Um assunto que precisamos ter | Coisa de Homem

Embora comum, o Câncer de Próstata é uma doença que pode ser detectada e tratada precocemente. Não dê bobeira, vá ao médico e faça os exames preventivos!

Novembro Azul

Câncer de próstata | Coisa de Homem

Novembro é o mês de combate ao câncer de próstata, segundo mais comum entre os homens no Brasil. Os sintomas só costumam aparecer quando o tumor já está em uma fase avançada. Por isso, o diagnóstico precoce e a prevenção são tão importantes.

Live sobre a campanha Novembro Azul

Live sobre a campanha Novembro Azul: cuidados relacionados ao câncer de próstata

Exploring the clinical and biological significance of the cell cycle-related gene CHMP4C in prostate cancer.

BACKGROUND: Prostate cancer (PCa) stands as the second most prevalent malignancy impacting male health, and the disease's evolutionary course presents formidable challenges in the context of patient treatment and prognostic management. Charged multivesicular body protein 4 C (CHMP4C) participates in the development of several cancers by regulating cell cycle functions. However, the role of CHMP4C in prostate cancer remains unclear. METHODS: In terms of bioinformatics, multiple PCa datasets were employed to scrutinize the expression of CHMP4C. Survival analysis coupled with a nomogram approach was employed to probe into the prognostic significance of CHMP4C. Gene set enrichment analysis (GSEA) was conducted to interrogate the functional implications of CHMP4C. In terms of cellular experimentation, the verification of RNA and protein expression levels was executed through the utilization of qRT-PCR and Western blotting. Upon the establishment of a cell line featuring stable CHMP4C knockdown, a battery of assays, including Cell Counting Kit-8 (CCK-8), wound healing, Transwell, and flow cytometry, were employed to discern the impact of CHMP4C on the proliferation, migration, invasion, and cell cycle function of PCa cells. RESULTS: The expression of CHMP4C exhibited upregulation in both PCa cells and tissues, and patients demonstrating elevated CHMP4C expression levels experienced a notably inferior prognosis. The nomogram, constructed using CHMP4C along with clinicopathological features, demonstrated a commendable capacity for prognostic prediction. CHMP4C knockdown significantly inhibited the proliferation, migration, and invasion of PCa cells (LNcaP and PC3). CHMP4C could impact the advancement of the PCa cell cycle, and its expression might be regulated by berberine. Divergent CHMP4C expression among PCa patients could induce alterations in immune cell infiltration and gene mutation frequency. CONCLUSIONS: Our findings suggest that CHMP4C might be a prognostic biomarker in PCa, potentially offering novel perspectives for the advancement of precision therapy for PCa.

Anti-Proliferative Activity of Poloxamer Cobalt Ferrite Nanoparticles against Human Prostate Cancer (DU-145) Cells: In-Vitro Study.

Prostate cancer is the second most frequent type of cancer death in men. This study refers to the novel hyperthermia application of poloxamer-coated cobalt ferrite as a new approach for thermal eradication of DU-145 human prostate cancerous cells under a radio frequency magnetic field (RF-MF). The hydrothermal method was applied for the synthesis of cobalt ferrite nanoparticles. Then, the structure, size, and morphology of nanoparticle were characterized. The cytotoxicity of the synthesized nanoparticles and RF-MF exposure on DU-145 prostate cancer cells was investigated separately or in combination with colony formation methods and MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assay. Transmission electron microscopy (TEM) confirmed the spherical morphology of nanoparticles with a size of 5.5 ± 2.6 nm. The temperature of cells treated with nanoparticles under RF-MF reached 42.73 ± 0.2°C after 15 min. RF-MF treatment or nanoparticles have not affected cell viability significantly. However, the combination of them eradicated 53% ± 4% of cancerous cells. In-vitro hyperthermia was performed on human prostate cancer cells (DU-145) with cobalt ferrite nanoparticles at specific concentrations that demonstrated a decrease in survival fraction based on colony formation assay compared to cells that were treated alone with nanoparticles or with RF-MF.

The miRNAs 203a/210-3p/5001-5p regulate the androgen/androgen receptor/YAP-induced migration in prostate cancer cells.

BACKGROUND: Prostate cancer (PCa) patients with elevated level of androgen receptor (AR) correlate with higher metastatic incidence. Protein expression of AR and its target gene prostate-specific antigen (PSA) are elevated in metastatic prostate tumors as compared to organ-confined tumors. Androgen treatment or elevation of AR promotes metastasis of PCa in cell culture and murine model. However, under androgen depleted condition, AR suppressed cell mobility and invasiveness of PCa cells. Androgen deprivation therapy in PCa patients is associated with higher risk of cancer metastasis. We therefore investigated the dual roles of AR and miRNAs on PCa metastasis. METHODS: The PC-3AR (PC-3 cells re-expressing AR) and LNCaP cells were used as PCa cell model. Transwell migration and invasion assay, wound-healing assay, zebrafish xenotransplantation assay, and zebrafish vascular exit assay were used to investigate the role of AR and androgen on PCa metastasis. Micro-Western Array, co-immunoprecipitation and Immunofluorescence were applied to dissect the molecular mechanism lying underneath. The miRNA array, miRNA inhibitors or plasmid, and chromatin immunoprecipitation assay were used to study the role of miRNAs on PCa metastasis. RESULTS: In the absence of androgen, AR repressed the migration and invasion of PCa cells. When androgen was present, AR stimulated the migration and invasion of PCa cells both in vitro and in zebrafish xenotransplantation model. Androgen increased phospho-AR Ser81 and yes-associated protein 1 (YAP), decreased phospho-YAP Ser217, and altered epithelial-mesenchymal transition (EMT) proteins in PCa cells. Co-IP assay demonstrated that androgen augmented the interaction between YAP and AR in nucleus. Knockdown of YAP or treatment with YAP inhibitor abolished the androgen-induced migration and invasion of PCa cells, while overexpression of YAP showed opposite effects. The miRNA array revealed that androgen decreased hsa-miR-5001-5p but increased hsa-miR-203a and hsa-miR-210-3p in PC-3AR cells but not PC-3 cells. Treatment with inhibitors targeting hsa-miR-203a/hsa-miR-210-3p, or overexpression of hsa-miR-5001-5p decreased YAP expression as well as suppressed the androgen-induced migration and invasion of PCa cells. Chromatin immunoprecipitation (ChIP) assay demonstrated that AR binds with promoter region of has-miR-210-3p in the presence of androgen. CONCLUSIONS: Our observations indicated that miRNAs 203a/210-3p/5001-5p regulate the androgen/AR/YAP-induced PCa metastasis.

Prostate ductal adenocarcinoma exhibiting a late recurrence in the anterior urethra 13 years post-total prostatectomy: a case report.

BACKGROUND: Prostate ductal adenocarcinoma, a rare histology observed in 0.4-0.8% of all prostate cancers, is treated similarly to acinar adenocarcinoma but tends to have a higher likelihood of metastasis, recurrence, and poorer prognosis. CASE PRESENTATION: A 73-year-old Asian-Japanese male presented with gross hematuria, with investigations revealing a prostate ductal adenocarcinoma. Subsequent radical prostatectomy indicated a Gleason score of 8 with no lymph node metastasis. Despite initial prostate-specific antigen level reductions post-prostatectomy and salvage radiation therapy due to recurring elevated prostate-specific antigen levels, no recurrence was evident until 13 years later. A tumor in the anterior urethra was identified as metastasis of his prostate ductal adenocarcinoma. CONCLUSION: This report presents an uncommon case of prostate ductal adenocarcinoma exhibiting a late recurrence in the anterior urethra 13 years post-radical prostatectomy.

Integrative analysis regarding the correlation between collagen-related genes and prostate cancer.

PURPOSE: Prostate cancer (PCa) is a common malignancy in men, with an escalating mortality rate attributed to Recurrence and metastasis. Recent studies have illuminated collagen's critical regulatory role within the tumor microenvironment, significantly influencing tumor progression. Accordingly, this investigation is dedicated to examining the relationship between genes linked to collagen and the prognosis of PCa, with the objective of uncovering any possible associations between them. METHODS: Gene expression data for individuals with prostate cancer were obtained from the TCGA repository. Collagen-related genes were identified, leading to the development of a risk score model associated with biochemical recurrence-free survival (BRFS). A prognostic nomogram integrating the risk score with essential clinical factors was crafted and evaluated for efficacy. The influence of key collagen-related genes on cellular behavior was confirmed through various assays, including CCK8, invasion, migration, cell cloning, and wound healing. Immunohistochemical detection was used to evaluate PLOD3 expression in prostate cancer tissue samples. RESULTS: Our study identified four key collagen-associated genes (PLOD3, COL1A1, MMP11, FMOD) as significant. Survival analysis revealed that low-risk groups, based on the risk scoring model, had significantly improved prognoses. The risk score was strongly associated with prostate cancer prognosis. Researchers then created a nomogram, which demonstrated robust predictive efficacy and substantial clinical applicability.Remarkably, the suppression of PLOD3 expression notably impeded the proliferation, invasion, migration, and colony formation capabilities of PCa cells. CONCLUSION: The risk score, derived from four collagen-associated genes, could potentially act as a precise prognostic indicator for BRFS of patients. Simultaneously, our research has identified potential therapeutic targets related to collagen. Notably, PLOD3 was differentially expressed in cancer and para-cancer tissues in clinical specimens and it also was validated through in vitro studies and shown to suppress PCa tumorigenesis following its silencing.

Bioinformatics analysis reveals that CBX2 promotes enzalutamide resistance in prostate cancer.

Enzalutamide (Enz) is commonly utilized as the initial treatment strategy for advanced prostate cancer (PCa). However, a notable subset of patients may experience resistance to Enz, resulting in reduced effectiveness. Utilizing Gene Expression Omnibus (GEO) databases, we identified CBX2 as a crucial factor in mediating resistance to Enz, primarily due to its inhibitory effect on the P53 signaling pathway. Silencing of CBX2 using small interfering RNA (siRNA) led to elevated levels of P53 expression in LNCaP cells. This indicates that CBX2 may have a critical effect on PCa Enz resistance and could serve as a promising therapeutic target for individuals with Enz resistance.

HHOMR: a hybrid high-order moment residual model for miRNA-disease association prediction.

Numerous studies have demonstrated that microRNAs (miRNAs) are critically important for the prediction, diagnosis, and characterization of diseases. However, identifying miRNA-disease associations through traditional biological experiments is both costly and time-consuming. To further explore these associations, we proposed a model based on hybrid high-order moments combined with element-level attention mechanisms (HHOMR). This model innovatively fused hybrid higher-order statistical information along with structural and community information. Specifically, we first constructed a heterogeneous graph based on existing associations between miRNAs and diseases. HHOMR employs a structural fusion layer to capture structure-level embeddings and leverages a hybrid high-order moments encoder layer to enhance features. Element-level attention mechanisms are then used to adaptively integrate the features of these hybrid moments. Finally, a multi-layer perceptron is utilized to calculate the association scores between miRNAs and diseases. Through five-fold cross-validation on HMDD v2.0, we achieved a mean AUC of 93.28%. Compared with four state-of-the-art models, HHOMR exhibited superior performance. Additionally, case studies on three diseases-esophageal neoplasms, lymphoma, and prostate neoplasms-were conducted. Among the top 50 miRNAs with high disease association scores, 46, 47, and 45 associated with these diseases were confirmed by the dbDEMC and miR2Disease databases, respectively. Our results demonstrate that HHOMR not only outperforms existing models but also shows significant potential in predicting miRNA-disease associations.

UPCARE: Urinary Extracellular Vesicles-Derived Prostate Cancer Assessment for Risk Evaluation.

In the quest for efficient tumor diagnosis via liquid biopsy, extracellular vesicles (EVs) have shown promise as a source of potential biomarkers. This study addresses the gap in biomarker efficacy for predicting clinically significant prostate cancer (csPCa) between the Western and Chinese populations. We developed a urinary extracellular vesicles-based prostate score (EPS) model, utilizing the EXODUS technique for EV isolation from 598 patients and incorporating gene expressions of FOXA1, PCA3, and KLK3. Our findings reveal that the EPS model surpasses prostate-specific antigen (PSA) testing in diagnostic accuracy within a training cohort of 234 patients, achieving an area under the curve (AUC) of 0.730 compared to 0.659 for PSA (p = 0.018). Similarly, in a validation cohort of 101 men, the EPS model achieved an AUC of 0.749, which was significantly better than PSA's 0.577 (p < 0.001). Our model has demonstrated a potential reduction in unnecessary prostate biopsies by 26%, with only a 3% miss rate for csPCa cases, indicating its effectiveness in the Chinese population.

Secreted factors from M1 macrophages drive prostate cancer stem cell plasticity by upregulating NANOG, SOX2, and CD44 through NFκB-signaling.

The inflammatory tumor microenvironment (TME) is a key driver for tumor-promoting processes. Tumor-associated macrophages are one of the main immune cell types in the TME and their increased density is related to poor prognosis in prostate cancer. Here, we investigated the influence of pro-inflammatory (M1) and immunosuppressive (M2) macrophages on prostate cancer lineage plasticity. Our findings reveal that M1 macrophage secreted factors upregulate genes related to stemness while downregulating genes associated with androgen response in prostate cancer cells. The expression of cancer stem cell (CSC) plasticity markers NANOG, KLF4, SOX2, OCT4, and CD44 was stimulated by the secreted factors from M1 macrophages. Moreover, AR and its target gene PSA were observed to be suppressed in LNCaP cells treated with secreted factors from M1 macrophages. Inhibition of NFκB signaling using the IKK16 inhibitor resulted in downregulation of NANOG, SOX2, and CD44 and CSC plasticity. Our study highlights that the secreted factors from M1 macrophages drive prostate cancer cell plasticity by upregulating the expression of CSC plasticity markers through NFκB signaling pathway.

Assessing the Performance of Deep Learning for Automated Gleason Grading in Prostate Cancer.

Prostate cancer is a dominant health concern calling for advanced diagnostic tools. Utilizing digital pathology and artificial intelligence, this study explores the potential of 11 deep neural network architectures for automated Gleason grading in prostate carcinoma focusing on comparing traditional and recent architectures. A standardized image classification pipeline, based on the AUCMEDI framework, facilitated robust evaluation using an in-house dataset consisting of 34,264 annotated tissue tiles. The results indicated varying sensitivity across architectures, with ConvNeXt demonstrating the strongest performance. Notably, newer architectures achieved superior performance, even though with challenges in differentiating closely related Gleason grades. The ConvNeXt model was capable of learning a balance between complexity and generalizability. Overall, this study lays the groundwork for enhanced Gleason grading systems, potentially improving diagnostic efficiency for prostate cancer.

Comparison of Imputation Methods for Categorical Real-World Prostate Cancer Data with Natural Order.

Missing values (NA) often occur in cancer research, which may be due to reasons such as data protection, data loss, or missing follow-up data. Such incomplete patient information can have an impact on prediction models and other data analyses. Imputation methods are a tool for dealing with NA. Cancer data is often presented in an ordered categorical form, such as tumour grading and staging, which requires special methods. This work compares mode imputation, k nearest neighbour (knn) imputation, and, in the context of Multiple Imputation by Chained Equations (MICE), logistic regression model with proportional odds (mice_polr) and random forest (mice_rf) on a real-world prostate cancer dataset provided by the Cancer Registry of Rhineland-Palatinate in Germany. Our dataset contains relevant information for the risk classification of patients and the time between date of diagnosis and date of death. For the imputation comparison, we use Rubin's (1974) Missing Completely At Random (MCAR) mechanism to remove 10%, 20%, 30%, and 50% observations. The results are evaluated and ranked based on the accuracy per patient. Mice_rf performs significantly best for each percentage of NA, followed by knn, and mice_polr performs significantly worst. Furthermore, our findings indicate that the accuracy of imputation methods increases with a lower number of categories, a relatively even proportion of patients in the categories, or a majority of patients in a particular category.

Dual-energy computed tomography with new virtual monoenergetic image reconstruction enhances prostate lesion image quality and improves the diagnostic efficacy for prostate cancer.

BACKGROUND: Prostate cancer is one of the most common malignant tumors in middle-aged and elderly men and carries significant prognostic implications, and recent studies suggest that dual-energy computed tomography (DECT) utilizing new virtual monoenergetic images can enhance cancer detection rates. This study aimed to assess the impact of virtual monoenergetic images reconstructed from DECT arterial phase scans on the image quality of prostate lesions and their diagnostic performance for prostate cancer. METHODS: We conducted a retrospective analysis of 83 patients with prostate cancer or prostatic hyperplasia who underwent DECT scans at Meizhou People's Hospital between July 2019 and December 2023. The variables analyzed included age, tumor diameter and serum prostate-specific antigen (PSA) levels, among others. We also compared CT values, signal-to-noise ratio (SNR), subjective image quality ratings, and contrast-to-noise ratio (CNR) between virtual monoenergetic images (40-100 keV) and conventional linear blending images. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic efficacy of virtual monoenergetic images (40 keV and 50 keV) compared to conventional images. RESULTS: Virtual monoenergetic images at 40 keV showed significantly higher CT values (168.19 ± 57.14) compared to conventional linear blending images (66.66 ± 15.5) for prostate cancer (P < 0.001). The 50 keV images also demonstrated elevated CT values (121.73 ± 39.21) compared to conventional images (P < 0.001). CNR values for the 40 keV (3.81 ± 2.13) and 50 keV (2.95 ± 1.50) groups were significantly higher than the conventional blending group (P < 0.001). Subjective evaluations indicated markedly better image quality scores for 40 keV (median score of 5) and 50 keV (median score of 5) images compared to conventional images (P < 0.05). ROC curve analysis revealed superior diagnostic accuracy for 40 keV (AUC: 0.910) and 50 keV (AUC: 0.910) images based on CT values compared to conventional images (AUC: 0.849). CONCLUSIONS: Virtual monoenergetic images reconstructed at 40 keV and 50 keV from DECT arterial phase scans substantially enhance the image quality of prostate lesions and improve diagnostic efficacy for prostate cancer.

The effect of health literacy on patient compliance in patients to whom prostate biopsies were recommended.

BACKGROUND: Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) is the gold standard diagnostic method for prostate cancer. In people with low health literacy, accurate and early diagnosis rates decrease, making it difficult to maintain health and compliance with treatment. In our study, we investigated how health literacy and sociocultural parameters affected compliance and awareness in patients with suspected prostate cancer, for whom TRUS-Bx was planned. METHODS: In the study, 98 male patients aged 50-80 years, recommended for TRUS-Bx, were included in our study. The data including age, prostate-specific antigen, prostate volume, digital rectal examination findings, education leveland area of residence of the patients included in the study were recorded. Health Literacy Survey-Turkey- Questionnaire 47 and Turkish Health Literacy Scale-32 forms were completed by the patients who agreed to participate in the study, and their scores were recorded. Patients scheduled for TRUS-Bx were divided into two groups: those who attended their appointments and underwent the biopsy, and those who did not attend their scheduled appointments. The effect of health literacy and other parameters on the TRUS-Bx requirement was examined between the two groups. Furthermore, 52 patients who underwent TRUS-Bx were divided into two groups as malignancy (malignant) detected and not-detected (benign) patients according to the pathology results, and the parameters were analyzed separately for these groups. RESULTS: The education level of the patients who underwent the TRUS-Bx procedure was found to be statistically higher (p = 0.026). Health Literacy Survey-Turkey- Questionnaire 47 and Turkish Health Literacy Scale-32 scores were statistically significantly higher in the TRUS-Bx group (p = 0.001, p < 0.001, respectively). In the logistic regression analysis, education level, Health Literacy Survey-Turkey- Questionnaire 47 and Turkish Health Literacy Scale-32 were found to be important predictors for awareness of the requirement for TRUS-Bx. CONCLUSION: The study's findings indicate that patients with higher health literacy and education levels were more likely to receive an early diagnosis and promptly proceed with the recommended TRUS-Bx after visiting a urologist.

Detection and management of localized prostate cancer in Nigeria: barriers and facilitators according to patients, caregivers and healthcare providers.

BACKGROUND: Prostate cancer mortality rates are high in Nigeria. While prostate cancer is highly curable with early detection and effective multidisciplinary management, the quality of care is suboptimal in this setting. Sustainable delivery of high-quality care for patients with localized prostate cancer is needed to save more lives. To inform future interventions to improve care, this study aimed to identify barriers and facilitators that influence prostate cancer detection and management in Nigeria. METHODS: Six focus group discussions (FGDs), stratified by stakeholders were conducted with a purposive sample of prostate cancer patients (n = 19), caregivers (n = 15), and healthcare providers (n = 18), in two academic tertiary hospitals in northern and southern Nigeria. A discussion guide organized based on the socio-ecological model was used. FGDs were recorded, transcribed, and analysed using the framework technique. RESULTS: Barriers and facilitators were identified at the individual, interpersonal, and organizational levels. Barriers to detection included limited knowledge and misperceptions among patients, caregivers, and community-based non-specialist healthcare providers, and limitations of centralized opportunistic screening; while facilitators included the potential for religious institutions to encourage positive health-seeking behaviour. Barriers to management included non-uniformity in clinical guideline usage, treatment abandonment amidst concerns about treatment and survival, absence of patient interaction platforms and follow-up support systems, difficulty in navigating service areas, low health insurance coverage and limited financial resource of patients. Facilitators of management included the availability of resource stratified guidelines for prostate cancer management and the availability of patient peers, caregivers, nurses, and medical social workers to provide correct medical information and support patient-centred services. Participants also provided suggestions that could help improve prostate cancer detection and management in Nigeria. CONCLUSION: This study identified multiple determinants affecting the detection and management of localized prostate cancer. These findings will inform the refinement of implementation strategies to improve the quality of prostate cancer care in Nigeria.