Prostate Cancer最新文献

Background: Prostate cancer is the most common malignancy in men. Sestrin2 (SESN2) has antitumor activity against several types of cancers. However, the effect of SESN2 on prostate cancer is not well known. In this study, we showed that SESN2 inhibits human prostate cancer. Materials and Methods: To investigate the contribution of Sestrin2 to prostate cancer, we performed a bioinformatic analysis of the Cancer Genome Atlas database and Gene Expression Profiling Interactive Analysis. Using the Sestrin2 overexpression vector, we identified proliferation, migration, and invasion in prostate cancer cells. Furthermore, the effect of Sestrin2 on autophagy was confirmed by Western blot analysis and immunofluorescence staining. Results: We showed that expression of SESN2 was reduced in prostate cancer tissues and cell lines, and low expression of SESN2 correlated with decreased survival in prostate cancer patients. We have shown that SESN2 inhibits cell viability and cell proliferation-related protein levels in PC3 and DU145 prostate cancer cells. SESN2 inhibited EMT-related protein and migration and invasion levels. SESN2 promoted autophagy by increasing autophagy-related protein levels and LC3-positive cells. SESN2 increased pAMPK and decreased pmTOR protein levels. Furthermore, we used rapamycin, an mTOR inhibitor, to determine whether the AMPK/mTOR signaling pathway regulates autophagy in prostate cancer cells. Conclusion: Our study suggests that SESN2 inhibits prostate cancer cells by inducing autophagy through the AMPK/mTOR signaling pathway. These results indicate that SESN2 might be a novel target for prostate cancer.

Background: Abiraterone acetate is an androgen-receptor pathway inhibitor commonly used for treatment of metastatic prostate cancer. The levels of androgens during treatment with abiraterone acetate with prednisone (AAP) are lower than those achieved by androgen-deprivation therapy only, potentially resulting in a high risk of skeletal muscle loss. Methods: The cohort included 43 patients treated with AAP for metastatic hormone-sensitive prostate cancer or metastatic castration-resistant prostate cancer. To detect and quantify sarcopenia, we utilized standard computer tomography (CT) imaging. Skeletal muscle mass index (SMI) was evaluated by assessing two adjacent axial sections at the level of the L3 vertebra. Results: Sarcopenia at the time of AAP initiation was present in 72.1% of patients. Body mass index (BMI) was inversely associated with the presence of sarcopenia at the time of AAP initiation. There was a statistically significant decrease in SMI over AAP treatment. Age > 75 years and the absence of previous radiotherapy were associated with a higher rate of SMI decrease during AAP therapy. Overall and progression-free survival was not significantly associated with SMI decrease during AAP therapy. Conclusions: SMI decline occurs during AAP treatment for mHSPC and mCRPC, and is more pronounced in patients over 75 years old and those without previous local treatment. There was no statistically significant association between survival outcomes and SMI decline during AAP therapy.

Introduction: Prostate cancer is the second most common cancer among men worldwide. This cancer has become extremely noticeable due to the increase of prostate cancer in Iranian men in recent years due to the lack of marriage and sexual intercourse, as well as the abuse of hormones in sports without any standards. Methods: The histopathology images from a treatment center to diagnose prostate cancer are used with the help of deep learning methods, considering the two characteristics of Tile and Grad-CAM. The approach of this research is to present a prostate cancer diagnosis model to achieve proper performance from histopathology images with the help of a developed deep learning method based on the manifold model. Results: Similarly, in addition to the diagnosis of prostate cancer, a study on the methods of preventing this disease was investigated in literature reviews, and finally, after simulation, prostate cancer presentation factors were determined. Conclusions: The simulation results indicated that the proposed method has a performance advantage over the other state-of-the-art methods, and the accuracy of this method is up to 97.41%.

Background: Prostate cancer (PC) ranks as the third cause of cancer-related deaths among Iranian men. The age-period-cohort (APC) model helps identify critical ages, periods, and high-risk birth cohorts to prevent and control PC. Thus, this research aimed to evaluate the effect of APC on PC mortality in Iran from 1990 to 2021. Method: Our data include the number of PC deaths and population, collected by the Global Burden of Disease (GBD) and categorized by 5-year age groups. We computed average annual percentage changes (AAPCs) and relative risks by using joinpoint regression analysis and APC models, respectively. Results: Crude and age-standardized mortality rates for PC were increasing, with AAPC of 2.254% (95% CI: 2.099% and 2.410%; p < 0.001) and 0.257% (95% CI: 0.088% and 0.428%; p < 0.001), respectively. Furthermore, an increase occurred in both age effect from ages 20-24 years (RR = 0.033; 95% CI: 0.023 and 0.046) to over 95 years (RR = 16.183; 95% CI: 14.702 and 17.814) and the period from 1992 (RR = 0.542; 95% CI: 0.516 and 0.570) to 2021 (RR = 1.892; 95% CI: 1.809 and 1.979). While, the cohort effect demonstrated a lower mortality rate in later born than earlier born (Coef = 2.302 for the < 1901 cohort compared to Coef = -2.249 for the 2002-2006 cohort). Conclusion: Our study indicated that the trend of PC deaths in Iran increased during 1990-2021, and the period effect confirms this. Considering fewer deaths in high-income countries due to the widespread implementation of PSA testing, the occurrence of the aging phenomenon in our country, and the upward trend in deaths related to the age effect, sensitizing people and policymakers to conduct PSA screening seems necessary.

Background: A need exists for effective treatments for prostate cancer (PCA) due its re-emergence following androgen deprivation therapy, a major clinical problem. In a previous study, we presented evidence on the chemopreventive and chemotherapeutic potential of luteolin, a flavonoid, in PCA including castration-resistant PCA. In this single-arm phase I study, we clinically examined the safety of the oral intake of luteolin in patients under active surveillance (AS). Methods: Between March and September in 2022, five patients with low-intermediate risk PCA and under AS were treated daily with 50 mg of oral luteolin for six months. We investigated the efficacy of oral luteolin in oncological outcomes and any adverse events (AEs) and examined prostate and blood specimens. Results: The median age of patients was 68 years (range: 60-78), and the median initial prostate-specific antigen level was 9.5 ng/mL. All patients were under AS without rapid progression. After treatment with luteolin, AEs were not noted in any patients for six months. All patients underwent a protocol biopsy. Of these, two patients showed a favorable response, one patient had stable disease, and two patients showed disease progression; robot-assisted radical surgery was subsequently performed for the latter. Immunohistochemical analysis revealed decreased expression of androgen receptor and NKX3.1 in noncancerous lesions after luteolin treatment. In addition, quantitative reverse transcription-PCR revealed that serum micro(mi)RNA expression in serum and prostate gland, including miR-29 and miR-30, tended to be upregulated after luteolin treatment compared with during the pretreatment phase. Conclusions: Our small phase I study of men with PCA suggests that daily treatment with 50 mg of an oral supplement of luteolin is safe and effective with regard to oncological outcomes, particularly in patients under AS.

Prostate cancer is the most common noncutaneous malignancy among men worldwide, including in Sudan, where it represents a significant public health challenge. CD147, a transmembrane glycoprotein implicated in tumor progression, invasion, and metastasis, has shown potential as a prognostic biomarker in various cancers. This retrospective case-control study aimed to evaluate CD147 expression in prostate adenocarcinoma among Sudanese men and its association with tumor grade. A total of 80 paraffin-embedded tissue samples, including 40 cases of prostate adenocarcinoma and 40 benign prostatic hyperplasia (BPH) controls, were analyzed using immunohistochemistry. CD147 expression was observed in 22.5% of adenocarcinoma cases compared to 7% of controls; however, the association was not statistically significant (p=0.07). Low-grade tumors were predominant in the cohort, consistent with early-stage diagnoses. The findings revealed no clear link between CD147 expression and tumor grade, diverging from prior studies that associate CD147 with advanced tumor stages. The nonsignificant results may be attributed to the small sample size, emphasizing the need for future research with larger, more diverse cohorts, advanced molecular techniques, and functional studies to better elucidate the role of CD147 in prostate cancer pathogenesis and its potential as a therapeutic target.

Background: Assessment of comorbid diseases is essential to clinical research and may risk-stratify patients for mortality independent of established methods such as the Charlson Comorbidity Index (CCI). Methods: In a retrospective study of U.S. Veterans, we examined the association between the number of medications, 1-year mortality, and overall survival in Veterans being treated for metastatic castration-resistant prostate cancer (mCRPC) between 2011 and 2017. Results: Among 8855 Veterans, a median of 11 medications and 6 medication classes were filled in the year prior to initial treatment of mCRPC with abiraterone or enzalutamide. The median patient age was 74 years, 25.7% of patients were Black, and the median CCI was 3. Despite being associated with fewer medications, increasing age was associated with an increased CCI. After adjusting for patient, tumor, and treatment factors, both the number of medications and the number of medication classes were associated with increased 1-year mortality with adjusted OR (95% CI) of 1.03 (1.03, 1.04) and 1.08 (1.06, 1.11), respectively. Medications within Anatomic Therapeutic Class (ATC) N (nervous system) and ATC G (genitourinary and sex hormones) were associated with decreased OS, HR 1.18 (1.11, 1.25) and HR 1.15 (1.10, 1.20), respectively. Medications within ATC C (cardiovascular) were associated with increased OS, HR 0.91 (0.86, 0.97). Within a subgroup of patients with comparable age and CCI, the increased number of medications was associated with the increased risk of death. Conclusions: The number and type of medications were independently associated with survival in patients undergoing treatment for mCRPC. With new therapies for treatment of advanced prostate cancer, patients are living longer, which increases the need for better understanding of the impact of comorbid diseases. Simple methods to assess disease burden and prognosticate survival have the potential to guide treatment decisions and improve the quality of life in this patient population.

Introduction: Genetic and environmental factors are involved in prostate cancer. The current study was conducted to study the relationship between G-137C, C-607A, and A-1447G polymorphisms in the promoter of IL-18 and CXCL10 inflammatory genes with prostate cancer.

Methods: As a genetic association study with a case-control design, the genomes of people living in Khorasan, Iran, were compared in two groups of cases and controls. The genotype of the A-1447G polymorphism present in the CXCL10 gene promoter was investigated by the PCR-RFLP method. PCR-SSP was used to study the genotype of G-137C and C-607A polymorphisms present in the IL-18 gene promoter. Odds ratio (OR) and 95% confidence interval (CI) were reported.

Results: One mutant allele in CXCL10 A-1447G polymorphism (AG) increased the chance of cancer (OR = 4.902, 95% CI = 2.70-8.87) and two mutant alleles (GG) increased more (OR = 7.174, 95% CI = 2.48-20.68). One mutant allele in IL-18 G-137C polymorphism (CG) increased the chance of cancer (OR = 5.583, 95% CI = 3.04-10.22) and two mutant alleles (CC) increased more (OR = 9.571, 95% CI = 3.10-29.46). One mutant allele in IL-18 C607A polymorphism (CA) increased the chance of cancer (OR = 5.359, 95% CI = 2.95-9.70) and two mutant alleles (AA) increased more (OR = 7.083, 95% CI = 2.61-19.15) (P < 0.001).

Conclusion: According to the results, the mutant alleles in polymorphisms CXCL10 A-1447G, IL-18 G-137C, and IL-18 C-607A alleles were associated with an increased chance of prostate cancer in this population.

This study evaluated the effects of docetaxel and androgen receptor signaling inhibitors as second-line treatments in patients with castration-resistant prostate cancer after androgen receptor signaling inhibitors as first-line treatment. This study retrospectively evaluated the clinical outcomes of second-line treatment with docetaxel or androgen receptor signaling inhibitor in patients with castration-resistant prostate cancer who received first-line treatment with androgen receptor signaling inhibitors. Clinical backgrounds and outcomes were compared between docetaxel and androgen receptor signaling inhibitors as second-line treatment. Of 59 patients, 21 (35.6%) and 38 (64.4%) received docetaxel and androgen receptor signaling inhibitors as second-line treatment after first-line treatment with androgen receptor signaling inhibitors, respectively. In the second-line setting, the median progression-free survival was longer with androgen receptor signaling inhibitor than with docetaxel (17 versus 6 months, P=0.014). In the first-line setting, the median progression-free survival was longer with androgen receptor signaling inhibitors than with docetaxel (32 versus 25 months, P=0.014); however, no significant difference was found in the overall survival. Multivariate analysis revealed that there was no significant association between second-line treatment and survival, and first-line treatment with abiraterone was identified as a prognostic factor for progression-free survival. Subgroup analysis showed that the abiraterone-enzalutamide sequence was more effective than the other three sequences for progression-free survival and overall survival. This study suggests that second-line treatment with an androgen receptor signaling inhibitor for castration-resistant prostate cancer after androgen receptor signaling inhibitors as first-line treatment may be more beneficial, particularly with abiraterone as the upfront treatment.