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BMC Urology Jul 2024In recent years, Genome-Wide Association Studies (GWAS) has identified risk variants related to complex diseases, but most genetic variants have less impact on... (Comparative Study)
Comparative Study
BACKGROUND
In recent years, Genome-Wide Association Studies (GWAS) has identified risk variants related to complex diseases, but most genetic variants have less impact on phenotypes. To solve the above problems, methods that can use variants with low genetic effects, such as genetic risk score (GRS), have been developed to predict disease risk.
METHODS
As the GRS model with the most incredible prediction power for complex diseases has not been determined, our study used simulation data and prostate cancer data to explore the disease prediction power of three GRS models, including the simple count genetic risk score (SC-GRS), the direct logistic regression genetic risk score (DL-GRS), and the explained variance weighted GRS based on directed logistic regression (EVDL-GRS).
RESULTS AND CONCLUSIONS
We used 26 SNPs to establish GRS models to predict the risk of biochemical recurrence (BCR) after radical prostatectomy. Combining clinical variables such as age at diagnosis, body mass index, prostate-specific antigen, Gleason score, pathologic T stage, and surgical margin and GRS models has better predictive power for BCR. The results of simulation data (statistical power = 0.707) and prostate cancer data (area under curve = 0.8462) show that DL-GRS has the best prediction performance. The rs455192 was the most relevant locus for BCR (p = 2.496 × 10) in our study.
Topics: Prostatic Neoplasms; Male; Humans; Prostatectomy; Neoplasm Recurrence, Local; Risk Assessment; Middle Aged; Aged; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Predictive Value of Tests; Genetic Risk Score
PubMed: 38956663
DOI: 10.1186/s12894-024-01524-6 -
BMC Urology Jul 2024Prostate cancer (PCa) is a complex and biologically diverse disease with no curative treatment options at present. This study aims to utilize computational methods to...
Prostate cancer (PCa) is a complex and biologically diverse disease with no curative treatment options at present. This study aims to utilize computational methods to explore potential anti-PCa compounds based on differentially expressed genes (DEGs), with the goal of identifying novel therapeutic indications or repurposing existing drugs. The methods employed in this study include DEGs-to-drug prediction, pharmacokinetics prediction, target prediction, network analysis, and molecular docking. The findings revealed a total of 79 upregulated DEGs and 110 downregulated DEGs in PCa, which were used to identify drug compounds capable of reversing the dysregulated conditions (dexverapamil, emetine, parthenolide, dobutamine, terfenadine, pimozide, mefloquine, ellipticine, and trifluoperazine) at a threshold probability of 20% on several molecular targets, such as serotonin receptors 2a/2b/2c, HERG protein, adrenergic receptors alpha-1a/2a, dopamine D3 receptor, inducible nitric oxide synthase (iNOS), epidermal growth factor receptor erbB1 (EGFR), tyrosine-protein kinases, and C-C chemokine receptor type 5 (CCR5). Molecular docking analysis revealed that terfenadine binding to inducible nitric oxide synthase (-7.833 kcal.mol) and pimozide binding to HERG (-7.636 kcal.mol). Overall, binding energy ΔG (Total) at 0 ns was lower than that of 100 ns for both the Terfenadine-iNOS complex (-101.707 to -103.302 kcal.mol) and Ellipticine-TOPIIα complex (-42.229 to -58.780 kcal.mol). In conclusion, this study provides insight on molecular targets that could possibly contribute to the molecular mechanisms underlying PCa. Further preclinical and clinical studies are required to validate the therapeutic effectiveness of these identified drugs in PCa disease.
Topics: Prostatic Neoplasms; Humans; Male; Molecular Docking Simulation; Computer Simulation; Antineoplastic Agents; Gene Expression Regulation, Neoplastic; Gene Expression Profiling
PubMed: 38956591
DOI: 10.1186/s12894-024-01521-9 -
BMC Urology Jul 2024This study delves into the complex interplay among prostate-specific antigen, alkaline phosphatase, and the temporal dynamics of tumor shrinkage in prostate cancer. By...
Relationship between prostate-specific antigen, alkaline phosphatase levels, and time-to-tumor shrinkage: understanding the progression of prostate cancer in a longitudinal study.
BACKGROUND
This study delves into the complex interplay among prostate-specific antigen, alkaline phosphatase, and the temporal dynamics of tumor shrinkage in prostate cancer. By investigating the longitudinal trajectories and time-to-prostate cancer tumor shrinkage, we aim to untangle the intricate patterns of these biomarkers. This understanding is pivotal for gaining profound insights into the multifaceted aspects of prostate cancer progression. The joint model approach serves as a comprehensive framework, facilitating the elucidation of intricate interactions among these pivotal elements within the context of prostate cancer .
METHODS
A new joint model under a shared parameters strategy is proposed for mixed bivariate longitudinal biomarkers and event time data, for obtaining accurate estimates in the presence of missing covariate data. The primary innovation of our model resides in its effective management of covariates with missing observations. Built upon established frameworks, our joint model extends its capabilities by integrating mixed longitudinal responses and accounting for missingness in covariates, thus confronting this particular challenge. We posit that these enhancements bolster the model's utility and dependability in real-world contexts characterized by prevalent missing data. The main objective of this research is to provide a model-based approach to get full information from prostate cancer data collected with patients' baseline characteristics ( , body mass index ( ), , , and ) and two longitudinal endogenous covariates ( and ).
RESULTS
The results reveal a clear association between prostate-specific antigen and alkaline phosphatase biomarkers in the context of time-to-prostate cancer tumor shrinkage. This underscores the interconnected dynamics of these key indicators in gauging disease progression.
CONCLUSIONS
The analysis of the prostate cancer dataset, incorporating a joint evaluation of mixed longitudinal prostate-specific antigen and alkaline phosphatase biomarkers alongside tumor status, has provided valuable insights into disease progression. The results demonstrate the effectiveness of the proposed joint model, as evidenced by accurate estimates. The shared variables associated with both longitudinal biomarkers and event times consistently deviate from zero, highlighting the robustness and reliability of the model in capturing the complex dynamics of prostate cancer progression. This approach holds promise for enhancing our understanding and predictive capabilities in the clinical assessment of prostate cancer.
Topics: Male; Alkaline Phosphatase; Humans; Longitudinal Studies; Prostatic Neoplasms; Disease Progression; Prostate-Specific Antigen; Aged; Time Factors; Middle Aged; Tumor Burden
PubMed: 38956570
DOI: 10.1186/s12894-024-01522-8 -
BMC Cancer Jul 2024Cancer is becoming a major health problem in Uganda. Cancer control requires accurate estimates of the cancer burden for planning and monitoring of the cancer control...
BACKGROUND
Cancer is becoming a major health problem in Uganda. Cancer control requires accurate estimates of the cancer burden for planning and monitoring of the cancer control strategies. However, cancer estimates and trends for Uganda are mainly based on one population-based cancer registry (PBCR), located in Kampala, the capital city, due to a lack of PBCRs in other regions. This study aimed at estimating cancer incidence among the geographical regions and providing national estimates of cancer incidence in Uganda.
METHODS
A retrospective study, using a catchment population approach, was conducted from June 2019 to February 2020. The study registered all newly diagnosed cancer cases, in the period of 2013 to 2017, among three geographical regions: Central, Western and Eastern regions. Utilizing regions as strata, stratified random sampling was used to select the study populations. Cases were coded according to the International Classification of Diseases for Oncology (ICD-0-03). Data was analysed using CanReg5 and Microsoft Excel.
RESULTS
11598 cases (5157 males and 6441 females) were recorded. The overall national age-standardized incidence rates (ASIR) were 82.9 and 87.4 per 100,000 people in males and females respectively. The regional ASIRs were: 125.4 per 100,000 in males and 134.6 per 100,000 in females in central region; 58.2 per 100,000 in males and 56.5 per 100,000 in females in Western region; and 46.5 per 100,000 in males and 53.7 per 100,000 in females in Eastern region. Overall, the most common cancers in males over the study period were cancers of the prostate, oesophagus, Kaposi's sarcoma, stomach and liver. In females, the most frequent cancers were: cervix, breast, oesophagus, Kaposi's sarcoma and stomach.
CONCLUSION
The overall cancer incidence rates from this study are different from the documented national estimates for Uganda. This emphasises the need to enhance the current methodologies for describing the country's cancer burden. Studies like this one are critical in enhancing the cancer surveillance system by estimating regional and national cancer incidence and allowing for the planning and monitoring of evidence-based cancer control strategies at all levels.
Topics: Humans; Uganda; Female; Male; Retrospective Studies; Incidence; Neoplasms; Middle Aged; Adult; Aged; Adolescent; Young Adult; Child; Infant; Registries; Infant, Newborn; Child, Preschool; Aged, 80 and over
PubMed: 38956523
DOI: 10.1186/s12885-024-12543-9 -
Scientific Reports Jul 2024Cancer mice models are critical for immune-oncology research; they provide conditions to explore tumor immunoenviroment aiming to advance knowledge and treatment...
Cancer mice models are critical for immune-oncology research; they provide conditions to explore tumor immunoenviroment aiming to advance knowledge and treatment development. Often, research groups breed their own mice colonies. To assess the effect of C57BL/6 mice breeding nuclei in prostate cancer development and intratumoral macrophage populations, an isotransplantation experiment was performed. C57BL/6J mice from two breeding nuclei (nA and nB) were employed for prostate adenocarcinoma TRAMP-C1 cell implantation; tumor growth period and intratumoral macrophage profile were measured. BL/6nB mice (54%) showed tumor implantation after 69-day growth period while BL/6nA implantation reached 100% across tumor growth period (28 days). No difference in total macrophage populations was observed between groups within several tumoral regions; significantly higher M2 macrophage profile was observed in tumor microenvironments from both mice groups. Nevertheless, BL/6nB tumors showed around twice the population of M1 profile (11-27%) than BL6nA (4-15%) and less non-polarized macrophages. The M1:M2 average ratio was 1:8 for group A and 1:4 for B. Our results demonstrate different tumor progression and intratumoral macrophage populations among mice from the same substrain. Data obtained in this study shows the relevance of animal source renewal for better control of murine cancer model variables.
Topics: Animals; Prostatic Neoplasms; Male; Tumor Microenvironment; Mice, Inbred C57BL; Mice; Macrophages; Disease Progression; Disease Models, Animal; Cell Line, Tumor
PubMed: 38956203
DOI: 10.1038/s41598-024-65960-y -
Scientific Reports Jul 2024Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable...
Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/βcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.
Topics: Male; Elastin; Humans; Cell Line, Tumor; Nanogels; Prostatic Neoplasms, Castration-Resistant; Drug Delivery Systems; Cell Survival; Drug Liberation; Antineoplastic Agents; Benzopyrans; Butyrates
PubMed: 38956125
DOI: 10.1038/s41598-024-65999-x -
European Radiology Jul 2024Risk calculators (RCs) improve patient selection for prostate biopsy with clinical/demographic information, recently with prostate MRI using the prostate imaging...
Prostate cancer risk assessment and avoidance of prostate biopsies using fully automatic deep learning in prostate MRI: comparison to PI-RADS and integration with clinical data in nomograms.
OBJECTIVES
Risk calculators (RCs) improve patient selection for prostate biopsy with clinical/demographic information, recently with prostate MRI using the prostate imaging reporting and data system (PI-RADS). Fully-automated deep learning (DL) analyzes MRI data independently, and has been shown to be on par with clinical radiologists, but has yet to be incorporated into RCs. The goal of this study is to re-assess the diagnostic quality of RCs, the impact of replacing PI-RADS with DL predictions, and potential performance gains by adding DL besides PI-RADS.
MATERIAL AND METHODS
One thousand six hundred twenty-seven consecutive examinations from 2014 to 2021 were included in this retrospective single-center study, including 517 exams withheld for RC testing. Board-certified radiologists assessed PI-RADS during clinical routine, then systematic and MRI/Ultrasound-fusion biopsies provided histopathological ground truth for significant prostate cancer (sPC). nnUNet-based DL ensembles were trained on biparametric MRI predicting the presence of sPC lesions (UNet-probability) and a PI-RADS-analogous five-point scale (UNet-Likert). Previously published RCs were validated as is; with PI-RADS substituted by UNet-Likert (UNet-Likert-substituted RC); and with both UNet-probability and PI-RADS (UNet-probability-extended RC). Together with a newly fitted RC using clinical data, PI-RADS and UNet-probability, existing RCs were compared by receiver-operating characteristics, calibration, and decision-curve analysis.
RESULTS
Diagnostic performance remained stable for UNet-Likert-substituted RCs. DL contained complementary diagnostic information to PI-RADS. The newly-fitted RC spared 49% [252/517] of biopsies while maintaining the negative predictive value (94%), compared to PI-RADS ≥ 4 cut-off which spared 37% [190/517] (p < 0.001).
CONCLUSIONS
Incorporating DL as an independent diagnostic marker for RCs can improve patient stratification before biopsy, as there is complementary information in DL features and clinical PI-RADS assessment.
CLINICAL RELEVANCE STATEMENT
For patients with positive prostate screening results, a comprehensive diagnostic workup, including prostate MRI, DL analysis, and individual classification using nomograms can identify patients with minimal prostate cancer risk, as they benefit less from the more invasive biopsy procedure.
KEY POINTS
The current MRI-based nomograms result in many negative prostate biopsies. The addition of DL to nomograms with clinical data and PI-RADS improves patient stratification before biopsy. Fully automatic DL can be substituted for PI-RADS without sacrificing the quality of nomogram predictions. Prostate nomograms show cancer detection ability comparable to previous validation studies while being suitable for the addition of DL analysis.
PubMed: 38955845
DOI: 10.1007/s00330-024-10818-0 -
Journal of Occupational and... Jul 2024Determine whether volunteer firefighters in Florida are at increased odds of developing cancer compared to non-firefighters.
OBJECTIVE
Determine whether volunteer firefighters in Florida are at increased odds of developing cancer compared to non-firefighters.
METHODS
A case-control study design was implemented to assess the odds of developing cancer among male and female volunteer firefighters in Florida. Gender-specific age and calendar year-adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) were estimated.
RESULTS
Male volunteer firefighters were at increased odds for developing prostate (aOR = 1.26; 95%CI;[1.10- 1.44]) and male genital cancers combined (1.22;[1.07-1.39]), while reduced odds for endocrine cancer (0.41;[0.17-1.00]), and all leukemias (0.55;[0.35-0.86]), including lymphocytic (0.48;[0.24-0.97]); and chronic lymphocytic (0.40;[0.17-0.97]) leukemias. Female volunteer firefighters were at increased odds of developing of kidney cancer (2.51;[1.29-4.91]).
CONCLUSIONS
Male volunteer firefighters are at increased odds for prostate and overall male genital cancers, while female volunteers are increased odds of kidney cancer.
PubMed: 38955796
DOI: 10.1097/JOM.0000000000003178 -
Radiography (London, England : 1995) Jul 2024Radiotherapy (RT) clinical trials allow patients to access cutting-edge innovative cancer treatments. Clinical Research Therapy Radiographers (CRRs) play an important...
INTRODUCTION
Radiotherapy (RT) clinical trials allow patients to access cutting-edge innovative cancer treatments. Clinical Research Therapy Radiographers (CRRs) play an important role in the management and care of RT trial patients. The COVID-19 pandemic caused major disruption to RT trial delivery. Measures to mitigate COVID-19 risk continue to have an effect on patient contact and communication within cancer centres in the United Kingdom (UK). This study aimed to explore patient perspectives regarding their recent RT trial experience in Northern Ireland (NI), UK.
METHODS
A single centre service evaluation was conducted in NI. Patients who were recruited into a RT clinical trial from January 2020 to January 2023 were invited to participate. Surveys were posted to 50 participants in April 2023. Quantitative and qualitative data was captured and analysed using descriptive statistics and Braun and Clarke's six-step thematic analysis framework respectively. Ethical approval was obtained through Ulster University and the NHS Trust.
RESULTS
Forty-three of the 50 invited participants responded (86%). Forty-two respondents (79%) had a prostate cancer diagnosis. Forty-one (98%) participants indicated that CRRs were always approachable, polite and courteous and would recommend taking part in a RT trial to friends and family. Identified areas for improvement included aspects regarding consent and participant decision-making.
CONCLUSION
This study suggests that despite the implemented measures to suspend research and mitigate COVID-19 risk, patients remained highly satisfied with the quality of care that they received through their participation in RT trials.
IMPLICATIONS FOR PRACTICE
The results of this service evaluation will facilitate maintenance and improvement of patient focused delivery of cancer trials within the host centre. This study builds on evidence highlighting the importance of the CRR role and role development for radiographers.
PubMed: 38955645
DOI: 10.1016/j.radi.2024.06.014 -
European Urology Focus Jul 2024Although intermittent androgen deprivation therapy was often recommended for metastatic hormone-sensitive cancer therapy in the past, we do not know whether its use can...
Although intermittent androgen deprivation therapy was often recommended for metastatic hormone-sensitive cancer therapy in the past, we do not know whether its use can be extrapolated to combination therapy. Trials evaluating intermittent therapy are necessary as this strategy could improve patient quality of life and reduce adverse events and costs.
PubMed: 38955606
DOI: 10.1016/j.euf.2024.06.008