUTS). This prospective observational analytical study included 220 patients who underwent prostate biopsy for LUTS and suspected CaP between 2019 and 2021. Pearson's correlation (r) was used to find association between various attributes. Receiver operating characteristic curve analysis was performed to determine cut-off values and find sensitivity, specificity, positive and negative predictive value of NLR and PLR. P-value <0.05 was considered statistically significant (α = 5%). Out of 263 patients, 43 were excluded. Among remaining 220 study patients, 166 had BPH and 54 CaP. Median values of NLR and PLR were significantly higher in CaP patients. There was a strong positive correlation noted between NLR, PLR, and CaP groups. Areas under receiver operating characteristic curve of NLR (p = 0.001) and PLR (p < 0.001) for predicting CaP were statistically significant, with cut-off values of >3.44 and > 165.96, respectively. In present study, we found significant increase in NLR and PLR in CaP patients. These parameters could be useful as pre-prostate biopsy predictors of CaP and help avoid unnecessary biopsies. [ABSTRACT FROM AUTHOR]

Background: Infiltrating immune cells have been reported as prognostic markers in many types of cancer. We aimed to assess the prognostic role of tumor-infiltrating lymphocytes, CD3+ cells, and CD8+ cells in prostatic cancer. Patients and methods: Immunohistochemistry was used to determine the expression of CD3 and CD8 in 60 prostatic cancer tumor samples. We used digital pathology to calculate the densities of these markers and determined an immunoscore based on the densities of both markers in intratumoral and stromal tissues. Results: Densities of CD3+ and CD8+ T cells in tumors were positively related to age and prostate-specific antigen. Immunoscore and tumor grade had a significant connection (P =0.0003), showing an inverse relationship, as high IS values were seen in low grades (I, II), while IS values tended to decrease in high grades III, IV, and V. There was a significant correlation with perineural invasion (P =0.0473), side of the tumor (P =0.0007), and Gleason score (P =0.0006). Conclusion: Immunoscoring of tumor-infiltrating CD3+ and CD8+ T cells contributes to combining computed technologies of image analysis and digital pathology in individual patients' care and transferring immunoscores from the research zone to clinical daily use. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is considered the most common malignant neoplasm in males worldwide and the 2nd important reason for cancer-related male deaths after bronchogenic carcinoma. Objective: The purpose of this research is to assess how diffusion weighted image (DWI) and apparent diffusion coefficient (ADC) value characterise prostatic cysts, senile prostatic hyperplasia, prostate cancer, and the normal prostatic gland. Patients and methods: We enrolled 60 cases with suspicious prostatic lesions,20 cases with benign prostatic hypertrophy, 20 cases prostate cancer and 20 with prostatic cyst along with 20 controls. All underwent magnetic resonance imaging (MRI) for prostatic assessment and Trans-rectal ultrasonography (TRUS) guided biopsy. Results: Prostate cancer had a considerably lower mean ADC value (p-value < 0.001) than normal central gland (CG), peripheral zone (PZ), and benign prostatic hyperplasia (BPH) nodules. The ADC value of the PZ tissue had been substantially higher than that of the normal central zone (CZ) (p<0.001). While the prostatic cyst's ADC value was much greater than CZ's (p < 0.001), the BPH lesion's ADC value had been significantly lower than CZ's (p < 0.001). Conclusions: DWI has been a useful tool for gathering information on the tissue properties of the prostate's various anatomical zones. In contrast to normal tissue, BPH, and prostate cysts, prostate carcinoma cause restricted diffusion of water, which may be used in the differential diagnosis of benign and malignant lesions. [ABSTRACT FROM AUTHOR]

The development of resistance to Docetaxel (DTX) compromises its therapeutic efficacy and worsens the prognosis of prostate cancer (PCa), while the underlying regulatory mechanism remains poorly understood. In this study, METTL14 was found to be upregulated in DTX‐resistant PCa cells and PCa tissues exhibiting progressive disease during DTX therapy. Furthermore, overexpression of METTL14 promoted the development of resistance to DTX in both in vitro and in vivo. Interestingly, it was observed that the hypermethylation of the E2F1 targeting site within DTX‐resistant PCa cells hindered the binding ability of E2F1 to the promoter region of METTL14, thereby augmenting its transcriptional activity. Consequently, this elevated expression level of METTL14 facilitated m6A‐dependent processing of pri‐miR‐129 and subsequently led to an increase in miR‐129‐5p expression. Our study highlights the crucial role of the E2F1‐METTL14‐miR‐129‐5p axis in modulating DTX resistance in PCa, underscoring METTL14 as a promising therapeutic target for DTX‐resistant PCa patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CSPCa) detection via target biopsy (TB), systematic biopsy (SB), and combined biopsy (CB) in patients with PI-RADS 5 lesions. Methods: Patients with at least one PI-RADS 5 lesion were retrospectively enrolled in a prospectively collected database. The patients underwent multiparametric magnetic resonance imaging (mpMRI) followed by transrectal TB of PI-RADS 5 lesions and SB. The PCa and CSPCa detection rates and cores of TB and SB were compared with those of CB. Results: In 585 patients, prostate biopsy revealed PCa in 560 cases (95.73%) and CSPCa in 549 cases (93.85%). PCa was detected in T2 patients (93.13%, 217/233) and in T3/4 patients (97.44%, 343/352). CSPCa was detected in T2 patients (89.27%, 208/233) and in T3/4 patients (96.87%, 341/352). The positive rates of TB for T2/3/4, T3/4, and T2 were 94.02%, 96.21%, and 90.56%, respectively. SB added 1.71% (10/585) PCa and 1.37% (8/585) CSPCa detection to TB. There was no difference between TB and SB in detecting different stages of cancer (p > 0.05). In the biopsy core analysis, TB had fewer biopsy cores and a higher detection rate than SB (all p < 0.05). Conclusions: In patients with PI-RADS score 5 lesions, TB can achieve the same detection rate as, with fewer biopsy cores than, CB. SB adds minimal clinical value and can be omitted for these patients. [ABSTRACT FROM AUTHOR]

Background: Deep learning has been used to detect or characterize prostate cancer (PCa) on medical images. The present study was designed to develop an integrated transfer learning nomogram (TLN) for the prediction of PCa and benign conditions (BCs) on magnetic resonance imaging (MRI). Methods: In this retrospective study, a total of 709 patients with pathologically confirmed PCa and BCs from two institutions were included and divided into training (n = 309), internal validation (n = 200), and external validation (n = 200) cohorts. A transfer learning signature (TLS) that was pretrained with the whole slide images of PCa and fine-tuned on prebiopsy MRI images was constructed. A TLN that integrated the TLS, the Prostate Imaging–Reporting and Data System (PI-RADS) score, and the clinical factor was developed by multivariate logistic regression. The performance of the TLS, clinical model (CM), and TLN were evaluated in the validation cohorts using the receiver operating characteristic (ROC) curve, the Delong test, the integrated discrimination improvement (IDI), and decision curve analysis. Results: TLS, PI-RADS score, and age were selected for TLN construction. The TLN yielded areas under the curve of 0.9757 (95% CI, 0.9613–0.9902), 0.9255 (95% CI, 0.8873–0.9638), and 0.8766 (95% CI, 0.8267–0.9264) in the training, internal validation, and external validation cohorts, respectively, for the discrimination of PCa and BCs. The TLN outperformed the TLS and the CM in both the internal and external validation cohorts. The decision curve showed that the TLN added more net benefit than the CM. Conclusions: The proposed TLN has the potential to be used as a noninvasive tool for PCa and BCs differentiation. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to assess the histopathological features of different types of hyperplasia of prostate, prostatic intraepithelial neoplasia and prostatic carcinoma in transurethral resection of prostate (TURP) samples and needle core biopsies. Methods: This prospective study was undertaken at the Akash Institute of Medical Sciences from 2019 to 2021. 120 patients were included in the study. Results: Most of the cases in the present study were in the range of 61 to 70 years of age (60 cases) followed by 71 to 80 years (37 cases) and 51 to 60 years (19 cases) respectively at the time of biopsy for symptomatic obstructive uropathy. Out of the total 120 cases studied, 109 cases (90.8%) were nonneoplastic and 11 cases (9.2%) harbored neoplasms. The most common clinical symptoms in nonneoplastic lesions are as follows: frequency, retention, hesitancy, urgency dysuria. On digital examination, of 109 non-neoplastic cases, 105 were firm whereas 4 cases were hard in consistency. Out of 11 neoplastic cases, all 11 cases were hard in consistency. On comparing neoplastic and nonneoplastic cases, hard nodule was significantly associated with neoplasms. Serum Prostate Specific Antigen levels were assayed using immunoassay and were available for 80 cases (67.5%). Among these 80 cases, PSA values in 04 (5%) were within normal range (up to 4 ng/dl). In the 109 cases of benign hyperplasia of prostate, varying proportions of glands and stroma was noted, from which, cases showing a characteristic pattern or predominance was identified. Of the 109 cases of benign prostatic hyperplasia, Corpora amylacea were seen in 30.2% of cases. The other findings were basal cell hyperplasia (3.7%) and squamous cell metaplasia (0.9%). Other stromal findings encountered were ectatic thick-walled blood vessels and stromal edema. Conclusion: TURP plays a significant role in the diagnosis of prostatic lesions. The benign lesions are more common the malignant ones. The modified Gleason score is applied for prostatic cancer, which is simple and accurate to grade these malignancies. [ABSTRACT FROM AUTHOR]

Aim: Recent observational and small-sample case-control studies have shown a relationship between gut microbiota composition and prostatic cancer (PCa). Nevertheless, the causal association between gut microbiota and PCa is still unclear. Herein, we used the Mendelian randomization (MR) method to explore the potential causal relationship between gut microbiota and PCa. Methods: In this two-sample MR study, data were extracted from the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis conducted by the MiBioGen consortium (n = 14,306) and the Dutch Microbiome Project (n = 8,208). Summary statistics for PCa were obtained fromthe FinnGen consortiumrelease data (n = 95,213). Inverse variance weighted (IVW), MR-Egger, strength test (F), and MR-PRESSO were used to examine the potential causal association between gut microbiota and PCa. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables. Results: IVW estimates suggested that the relative abundance of Akkermansia muciniphila (odds ratio [OR] = 0.7926, 95% confidence interval [CI]: 0.6655-0.9440) and Bacteroides salyersiae (OR = 0.9023, 95% CI: 0.8262-0.9853) were negatively associated with the odds of PCa, while that of Eubacterium biforme (OR = 1.1629, 95% CI: 1.0110-1.3376) was positively associated with the odds of PCa. In addition, we explored these relationships among patients without other cancers and similarly found that the relative abundance of Akkermansia muciniphila, Bacteroides salyersiae, and Eubacterium biforme were linked to PCa (all P < 0.05). Conclusion: Gut microbiota potentially influenced the occurrence of PCa. Our findings may provide some new ideas for researching the methods of PCa prevention. In addition, further studies are needed to explore the causal association and specific underlyingmechanisms between gutmicrobiota and PCa. [ABSTRACT FROM AUTHOR]

[Objectives] This study was conducted to explore the action mechanism of chemical components from stems of Isodon suzhouensis on prostate cancer based on UPLC-Q-TOF-MS/MS technique, network pharmacology, and molecular docking validation. #Methods] UPLC-Q-TOF-MS/MS was applied to search active components in stems of I. suzhouensis, and SwissTargetPrediction and PharmaMapper databases were used to predict their potential targets. The GeneCards database was adopted to screen the targets of prostate cancer, and the targets of the active components and the targets of prostate cancer were intersected to obtain common targets. A protein-protein interaction network was constructed, and also, an "active component-target-disease-pathway" network was constructed using Metascape for gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Moreover, AutoDock was adopted to perform molecular docking verification on key active components and core targets. #Results] Sixty three active components were screened from stems of I. suzhouensis, and they had 233 common targets with prostate cancer, mainly involving biological processes such as protein phosphorylation, response to hormones, active regulation of cell movement, cell response to lipids, and response to oxidative stress, as well as pathways in cancer, prostate cancer, micro ribonucleic acids in cancer, p53 signaling pathway, NF-KB signaling pathway and other signaling pathways, exerting anti-tumor effects. Molecular docking showed that the top 5 key active components had good binding ability with the top 5 core targets. [Conclusions] Active components from stems of I suzhouensis can exert therapeutic effects on prostate cancer through multiple targets and pathways. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a major type of cargos encapsulated in extracellular vesicles (EVs) and regulate the progression of prostatic cancer (PC). This study was conducted to explore the role of tumor-derived EVs in PC cell proliferation, invasion, and migration via shuttle of circRNA formin 2 (circFMN2). RT-qPCR or Western blot assay showed that circFMN2 was upregulated while KLF2 and RNF128 were downregulated in PC tissues and cells. EVs were separated from PC cells and characterized and its internalization in PC cells was examined, which suggested that PC-EVs mediated the shuttle of circFMN2 to upregulate circFMN2 expression in PC cells. PC cell functions were determined by cell counting kit-8, colony formation and Transwell assays, which suggested that PC-EVs fueled the proliferation, invasion, and migration of PC cells. At cellular level, PC-EVs mediated the shuttle of circFMN2 to upregulate circFMN2 expression in PC cells, and circFMN2 binding to HuR decreased the HuR-KLF2 interaction and repressed KLF2 expression, which further reduced the KLF2-RNF128 promoter binding and repressed RNF128 transcription. Overexpression of KLF2/RNF128 ablated the effects of PC-EVs on the proliferation, invasion, and migration of PC cells. The xenograft tumor models and lung/liver metastasis models were established and revealed that PC-EVs accelerated tumorigenesis and metastasis in vivo via delivery of circFMN2 and repression of KLF2/RNF128. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer (PCa) is the most common type of cancer in males, and the metastatic form is a leading cause of death worldwide. There are currently no curative treatments for this subset of patients. To decrease the mortality of this disease, greater focus must be placed on developing therapeutics to reduce metastatic spread. We focus on dissemination to the bone since this is both the most common site of metastatic spread and associated with extreme pain and discomfort for patients. Our strategy is to exploit microRNAs (miRNAs) to disrupt the spread of primary PCa to the bone. Methods: PCa cell lines were transduced to overexpress microRNA-379 (miR-379). These transduced PCa cells were assessed using cell growth, migration, colony formation and adhesion assays. We also performed in vivo intracardiac injections to look at metastatic spread in NSG mice. A cytokine array was also performed to identify targets of miR-379 that may drive metastatic spread. Results: PCa cells with increased levels of miR-379 showed a significant decrease in proliferation, migration, colony formation, and adhesion to bone cells in vitro. In vivo miR-379 overexpression in PC3 cells significantly decreased metastatic spread to bone and reduced levels of miR-379 were seen in patients with metastases. We identified GDF-15 to be secreted from osteoblasts when grown in conditioned media from PCa cells with reduced miR-379 levels. Discussion: Taken together, our in vitro and in vivo functional assays support a role for miR-379 as a tumour suppressor. A potential mechanism is unravelled whereby miR-379 deregulation in PCa cells affects the secretion of GDF-15 from osteoblasts which in turn facilitates the metastatic establishment in bone. Our findings support the potential role of miR-379 as a therapeutic solution for prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is one of the common malignant tumors worldwide. MiR-183-5p has been reported involved in the initiation of human PCa, this study aimed to investigate whether miR-183-5p affects the development of prostate cancer. Methods: In this study, we analyzed the expression of miR-183-5p in PCa patients and its correlation with clinicopathological parameters based on TCGA data portal. CCK-8, migration assay and invasion and wound-healing assay were performed to detect proliferation, migration and invasion in PCa cells. Results: We found the expression of miR-183-5p was significantly increased in PCa tissues, and high expression of miR-183 was positively associated with poor prognosis of PCa patients. Over-expression of miR-183-5p promoted the migration, invasion capacities of PCa cells, whereas knockdown of miR-183-5p showed reversed function. Furthermore, luciferase reporter assay showed TET1 was identified as a direct target of miR-183-5p, which was negatively correlation with miR-183-5p expression level. Importantly, rescue experiments demonstrated TET1 over-expression could reverse miR-183-5p mimic induced-acceleration of PCa malignant progression. Conclusion: Our results indicated that miR-183-5p could act as a tumor promoter in PCa and it accelerated the malignant progression of PCa by directly targeting and down-regulating TET1. [ABSTRACT FROM AUTHOR]

Background: Most occurrences of prostatic disease are caused by benign prostatic hyperplasia (BPH), then prostatic cancer. An adult male with prostatic hyperplasia requires a thorough study because prostate cancer is the second most frequently diagnosed malignancy in males. Different prostatic lesions have the same clinical characteristics; however, identification is crucial because treatment and prognosis vary greatly. Material & Methods: Study Design: A prospective hospital based observational study. Study area: Department of Pathology, Government Medical College, Kadapa, Andhra Pradesh. Study Period: 1 year. Study population: This prospective study includes TURP specimens that were collected during the study period. Sample size: The study consisted of 100 cases. Sampling method: Simple random technique. Results: Foci of Prostatic Intra-Epithelial Neoplasia (PIN) were identified in 10% of all cases that were studied. 40% of the HG PIN lesions were identified in association with adenocarcinoma of prostate and the rest (60%) were found along with BPH. Highest incidence of PIN was noted in 7th decade followed by 6th decade. Atypical adenomatous hyperplasia was found in 4 (4%) of all cases. Conclusion: Malignant lesions are less frequent than benign ones. BPH is the most common type of prostatic lesion among the histopathological patterns. In order to recognise premalignant lesions, proliferative activity, and degree of inflammation, it is required to examine all prostate biopsies (TURP and needle core). [ABSTRACT FROM AUTHOR]

Background: Prostatic cancer ranks 2nd amongst men in worldwide while 4th in Egypt. Many factors are used to predict patients' survival. PSA kinetics are one of the main prognostic factors used for treatment response in advanced or relapsed cases. However, its application as prognostic marker is lacking in Egyptian clinical settings and research. Aim of Study: In this retrospective study, we aimed to assess correlation between PSA kinetics among locally advanced and metastatic prostatic cancer patients and their survival status for prognostic aspects. Methods: We conducted a retrospective cohort study at Clinical Oncology department, Ain Shams University hospitals from January 2013 till December 2022 (10 years). All prostate cancer patients who were initially hormonal sensitive locally advanced or metastatic that later developed biochemical failure during follow up period were included in our study. Results: Our study included 77 patients with a mean age of 66.467.4 years. Three cases were locally advanced while 74 cases were metastatic. The most frequent mode of ADT monotherapy prior biochemical failure was GnRH analogue in 55 cases. Upon disease progression, most of the cases were shifted to abiraterone acetate. The initial median PSA value was 100 (49.1-193.9) ng/ml. It took about 9 (6-14) months (median TTN) with a median declining rate of 10.5 (3.75-35.1) % for their PSA values to reach nadir level of median 1.2 (0.21-5.27) ng/dl. When ADT failed, PSA levels increased again reaching a median value of 8.9 (3.75-35.2) ng/ml. The median PSA velocity after progression was 35.2 (2.8-208) ng/dl/yr while median PSA DT was 3.6 (1.3-7.25) months. Univariate analysis revealed PSA nadir <0.76 ng/dl level (P value= 0.003) and TTN >11 m (p value = 0) significantly associated with longer PFS and improved survival. However, PSA DT<3.1 (p value=0.017) predicts higher mortality. Meanwhile, multivariate results showed that PSA declining rate (P value= 0.047) and age > 67 years (P value 0.016) were statistically significant as independent factors when associated to PFS. Conclusion: TTN > 11 months and PSA nadir <0.76 during initial treatment was associated with prolonged PFS and OS. They were associated with better clinical response to treatment in castration resistant prostate cancer patients. Thus, it could be helpful for decision making of early treatment strategy in castration resistant cases. [ABSTRACT FROM AUTHOR]

For many years, luteinizing hormone-releasing hormone or gonadotropinreleasing hormone (GnRH) analogs have been used to treat androgen or estrogen-dependent tumors. However, emerging evidence shows that the GnRH receptor (GnRH-R) is overexpressed in several cancer cells, including ovarian, endometrial, and prostate cancer cells, suggesting that GnRH analogs could exert direct antitumoral actions in tumoral tissues that express GnRH-R. Another recent approach based on this knowledge was the use of GnRH peptides for developing specific targeted therapies, improving the delivery and accumulation of drugs in tumoral cells, and decreasing most side effects of current treatments. In this review, we discuss the conventional uses of GnRH analogs, together with the recent advances in GnRH-based drug delivery for ovarian, breast, and prostatic cancer cells. [ABSTRACT FROM AUTHOR]

Prostate carcinoma is one of the most commonly diagnosed visceral malignancies and the fifth leading cause of cancer-related mortality in males. Reportedly, a series of dietary lipids are identified as 1-cis-4-cis-pentadiene polyunsaturated fatty acids (PUFAs), which play a dominant role in prostate carcinogenesis. Four species of human lipoxygenases (LOXs), a family of nonheme iron-containing enzymes, mediate the deoxygenation of the aforementioned PUFAs. 15-LOX-1 in particular metabolizes the ω -6 lipids and generates certain metabolites (e.g., 13-(S)-hydroxyoctadecaenoic acid) which results in vascular homeostasis, cell proliferation and tissue differentiation in the prostate. Furthermore, in prostate cancer (PCa), the expression of 15-LOX-1 is elevated and positively correlated with the Gleason score of the tumor (an indicator of the disease severity). As membrane receptors, kinases and transcriptional factors are all affected by carcinogenic signals of 15-LOX-1, therapeutic agents that directly inhibit this enzyme can be advantageous in the treatment of PCa. To our knowledge, there are limited effective treatments for PCa, and there is no therapy for its metastatic condition. In this respect, 15-LOX-1, as an appropriate candidate for drug development, was subjected to homology modeling, phylogenic assessment, cross-docking analysis and molecular dynamics (MD) simulation to identify an eligible inhibiting agent amongst a library of 30 potential targeting compounds for PCa management. Prostate carcinoma is one of the most commonly diagnosed visceral malignancies and the fifth leading cause of cancer-related mortality in males. To our knowledge, there are limited effective treatments for prostate cancer. In this respect, human 15-Lipoxygenase-1 (15-LOX-1), as an appropriate candidate, was subjected to in-silico explorations. We report the potential for using 15-LOX-1 inhibitors, such as CHEMBL1270113, as a therapeutic approach to restore the balance between the function of lipoxygenase family members and inflammatory mediators. [ABSTRACT FROM AUTHOR]

Background: Benign prostatic hyperplasia (BPH) and prostatic cancer are a significant source of morbidity and mortality among adult males. The other prostatic lesions include inflammatory condition and in situ lesions. TURP is necessary to identify these lesions and specifically for prostatic cancer. Objectives: To evaluate the histomorphological spectrum of various prostatic lesions in TURP specimens. Materials and Methods: Total of 85 TURP specimens received during period of two years, April 2018 to March 2020 were studied. Cases were studied with regard to complete history, clinical examination and histopathological findings. Diagnostic criteria was adapted from guidelines laid down by World Health Organization (WHO). Results: A total of 85 prostate TURP specimens were studied over a 2-year period which included 81 cases of benign lesions (95.2%) and 4 cases of malignant lesions (4.8%). Among the benign lesions Benign prostatic hyperplasia (BPH) 54, BPH with prostatitis 24 and granulomatous prostatitis 2, 4 cases of malignant lesions. Conclusion: TURP plays a significant role in the diagnosis of prostatic lesions. The benign lesions are more common the malignant ones. The modified Gleason score is applied for prostatic cancer, which is simple and accurate to grade these malignancies. [ABSTRACT FROM AUTHOR]

Background: Previous research exploring the role of race on prostate cancer (PCa) outcomes has demonstrated greater rates of disease progression and poorer overall survival for African American (AA) compared to Caucasian American (CA) men. The current study examines self-reported race as a predictor of longterm PCa outcomes in patients with low and favorable-intermediate risk disease treated with external beam radiation therapy (EBRT). Methods: This retrospective cohort study examined patients who were consented to enrollment in the Center for Prostate Disease Research Multicenter National Database between January 01, 1990 and December 31, 2017. Men self-reporting as AA or CA who underwent EBRT for newly diagnosed National Comprehensive Cancer Network-defined low or favorable-intermediate risk PCa were included. Dependent study outcomes included: biochemical recurrence-free survival, (ii) distant metastasis-free survival, and (iii) overall survival. Each outcome was modeled as a time-to-event endpoint using race- stratified Kaplan--Meier estimation curves and multivariable Cox proportional hazards analysis. Results: Of 840 men included in this study, 268 (32%) were AA and 572 (68%) were CA. The frequency of biochemical recurrence, distant metastasis, and deaths from any cause was 151 (18.7%), 29 (3.5%), and 333 (39.6%), respectively. AA men had a significantly younger median age at time of EBRT and slightly higher biopsy Gleason scores. Multivariable Cox proportional hazards analyses demonstrated no racial differences in any of the study endpoints. Conclusions: These findings reveal no racial disparity in PCa outcomes for AA compared to CA men, in a long-standing, longitudinal cohort of patients with comparable access to cancer care. [ABSTRACT FROM AUTHOR]

Prostatic cancer is a complex cancer that many factors contribute to. In clinical practice, statins and oral anti-diabetic drugs, is the main adjuvant treatment for prostatic cancer patients. In this paper, a kind of typical complex network – the sample specific network (SSN) was used to screen out differentially expressed genes (DEGs) between prostatic cancer and normal tissue. And by the degree of SSN, driving mutation genes (DMGs) were determined. Pearson correlation coefficient was used to construct SSN, in order to describe the special characteristics of the sample. In this way, people can realise personalised medical service. After the prediction of the degree top 30, top 20, top 10, and top 5 genes, the accuracy of prediction of driving genes with the top 5 genes is the highest. Different single samples of SSN from prostate cancer have specificity, but there is a common edge or network with the specific subnetwork of driving gene. The driving genes of prostate cancer can be predicted by our method. [ABSTRACT FROM AUTHOR]

Over the past years, drug development direction has focused on the investigation of molecules that selectively target one protein. Executing rational combinations of targeted molecules will selectively regulate several pathways simultaneously. We aimed in this study to clear the relative therapeutic action between the outstanding agents silver nanoparticles (AgNPs), Spirulina (Sp), and a combination of them against bicalutamide (Casodex®) for the management of prostate cancer (PCa). PCa in rats was induced using bicalutamide and testosterone, followed by (7,12-dimethylbenz[a]anthracene). Rats were divided into six groups with 12 rats in each group. Group I was assigned as the control (co), group II as the PCa model, group III treated with AgNPs, group IV treated with Spirulina extract, group V treated with a combination of AgNPs plus Spirulina, and group VI treated with bicalutamide. Compared with bicalutamide treatment, AgNP treatment reduced the serum prostatic acid phosphatase (PAP) activity, improving PSA ratio, normalizing the IL-6 level, overcoming hormonal disturbance induced in PCa rats, and up-regulating P53, but it couldn't cure the pathological changes. Spirulina was significant up-regulated P53 and Caspase-3, in addition to regression of the histological pattern of high-grade prostatic intraepithelial neoplasia although the IL-6 level was still significantly high. Combination treatment decreased the PAP activity and up-regulating the expression of P53 and BAX, improving the pathological changes, increasing the E2 level and up-regulating the expression of BCL2 and TNF-α. Each of treatments has benefits and disadvantages over bicalutamide which need more experiments to discover the best combination, concentration, particle size and duration. [ABSTRACT FROM AUTHOR]

Metastasis of malignant tumors to the temporal bone is relatively rare. We report a case of facial nerve palsy due to the metastatic prostatic cancer to the temporal bone with favorable and functional results. A 76-year-old man with no history of malignant tumor was referred to our hospital with a complaint of right facial nerve palsy. Based on radiological findings and a biopsy from the prostate, the patient was finally diagnosed as having metastatic prostatic cancer to the right temporal bone. More than 18 months had passed after start of the hormonal therapy, the metastatic lesion of the temporal bone had diminished, and the facial nerve palsy gradually improved. The present case suggests that favorable and functional results even in advanced metastatic prostatic cancers to temporal bone, if hormonal therapy is effective. We must keep in mind the possibility of metastatic tumor in the treatment of facial nerve palsy. [ABSTRACT FROM AUTHOR]

Background: Tumor cells exhibit enhanced metabolism of nutrients to satisfy the demand of sustained proliferation in vivo. Seminal reports have presented evidence that tryptophan (Trp) metabolic reprogramming induced by aberrant indoleamine 2,3-dioxygenases could promote tumor development in several cancer types. However, the underlying mechanism of Trp metabolism associated tumor progression is not fully understood.Materials and Methods: Prostatic cell lines LNCaP and VCaP were purchased from the Cell Bank of the Chinese Academy of Sciences (China). Human prostatic tumor tissue samples were obtained from the Tongji Hospital. Female NOD-SCID mice (6 ~ 8 weeks) were purchased from Huafukang Co. (China) and raised in SPF room. Commercial kits and instruments were used for cell apoptosis analysis, real-time PCR, western blotting, ELISA analysis and other experiments.Result: Comparing the tumor tissues from prostatic cancer patients, we found elevated expression of tryptophan 2, 3-dioxygenase 2 (TDO2), and elevated Trp metabolism in chemo-resistant tumor tissues. In vitro, overexpression of TDO2 significantly promoted the Trp metabolism in prostatic cancer cell lines LNCaP and VCap, resulting in the multidrug resistance development. Mechanistically, we demonstrated that Trp metabolite kynurenine (Kyn) promoted the upregulation and nuclear translocation of transcription factor aryl hydrocarbon receptor (AhR). Subsequently, AhR collaborated with NF-κB to facilitate the activation of c-Myc. In turn, c-Myc promoted the up-regulation of ATP-binding cassette (ABC) transporters and Trp transporters, thereby contributing to chemoresistance and strengthened Trp metabolism in prostatic cancer. Interrupt of Trp/TDO2/Kyn/AhR/c-Myc loop with c-Myc inhibitor Mycro-3 efficiently suppressed the chemoresistance and improved the outcome of chemotherapy, which described a new strategy in clinical prostatic cancer treatment.Conclusion: Our study demonstrates that elevated TOD2 expression promoted Trp metabolism and metabolite Kyn production, thus resulting in the activation of AhR/c-Myc/ABC-SLC transporters signaling pathway. Interrupt of Trp metabolism/c-Myc loop efficiently suppressed the drugs resistance induced by TDO2, which represented potential target to improve the outcome in drug-resistant prostatic cancer treatment. [ABSTRACT FROM AUTHOR]

The crosstalk between tumor microenvironment and cancer cells is emerging as a critical determinant in tumor progression. However, the underlying mechanism of tumor microenvironment‐induced cancer development remains controversial. Here, our study provides evidence to suggest that tumor‐associated macrophage (TAM) enrichment is found in chemoresistant prostatic tumor tissues. Those TAMs are demonstrated to promote chemoresistance and distant metastasis in prostatic cancer through secretion of CCL5. Mechanistically, TAM coculture or additional CCL5 can mediate the STAT3‐dependent epithelial–mesenchymal transition process, resulting in distant metastasis in prostatic cancer. Meanwhile, activation of STAT3 induced by CCL5 can mediate upregulation of the transcription factor Nanog, leading to drug resistance. In vivo study further demonstrated that blockade of STAT3 signals significantly reverses chemoresistance and suppresses lung metastasis in colorectal tumor‐bearing mice, suggesting a novel strategy for clinical prostatic cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Bone metastasis after failure of castration therapy is the main reason of death in patients with prostate cancer (PCa). Therefore, full awareness of the metastasis mechanism of PCa and discovery of new therapeutic targets are necessary. Studies showed that lncRNA was involved in the development of cancer. However, its potential role and molecular mechanism in PCa metastasis are still unclear. YKL-40 is an 18 glycosyl hydrolase family protein encoded by CHI3L1, which is involved in the invasion and metastasis of various tumors. A previous study of the authors found that YKL-40 was related to the invasion and metastasis of PCa cells. However, the cause of its abnormal expression in PCa remains unclear. The present study explored the role of lncRNA KCNQ1OT1/miR-211-5p/CHI3L1 regulatory axis in the proliferation, invasion, and metastasis of PCa. Methods: RT-PCR and Western blot were used to measure the expression profiles of KCNQ1OT1 and YKL. CCK-8 and Transwell assays were used to examine their effects on cell proliferation and migration. Double luciferase reporter assay was used to verify the interactions between miR-211-5p and CHI3L1 3′-UTR. Results: KCNQ1OT1 expression was upregulated in PCa tissues and cells. Downregulating this expression inhibited PCa cell invasion, proliferation, and metastasis. KCNQ1OT1 bound miR-211-5p competitively, and miR-211-5p targeted CHI3L1 3′-UTR. miR-211-5p expression was downregulated, whereas CHI3L1 (YKL-40) expression was upregulated. miR-211-5p levels were negatively correlated with KCNQ1OT1 expression and CHI3L1 mRNA. The decrease in YKL-40 expression in PCa cells induced by the downregulation of KCNQ1OT1 expression could be offset by miR-211-5p inhibitor transfection. Conclusion: This study showed that lncRNA KCNQ1OT1, as a ceRNA, upregulated CHI3L1 and promoted PCa progression through competitive binding to miR-211-5p. [ABSTRACT FROM AUTHOR]

In order to explore the diagnostic value of prostate targeted puncture guided by MRI combined with ultrasound fusion imaging (MR-TRUS) in patients with prostate cancer of PI-RADS score ≥ 3 points, 100 patients who sought medical care in our hospital were enrolled. All of them were performed targeted biopsy via both MR-TRUS guided puncture and traditional puncture. And all the patients were tested the level of prostate specific antigen (PSA). According to 4 < PSA ≤ 10 µ g /L, 10 < PSA ≤ 20 µ g /L, 20 < PSA ≤ 50 µ g/L, and PSA > 50 µ g /L, the MR-TRUS guided puncture group (group A) and the traditional puncture group (group B) were both divided into 4 subgroups. The sensitivity, specificity and accuracy of different puncture methods for the diagnosis of prostate cancer were compared according to the postoperative pathological results. The results showed that the diagnostic rates of each subgroup in the group A were 28.57%, 66.67%, 70% and 91.67%, while the diagnostic rates of each subgroup in the group B were 9.52%, 25.00%, 60.00% and 86.11%, respectively. Compared with the traditional puncture method, MR-TRUS guided puncture significantly improved the diagnostic rate in patients of PSA ≤ 10 µ g/L and 10 < PSA ≤ 20 µ g/h (P<0.05). The diagnostic rate of the two puncture methods was not significantly different in patients of 20 < PSA ≤ 50 µ g/L and PSA > 50 µ g/L (P > 0.05). Compared with the traditional puncture method, the sensitivity and accuracy of MR-TRUS guided puncture were significantly improved (P < 0.05). In summary, patients of PSA ≤ 10 µ g/L and 10 PSA ≤ 20 µ g/L should undergo targeted puncture guided by MRI and ultrasound fusion, which can significantly improve the diagnosis rate of prostate cancer. [ABSTRACT FROM AUTHOR]

Cancer of the prostate is one of the commonest cancers in males and is a principal reason of deaths related to malignancies. The prostatic specific antigen(PSA) screening test is not routinely done, so,majority of affected personswill present with progressive level of cancer. Neutrophils to lymphocytes ratio (NLR) was previously proposed as aneasyindicatorin patients needing critical care for the systematic inflammatory response. It was identified also as a crucialindicator of severity for some cancers of the solid type. This ratio can notably easy to be addressed from a full blood count in asample of blood. This study was conducted to estimate the role of NLR as aseverity indicator in patients having prostatic cancer. A retrospective, cross sectional study is this, that contain 425 participants already diagnosed with prostatic cancer, who attended Al-Amal National Hospital of clinical oncology and nuclear medicine in Baghdad-Iraq over the period of June 2013 to June 2015, and on regular follow up until June 2017. The data collected from patients’ files documentation. All patients had pre-treatment complete blood counts (CBC) anda differential leucocyte count; pre-treatment PSA; histopathological report for Gleason’s score (GS) and full documentation of patients’ follow-up. Accordingly, only 100 patients’ documents had these full criteria, and 325 patients with incomplete data were excluded. All participants were then divided into 2 groups according to their pre-treatment NLR: The group with low (<3) NLR (n=36), and the other group are those with high (≥ 3) NLR (n=64). Results demonstrated that there are significant statisticaldifferences between pre-treatment NLR and baseline PSA level (p = 0.0001) and between it and Gleason’s score (p = 0.0001). In addition, no statistical significant difference was found between NLR and T-staging (tumor extension) (p = 0.1), but it showed one with nodal involvement (p = 0.0001), with distant metastasis (p = 0.0001) and with number of organ metastasis (p = 0.0001). Strong association was found between high pre-treatment NLR and Gleason’s score upgrading, high baseline PSA and disease progression. The pre-treatment NLR is an effective, not a costly means, thatcan besimply accessed in various situations of healthcare systems and can be used as a supportive tool in decision-making for treatment of early as well as advanced prostatic cancer cases. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second most frequent cancer diagnosis made in men and the fifth leading cause of death worldwide. Prostate cancer may be asymptomatic at the early stage and often has an indolent course and may require minimal or even no treatment. More advanced stage of the disease may present with urinary retention and back pain, as axis skeleton is the most common site of bony metastatic disease. The aim of this study is to examines the expressin of annexin A5 proteins in prostatic adenocarcinoma in correlation with some clinico-pathological parameters in a sample of Iraqi patients. A retrospective cross-sectional study included 30 patients diagnosed with prostatic adenocarcinoma and other 30 patients diagnosed with benign prostatic hyperplasia BPH in Baghdad, Iraq from Oct. 2018 - Oct. 2019 were evaluated. Of the 60 patients enrolled in this study; 65% of patients showed positive Annexin A5 expression whie 35% was ngative. Although, there's no statistical significant association in Annexin A5 expression between benign and malignant lesions but in prostatic cancer patients we noticed that threre's significant association between perineural invasion and Annexin A5 expression. Annexin A5 expression can be a potential marker for tumor aggressiveness and invasion that make it candidate for more aggressive management. [ABSTRACT FROM AUTHOR]

Background: Men normally have shorter heart rate-corrected QT interval (QTc) than women, at least in part due to accelerating effects of testosterone on ventricular repolarization. Accumulating data suggest that androgen-deprivation therapy (ADT) used for the treatment of prostatic cancer, may increase Torsades de Pointes (TdP) risk by prolonging QTc. However, the evidence for such an association is currently limited to few case reports, in most cases deriving from the analysis of uncontrolled sources such as pharmacovigilance databases. Objective: To better determine the clinical impact of ADT on TdP development, we examined the prevalence of this therapy in a consecutive cohort of 66 TdP patients, prospectively collected over a ~10 years period. Methods and Results: We found and described four patients who were under ADT for prostatic cancer when TdP occurred, and in two cases degenerated to cardiac arrest. Notably, in this unselected population, ADTs unexpectedly represented the second most frequently administered QT-prolonging medication in males (4/24, 17%), after amiodarone. Moreover, in the ADT patients, a blood withdrawal was performed within 24 h from TdP/marked QTc prolongation occurrence and circulating concentration of androgens and gonadothropins were measured. As expected, all cases showed markedly reduced testosterone levels (total, free, and available). Conclusion: We provide evidence that a significant proportion of patients developing TdP were under treatment with ADT for prostatic cancer, thus confirming the clinical relevance of previous pharmacovigilance signals. An accurate assessment of the arrhythmic risk profile should be included in the standard of care of prostatic cancer patients before starting ADT. [ABSTRACT FROM AUTHOR]

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Purpose: The goal of this study was to retrospectively compare systematic ultrasound-guided prostate biopsy (US-PB) and multiparametric magnetic resonance imaging-ultrasound fusion prostate biopsy (MRI-PB) in men undergoing primary or repeated biopsies. Methods: A population of 2,200 patients with a prostate-specific antigen (PSA) level >4.0 ng/dL and/or an abnormal rectal examination was divided into two groups. All patients underwent US-PB (n=1,021) or MRI-PB (n=1,179) between April 2015 and April 2019. Population demographics, including age, PSA level, digital rectal examination results, prostate volume, number of previous negative biopsies, Prostate Imaging Reporting and Data System (PI-RADS) version 2 (V2) score, and biopsy results, were acquired and compared with respect to these variables. Univariate regression analysis of the risk factors for a higher Gleason score (GS) was performed. Results: The cancer detection rate (CDR) was 23.8% (243 of 1,021) in the US-PB group and 31.3% (399 of 1,179) in the MRI-PB group. Of those, 225 patients (22.0%) in the US-PB group and 374 patients (31.7%) in the MRI-PB group had clinically significant prostate cancer (csPCa). The patients with csPCa in the MRI-PB group included 10 (40%), 50 (62.5%), 184 (94.8%), and 32 (94.1%) patients with PI-RADS V2 scores of 2, 3, 4, and 5, respectively. Of the patients with csPCa, 155 (91.7%) in the US-PB group were diagnosed on the basis of the primary biopsy, compared to 308 (94.4%) in the MRI-PB group. We found the PI-RADS V2 score to be the best predictor of a higher GS. Conclusion: MRI-PB showed a high CDR for csPCa. MRI-PB could be a reasonable approach in patients with high PI-RADS V2 scores at primary biopsy. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence and prognostic value of ERG in prostatic cancer. The association of ERG status and other clinic-pathologic features were also studied. Materials and Methods: Tissue paraffin blocks of patients who had diagnosis of prostatic acinar adenocarcinoma during 2006 to 2013 at Faculty of Medicine Vajira Hospital were identified. The original H&E stained slides were reviewed to select 2 areas with the most prominent Gleason pattern for tissue sampling. The selected tissue samples were embedded in tissue microarray (TMA) blocks and processed for ERG staining. Intensity and area of positive ERG stain were evaluated independently by two pathologists. Clinico-pathological data collected were age, pre-operative prostate-specific antigen (PSA), tumor stage, PSA biochemical-relapse, and pathological information of peri-neural or lymphovascular invasion, surgical margin, the International Society of Urological Pathology (ISUP) grade group, and Gleason score were collected and analyzed. Results: Among 107 samples, positive ERG staining was found in 31.8% (34 cases). Features which were significantly associated with ERG positive comparing to those in ERG negative were: younger age, 67.7±8.5 years vs. 72.6±8.6 years (p = 0.008); lower Gleason score (6 and 7), 79.4% (27 cases) vs. 20.6% (7 cases) (p = 0.010) and lower ISUP grade group (group 1, 2 and 3), 82.4% (28 cases) vs. 17.6% (6 cases) (p = 0.004), respectively. No significant different association between ERG status and other clinic-pathologic features including survivals. The 5-year overall survival and 5-year disease-free survival (95% confidence intervals) of the patients with ERG positive and negative were: 84.4% (70.1 to 98.7%) vs. 77.1% (66.1 to 88.1%) (p = 0.399) and 77.4% (60.9 to 93.9%) vs. 78.2% (67.6 to 88.8%) (p = 0.571), respectively. Conclusion: The prevalence of ERG-positive in prostate cancer patients was 31.8%. The patients with ERG positive were younger, more of low Gleason score and low ISUP grade group. No significant association between ERG status and other clinic-pathologic parameters as well as survivals were found. [ABSTRACT FROM AUTHOR]

The aim of this study was to define the pattern of relapse of postoperative prostate cancer in patients by using 68Ga-labeled prostate-specific membrane antigen positron-emission tomography/computed tomography ([68Ga]-PSMA PET/CT). Forty patients received a (68Ga)-PSMA PET/CT for biochemical failure. Following the Radiation Therapy Oncology Group (RTOG) guidelines, the pelvic clinical target volume has been contoured. Bone metastases were considered as outside the clinical target volume. Two subgroups of patients were defined, patients having relapse: (1) inside, or (2) outside the clinical target volume. Globally, eight patients out of 32 presented with a positive lymph node failure inside the clinical target volume according to RTOG guidelines (25%), 22 patients had nodal relapses outside this clinical target volume (68.75%) and in two patients nodal relapses occurred both inside and outside of the clinical target volume (6.25%). Overall, 36 positive lymph node lesions were identified: of these, 23 nodal relapses were identified within the clinical target volume contoured according to RTOG and/or at the lomboaortic level (63%). To cover 95% of these 23 relapses, a hypothetical clinical target volume should encompass the nodal regions of the RTOG-defined clinical target volume as well as the paraaortic lymph node level up to T12-L1. Most of the patients in the present study, presented with distant lymph node and/or bone metastases. Therefore, larger target volumes should be adopted to treat at least 95% of lymph node regions at risk for an occult relapse. [ABSTRACT FROM AUTHOR]

Introduction: Although the literature about prostate cancer is vast in tracking discussion about diagnosis and treatment of prostate cancer, there are few publications about the best form of surgical specimen processing of radical prostatectomy. After the surgery, the urologist limits his responsibility to forward surgical specimen for analysis. Aim: To evaluate if the urologist manipulation trying to locate and demarcate suspicious areas of a tumour can improve the microscopic examination. Materials and Methods: Twenty surgical specimens of radical prostatectomy performed in patients with localised prostate cancer were macroscopically analysed by a single urologist and suspicious areas for cancer were marked with surgical thread. Later these areas were correlated with the findings in the microscopic study. Results: It was observed that in 75.8% of cases, there was a positive correlation between the pit and the clinical pathology report on the cancer presence, and in 50% of cases, the demarcated areas corresponded to the area of most considerable extent of cancer throughout the prostate. Conclusion: The demarcation of cancer suspected areas by Urologist, in surgical specimens from radical prostatectomy may provide additional information to the pathologist, directing the histopathological analysis of the prostate to the areas with more significant tumour extension compared to the other sections. [ABSTRACT FROM AUTHOR]

Abstract Evidence indicates that prostates exposed to environmental endocrine disruptors and trace metals will cause adverse health outcomes. We assessed the association between urinary phthalate metabolites and serum trace metal levels, and oxidative damage in benign prostatic hyperplasia (BPH) patients, prostate cancer (PCa) patients, and healthy controls. Levels of cadmium (Cd), nickel (Ni), and copper (Cu) were significantly higher in BPH patients than in controls, and mercury (Hg) was highest in PCa patients. An Hg level >1 μg/L posed a significant risk (OR: 42.86, 95% CI: 1.092–1684) for PCa, but a zinc (Zn) level >1 μg/L was marginally negative (OR: 0.979, 95% CI: 0.957–1.002). We also found strong associations between PCa and mono-isononyl phthalate (MiNP), and between BPH and mono-isodecyl phthalate (MiDP), malonyldialdehyde (MDA) were significantly higher in PCa and BPH patients than in controls; 8‑hydroxydeoxyguanosine (8‑OH‑dG) and DNA strand breakage were highest in BPH patients and lowest in controls. When the prostate was simultaneously co-exposed to phthalates and trace metals, phthalates had a less significant effect on PCa and BPH. Thus, we hypothesize that, for patients with prostate disease, exposure to trace metals is more significant than is exposure to phthalates. Highlights • Trace elements and phthalate were analyzed in 60 subjects. • The most abundant metals were Hg in prostate cancer. • The most abundant metals were Cd, Cu and Ni in BPH. • Exposure to trace metals is more significant than is exposure to phthalates. • Exposure to phthalates and the pathogenesis of PCa and BPH are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer (PCa) is one of the most common malignancies in men. However, a lack of understanding of the mechanism underlying PCa metastasis has strongly limited the effectiveness of therapy for this disease. Thus, investigating the mechanism of PCa may help improve the prognosis of PCa patients. The goal of this study was to investigate the role of microRNA-194 (miR-194) in PCa. Materials and methods: The expression of miR-194 and cadherin 2 (CDH2) at the transcriptional level was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The MTT assay cell apoptosis assay and Western blotting were used to determine the role of miR-194 and CDH2 in the PC3 human PCa cell line. The dual luciferase reporter assay system was performed to clarify the relationship between miR-194 and CDH2. qRT-PCR results showed that miR-194 was downregulated and CDH2 was upregulated in PC3 cells. Results: Transfection with miR-194 mimics decreased cell viability and increased the rate of apoptosis compared with the control group of PC3 cells. Bioinformatics and the luciferase reporter assay indicated that CDH2 was a target of miR-194, and Western blot analysis suggested that CDH2 was negatively regulated by miR-194. Further studies revealed that the downregulation of CDH2 suppressed cell viability and promoted the apoptosis of PC3 cells and that miR-194 directly targeted CDH2 in PC3 cells. Finally, the in vivo experiments showed that miR-194 mimics suppressed tumor growth and induced apoptosis in a greater proportion of cells by decreasing the expression of CDH2 compared with the control group. Conclusion: The results of this study showed that miR-194 targeted CDH2 to regulate PCa cell survival in vitro and suppress tumor growth in vivo. These findings suggest that miR-194 may be a useful therapeutic target in PCa. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is one of the most common malignant cancers in male and docetaxel is commonly used as an effective chemotherapeutic drug for PCa patients. However, docetaxel resistance inhibits the therapeutic effect of this agent, thus investigating the mechanism of chemoresistance to docetaxel of PCa may help to improve the prognosis of PCa patients. In our present study, we found that miR-223-3p was up-regulated in PCa cell lines (C4-2, LNCap, PC3, DU-145). Transfection with miR-223-3p inhibitor increased chemo-sensitivity to docetaxel and cell apoptosis rate in PCa cells compared with docetaxel + miR-223-3p mock group, especially in DU-145 cells which were more resistant to docetaxel. Bioinformatics study and luciferase reporter assay indicated that FOXO3 was a target of miR-223-3p and the results from western blot suggested that FOXO3 was negatively regulated by miR-223-3p. Further study revealed that up-regulation of FOXO3 by transfection with pCMV-FOXO3 decreased the IC 50 values of docetaxel and increased cell apoptosis rate compared with docetaxel + pCMV-vector group, suggesting that overexpressed FOXO3 suppressed cell survival and sensitized PCa cells to docetaxel. Moreover, siRNA-mediated knockdown of FOXO3 abolished the effects of miR-223-3p inhibitor on chemo-sensitivity and apoptosis in PCa cells by increasing chemoresistance and decreasing cell apoptosis rate. Finally, the in vivo experiments showed that miR-223-3p inhibitor sensitized prostatic cancer mouse model to docetaxel by increasing the expression of FOXO3. In conclusion, our present study indicated that miR-223-3p regulated cell chemo-sensitivity by targeting FOXO3 in prostatic cancer both in vitro and in vivo , providing new potential therapeutic strategy for PCa treatment. [ABSTRACT FROM AUTHOR]

Prostate cancer is a prevalent form of cancer that primarily affects men, with a high incidence and mortality rate. It is the second most common cancer among males, following lung cancer. Typically occurring in individuals aged 50 and above, this malignant tumor originates from abnormal cells in the prostate tissue. If left untreated, it can spread to nearby tissues, lymph nodes, and even bones. Current treatment methods include surgery, radiotherapy, and chemotherapy. However, these treatments have certain limitations and side effects. Therefore, researching and developing new small-molecule drugs to treat prostate cancer is of great significance. In recent years, many small-molecule drugs have been proven to have therapeutic effects on prostate cancer. The purpose of this review is to give a comprehensive look at the clinical uses and synthetic methods of various significant small-molecule drugs that have been approved to treat prostate cancer, to facilitate the development of more powerful and innovative drugs for the effective control of prostate cancer. [Display omitted] • An overview of clinically approved small-molecule drugs to treat prostatic cancer is timely provided. • Clinical applications and synthetic routes of 24 representative drugs are meticulously highlighted. • Brief discussion and challenge are also conducted to guide future drug design. [ABSTRACT FROM AUTHOR]

Objectives The aim of the current report is to provide an update in the imaging interpretation of prostate cancer on multiparametric magnetic resonance imaging (mpMRI), with a special focus on how to discriminate pathological tissue from the most common pitfalls that may be encountered during daily clinical practice using the Prostate Imaging Reporting and Data System (PI-RADS) version 2 guidelines. Methods All the cases that are shown in this pictorial review comply with the European Society of Urogenital Radiology (ESUR) guidelines for technical mpMRI requirements. Results Despite the standardised manner to report mpMRI (PI-RADS v. 2), some para-physiologic appearances of the prostate can mimic cancer. As such, it is crucial to be aware of these pitfalls, in order to avoid the under/overestimation of prostate cancer. Conclusions A detailed knowledge of normal and abnormal findings in mpMRI of the prostate is pivotal for an accurate management of the wide spectrum of clinical scenarios that radiologists may encounter during their daily practice. Teaching Points [ABSTRACT FROM AUTHOR]

Background & Objective: As the prostate adenocarcinoma is one of the most common malignant tumors in males, looking for a marker to effectively predict aggressiveness and metastatic potential in an apparently localized cancer in initial needle biopsy specimens can help the clinicians to make more appropriate decision for treatment, planning, and choosing appropriate targeted therapy. The present study assessed the value of Endothelin-1 expression to predict prognosis of prostatic cancer Methods: In a cross sectional study, 83 patients who underwent radical prostatectomy in Hasheminejad Kidney Center in 2008 through 2012 were assigned to two groups including 43 with and 40 without extra-prostatic extension (EPE). Endothelin-1 staining was performed on Paraffin Embedded blocks of preoperative needle biopsies. Results: The expression of Endothelin-1 increased in 72% of patients in the group with EPE (P<0.001). The group with Endothelin-1 positivity showed higher serum level of prostate specific antigen (PSA) (p = 0.039). Endothelin-1 expression was positive in 67% of patients with perineurial invasion (P<0.001). Adjusting the baseline variables of PSA and PN in a multivariable logistic regression model, the Endothelin-1 positivity could effectively predict EPE in patients with prostatic cancer (OR: 5.46, p = 0.010). Conclusion: Correlation of Endothelin-1 expression in needle biopsy specimens in expected with extra-prostatic extension of tumor in radical prostatectomy specimens, perineurial invasion and serum PSA level at the time of diagnosis. [ABSTRACT FROM AUTHOR]

• Briganti nomograms discrimination decreases with increasing delay between biopsy and surgery. • Including the time elapsed between biopsy and surgery to the Briganti nomograms can improve their calibration. • The indication of lymphadenectomy should be carefully evaluated in men undergoing prostatectomy after a significant delay from biops. We aimed to investigate whether the performance characteristics of available nomograms predicting lymph node invasion (LNI) in prostate cancer patients undergoing radical prostatectomy (RP) change according to the time elapsed between diagnosis and surgery. We identified 816 patients who underwent RP with extended pelvic lymph node dissection (ePLND) after combined prostate biopsy at 6 referral centers. We plotted the accuracy (ROC-derived area under the curve [AUC]) of each Briganti nomogram according to the time elapsed between biopsy ad RP. We then tested whether discrimination of the nomograms improved after accounting for the time elapsed between biopsy ad RP. The median time between biopsy and RP was 3 months. The LNI rate was 13%. The discrimination of each nomogram decreased with increasing time elapsed between biopsy and surgery, where the AUC of the 2019 Briganti nomogram was 88% vs. 70% for men undergoing surgery <2 vs. >6 months from the biopsy. The addition of the time elapsed between biopsy ad RP improved the accuracy of all available nomograms (P < 0.003), with the Briganti 2019 nomogram showing the highest discrimination. Clinicians should be aware that the discrimination of available nomograms decreases according to the time elapsed between diagnosis and surgery. The indication of ePLND should be carefully evaluated in men below the LNI cut-off who had a diagnosis more than 6 months before RP. This has important implications when considering the longer waiting lists related to the impact of COVID-19 on healthcare systems. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to analyze the differences between TRUSguided transrectal prostate biopsy (TR) and transperineal prostate biopsy (TP) in the diagnosis of prostate cancer. The two biopsy methods were evaluated in terms of diagnostic sensitivity and of early and late complications. Methods: This retrospective study was realized through the review of clinical records of 219 men that received a prostate biopsy between 2004 and 2014. The biopsy was performed because of elevated prostate-specific antigen (PSA), abnormal digital rectal examination findings (DRE), abnormal transrectal ultrasound (TRUS) findings and symptoms due to prostate diseases. The cohort study was subdivided in two groups: 108 patients received a transrectal biopsy between 2004 and 2006 and 111 received a transperineal biopsy between 2007 and 2014. In both groups, first biopsy was performed with 12 cores scheme whereas second or third biopsy were performed with 18 cores scheme; in this study we excluded patients who underwent to biopsies with different number cores to reduce the bias. Both groups were evaluated on the basis of age, total PSA, PSA ratio (F/T), DRE/TRUS findings, presence/absence of low urinary tracts symptoms (LUTS), presence/absence of benign prostatic hyperplasia (BPH), histologic findings of biopsy cores and immediate/postoperative complications. Then, it was evaluated the overall cancer detection rate and the stratified cancer rate on the basis of the previous reported parameters. Finally, we analyzed the early and late complication rate in both groups. U Mann-Whitney test was used to evaluate the quantitative variables and x2-test or Fisher exact test for qualitative variables. p < 0.05 was considered statistically significant. Results: 66 cancers were detected in 219 patients of the study; 29 cancers were detected in the TP group and 37 in the TR group. There were no statistically significant differences in the overall cancer rate detected in both groups (26.13% e 34.26% respectively; p = 0.190). However, TP biopsy detected more cancers at first biopsy than TR biopsy (89.7% vs 78.4% respectively; p = 0.021). Moreover, TP biopsy detected more cancers in those patients with low cancer suspect (PSA < 4 ng/ml, F/T > 15%, negative TRUS), instead TR biopsy had more sensitivity in detecting cancer in those patients with high cancer suspect (PSA > 10 ng/ml, F/T < 15%, TRUS with abnormal lesions). The presence of BPH did not influence sensitivity in both cases. There were no significant differences in the early complication rate whereas a statistically significant difference was observed in the late complication rate (4% vs 11% in TP and TR biopsy, respectively; p = 0.019). Conclusions: No statistically significant differences in sensitivity were observed between TP and TR biopsy, but TP biopsy detected more cancers at first time biopsy. Complications rate was lower in the TP group. Therefore, we conclude that the Urologist has the final choice in deciding the most appropriate biopsy technique, considering sensitivity and complications. [ABSTRACT FROM AUTHOR]

Background : To assess the prognostic stratification of prostatic cancer according to modified Gleason Grading System Methods: In this observational study 65 patients having prostatic carcinoma, who underwent prostatectomy by different surgical procedures were included. Lab request forms and histopathology reports of these patients were reviewed for prognostic grade groups. Gleason grade ≤6; 3 + 4; 4 + 3; 8 and 9-10 were assigned by two histopathologists separately to each prostatic cancer in addition to already assigned Gleason grades. Results: Sixty five patients were found to be diagnosed with prostatic carcinoma. Age ranged from 64-85 years. Eight patients were found incidentally to have prostatic cancer in T1 stage with six having grade group I cancer, one with grade group II and the one with a grade group III cancer. The remaining 57 cases were already diagnosed before surgery by different diagnostic tests. Out of these 57 cases 15 had Gleason grade 7 cancer (7 with grade group II and 8 with grade group III), 18 had Gleason grade 8 (All with grade group IV) and 24 cases had combined Gleason grade 9 and 10 cancer (All with grade group V). Cancer of all of these 57 cases was beyond T1 stage. Thirty cases were in stage T2, 20 in stage T3 and only 7 in stageT4. Conclusion: While retaining the essence of the conventional Gleason system, the 2014 modified system of grade groups categorize patients of prostatic carcinoma, prognostically with more accuracy acceptable to both clinicians and patients. [ABSTRACT FROM AUTHOR]

Peripheral blood plasma profiles of circulating microRNA expression were analyzed in patients with prostatic cancer and benign hyperplasia. In prostatic cancer, significant increase in hsa-miR-619-5p and hsa-miR-1184 microRNA expression and significant decrease in hsalet-7b-5p and hsa-let-7c-5p microRNA expression were observed. The role of the relationship between the microRNA expression and the activities and functions of host genes with introns encoding these microRNA is discussed. [ABSTRACT FROM AUTHOR]

We analyzed microRNA profile in hemolysis-free blood plasma of patients with prostatic cancer. The metastatic form of prostatic cancer was found to be associated with increased levels of hsa-miR-22-3p, hsa-miR-663a, and hsa-miR-4674 in comparison with non-metastatic form. Common candidate target genes of these microRNA include JUNB, KMT2A, and XPO6. [ABSTRACT FROM AUTHOR]