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Pharmacotherapy Jul 2024
Correction to "Risk of incident antidepressant-treated depression associated with use of 5α-reductase inhibitors compared with use of α-blockers in men with benign prostatic hyperplasia: A population-based study using the Clinical Practice Research Datalink".
PubMed: 38952241
DOI: 10.1002/phar.2951 -
Current Medicinal Chemistry Jun 2024Cyclin-dependent kinase 1 (CDK1) regulates the cell cycle and is highly expressed in most tumors. CDK1 expression has been associated with poor disease prognosis. This...
OBJECTIVE
Cyclin-dependent kinase 1 (CDK1) regulates the cell cycle and is highly expressed in most tumors. CDK1 expression has been associated with poor disease prognosis. This study aimed to identify the prognostic value of CDK1 in pan-cancer and investigate the association between CDK1 expression and immune cell infiltration.
METHODS
CDK1 expression and its correlation with prognosis in pan-cancer were analyzed using online databases. Immune infiltration was assessed by ESTIMATE and CIBERSORT algorithms. We then evaluated the relationship between CDK1 expression and tumor mutational burden (TMB), microsatellite instability (MSI), or tumor-infiltrating immune cells. In addition, we performed the co-expression analysis of immune-related genes and GO analysis with CDK1 expression in pan-cancer. Finally, we compared the CDK1 expression profile with the immune-related genes in 30 pairs of clinical gastrointestinal tumor samples.
RESULTS
Our analysis demonstrated overexpression of CDK1 in most tumor tissues, especially in gastrointestinal tumors. The high expression of CDK1 was associated with poor overall survival, disease-specific survival, disease-free interval, and progression-free interval in kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), prostate adenocarcinoma (PRAD), and sarcoma (SARC). Besides, CDK1 expression was significantly associated with TMB in 22 cancer types and MSI in 8 cancer types as well as greater frequencies of MSI-high (MSI-H) status and high tumor mutational burden (TMB-H) in uterine corpus endometrial carcinoma (UCEC), stomach adenocarcinoma (STAD), sarcoma (SARC), rectum adenocarcinoma (READ), mesothelioma (MESO), head and neck squamous cell carcinoma (HNSC), and colon adenocarcinoma (COAD). In addition, CDK1 expression correlated with immune cell infiltrating levels, such as M0, M1, or M2 macrophages, memory CD4 T cells, T follicular helper cells, and naive B cells. Our data showed that CDK1 was remarkably correlated with 47 immune-related and immune checkpoint genes in many cancer types. Furthermore, CDK1 was up-regulated in gastrointestinal tumor samples, especially in gastric cancer and intestinal cancer. CDK1 was positively correlated with IDO1 in gastric cancer and PD-1 in intestinal cancer.
CONCLUSION
Taken together, our data demonstrated the roles of CDK1 in oncogenesis and metastasis in pan-cancer. Thus, CDK1 is a potential prognostic biomarker and a target for tumor immunotherapy.
PubMed: 38952160
DOI: 10.2174/0109298673322212240620111356 -
Neuroepidemiology Jun 2024Biological and scarce epidemiological evidence suggested that phosphodiesterase-5 inhibitors (PDE5i) might reduce dementia risk. We aimed to examine the association...
Biological and scarce epidemiological evidence suggested that phosphodiesterase-5 inhibitors (PDE5i) might reduce dementia risk. We aimed to examine the association between PDE5i and dementia using real-world data. Two retrospective cohorts within the database of Clalit, the largest healthcare provider in Israel (2005-2023), were studied. The first cohort included new daily users, older than 50 years of age, of low dose tadalafil, prescribed for benign prostatic hypertrophy (BPH), propensity-score matched to new-users of alpha-1 blockers, and analyzed using 2-year lag time. The second cohort included patients with erectile dysfunction, with/without any PDE5i treatment, using time-dependent analysis. Individuals in the cohorts were followed through May 2023 for the occurrence of dementia. The first cohort included 5,204 tadalafil initiators propensity-score matched to 18,565 alpha-1 blockers initiators. There was no association between tadalafil use and dementia risk HR=0.99 95%CI (0.88, 1.12), p=0.927. Similar results were obtained in a competing risk analysis, and in a sensitivity analysis in which we restricted the cohort to patients older than 60 years at cohort entry. The second cohort of 133,336 patients with erectile dysfunction included new-users and non-users of any PDE5i.In a mean follow-up of 7.9 years, 8,631 patients were newly diagnosed with dementia. In a time-dependent multivariable analysis PDE5i use was not associated with reduced dementia risk HR=0.95 (95%CI, 0.86-1.04). Results were not changed in sensitivity analyses (patients older than 60 years, or stratification by PDE5i type). This study suggests that use of PDE5 inhibitors is not associated with decreased risk of dementia.
PubMed: 38952132
DOI: 10.1159/000540057 -
BMC Urology Jul 2024The ARASENS trial recruited 1306 men with metastatic hormone sensitive prostate cancer. It investigated the effect of androgen deprivation therapy (ADT) and systemic...
The ARASENS trial recruited 1306 men with metastatic hormone sensitive prostate cancer. It investigated the effect of androgen deprivation therapy (ADT) and systemic therapy docetaxel in combination with a third novel drug - daralutamide, compared with placebo on overall survival. Triple therapy with ADT, docetaxel and darolutamide resulted in improved overall survival rates as compared with ADT, docetaxel and placebo (HR 0.68; 95% CI, 0.57-0.80; p < 0.001). The side effect profile for both treatments was similar. This randomised, double blinded, placebo controlled study, was assessed to have a low risk of bias using the Cochrane Risk of Bias 2 tool.
Topics: Male; Humans; Prostatic Neoplasms; Benzamides; Randomized Controlled Trials as Topic; Survival Rate; Androgen Antagonists; Docetaxel; Pyrazoles
PubMed: 38951868
DOI: 10.1186/s12894-024-01507-7 -
BMC Cancer Jul 2024Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying...
INTRODUCTION
Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa.
METHODS
A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients.
DISCUSSION
If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community.
TRIAL REGISTRATION
The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213.
Topics: Humans; Male; Extracellular Vesicles; Cross-Over Studies; Prostatic Neoplasms; Exercise; Muscle, Skeletal; Exercise Therapy; Cytokines; Aged; Middle Aged; Myokines
PubMed: 38951803
DOI: 10.1186/s12885-024-12530-0 -
International Journal of Impotence... Jun 2024Traditionally, semen analysis has been viewed solely as a tool for assessing male fertility. However, emerging research suggests that abnormal semen parameters may serve... (Review)
Review
Traditionally, semen analysis has been viewed solely as a tool for assessing male fertility. However, emerging research suggests that abnormal semen parameters may serve as indicators of broader health issues beyond reproductive function. Studies have revealed significant associations between abnormal semen parameters and an increased risk of chronic diseases such as prostate cancer, diabetes, ischemic heart disease, and metabolic disorders. These findings challenge the conventional understanding and position semen analysis as a potential screening tool for overall male health. The correlation between abnormal semen parameters and conditions like erectile dysfunction further underscores the multifaceted implications of semen quality. This suggests that abnormal semen parameters may be a risk factor for poorer overall health and a higher likelihood of developing comorbidities over time. Given these compelling associations, there is a growing call to integrate semen analysis into routine health assessments for young men, particularly in conjunction with established general health screenings. This proactive approach aligns with a preventative healthcare paradigm, facilitating early detection of underlying health concerns and timely interventions. However, overcoming cultural, logistical, and cost-related barriers is crucial for the successful implementation of this shift in reproductive health.
PubMed: 38951639
DOI: 10.1038/s41443-024-00949-9 -
Scientific Reports Jul 2024Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study... (Comparative Study)
Comparative Study
Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.
Topics: Humans; Male; Prostatic Neoplasms; Prostatectomy; Positron Emission Tomography Computed Tomography; Aged; Prospective Studies; Gallium Radioisotopes; Middle Aged; Neoplasm Recurrence, Local; Gallium Isotopes; Prostate-Specific Antigen; Edetic Acid; Oligopeptides
PubMed: 38951530
DOI: 10.1038/s41598-024-65399-1 -
Japanese Journal of Radiology Jun 2024Until March 2018, patients with high-risk localized prostate cancer had been administered high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy...
PURPOSE
Until March 2018, patients with high-risk localized prostate cancer had been administered high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) without additional hormone therapy (HT) at our institution. In this study, we aimed to evaluate long-term outcomes of this treatment.
MATERIALS AND METHODS
Patients with prostate cancer who received HDR-BT and EBRT between April 1997 and March 2021 and who were followed up for at least 6 months were included in the study. High-risk groups were classified into five levels according to the National Comprehensive Cancer Network guidelines. The EBRT and HDR-BT doses were 39-45 Gy/13-25 fractions. and 16.5-22 Gy/2-4 fractions, respectively. None of the patients received HT during initial treatment. The Kaplan-Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. Biochemical failure was also determined.
RESULTS
Seventy-two patients were enrolled in the study, with a median follow-up of 91.9 months. The median age and initial prostate-specific antigen (iPSA) level were 71 years and 10.95 ng/mL, respectively. The median biologically effective dose for HDR-BT plus EBRT was 270.3 Gy. The 5- and 7-year bFFF, CSS, and OS rates were 85.2 and 74.2%, 100 and 100%, and 95.7 and 91.9%, respectively. Only the iPSA ≤ 20 group was associated with the higher bFFF rate. The 7-year bFFF rates in the groups with iPSA ≤ 20 and iPSA > 20 were 86.6 and 48.6%, respectively.
CONCLUSION
HDR-BT plus EBRT without HT might be an alternative treatment option for patients with high-risk localized prostate cancer and iPSA levels ≤ 20. Further studies are required to validate the efficacy of this treatment strategy.
PubMed: 38951462
DOI: 10.1007/s11604-024-01621-4 -
Plant Foods For Human Nutrition... Jul 2024Chronic diseases like cancer and diabetes are the major public health concerns of India and worldwide. Nowadays, plant-derived products are in great demand for the...
Chronic diseases like cancer and diabetes are the major public health concerns of India and worldwide. Nowadays, plant-derived products are in great demand for the treatment of these diseases. Pumpkin seeds are traditionally implicated for their pharmacological properties, as exemplified by benign prostatic hyperplasia. Earlier, pumpkin seed proteins were extracted by the Osborne method, and their functional and nutritional qualities were evaluated. Here, the aim is to assess in vitro, the anticancer and antidiabetic properties of seed protein fractions. HepG2, MDA-MB-231, and MCF-7 cell lines were treated with water-soluble (WF) and alkali-soluble fractions (AF) to assess cytotoxicity, while pancreatic β-cells and insulin resistance (IR) - HepG2 cell lines were treated with WF to evaluate the antidiabetic potential. WF and AF showed cytotoxic effects towards HepG2 and MDA-MB-231 cell lines, suggesting apoptosis-mediated anticancerous activity. WF potentiates glucose-stimulated insulin secretion in pancreatic β-cells, in a dose-dependent manner. In IR-HepG2 cell line studies, control, metformin, and WF-treated groups showed uptake of glucose, when compared to the diabetic group, which is well-correlated with the upregulated expressions of GLUT2 and GLUT4 transporters in these groups. These results indicate that proteins from WF and AF may have anticancerous and antidiabetic properties and thus have the potential to utilize pumpkin proteins in the management of cancer and diabetes.
PubMed: 38951376
DOI: 10.1007/s11130-024-01205-7 -
Journal of Cancer Survivorship :... Jul 2024Prostate cancer survivors may benefit from a supportive social environment. We investigated associations of social integration and long-term physical and psychosocial...
PURPOSE
Prostate cancer survivors may benefit from a supportive social environment. We investigated associations of social integration and long-term physical and psychosocial quality of life among prostate cancer survivors who were participants in the Health Professionals Follow-up Study.
METHODS
We included 1,428 individuals diagnosed with non-metastatic prostate cancer between 2008 and 2016. Social integration was measured by the Berkman-Syme Social Network Index (SNI) and marital status. We fit generalized linear mixed effect models for associations of SNI and marital status with patient reported outcome measures on physical and psychosocial quality of life captured between 2008 and 2020, adjusting for age, race, employment status, body mass index, comorbidities, smoking history, and clinical factors.
RESULTS
Among those with baseline SNI (N = 1,362), 46.4% were socially integrated, 20.3% were moderately integrated, 27.4% were moderately isolated, and 5.9% were socially isolated. Among those reporting baseline marital status (N = 1,428), 89.5% were married. Socially integrated survivors (vs. socially isolated) reported fewer depressive signs and better psychosocial wellbeing. Physical quality of life did not differ by social integration. Married survivors (vs. not married) reported fewer urinary symptoms, but there were no differences in bowel, sexual, or vitality/hormonal symptoms.
CONCLUSIONS
Among prostate cancer survivors, being socially integrated was associated with fewer depressive signs and better psychosocial wellbeing, and married prostate cancer survivors had fewer urinary symptoms.
IMPLICATIONS FOR CANCER SURVIVORS
This study highlighted aspects of long-term physical and psychosocial quality of life that are more favorable among prostate cancer survivors with a supportive social environment.
PubMed: 38951371
DOI: 10.1007/s11764-024-01632-0