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Background. The involvement of women, as health influencers, has been instrumental in improving health outcomes and quality of life. In sub‐Saharan Africa, poor knowledge, attitudes, and beliefs about cancers have contributed to late detection and increased mortality. Although pharmacists have provided optimum pharmaceutical care in ensuring that prostate cancer (PCa) patients obtain maximum clinical benefits from pharmacotherapy, late detection has hindered pharmacotherapeutic outcomes. The application of the PCaKAB‐Gh tool to women has the potential to investigate their lapses in PCa knowledge, attitudes, and beliefs and further equip pharmacists and other healthcare professionals to design educational interventions. Ultimately, Ghanaian women will be well‐positioned to advise and motivate their men to screen for PCa. Method. Our pilot and psychometric studies recruited 400 and 500 participants from the Kumasi Central Market and the New Agogo Community Market, respectively. In this large population application of the PCaKAB‐Gh tool, 2000 women were simply randomly enrolled from these markets and data were collected using paper questionnaires with ethical approval. Data were entered into IBM SPSS (version 24) after cleaning and coding for analysis. The knowledge on signs and symptoms was scored and graded as "low" (≤2), "moderate" (3–5), and "high" (5–8), whilst the knowledge on causes and risk factors was stratified as "low" (≤1), "moderate" (2‐3), and "high" (4‐5). Pearson's correlation was conducted to investigate the relationship between women's educational status and knowledge, attitudes, and beliefs. Statistical significance was established as a p < 0.05. Results. Christians and Muslims accounted for about 70% and 24% of the participants, respectively, whilst over 50% of the participants were Akans. Over 50% and 30% of the 2000 participants had high and moderate knowledge about the signs and symptoms of PCa, respectively. Knowledge about the causes and risk factors was approximately 30% high and 50% moderate amongst the participants. Negative attitudes and beliefs outcomes were observed in about 25% and 55% of the participants. A p < 0.001 was achieved in Pearson's correlation between the educational level of respondents and knowledge on signs and symptoms (r = −0.102), knowledge on causes and risk factors (r = 0.111), attitudes (r = −0.122), and beliefs (r = 0.228). Conclusions. Our study established that market women had better knowledge on the signs and symptoms of PCa compared to the causes and risk factors. Their beliefs about PCa were worse compared to their attitudes. The development and administration of educational interventions, relying on the outcomes of this study, must involve markets, churches, and mosques as educational sites with special attention to addressing negative beliefs through a broader community‐based engagement. [ABSTRACT FROM AUTHOR]

Introduction. Treatment evidence for malignancies metastatic to the prostate in young patients is scarce. Herein, we present a case of prostatic metastasis from testicular cancer treated with induction chemotherapy followed by robot‐assisted radical prostatectomy. Case Presentation. The patient is a 34‐year‐old male who underwent radical orchiectomy for a left testicular tumor two years ago and was diagnosed with a mixed germ cell tumor. He was followed up without adjuvant therapy, but symptoms of dysuria lead to suspicion of a prostate tumor, which was diagnosed by prostate biopsy as seminoma of the prostate. After four cycles of chemotherapy, normalization of tumor markers, and tumor shrinkage on imaging, he underwent robot‐assisted radical prostatectomy. No recurrence has been observed nine months after treatment. Conclusion. In men with a history of testicular cancer presenting with lower urinary tract symptoms, it is important to consider recurrent prostate metastases. [ABSTRACT FROM AUTHOR]

Background. MRI is an important tool for accurate detection and targeted biopsy of prostate lesions. However, the imaging appearances of some prostate cancers are similar to those of the surrounding normal tissue on MRI, which are referred to as MRI-invisible prostate cancers (MIPCas). The detection of MIPCas remains challenging and requires extensive systematic biopsy for identification. In this study, we developed a weakly supervised UNet (WSUNet) to detect MIPCas. Methods. The study included 777 patients (training set: 600; testing set: 177), all of them underwent comprehensive prostate biopsies using an MRI-ultrasound fusion system. MIPCas were identified in MRI based on the Gleason grade (≥7) from known systematic biopsy results. Results. The WSUNet model underwent validation through systematic biopsy in the testing set with an AUC of 0.764 (95% CI: 0.728-0.798). Furthermore, WSUNet exhibited a statistically significant precision improvement of 91.3% (p < 0.01) over conventional systematic biopsy methods in the testing set. This improvement resulted in a substantial 47.6% (p < 0.01) decrease in unnecessary biopsy needles, while maintaining the same number of positively identified cores as in the original systematic biopsy. Conclusions. In conclusion, the proposed WSUNet could effectively detect MIPCas, thereby reducing unnecessary biopsies. [ABSTRACT FROM AUTHOR]

Objective. This study was to construct a ceRNA (lncRNA-miRNA-mRNA) regulatory network for prostate cancer (PCa) and to explore the prognostic correlation, key biological functions, and pathways of core RNAs. Methods. Three subgene expression matrices (miRNA, lncRNA, and mRNA expression matrix) were taken from the TCGA database and used in this investigation. Differential expression analysis and differential expression miRNAs were carried out. Next, the ceRNA (lncRNA-miRNA-mRNA) regulatory complex was used to visualize our data and show how they interacted. Ultimately, the primary molecular roles and biological pathways of PCa were identified using enrichment analysis by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). An effect of AC016773.1 on prostate cancer cell proliferation was investigated by knocking out AC016773.1 in an animal model. The interrelationship between AC016773.1 and hsa-mir-25 was validated using RNA immunoprecipitation technology. Results. The lncRNA, miRNA, and mRNA expression matrices obtained from the TCGA database contain 16901, 1881, and 19962 transcripts, respectively. Through differential expression analysis, we obtained 2010 de lncRNA comparative information, 75 lncRNA and miRNA interaction pairs, and 31 targeted de mRNAs. Through the differential expression analysis of RNA nodes in the ceRNA regulatory network, we found that compared with the NP group, in the PCa group, there were 14 lncRNAs upregulated and 25 lncRNAs downregulated, 1 miRNA upregulated and 3 miRNA downregulated, and 10 mRNA upregulated and 21 mRNA downregulated. In KEGG enrichment analysis, the pathways identified by targeted DE-mRNAs were mainly related to calcium signaling pathway, EGFR tyrosine kinase inhibitor resistance, melanoma, PI3K−Akt signaling pathway, and proteoglycans in cancer. In animal models, it was found that knocking down AC016773.1 significantly reduced tumor volume and weight, indicating that AC016773.1 may promote the proliferation of PCa cells. The use of RNA immunoprecipitation technology indicates a direct binding between AC016773.1 and hsa-mir-25. Conclusion. We elucidated the network regulatory relationship of lncRNA-miRNA-mRNA in PCa and further explored the key molecular functions, biological pathways, and prognostic value of targeted DE-mRNAs. [ABSTRACT FROM AUTHOR]

Objective. To characterise cancer diagnosis in Scottish primary care in 2018/19 and draw comparisons with diagnostic activity in 2014. Methods. A national audit of cancer diagnosis undertaken in Scottish general practices. Participating GPs collected diagnostic pathway data on patients diagnosed with cancer in 2018/19 from medical records. These data were supplemented by linkage to the Scottish Cancer Registry and previous audit data from 2014. Analyses explored and compared patient demographics, presentation, diagnostic routes, and intervals. Results. Seventy-three practices submitted data on 2,014 cases in 2014 and 90 practices submitted data on 2,318 cases in 2018/2019. Individual demographics and types of cancer were similar. There was a higher proportion of USC (urgent suspected cancer) referrals in 2019 than 2014 (42.9% vs 38.1%, p = 0.008) but a similar proportion of emergency presentations (19.2% vs 20.4%). Primary care (median 4 (IQR 0–22) vs 5 (0–23)) and diagnostic intervals (27 (10–59) vs 30 (13–68)) were similar in both periods. Significantly fewer (24.5% vs 28.3, p = 0.015) had a diagnostic interval >60 days in 2019 than 2014. Harder to diagnose cancers were more likely to present as emergencies and be subject to prolonged delays in both cohorts. Conclusions. The 2014 and 2018/19 cohorts were broadly similar. There is limited evidence that USC use had increased between 2014 and 2018/19. Harder to diagnose cancers are still most likely to present as emergencies and be subject to delays. Overall, it seems there were small improvements in cancer diagnosis prepandemic and a further audit could examine evidence for a postpandemic recovery. [ABSTRACT FROM AUTHOR]

Zinc dyshomeostasis is manifested in breast and prostate cancer cells. This study attempted to uncover the molecular details prodded by the change of extracellular zinc by employing a panel of normal and cancerous breast and prostate cell lines coupled with the top-down proteomics with two-dimensional gel electrophoresis followed by liquid chromatography-tandem mass spectrometry. The protein samples were generated from MCF-7 breast cancer cells, MCF10A normal breast cells, PC3 prostate cancer cells, and RWPE-1 normal prostate cells with or without exogenous zinc exposure in a time course (T0 and T120). By comparing the cancer cells vs respective normal epithelial cells without zinc treatment (T0), differentially expressed proteins (23 upregulated and 18 downregulated in MCF-7 cells; 14 upregulated and 30 downregulated in PC3 cells) were identified, which provides insights into the intrinsic differences of breast and prostate cancer cells. The dynamic protein landscapes in the cancer cells prodded by the extracellular zinc treatment reveal the potential roles of the identified zinc-responsive proteins (e.g., triosephosphate isomerase, S100A13, tumour proteins hD53 and hD54, and tumour suppressor prohibitin) in breast and prostate cancers. This study, for the first time, simultaneously investigated the two kinds of cancer cells related to zinc dyshomeostasis, and the findings shed light on the molecular understanding of the breast and prostate cancer cells in response to extracellular zinc variation. [ABSTRACT FROM AUTHOR]

Prostate cancer accounts for 20.3% of all cancers in men in sub-Saharan Africa. Early screening among at-risk groups is challenging in Uganda, with limited data on prostate cancer screening uptake in most districts, including newly established ones. The purpose of this study was to determine factors influencing the uptake of prostate cancer screening among men aged ≥ 40 in Kazo Town Council, Kazo District, a newly created district. We used a descriptive cross-sectional study design that employed both quantitative and qualitative data collection methods. Participants were recruited through simple random sampling between November 2020 and January 2021. Structured questionnaires were used for quantitative data (n = 300). Statistical analyses to determine associations were carried out using inferential and chi-square tests followed by logistic regression. In-depth interviews were conducted with 10 key informants and analyzed thematically to explore a range of perceptions related to prostate cancer screening. Only 10 (3.33%; 95% CI: 0.018-0.60) respondents had ever screened for prostate cancer. Lack of privacy (p < 0.033), access to prostate cancer information (p < 0.014), and distance to health facilities (p < 0.001) were significantly associated with the uptake of prostate cancer screening. Marital status (OR = 7.93 ; 95% CI: 1.85-33.99; p = 0.005), positive health worker attitudes (OR = 0.002 ; 95% CI: 0.000-0.023, p < 0.001), and perceived affordability (OR = 0.001 ; 95% CI: 0.000-0.011, p < 0.001) were independently associated with uptake of prostate cancer screening. Key barriers included lack of information, access to screening centres, and fear of screening. The level of uptake of prostate cancer screening was considerably low among men aged 40 and above in the Kazo District. Targeted community interventions to improve access to prostate cancer information, screening, sensitization, and addressing perceived and actual barriers are needed in newly created districts to bolster the uptake of prostate cancer screening. This has implications for prioritizing research evaluating district resource allocation to support optimized and integrated evidence-based service delivery in primary healthcare centres, especially for specialized services in newly created districts. [ABSTRACT FROM AUTHOR]

Background. Although prostate cancer patients initially respond to androgen deprivation therapy, most patients progress to a resistant phenotype. Castration resistance is due, in part, to intratumoral and/or adrenal synthesis of androgens, overexpression or mutation of the androgen receptor (AR), stabilization of AR by chaperones, and ligand-independent activation of AR. Increasing evidence also links disruption of calcium homeostasis to progression of prostate cancer. Our previous study shows that heavy metal cadmium activates the AR through a ligand-independent mechanism. Cadmium mimics calcium in biological systems due to their similar ionic charge and radius. This study determines whether calcium activates AR and whether first- and second-generation antiandrogens block the ability of calcium to activate the receptor. Methods. The expression of androgen-responsive genes and calcium channels was measured in prostate cells using a quantitative real-time polymerase chain reaction assay. Cell growth was measured. Results. To ask whether calcium activates AR, prostate cells were treated with calcium in the absence and presence of the first-generation antiandrogens hydroxyflutamide and bicalutamide and the second-generation antiandrogen enzalutamide, and the expression of androgen-responsive genes and cell growth was measured. In the normal PWR-1E cells and HEK293T cells transiently expressing AR, treatment with calcium increased the expression of androgen-responsive genes by approximately 3-fold. The increase was blocked by enzalutamide but was not consistently blocked by the first-generation antiandrogens. In LNCaP cells which contain a mutant AR, treatment with calcium also increased the expression of androgen-responsive genes by approximately 3-fold, and the increase was more effectively blocked by enzalutamide than by hydroxyflutamide or bicalutamide. Treatment with calcium also increased cell growth that was blocked by enzalutamide. To ask whether dysregulation of calcium channels is associated with castration resistance, calcium channels were measured in the normal PWR-1E prostate cells, the hormone-responsive LNCaP cells, and the castration-resistant VCaP and 22RV1 cells. Compared to normal prostate cells, the hormone-responsive and hormone-resistant cells overexpressed several calcium channels. Conclusions. The results of this study show that calcium activates AR and increases cell growth and that calcium channels are overexpressed in hormone-responsive and hormone-resistant prostate cancer cells. Taken together, the results suggest a novel role of calcium in the castration-resistant phenotype. [ABSTRACT FROM AUTHOR]

Aim. To describe the process of developing a resource, the "Prostate Cancer Outcomes Report Card," that provides information for men with prostate cancer and their family members about the outcomes of different treatment approaches. Methods. The project consisted of two phases. The first phase involved analysis of real-world data and translating outcomes into a format that consumers found easy to understand and interpret. The Report Card was developed in consultation with a consumer advisory group (n = 8). The second phase involved refinements of the resource through exploratory qualitative interviews with consumers (n = 14), an online survey among the general public (n = 134), and clinician feedback (n = 8). Results. Consumer engagement to explore preferences about the content and visual presentation from the end-users' perspective was crucial in designing this report. Consumers required trustworthy, comprehensive, simple, and up-to-date information collated in one place to help them understand the risks and benefits of their treatments. Presenting survival, cancer recurrence, and functional outcomes by treatment type and risk category was highly commended while data on high survival rates were considered reassuring. We identified high levels of unmet psychosocial and supportive care need, with differences in individual preferences around extent of information required. Conclusions. Communicating registry data about real-world outcomes in a consumer-friendly way may help fill a gap in information needs among prostate cancer survivors. Providing relatively simple and easily understandable evidence in a single consumer-oriented report may help prostate cancer survivors become better informed and facilitate patient-provider communication and shared decision making. [ABSTRACT FROM AUTHOR]

Prostate cancer invariably impacts men's health and well-being and remains the most common male cancer. This study explored how men with prostate cancer who were scheduled for radical prostatectomy made sense of their cancer diagnosis. A narrative analysis was performed of 18 men's life stories at three different time points: preoperatively (n = 13), three months postoperatively (n = 10), and six to nine months postoperatively (n = 11). In total, 34 interviews were undertaken in Ireland to examine how men talked over time. Riessman's narrative analytic technique and structural and thematic analysis were used as the analytic framework. The following four themes emerged which reflected how men made sense of their prostate cancer diagnosis: seeking coherence, connecting through collective masculinity, rejecting a survivorship identity, and positioning prostate cancer. Seeking coherence was evident in the preoperative phase whilst the other three themes emerged in both postoperative time points. Whilst the experience of prostate cancer was an individualised one, masculine identity and narrative positioning underpinned every aspect of men's accounts. Subscription to and expression of a masculine identity underpinned all aspects of the men's narratives. In conclusion, it is recommended that care interventions targeted towards meeting the unmet needs of this group account for this highly masculinised experience. Appropriately sequenced information and support which is gender sensitive to individualised and collective identity expression is crucial. Acknowledgment of masculinised language is also recommended for men's individual and collective recovery from this life-altering experience. [ABSTRACT FROM AUTHOR]

An inverse association between use of antiepileptic drugs (AEDs) and prostate cancer (PCa) has been suggested, putatively due to the histone deacetylases inhibitory (HDACi) properties of the AEDs. In a case-control study in Prostate Cancer data Base Sweden (PCBaSe), PCa cases diagnosed between 2014 and 2016 were matched to five controls by year of birth and county of residence. AED prescriptions were identified in the Prescribed Drug Registry. Odds ratios (ORs) and 95% confidence intervals for risk of PCa were estimated using multivariable conditional logistic regression, adjusted for civil status, education level, Charlson comorbidity index, number of outpatient visits, and cumulative duration of hospital stay. Dose responses in different PCa risk categories and HDACi properties of specific AED substances were further explored. 1738/31591 (5.5%) cases and 9674/156802 (6.2%) controls had been exposed to AED. Overall, users of any AED had a reduced risk of PCa as compared to nonusers (OR: 0.92; 95% CI: 0.87–0.97) which was attenuated by adjustment to healthcare utilisation. A reduced risk was also observed in all models for high-risk or metastatic PCa in AED users compared to nonusers (OR: 0.89; 95% CI: 0.81–0.97). No significant findings were observed for dose response or HDACi analyses. Our findings suggest a weak inverse association between AED use and PCa risk, which was attenuated by adjustment for healthcare utilisation. Moreover, our study showed no consistent dose-response pattern and no support for a stronger reduction related to HDAC inhibition. Further studies focusing on advanced PCa and PCa treatments are needed to better analyse the association between use of AED and risk of PCa. [ABSTRACT FROM AUTHOR]

In elderly men, prostate cancer is a leading cause of death. Tumor cells require more energy to progress than normal cells, and this energy is mainly dependent on the large amount of ATP support generated by lipid metabolism. Therefore, in this study, we focused on long noncoding RNAs related to lipid metabolism in prostate cancer to discover the biological mechanisms of lipid metabolism regulation. The TCGA-PRAD cohort was used in this study for computational biology analysis. In lipid metabolism biological pathways, 1959 long noncoding RNAs were identified by Pearson correlation coefficient analysis of protein-coding genes, then univariate regression with P values fewer than 0.05. We further identified 784 lncRNAs that were lipid metabolism-related lncRNAs considered to have prognostic value for disease-free survival. Subsequently, we constructed two lncRNA expression patterns of lipid metabolism based on these lncRNAs by nonnegative matrix dimensionality reduction. These two expression patterns showed significant differences in disease-free survival curves for those diagnosed with prostate cancer. We found significant differences in mRNA surveillance pathway and mRNA processing between C1 and C2 groups based on the WGCNA method to explore the biological characteristics of these two expression patterns. Finally, we constructed a disease-free survival (PFS) model based on these lncRNAs. The results identified lncRNAs involved in lipid metabolism and revealed differences in their expression patterns. Additionally, the results offer candidate ideas and approaches concerning the precision treatment of prostate cancer by studying lipid metabolism by candidate long noncoding RNAs. [ABSTRACT FROM AUTHOR]

Background. TP53 is a very common tumor suppressor gene and has implicated in various cancers. A systematic immunological analysis of TP53 somatic mutation classification in multiple cancers is still lacking. Methods. To assess the immunological value of TP53 somatic mutation classification in various cancers, we integrated a series of bioinformatics methods to analyze the role of TP53 gene across the public databases, such as UCSC Xena, Cancer Cell Line Encyclopedia (CCLE), Ensembl, and Genotype−Tissue Expression (GTEx). Results. The results revealed that the TP53 expression level had significant difference in tumor tissues and normal tissues, and it had a high expression level in most malignant tumors. Moreover, the missense mutation is the most common type of TP53 mutation in most cancers. In addition, the Cox proportional hazards model analysis and Kaplan−Meier (KM) survival analysis demonstrated that the TP53 expression is a high-risk factor in brain lower-grade glioma (LGG), prostate adenocarcinoma (PRAD), and uterine carcinosarcoma (UCS), which is opposite in uterine corpus endometrial carcinoma (UCEC). Besides, compared to the TP53 nontruncating mutation classification samples, we found that TP53 truncating mutation samples had lower TP53 expression levels in certain types of cancer. Notably, TP53 was associated with the mismatch repair (MMR) gene in some cancers which contained truncating or nontruncating mutation. Based on the classification of truncating or nontruncating mutation, we also discovered that TP53 expression was positively or negatively correlated with the immune score, stromal score, and the levels of immune cell infiltration in different cancers. Conclusions. Our research reveals an overarching landscape of immunological value on TP53 status in various malignant tumors. According to our results, we demonstrate that TP53 also plays an immunological role in various cancers. [ABSTRACT FROM AUTHOR]

Background. RAB11A, a member of the GTPase family, acts as a regulator in diverse cancers development. The dysregulation of the FAK/AKT signaling pathway is mainly related to tumorigenesis. This study aimed to investigate the possible effect of RAB11A in prostate cancer and further explore the potential mechanisms. Results. In this study, we illustrated the tumor-promoting effects of RAB11A based on in vivo and in vitro experiments. RAB11A expression was upregulated in prostate cancer cells. RAB11A knockdown decreased the prostate cancer cell proliferation, migration, and invasion. RAB11A also induced the epithelial-mesenchymal transition. PF562271 suppressed the malignant characteristics of prostate cancer cells caused by RAB11A knockdown. Furthermore, the interference of RAB11A reduced the tumor growth and the protein levels of p-FAK/FAK and p-AKT/AKT in vivo. Conclusion. RAB11A promotes cell malignant progression and tumor formation in prostate cancer via activating FAK/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Calcium/calmodulin-dependentprotein kinase II inhibitor I (CAMK2N1) as one of the tumor suppressor genes is significantly downregulated in prostate cancer (PCa). Reduced expression of CAMK2N1 is positively correlated with PCa progression. However, the mechanisms of CAMK2N1 downregulation in PCa are still unclear. The promoter region of CAMK2N1 contains a large number of CG loci, providing the possibility for DNA methylation. Consequently, we hypothesized that DNA methylation can result in the reduced expression of CAMK2N1 in PCa. In the presented study, the DNA methylation level of CAMK2N1 in prostate cells and clinical specimens was determined by bisulfite sequencing (BS), pyrosequencing, and in silico analysis. Results showed that CAMK2N1 was highly methylated in PCa cells and tissues compared to normal prostate epithelial cells and nonmalignant prostate tissues, which was associated with the clinicopathological characteristics in PCa patients. Afterwards, we explored the expression of CAMK2N1 and its DNA methylation level by qRT-PCR, western blot, BS, and methylation-specific PCR in PCa cells after 5-Aza-CdR treatment or DNMT1 genetic modification, which demonstrated that the reduced expression of CAMK2N1 can be restored by 5-Aza-CdR treatment via demethylation. Moreover, DNMT1 formed a positive feedback loop with CAMK2N1 in PCa cells. The expression of CAMK2N1 was downregulated by DNMT1-mediated DNA methylation, which reversely induced DNMT1 expression through activating AKT or ERK signaling pathway. Finally, functional assays including wound healing, invasion, and migration assay, as well as the xenograft model in nude mice indicated that CAMK2N1 inhibited the invasion, migration, and proliferation of PCa cells and these effects were reversed by DNMT1 overexpression. In conclusion, DNMT1-mediated hypermethylation of CAMK2N1 not only downregulates the gene expression but also promotes the progression of PCa. [ABSTRACT FROM AUTHOR]

Background. Promoter methylation of glutathione-S-transferase p 1 (GSTP1) is related to the occurrence of prostate cancer (PCa), but reports are inconsistent about the accuracy of GSTP1 promoter methylation in PCa diagnosis and prognosis. Therefore, we systematically evaluated the diagnostic and prognostic value of GSTP1 promoter methylation in PCa. Methods. The PubMed, EMBASE, Web of Science, and PMC databases were searched for all relevant studies from the date of inception to November 31, 2021. We compared differences in the incidence of GSTP1 promoter methylation in cfDNA between prostate cancer patients and controls. The odds ratio (OR) and hazard ratio (HR) were used as effect sizes, and the result of each effect size is expressed as a 95% confidence interval (95% CI). Results. Our meta-analysis showed that the combined sensitivity and specificity of GSTP1 promoter methylation in cfDNA for the diagnosis of prostate cancer were 0.37 (95% CI = 0.23, 0.53) and 0.97 (95% CI = 0.88, 0.99), respectively. The area under the curve (AUC) with 95% CI was 0.78 (95% CI = 0.75, 0.82). For prognostic variables, hypermethylation of GSTP1 was associated with shorter survival in PCa (HR = 2.57, 95% CI = 1.30, 5.10), with statistical significance in between-study heterogeneity (I2 = 72%, P = 0.006). The results of the subgroup analysis indicated that the heterogeneity of studies may be due to differences in the observed indicators. Conclusions. The results of the meta-analysis substantiate the high specificity of promoter methylation of GSTP1 in cfDNA for the diagnosis of prostate cancer, and it may be used to more precisely evaluate the prognosis of patients with prostate cancer. It may be helpful for the early detection of prostate cancer, but it still must be combined with traditional prostate-specific antigen (PSA) or other methylated genes to accomplish this goal. [ABSTRACT FROM AUTHOR]

Cancer has a disproportionately large influence on the death rate of adults. A patient needs to get a diagnosis of their condition as quickly as is humanly feasible in order to have the greatest chance of surviving their sickness. Skilled medical professionals use medical imaging and other traditional diagnostic methods to search for clues that may indicate the presence of malignant tendencies inside the body. Nevertheless, manual diagnosis may be time-consuming and subjective owing to the wide range of interobserver variability induced by the enormous number of medical imaging data. This variability is caused by the fact that medical imaging data are collected. Because of this, the process of accurately diagnosing a patient could become more difficult. To execute jobs that included machine learning and the interpretation of complicated imagery, cutting-edge computer technology was necessary. Since the 1980s, researchers have been working on developing a computer-aided diagnostic system that would help medical professionals in the early diagnosis of various malignancies. According to the most recent projections, prostate cancer will be discovered in the body of one out of every seven men at some time throughout the course of their life. It is unacceptable how many men are being told that they have prostate cancer, and the condition is responsible for the deaths of a rising number of men every year. Because of the high quality and multidimensionality of the MRI pictures, you will also need a powerful diagnosis system in addition to the CAD tools. Since it has been shown that CAD technology is beneficial, researchers are looking at methods to improve the accuracy, precision, and speed of the systems that use it. The effectiveness of CAD technology has been shown. This research proposes a strategy that is both effective and efficient for the processing of images and the extraction of features as well as for machine learning. This work makes use of MRI scans and machine learning in an effort to detect prostate cancer at an early stage. Histogram equalization is used while doing the preliminary processing on photographs. The image's overall quality is elevated as a result. The fuzzy C means approach is used in order to segment the images. Using a Gray Level Cooccurrence Matrix (GLCM), it is feasible to extract features from a dataset. The KNN, random forest, and AdaBoost classification algorithms are used in the classification process. [ABSTRACT FROM AUTHOR]

Background. This study is aimed at constructing a nomogram to predict the risk of clinically significant prostate cancer (csPCa) based on the aggregate index of systemic inflammation (AISI) and prostate imaging-reporting and data system version (PIRADS) score. Methods. Clinical data on patients who had undergone initial prostate biopsy from January 2019 to December 2021 were collected. Patients were randomized in a 7 : 3 ratio to the training cohort and the validation cohort. Potential risk factors for csPCa were identified by univariable and multivariate logistic regression. Nomogram was conducted with these independent risk factors, and calibration curves, the receiver operating characteristic (ROC), and decision curve analysis (DCA) were employed to assess the nomogram's ability for prediction. Results. A total of 1219 patients were enrolled in this study. Multivariate logistic regression identified that age, AISI, total prostatic specific-antigen (tPSA), free to total PSA (f/tPSA), prostate volume (PV), and PIRADS score were potential risk predictors of csPCa, and the nomogram was developed based on these factors. The area under the curve (AUC) of the training cohort and validation cohort was 0.884 (95% CI: 0.862-0.906) and 0.899 (95% CI: 0.867-0.931). The calibration curves showed that the apparent curves were closer to the ideal curves. The DCA results revealed that the nomogram model seemed to have clinical application value per DCA. Conclusion. The nomogram model can efficiently predict the risk of csPCa and may assist clinicians in determining if a prostate biopsy is necessary. [ABSTRACT FROM AUTHOR]

Background. With the growth and aging of population, the incidence of prostate cancer will increase year by year, which is bound to bring greater economic burden to the society. There has been greater interest in the anticancer effects of statin in recent years. It is controversial whether statin use is associated with the risk of prostate cancer (PCa). Thus, we conducted a meta-analysis and systematic review to explore the effects of statin use and their duration and cumulative dose on the overall incidence of PCa. Method. The study was conducted according to the latest guidelines for PRISMA 2020. We searched PubMed and other databases for studies about the association of statin use with the risk of incident prostate cancer between January 1, 1990, and April 11, 2022. Two independent researchers extracted data and evaluated the quality of the studies. R x64 4.1.2 and random-effects model were used for data statistics. Relative risk (RR) and odds ratio (OR) effective values with a 95% confidence interval (95% CI) were used to assess the main results. Results. The results of 6 RCT and 26 cohort studies showed that statins did not significantly associate with the incidence of PCa (RR = 0.94, 95% CI: 0.82–1.08). The similar results were obtained from 9 case-control studies (OR = 1.03, 95% CI: 0.99–1.07). However, statins were associated with a lower risk of Pca (RR = 0.44, 95% CI: 0.28–0.70) when the cumulative defined daily dose (cDDD) was high. Using statins for more than five years could be associated with a reduced incidence of Pca (RR = 0.47, 95% CI: 0.23–0.97). There was a significant heterogeneity in these studies (RCT and cohort study: I2 = 98%, P < 0.01; case-control study: I2 = 72%, P < 0.01). Conclusion. We concluded that statins had a neutral association with the overall risk of PCa. High cDDD and long duration were associated with a lower risk of PCa. [ABSTRACT FROM AUTHOR]

Background.Overexpression of sphingosine kinase 1 (SphK1) is casually associated with many types of cancer, and inhibitors of SphK1 sensitize tumors to chemotherapy. SphK1 is expressed as two major isoforms, SphK1a and SphK1b. To date, no information has been reported on the SphK1 isoform expression profile and its clinical relevance. Objective. The objective is to examine the expression profile of the SphK1a and SPhK1b isoforms in human cancer and noncancer tissues and cell lines and explore their clinical relevance. Methods. We used PCR to qualitatively examine the expression profile of these two isoforms in breast, liver, and prostate cancer tissues plus paired adjacent tissues and in 11 cancer and normal cell lines (breast, cervical, bone, prostate, colon, brain, mesothelioma tumor and benign, and human kidney cells). Results. We found that SphK1a was ubiquitously expressed in all cancer cells and tissues tested; in contrast, SphK1b was only expressed in selective cell types in breast, prostate, and lung cancer. Conclusions. Our data suggest that SphK1a is important for generic SphK1/S1P functions, and SphK1b mediates specialized and/or unique pathways in a specific type of tissue and could be a biomarker for cancer. This discovery is important for future SphK1-related cancer research and may have clinical implications in drug development associated with SphK1-directed cancer treatment. [ABSTRACT FROM AUTHOR]

Antrodia salmonea (AS) is a genus of Antrodia, an epiphyte of Cunninghamia konishii in Taiwan. AS has been reported to have potential therapeutic effects on different diseases, including diarrhea, abdominal pain, and hypertension. AS has been reported to have anticancer effects on numerous cancer types, such as ovarian carcinoma and triple-negative breast cancer. Our previous studies demonstrated that antrocins and triterpenoids are possibly bioactive compositions. However, the effects of AS on prostate cancer remain unknown. Therefore, we investigated the role of AS in prostate cancer growth, apoptosis, and cell cycle regulation. The results showed that AS extracts significantly inhibited the proliferation of prostate cancer LNCaP cells in a dose-dependent manner and increased the levels of apoptotic markers (cleaved PARP and cleaved caspase 3/8/9). In addition, the cell cycle-related proteins CDK1, CDK2, CDK4, and their respective specific regulators Cyclin B1, Cyclin A, and Cyclin D were also affected. Besides, AS treatment increased p53 protein levels and slowed its degradation in LNCaP cells. Interestingly, we found that AS treatment reduced both total protein and Ser-81 phosphorylation levels of the androgen receptor (AR). Notably, the increase of nuclear p53 was accompanied by the down-regulation of AR, suggesting a reverse regulation between p53 and AR in LNCaP cells was triggered by AS treatment. These findings suggest that AS extracts trigger the apoptosis of prostate cancer cells through the reverse regulation of p53 and AR and elucidate that AS extracts might be a potential treatment for androgen-dependent prostate cancer in the near future. [ABSTRACT FROM AUTHOR]

Objective. Although the prognostic effect of statins on patients with prostate cancer (PCa) has been frequently evaluated, a consistent result is still lacking. We aimed to evaluate the association between statin use and mortality among patients with PCa after definite therapies. Methods. A systematic search of PubMed and other databases for cohort studies about the effect of statins on patients with PCa was performed until April 2022. Meta-analysis was performed using R software version 4.1.2. Results. 24 cohort studies involving 369, 206 participants were finally included. We found statin use significantly reduced the risk of prostate cancer-specific mortality (PCSM) with a pooled hazard ratio (pHR) = 0.76 (95% CI: 0.69–0.84, 18 studies), especially for postdiagnostic statin users: pHR = 0.81 (95% CI: 0.77–0.85) and patients who accepted androgen deprivation therapy (ADT): pHR = 0.69 (95% CI: 0.59–0.81). Statin use was also associated with a 24% reduction in the risk of all-cause mortality (ACM): pHR = 0.76 (95% CI: 0.68–0.85, 17 studies), especially for postdiagnostic statin users: pHR = 0.81 (95% CI: 0.78–0.85) and patients treated with ADT: pHR = 0.72 (95% CI: 0.63–0.82) or radiotherapy (RT): pHR = 0.68 (95% CI: 0.50–0.93). Conclusion. In conclusion, the use of statins could promote the prognosis of patients with PCa, especially for postdiagnostic users. For patients who received either ADT or radical prostatectomy (RP), statin use could decrease the PCSM. As for those who received either ADT or RT, statin use could decrease the ACM. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate psychological resilience and demoralisation and their predictors and mediators in prostate cancer survivors (PCSs). Methods: A cross‐sectional research design was used. PCSs (N = 122; mean time since diagnosis = 54.79 months, range in 13 years and 2 months) were recruited using convenience sampling at the outpatient department of a hospital in Taiwan. Data collection was conducted using self‐report structured questionnaires, including one for demographic and disease characteristics, the Expanded Prostate Cancer Index Composite, Cancer Survivors' Self‐Efficacy Scale, Connor–Davidson Resilience Scale and the Demoralisation Scale. Results: In PCSs, a lower most‐recent level of prostate‐specific antigen and higher cancer‐specific self‐efficacy were associated with better psychological resilience. Further, fewer hormonal, bowel and urinary symptoms and bother; higher cancer‐specific self‐efficacy; and better psychological resilience were associated with less demoralisation. Cancer‐specific self‐efficacy was a mediator for the relationship between urinary symptoms and bother and demoralisation, while psychological resilience mediated the relationship between cancer‐specific self‐efficacy and demoralisation. Conclusions: The results reveal that cancer‐specific self‐efficacy is a protective factor against demoralisation and increases psychological resilience in PCSs. Better psychological resilience and fewer physical symptoms and bother are associated with less demoralisation in PCSs. [ABSTRACT FROM AUTHOR]

Objective: The primary goal of the Campania Oncology Network (ROC) was to reduce cancer delay and care fragmentation through the establishment of cancer‐specific multidisciplinary oncologic groups (GOMs) and diagnostic and therapeutic assistance paths (PDTAs). Methods: Five cancer centres of the ROC, with their own cancer specific GOM, were selected. In our analysis, we have focused on four neoplasms: lung, colon, ovarian and prostate cancers. The median time for pre‐GOM and GOM Times was calculated for each tumour site. Univariate and multivariate logistic regressions were performed to individuate risk factors for pre‐GOM and GOM Time. Results: Significant differences were observed for prostate cancer compared to other patients either for pre‐GOM or GOM Times. Significant risks were found for ovarian and prostate cancers in pre‐GOM time and for prostate cancer in GOM‐Time. Conclusions: This experience will produce knowledge and data to guide decision‐making and to manage more effectively the challenges of fighting cancer in Campania region. The Valutazione Percorso Rete Oncologica Campana (ValPeROC) study evaluates, for the first time, the ROC activity, through the analysis of key performance indices. Pre‐GOM and GOM Time represent the quality of the entire regional health system and are useful to define models, which can evaluate the performance of the ROC over time. [ABSTRACT FROM AUTHOR]

Objective: Individuals diagnosed with low risk, localised prostate cancer (PCa) face a difficult decision between active surveillance (AS) and definitive treatment. We aimed to explore perceived influences on treatment decision‐making from the patient and partner's perspectives. Methods: Patients (and partners) who met AS criteria and had chosen their treatment were recruited. Semi‐structured individual interviews were conducted via telephone to explore experiences of diagnosis, impact on patient lifestyle, experiences with physicians, treatment preferences/choice, treatment information understanding and needs, and overall decision‐making process. Interviews were audio recorded, transcribed verbatim, and analysed using Reflexive Thematic Analysis. Results: Twenty‐four male patients (18 chose AS) and 12 female partners participated. Five themes relating to social‐ecological influences on treatment choice were identified: (1) partner support and direct influence on patient treatment choice, (2) patient and partner vicarious experiences may influence treatment decisions, (3) the influence of the patient's life circumstances, (4) disclosing to wider social networks: friends, family, and co‐workers, and (5) the importance of a good relationship and experience with physicians. Additionally, two themes were identified relating to information patients and partners received about the treatment options during their decision‐making process. Conclusions: A range of individual and social influences on treatment decision‐making were reported. Physicians providing treatment recommendations should consider and discuss the patient and partner's existing beliefs and treatment preferences and encourage shared decision‐making. Further research on treatment decision‐making of partnered and non‐partnered PCa patients is required. We recommend research considers social ecological factors across the personal, interpersonal, community, and policy levels. [ABSTRACT FROM AUTHOR]

Information about the level of distrust in healthcare systems is very limited in Chinese populations, and no validated instrument has been developed to measure this distrust. Therefore, to begin addressing this research gap, this study evaluated the psychometric properties of a traditional Chinese version of the Revised Health Care System Distrust Scale and used it to assess the level of distrust in a healthcare system. The study involved a community‐based personal interview survey of individuals in Hong Kong. A total of 340 men were randomly recruited. In addition to the distrust instrument, the two‐item Trust in Physician Scale and the Patient Health Questionnaire‐9 were used. The two‐factor structure of the distrust scale was confirmed. The item‐total correlations corrected for overlap were >0.4 for both the Competence and Values Distrust subscales, confirming the internal construct validity of the scale. The Cronbach's alpha coefficient was 0.77 for both subscales. The scores of both the Competence and Values subscales were moderately negatively correlated with the total score of the Trust in Physician Scale, providing support for convergent validity. Regarding known‐group validity, the scale could differentiate people according to marital status, monthly personal income and severity of depressive symptoms. Moreover, we found that men who had previously undergone prostate cancer screening had higher Values Distrust scores than those who had not. The descriptive analysis showed that only about half of the participants reported that they received high‐quality medical care and that the healthcare system provided excellent medical care, suggesting that more effort is needed to improve the quality of care and people's satisfaction with healthcare in Hong Kong. In summary, the translated traditional Chinese version of the Revised Health Care System Distrust Scale used in this study is a valid and reliable scale for assessing the level of distrust in a healthcare system. [ABSTRACT FROM AUTHOR]

Background: Cancer patients frequently experience unrelieved pain as a significant symptom. However, several studies have found that cancer‐related pain is frequently undertreated. Purpose: This study aimed to understand the pain experiences of cancer patients who were newly engaged in a multidisciplinary pain management program (PMP) at King Hussein Cancer Centre and still receiving cancer treatments and cancer pain management. Methods: A qualitative study design and semi‐structured interviews were used to obtain data from 21 cancer patients who were purposefully selected. All patients had advanced cancer, including skeleton metastases. All female participants had breast cancer, and all male participants had prostate cancer. Results: It was found that the patient−healthcare professional relationship and satisfaction with services emerged as two themes in healthcare professionals' pain management. Conclusion: The results from this study can offer a new understanding of the knowledge related to satisfaction of patients with cancer in terms of the quality of pain management. Additional qualitative studies are required to replicate the findings in populations from different backgrounds, ethnicities, and cultures experiencing cancer pain. [ABSTRACT FROM AUTHOR]

Introduction: Whilst there has been a wealth of research on benefits of physical activity (PA) in people with cancer, with three published reviews of reviews, no review of reviews has focused on older adults (65 years or older) who may have unique biological characteristics and barriers. We summarised PA effectiveness from reviews where majority of study participants were 65 years or older. Methods: Six databases were searched for systematic reviews of randomised controlled studies (RCTs)/quasi‐RCTs examining any type of PA in reviews where majority of study participants were aged 65 years or older. Two reviewers conducted the search and analysis according to PRISMA and JBI guidelines. Results: Fifteen reviews involving 76 different primary studies (5404 participants) were included. The majority (3827; 71%) had prostate cancer. PA was associated with benefits across multiple physical outcomes (muscle mass, functional performance, strength), improved fatigue and health service outcomes. In contrast to younger adults, there was no improvement in anxiety and mixed findings for quality of life and depression. Conclusion: PA is associated with multiple benefits in older adults with cancer, with some differences compared to younger individuals which may reflect biological or behavioural determinants. Future research should focus on mechanisms underlying PA effectiveness and underrepresented populations. [ABSTRACT FROM AUTHOR]

Objective: Evidence on the benefits of physical activity (PA) during cancer has caused a paradigm shift from people with cancer being advised to save energy (rest paradigm) to guidelines recommending them to engage in regular PA (activity paradigm). This study examined the rest and the activity paradigm among people with cancer based on the theory of planned behaviour (TPB). Methods: A cross‐sectional survey was completed by N = 1244 people (58% women; M = 59.95 years) with breast, prostate and colorectal cancer, including 15 items on rest and activity attitudes. To explain the intention to engage in PA, hierarchical regression analyses were calculated. Results: The two‐dimensional structure of attitudes (rest and activity) was confirmed. The agreement with the activity paradigm (M = 4.11; SD = 0.78) was higher compared to the rest paradigm (M = 2.56; SD = 0.78, p <.001). The TPB was an appropriate model to explain the intention to engage in PA (R2 =.59), showing that the activity paradigm, but not the rest paradigm, was significantly associated with participants' intention for PA. Conclusion: Results indicate that the paradigm shift has successfully reached attitudes of people with cancer. Interventions focusing on the benefits of PA rather than addressing rest cognitions promise higher effectiveness in affecting PA levels. Clinical trial registration number: NCT02678832. [ABSTRACT FROM AUTHOR]

Objective. The purpose was to compare the accuracy of extraprostatic extension (EPE) grade on MRI predicting EPE with Partin tables, Memorial Sloan Kettering Cancer Center nomogram (MSKCCn), and combined models and to analyze the clinical incremental value of EPE grade. Materials and Methods. 105 prostate cancer patients confirmed by pathology after radical prostatectomy in our hospital from 2017 to 2021 were selected. The clinical stage, PSA, Gleason score, number of positive biopsy cores, and percentage of positive biopsy cores were recorded. Evaluate EPE grade according to EPE grade criteria, and calculate the probability of predicting EPE with Partin tables and MSKCCn. EPE grade is combined with Partin tables and MSKCCn to construct EPE grade+Partin tables and EPE grade+MSKCCn models. Calculate the area under the curve (AUC), sensitivity, and specificity of EPE grade, Partin tables, MSKCCn, EPE grade+Partin tables, and EPE grade+MSKCCn and compare their diagnostic efficacy. The clinical decision curve was used to analyze the clinical net income of each prediction scheme. Results. The AUC of EPE grade was 0.79, Partin tables was 0.50, MSKCCn was 0.78, the EPE grade+Partin table model was 0.79, and the EPE grade+MSKCCn model was 0.83. After EPE grade was combined with Partin tables and MSKCCn, the diagnostic efficiency of clinical model was significantly improved (P < 0.05). There was no significant difference in the diagnostic efficacy of the combined model compared with the single EPE grade (P > 0.05). The calibration curve of the combined model shows that it has a good calibration degree for EPE. In the analysis of the decision curve, the net income of the EPE grade is higher than that of Partin tables and MSKCCn and is equal to the EPE grade+Partin tables and is slightly lower than that of EPE grade+MSKCCn. The clinical net income of the combined model is obviously higher than that of individual clinical models. Conclusion. The accuracy of EPE classification in predicting prostate cancer EPE is high, and combined with the clinical model, it can significantly improve the diagnostic efficiency of the clinical model and increase the clinical benefit. [ABSTRACT FROM AUTHOR]

Object. Extracellular acidosis of the tumor microenvironment plays an important role in cancer progression. In the 2D monolayer and 3D spheroid cultures of prostate cancer cells, we investigated the efficacy of curcumin in targeting glycolysis and the role of ERK1/2 as an upstream signaling molecule in this process. Methods. Cell viability, glycolytic activity, Annexin V-PE binding activity, reactive oxygen species levels, mitochondrial membrane potential, ATP content, Western blot analysis, and spheroid viability were measured for this study. Results. Acidic pH-tolerant prostate cancer cells, PC-3AcT and DU145AcT, increased cytotoxicity with ERK1/2 inhibition in a curcumin concentration-dependent manner at concentrations that resulted in >90% cell viability in normal prostate epithelial HPrEC cells. ERK1/2 inhibition by curcumin and/or PD98059 suppressed cell growth, reduced glucose consumption, and downregulated the expression of key regulatory enzymes in glucose metabolism including hexokinases, phosphofructokinase, and pyruvate dehydrogenase. In addition, these compounds caused loss of mitochondrial membrane potential with increased intracellular ROS levels, decreased levels of complexes I, III, and IV in the mitochondrial electron transport chain, and cellular ATP depletion, leading to upregulation of marker proteins in apoptosis (cleaved caspase-3 and cleaved PARP) and necroptosis (p-MLKL and p-RIP3). The results of curcumin and/or PD98059 treatment in 3D cultures showed similar trends to those in 2D cultures. Conclusion. Taken together, the results provide mechanistic evidence for the antiglycolytic and cytotoxic roles of curcumin through inhibition of the MEK/ERK signaling pathway in prostate carcinoma cells preadapted to acidic conditions. [ABSTRACT FROM AUTHOR]

Purpose. To access the incidence and predictors of Gleason grade group upgrading from cognitive MR-targeted fusion prostate biopsy to radical prostatectomy in a Chinese cohort. Materials and Methods. We included 199 patients in our institution between January 2016 and June 2021. Multivariable logistic regression model and nomograms were utilized to analyze the collected data. Results. The concordance rate of biopsy Gleason grade group and radical prostatectomy was 50.3% (100 in 199). Upgrading occurred in 80 (40.2%) patients and 37 (68.5%) patients have an upgrading Gleason grade group when the biopsy Gleason grade group was 1. Multivariable logistic regression models were established to analyze the incidence and predictors of Gleason grade group upgrading from cognitive MR-targeted fusion prostate biopsy to radical prostatectomy. Biopsy Gleason grade group, prostate volume, and patient year were confirmed to be individual predictors of upgrading. Based on the logistic regression models, nomograms for predicting probability of prostate Gleason grade group upgrading were generated. Conclusions. We established a logistic regression model to predict the accuracy of prostate biopsy GG and provide the probability of upgrading. Clinicians should be more cautious when deciding the treatment strategy especially for prostate cancer biopsy GG1 patients. Future studies should expand the sample size and include more variables to improve the accuracy of predicting upgrading and prostate cancer early screening program is urgently needed in our city in China. [ABSTRACT FROM AUTHOR]

Objective. The aim is to study the different roles of single and joint application of magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) in prostate malignant tumors. Methods. 72 patients with prostate masses who underwent CEUS and MRI examination in our hospital from October 2021 and March 2022 were enrolled in this research. The differentially diagnostic roles of CEUS, MRI, and CEUS combined MRI for prostate cancer was assessed on basis of pathological findings as the reference standard. The specificity and sensitivity of the joint application for prostate malignant tumors with various prostate-specific antigen (PSA) levels were also evaluated. Results. The sensitivity of CEUS, MRI, and the joint application for prostate cancer were 72.1%, 74.4%, and 90.7%, respectively. Compared with single application, the sensitivity of CEUS combined with MRI was significantly higher. The specificity of MRI, CEUS, and the combination of the two for prostate cancer were 82.8%, 79.3%, and 89.7%, respectively, and the statistical differences for specificity were not found. The area under ROC curve (AUC) of CEUS combined with MRI in prostate malignant tumor diagnosis was obviously more than that of CEUS and MRI (P < 0.05). CEUS combined with MRI has relative high sensitivity in these patients with different levels of PSA. Conclusions. Contrast-enhanced ultrasound combined with MRI can significantly improve the sensitivity and specificity of prostate cancer diagnosis so that patients can be better diagnosed in advance. [ABSTRACT FROM AUTHOR]

Aim. This study aimed to learn the antineoplastic activity of curcumol (Cur) on prostate cancer (PCa) and elucidate its potential molecular mechanism. Methods. The proliferation, invasion, and migration of PCa cells (PC3 and 22RV1) were detected by the cell counting kit 8 (CCK8), transwell, and wound healing assay, respectively. The expression of genes and proteins was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB), respectively. The protein expression in tissues and cells was tested through immunohistochemistry (IHC) and immunocytochemistry (ICC). Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the level of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). The interaction between microRNA125a (miR-125a) and the signal transducer and activator of transcription 3 (STAT3) was confirmed via dual-luciferase reporter assay. Results. Cur effectively restrained the proliferation, invasion, and migration of PC3 and 22RV1 cells. After Cur intervention, miR-125a, miR-375, miR-149, miR-183, and miR-106b were all upregulated in PC3 cells, among which miR-125a was the most significantly upregulated. Dual-luciferase reporter assay combined with qRT-PCR and WB experiments confirmed that miR-125a targeted STAT3. Both in vitro and in vivo, Cur enhanced miR-125a expression and suppressed the activation of the STAT3 pathway in PCa. Also, Cur effectively inhibited the growth of PCa. Conclusion. Cur inhibited the development of PCa by miR-125a/STAT3 axis. This may provide a potential agent for treating PCa. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the most common cancers in men worldwide, second only to lung cancer. The most common method used in diagnosing prostate cancer is the microscopic observation of stained biopsies by a pathologist and the Gleason score of the tissue microarray images. However, scoring prostate cancer tissue microarrays by pathologists using Gleason mode under many tissue microarray images is time-consuming, susceptible to subjective factors between different observers, and has low reproducibility. We have used the two most common technologies, deep learning, and computer vision, in this research, as the development of deep learning and computer vision has made pathology computer-aided diagnosis systems more objective and repeatable. Furthermore, the U-Net network, which is used in our study, is the most extensively used network in medical image segmentation. Unlike the classifiers used in previous studies, a region segmentation model based on an improved U-Net network is proposed in our research, which fuses deep and shallow layers through densely connected blocks. At the same time, the features of each scale are supervised. As an outcome of the research, the network parameters can be reduced, the computational efficiency can be improved, and the method's effectiveness is verified on a fully annotated dataset. [ABSTRACT FROM AUTHOR]

Cirsilineol has been reported to exhibit anticancer effects against several human cancer cell lines. The present study was designed to evaluate the anticancer effects of cirsilineol against the human DU-145 prostate cancer cells. The results showed that cirsilineol suppressed the proliferation of DU-145 cancer cells in a dose-dependent manner with minimal cytotoxic effects against the normal cells. The IC50 of cirsilineol was found to be 7 μM and 110 μM against prostate cancer DU-145 and normal HPrEC prostate cells, respectively. Acridine orange and ethidium bromide (AO/EB) staining showed that cirsilineol induced apoptosis in DU-145 prostate cancer cells. The Annexin V/PI staining further confirmed the induction of apoptosis in DU-145 cells. The western blot analysis showed that cirsilineol suppressed the expression of Bax and upregulated the expression of Bcl-2 in prostate cancer DU-145 cells. Moreover, cirsilineol caused a dose-dependent increase in reactive oxygen species (ROS) levels in prostate cancer. Wound healing and Transwell assays showed that cirsilineol inhibits migration and invasion of DU-145 prostate cancer cells. Summing up, the results suggest that cirsilineol suppresses the proliferation of prostate cancer cells and may prove to be a beneficial lead molecule for the development of chemotherapy for prostate cancer. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most common cancer affecting men, with increasing global mortality and morbidity rates. Despite the progress in the diagnosis and treatment of PCa, patient outcomes remain poor, and novel therapeutic targets for PCa are urgently needed. Recently, circular RNAs (circRNAs) have been studied in-depth as potential biomarkers for many diseases. In this study, circRNA microarrays using four pairs of PCa tissues were utilized to show that circGFRA1 was upregulated in PCa tumor tissues. CircGFRA1 is suggested to play an oncogene role in PCa progression as the silencing of circGFRA1 inhibited the proliferation, migration, and immune escape activity of PCa cells. Furthermore, by utilizing bioinformatics analysis, RIP, RNA pull-down, and luciferase reporter assays, our results showed that LMX1B could bind to the GFRA1 promoter and regulate circGFRA1 expression in PCa cells and circGFRA1 upregulated HECTD1 expression through sponging miR-3064-5p. This novel LMX1B/circGFRA1/miR-3064-5p/HECTD1 axis identified in PCa provides new insights for developing novel therapeutic strategies for PCa. [ABSTRACT FROM AUTHOR]

Objective: Signs and symptoms are important in monitoring prostate cancer, but there is a lack of understanding about the men's interpretation of signs and symptoms in relation to disease progression in advanced phases of the disease. The aim was to illuminate the experience of signs and symptoms in relation to disease progression in men with metastatic castration‐resistant prostate cancer (mCRPC). Method: Thirty longitudinal interviews were conducted with 11 men undergoing life‐prolonging treatment for mCRPC. Conventional content analysis was used. Results: The results illuminate an uncertainty that the men experience when interpreting signs and symptoms. The overarching theme was The experience of an uncertain illness situation within the framework of progression, with four subthemes: Symptoms triggering thoughts about disease progression; Making sense of signs, also in the absence of symptoms; Making sense of symptoms during treatment; Progression triggering thoughts about the remainder of life. Conclusion: In the uncertain illness situation, the men strive to make sense of signs and symptoms based on previous experiences and in relation to disease progression. Understanding the men's perspectives on signs and symptoms in this late phase may help health care professionals communicate about disease progression considering the balance between treatment outcome and quality of life. [ABSTRACT FROM AUTHOR]

Introduction: The impact of radical prostatectomy on the social well‐being of survivors remains poorly understood. This meta‐synthesis therefore aimed to integrate the findings of qualitative research evaluating the impact of surgery on the patient relationships with partners, family and wider societal interactions. Methods: Medline, CINAHL, PsycINFO and Embase were searched for qualitative studies evaluating social well‐being dimensions. A thematic meta‐synthesis was conducted to inductively construct descriptive themes and overarching analytical themes. Results: Thirty‐one articles were included, with seven descriptive themes under two analytical themes generated to describe the experiences of 469 participants. 'Pathway to Conversion' encompassed three themes on the evolving social behaviour of men with both partners and family to adapt to their new normality postoperatively. 'A Man on My Own' discussed four themes focussing on both intimate and wider social relations, describing the stigma, shame and embarrassment felt by patients due to changes in their perceived body image and physical function. This resulted in men feeling alone, unsupported and seeking isolation. Conclusion: Radical prostatectomy's impact on survivors' social well‐being extends beyond surgery and causes a shift in their relationship dynamics with partner and family, highlighting the importance of preoperative and postoperative clinician's counselling to both patient and partner. [ABSTRACT FROM AUTHOR]

Objective: Determine if cancer survivors have lower participation in paid work, more limitations in daily activities or more limitations in leisure compared with those without cancer, stratified by age (working age ≤65 years; retirement age >65 years). Secondary objectives are identifying sociodemographic or clinical factors associated with work, daily activities or leisure and analysis of the relationship between work, daily activities and leisure. Methods: Secondary analyses, using logistic regression, were performed on three cohorts (lymphoma, prostate and thyroid cancer) from the Dutch Patient Reported Outcomes Following Initial treatment and Long‐term Evaluation of Survivorship (PROFILES) registry and a nationally representative non‐cancer sample. Results: Working‐age cancer survivors (n = 926) were significantly (p < 0.001) less likely to participate in paid work and more likely to report limitations in daily activities and leisure compared to the non‐cancer cohort (n = 1279). Among retirement aged cancer survivors (n = 1046), paid work was significantly more likely (p < 0.001), as were limitations in leisure (p < 0.05), compared with the non‐cancer controls (n = 334). Conclusions: Cancer impacts daily activities and leisure, as well as paid work. These roles are important for cancer survivors' quality of life, suggesting support to return to these activities may be an important component of survivorship care. [ABSTRACT FROM AUTHOR]

The purpose of this systematic review and synthesis of studies reporting qualitative data was to understand the gendered experiences of female partners of prostate cancer survivors to inform psychosocial support for women. We searched Medline, PsycINFO, EMBASE, AMED, CINAHL, Cochrane Database of Systematic Reviews, and Sociological Abstracts for articles on 15 and 16 April 2019, and again on 30 November 2020. English language articles published in peer‐reviewed journals were included if they reported solely on findings describing the perspectives of the female partners. Extracted data were analysed using line‐by‐line coding, organisation of codes into descriptive themes, and development of analytical themes. A theoretical framework was then selected to organise the relationships between issues that were found to be central to the experiences of female partners. Of 4839 articles screened, 14 met inclusion criteria, reporting 13 studies with a total sample of 359 female partners. Ussher and Sandoval's theory to describe the gendered positionings of cancer caregivers accommodated the thematic findings. The overarching theme reflected the substantive psychosocial impact of prostate cancer on female partners. Women's experiences were influenced by self‐positioning (as part of a couple; provider of support to their male partner; resilient; and guided by faith and spirituality), being positioned by their partners' response (manager of male partner's psychological distress or strengthened by male partner's positive response) and by their broader contexts (family members and social networks; clinicians and the health system; and cultural values and customs). Findings highlight the need to avoid reductionist approaches to gender. Greater consideration of 'contextualised femininities', or conceptualising the influence of gender roles, relations, and identities within the wider life course contexts of female partners is required in the design and delivery of psychosocial support services. [ABSTRACT FROM AUTHOR]

Objective. The aim of the study is to investigate the role and possible mechanism of fascin-1 (FSCN1) in the invasion, migration, glycolysis, and epithelial-mesenchymal transition (EMT) of prostate cancer. Methods. Real-time quantitative polymerase chain reaction (qRT-PCR) was utilized to determine the mRNA expression level of FSCN1 in prostate cancer tissues and prostate cancer cells PC-3 and DU145. The transwell and the scratch test were applied to detect the invasion and migration abilities of cells, respectively. A metabolic assay was used for measuring the glucose consumption, lactate production, and the extracellular acidification rate (ECAR) in cells; western blot was used for checking FSCN1, EMT, and yes-associated protein/transcriptional co-activators with the PDZ-binding motif (YAP/TAZ) signaling pathway-related protein expression level in cells or tissues. Results. FSCN1 was significantly highly expressed in prostate cancer tissues and cells. On the one hand, interference with the expression of FSCN1 could inhibit the invasion, migration, EMT, and glycolysis of prostate cancer cells. On the other hand, overexpression of FSCN1 promoted the invasion, migration, EMT, and glycolysis of prostate cancer cells. Besides, further mechanistic studies revealed that FSCN1 could activate the YAP/TAZ signaling pathway in prostate cancer cells. Conclusion. FSCN1 promotes invasion, migration, EMT, and glycolysis in prostate cancer cells by activating the YAP/TAZ signaling pathway. FSCN1 may be used as a biomarker for the diagnosis or treatment in prostate cancer. [ABSTRACT FROM AUTHOR]

Prostate carcinoma (PC) is a disease of the male genitourinary system and a relatively common malignant tumor. In order to investigate the disparities in the expression of microRNA-323 (miR-323), microRNA-409-3p (miR-409-3p), and vascular endothelial growth factor (VEGF) in prostate carcinoma with different clinicopathological features and analyze their correlation with prognosis. Thirty-two sufferers with prostate carcinoma and forty-three sufferers with benign prostatic hyperplasia are included. The results show that the detection of miR-323, miR-409-3p, and VEGF scales can provide reference value for clinical guidance of prostate carcinoma prognosis. [ABSTRACT FROM AUTHOR]

A technique to predict crucial clinical prostate cancer (PC) is desperately required to prevent diagnostic errors and overdiagnosis. To create a multimodal model that incorporates long-established messenger RNA (mRNA) indicators and conventional risk variables for identifying individuals with severe PC on prostatic biopsies. Urinary has gathered for mRNA analysis following a DRE and before a prostatic examination in two prospective multimodal investigations. A first group (n = 489) generated the multimodal risk score, which was then medically verified in a second group (n = 283). The reverse transcription qualitative polymerase chain reaction determined the mRNA phase. Logistic regression was applied to predict risk in patients and incorporate health risks. The area under the curve (AUC) was used to compare models, and clinical efficacy was assessed by using a DCA. The amounts of sixth homeobox clustering and first distal-less homeobox mRNA have been strongly predictive of high-grade PC detection. In the control subjects, the multimodal method achieved a total AUC of 0.90, with the most important aspects being the messenger riboneuclic acid features' PSA densities and previous cancer-negative tests as a nonsignificant design ability to contribute to PSA, aging, and background. An AUC of 0.86 was observed for one more model that added DRE as an extra risk component. Two methods were satisfactorily verified without any significant changes within the area under the curve in the validation group. DCA showed a massive net advantage and the highest decrease in inappropriate costs. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the clinical and prognostic role of PDZ and LIM domain protein (PDLIM) genes and the association to epithelial-mesenchymal transition (EMT) and immune cell infiltration in patients with prostate cancer (PRAD).Methods: The data of RNA-seq, DNA methylation, and clinical features of PRAD patients were collected from The Cancer Genome Atlas (TCGA) database to define the prognostic value of PDLIM gene expression and the association with EMT and immune cell infiltration. A tissue microarray including 134 radical prostatectomy specimens was served as validation by immunohistochemistry (IHC) staining analysis.Results: The mRNA levels of PDLIM1/2/3/4/6/7 were significantly downregulated, while PDLIM5 was upregulated in PRAD (P < 0.05). High expression of PDLIM2 mRNA suggests poor progression free interval in PRAD patients. DNA methylation of PDLIM2 was correlated with its mRNA expression level, and that the cg22973076 methylation site in PDLIM2 was associated with shorter PFI (P < 0.05) in PRAD. Single-sample gene-set enrichment and gene functional enrichment results showed that PDLIM2 was correlated with EMT and immune processes. Spearman's test showed a significant correlation with six reported EMT signatures and several EMT signature-related genes. Tumor microenvironment analysis revealed that the PDLIM2 mRNA expression was positively correlated with the immune score, stromal score, and various tumor infiltrating immune cells. Additionally, the results showed that patients in the high-PDLIM2 mRNA expression group may be more sensitive to immune checkpoint blockade therapy. Finally, IHC analysis further implicated the protein level of PDLIM2 was upregulated in PRAD and acts as a novel potential biomarker in predicting tumor progression.Conclusion: Our study suggests that PDLIM family genes might be significantly correlated with oncogenesis and the progression of PRAD. PDLIM2 correlated with EMT and immune cell infiltration by acting as an oncogene in PRAD, which may serve as a potential prognostic biomarker for PRAD patients. [ABSTRACT FROM AUTHOR]

Cancer of the prostate is an indicated type that is often recorded as a kind of cancer in men and the second critical cause of mortality through cancer cases. Many pharmacological investigations have shown that numerous herbal substances possess anticancer action. Amygdalin (AMD) has antitumour capabilities and works as an antioxidant, antibacterial, anti-inflammatory, and immune-regulating characteristics. The anticancer effects of amygdalin and its metabolizing enzymes, rhodanese (RHD) and betaglucosidase (BGD), were examined in vivo, as well as their antitumour processes. Novel, effective combination agents are necessary to increase existing cancer treatment rates. This research was aimed at determining the anticarcinogenic impact of amygdalin (AMD) in vivo. This research was aimed at determining the RHD and BGD on the anticarcinogenic impact of AMD in vivo. Subcutaneously, PC3 prostate cancer cell lines were implanted into nude mice. Mice were treated every day with 0.5 ml of 50 mg/ml (AMD), AMD+ (RHD 0.1 mg/ml), AMD+(BGD 0.1 mg/ml), and doxorubicin (DOX 50 mg/ml). Mice were normalized for negative control with untreated mice. In in vivo, morphopathological alterations in the tumour tissue were analyzed by histopathological staining methods. After 35 days of therapy, tumour growth and size inhibition were evident, indicating a function for the metabolic enzymes BGD and RHD in regulating AMD's anticancer effect in vivo. We concluded the critical role of metabolic enzymes BGD and RHD in elevating the antigrowth of PC3 cancer cell lines in Balb/c nude mice treated with AMD. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is one of the most common types of cancer among men, and coffee is associated with a reduced risk of developing PCa. Therefore, we aim to review possible coffee molecular mechanisms that contribute to PCa prevention. Coffee has an important antioxidant capacity that reduces oxidative stress, leading to a reduced mutation in cells. Beyond direct antioxidant activity, coffee stimulates phase II enzymatic activity, which is related to the detoxification of reactive metabolites. The anti-inflammatory effects of coffee reduce tissue damage related to PCa development. Coffee induces autophagy, regulates the NF-κB pathway, and reduces the expression of iNOS and inflammatory mediators, such as TNF-α, IL-6, IL-8, and CRP. Also, coffee modulates transcriptional factors and pathways. It has been shown that coffee increases testosterone and reduces sex hormone-binding globulin, estrogen, and prostate-specific antigen. Coffee also enhances insulin resistance and glucose metabolism. All these effects may contribute to protection against PCa development. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is highly prevalent and impacts profoundly on patients' quality of life, leading to a range of supportive care needs. Methods: An updated systematic review and thematic synthesis of qualitative data using the Preferred Reporting Items for Systematic Reviews (PRISMA) reporting guidelines, to explore prostate cancer patients' experience of, and need for, supportive care. Five databases (Medline, Embase, PsycInfo, Emcare and ASSIA) were searched; extracted data were synthesised using Corbin and Strauss's 'Three Lines of Work' framework. Results: Searches identified 2091 citations, of which 105 were included. Overarching themes emerged under the headings of illness, everyday life and biographical work. Illness work needs include consistency and continuity of information, tailored to ethnicity, age and sexual orientation. Biographical work focused on a desire to preserve identity in the context of damaging sexual side effects. Everyday life needs centred around exercise and diet support and supportive relationships with partners and peers. Work‐related issues were highlighted specifically by younger patients, whereas gay and bisexual men emphasised a lack of specialised support. Conclusion: While demonstrating some overarching needs common to most patients with prostate cancer, this review offers novel insight into the unique experiences and needs of men of different demographic backgrounds, which will enable clinicians to deliver individually tailored supportive care. [ABSTRACT FROM AUTHOR]

Background. The characteristics and outcomes of patients with intrahepatic cholangiocarcinoma (ICC) with prior malignancy are poorly clarified. This study is aimed at exploring the impact of prior malignancy on the long-term outcomes of ICC patients. Methods. Using the Surveillance, Epidemiology, and End Results (SEER) program, ICC patients diagnosed between 2004 and 2018 were identified. Kaplan-Meier curves and Cox analysis were used to evaluate the impact of prior malignancy on the prognosis of ICC patients. Results. A total of 9667 ICC patients were identified; among them, 782 (8.09%) had a history of prior cancer. Prostate, breast, colorectal, bladder, and liver/gallbladder/other biliary cancers were the most common types of prior cancer. Patients with prior cancer had better tumor-related profiles than those without prior cancer, namely, the former patients showed a lower proportion of positive AFP levels and vascular invasion, a lower AJCC stage, a smaller tumor size, and a lower stage of tumor grade. The median survival times after the diagnosis of ICC were 10 and 11.5 months for patients with and without prior cancer, respectively. Multivariate regression analysis suggested that prior cancer did not contribute to inferior overall survival (OS, HR 0.870, 95% CI 0.797-0.950, and p = 0.002) or cancer-specific survival (CSS, HR 0.820, 95% CI 0.741-0.906, and p < 0.001). Conclusions. A history of prior cancer does not lead to worse OS or CSS for ICC patients. The exclusion of patients with prior cancer from clinical trials should be reconsidered. [ABSTRACT FROM AUTHOR]

Despite the breakthrough in the development of anticancer therapies, plant-derived chemotherapeutics continue to be the basis of treatment for most types of cancers. Fridericia platyphylla is a shrub found in Brazilian cerrado biome which has cytotoxic, anti-inflammatory, and analgesic properties. The aim of this study was to investigate the antiproliferative potential of the crude hydroethanolic extract, subfraction (containing 59.3% of unusual dimeric flavonoids Brachydin E and 40.7% Brachydin F), as well as Brachydin E and Brachydin F isolated from F. platyphylla roots. The cytotoxic activity was evaluated in glioblastoma, lung, prostate, and colorectal human tumor cell lines. The crude hydroethanolic extract did not present cytotoxic activity, but its subfraction presented lower IC50 values for glioblastoma (U-251) and prostate adenocarcinoma (PC-3) cell lines. Brachydins E and F significantly reduced cell viability, proliferation, and clonogenic potential of PC-3, inducing them to the process of regulated cell death. In silico studies have indicated nuclear receptors as targets for Brachydins E and F, and molecular docking has pointed out their binding into glucocorticoid receptor (GR) ligand pocket. Targeting GR pathway has been described as a therapeutic strategy, especially for prostate cancer. These results suggest that Brachydin E and Brachydin F are promising compounds to be further explored for their antitumor effects. [ABSTRACT FROM AUTHOR]