Efectividad del entrenamiento muscular pélvico temprano en la fuerza de suelo pélvico, síntomas de incontinencia urinaria, función sexual y calidad de vida en pacientes posprostatectomía radical: revisión sistemática de ensayos clínicos aleatorizados / Effectiveness of early pelvic muscle training on pelvic floor strength, urinary incontinence symptoms, sexual function, and quality of life in post-radical prostatectomy patients: Systematic review of randomized clinical trials

Este estudio tuvo como objetivo evaluar la efectividad del entrenamiento muscular pélvico temprano para reducir los síntomas de incontinencia urinaria, mejorar la calidad de vida, función sexual y aumentar la fuerza de suelo pélvico en pacientes posprostatectomía radical. Se realizó una búsqueda en 8 bases de datos hasta el 26 de octubre de 2022, se evaluó la calidad metodológica y el riesgo de sesgo de 14 estudios incluidos (n=1236), se calculó la evidencia y el metaanálisis. El entrenamiento redujo significativamente los síntomas de incontinencia urinaria en comparación con un grupo control (DME=−2,80; IC 95%=−5,21 a −0,39; p=0,02), con heterogeneidad significativa (I2=83%; p=<0,0001) y evidencia moderada. Además, presentó evidencia moderada para mejorar la calidad de vida, y muy baja para mejorar la función sexual y fuerza de suelo pélvico. Estos resultados deben ser observados con precaución debido a la heterogeneidad significativa de los estudios analizados. (AU)

This study aimed to evaluate the effectiveness of early pelvic muscle training in reducing urinary incontinence symptoms, improving quality of life, sexual function, and increasing pelvic floor strength in post-radical prostatectomy patients. A search was carried out in 8 databases until October 26, 2022, the methodological quality and the risk of bias of 14 included studies (n=1236) were evaluated, moreover, the evidence and the meta-analysis were calculated. The intervention significantly reduced urinary incontinence symptoms compared to a control group (SMD=−2.80, 95% CI=−5.21 to −0.39, P=.02), with significant heterogeneity (I2=83%; P=<.0001) and moderate evidence. In addition, it presented moderate evidence to improve quality of life, and very low evidence to improve sexual function and pelvic floor strength. These results should be viewed with caution due to the significant heterogeneity of the studies analysed. (AU)

On the necessity of specialized knowledge-based models for SBRT prostate treatments plans.

PURPOSE: Test whether a well-grounded KBP model trained on moderately hypo-fractionated prostate treatments can be used to satisfactorily drive the optimization of SBRT prostate treatments. MATERIALS AND METHODS: A KBP model (SBRT-model) was developed, trained and validated using the first forty-seven clinically treated VMAT SBRT prostate plans (42.7 Gy/7fx or 36.25 Gy/5fx). The performance and robustness of this model were compared against a high-quality KBP-model (ST-model) that was already clinically adopted for hypo-fractionated (70 Gy/28fx and 60 Gy/20fx) prostate treatments. The two models were compared in terms of their predictions robustness, and the quality of their outcomes were evaluated against a set of reference clinical SBRT plans. Plan quality was assessed using DVH metrics, blinded clinical ranking, and a dedicated Plan Quality Metric algorithm. RESULTS: The plan libraries of the two models were found to share a high degree of anatomical similarity. The overall quality (APQM%) of the plans obtained both with the ST- and SBRT-models was compatible with that of the original clinical plans, namely (93.7 ± 4.1)% and (91.6 ± 3.9)% vs (92.8.9 ± 3.6)%. Plans obtained with the ST-model showed significantly higher target coverage (PTV V95%): (97.9 ± 0.8)% vs (97.1 ± 0.9)% (p < 0.05). Conversely, plans optimized following the SBRT-model showed a small but not-clinically relevant increase in OAR sparing. ST-model generally provided more reliable predictions than SBRT-model. Two radiation oncologists judged as equivalent the plans based on the KBP prediction, which was also judged better that reference clinical plans. CONCLUSION: A KBP model trained on moderately fractionated prostate treatment plans provided optimal SBRT prostate plans, with similar or larger plan quality than an embryonic SBRT-model based on a limited number of cases.

CRISPR-Cas9 genome and long non-coding RNAs as a novel diagnostic index for prostate cancer therapy via liposomal-coated compounds.

CRISPR/Cas9 is a recently discovered genomic editing technique that altered scientist's sight in studying genes function. Cas9 is controlled via guide (g) RNAs, which match the DNA targeted in cleavage to modify the respective gene. The development in prostate cancer (PC) modeling directed not only to novel resources for recognizing the signaling pathways overriding prostate cell carcinoma, but it has also created a vast reservoir for complementary tools to examine therapies counteracting this type of cancer. Various cultured somatic rat models for prostate cancer have been developed that nearly mimic human prostate cancer. Nano-medicine can passively target cancer cells via increasing bioavailability and conjugation via specific legend, contributing to reduced systemic side-effects and increased efficacy. This article highlights liposomal loaded Nano-medicine as a potential treatment for prostate cancer and clarifies the CRISPR/Cas9 variation accompanied with prostate cancer. PC is induced experimentally in western rat model via ethinyl estradiol for 4 weeks and SC. dose of 3, 2'- dimethyl-4-aminobiphenyl estradiol (DAE) (50mg/kg) followed by treatment via targeted liposomal-coated compounds such as liposomal dexamethasone (DXM), liposomal doxorubicin (DOX) and liposomal Turmeric (TUR) (3mg/kg IP) for four weeks in a comparative study to their non-targeted analogue dexamethasone, doxorubicin and Turmeric. 3, 2'- dimethyl-4-aminobiphenylestradiol elicit prostate cancer in western rats within 5 months. Simultaneous supplementations with these liposomal compounds influence on prostate cancer; tumor markers were investigated via prostate-specific antigen (PSA), Nitric oxide (NOX) and CRISPR/Cas9 gene editing. Several long non-coding RNAs were reported to be deregulated in prostate cell carcinoma, including MALAT1. On the other hand, gene expression of apoptotic biomarkers focal adhesion kinase (AKT-1), phosphatidylinistol kinase (PI3K) and glycogen synthase kinase-3 (GSK-3) was also investigated and further confirming these results via histopathological examination. Liposomal loaded dexamethasone; doxorubicin and Turmeric can be considered as promising therapeutic agents for prostate cancer via modulating CRISPR/Cas9 gene editing and long non coding gene MALAT1.

Chronic radiation proctitis refractory to steroid enema was successfully treated by metformin and sodium butyrate: a case report.

BACKGROUND: Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy. CASE PRESENTATION: A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect. CONCLUSIONS: M-B enema and suppository may be an effective treatment for chronic RP.

Comprehensive Analysis of CXCR4, JUNB, and PD-L1 Expression in Circulating Tumor Cells (CTCs) from Prostate Cancer Patients.

CXCR4, JUNB and PD-L1 are implicated in cancer progression and metastasis. The current study investigated these biomarkers in CTCs isolated from metastatic prostate cancer (mPCa) patients at the RNA and protein levels. CTCs were isolated from 48 mPCa patients using the Ficoll density gradient and ISET system (17 out of 48). The (CK/PD-L1/CD45) and (CK/CXCR4/JUNB) phenotypes were identified using two triple immunofluorescence stainings followed by VyCAP platform analysis. Molecular analysis was conducted with an EpCAM-dependent method for 25/48 patients. CK-8, CK-18, CK-19, JUNB, CXCR4, PD-L1, and B2M (reference gene) were analyzed with RT-qPCR. The (CK+/PD-L1+/CD45-) and the (CK+/CXCR4+/JUNB+) were the most frequent phenotypes (61.1% and 62.5%, respectively). Furthermore, the (CK+/CXCR4+/JUNB-) phenotype was correlated with poorer progression-free survival [(PFS), HR: 2.5, p = 0.049], while the (CK+/PD-L1+/CD45-) phenotype was linked to decreased overall survival [(OS), HR: 262.7, p = 0.007]. Molecular analysis revealed that 76.0% of the samples were positive for CK-8,18, and 19, while 28.0% were positive for JUNB, 44.0% for CXCR4, and 48.0% for PD-L1. Conclusively, CXCR4, JUNB, and PD-L1 were highly expressed in CTCs from mPCa patients. The CXCR4 protein expression was associated with poorer PFS, while PD-L1 was correlated with decreased OS, providing new biomarkers with potential clinical relevance.

Novel role of LLGL2 silencing in autophagy: reversing epithelial-mesenchymal transition in prostate cancer.

PURPOSE: Prostate cancer (PCa) is a major urological disease that is associated with significant morbidity and mortality in men. LLGL2 is the mammalian homolog of Lgl. It acts as a tumor suppressor in breast and hepatic cancer. However, the role of LLGL2 and the underlying mechanisms in PCa have not yet been elucidated. Here, we investigate the role of LLGL2 in the regulation of epithelial-mesenchymal transition (EMT) in PCa through autophagy in vitro and in vivo. METHODS: PC3 cells were transfected with siLLGL2 or plasmid LLGL2 and autophagy was examined. Invasion, migration, and wound healing were assessed in PC3 cells under autophagy regulation. Tumor growth was evaluated using a shLLGL2 xenograft mouse model. RESULTS: In patients with PCa, LLGL2 levels were higher with defective autophagy and increased EMT. Our results showed that the knockdown of LLGL2 induced autophagy flux by upregulating Vps34 and ATG14L. LLGL2 knockdown inhibits EMT by upregulating E-cadherin and downregulating fibronectin and α-SMA. The pharmacological activation of autophagy by rapamycin suppressed EMT, and these effects were reversed by 3-methyladenine treatment. Interestingly, in a shLLGL2 xenograft mouse model, tumor size and EMT were decreased, which were improved by autophagy induction and worsened by autophagy inhibition. CONCLUSION: Defective expression of LLGL2 leads to attenuation of EMT due to the upregulation of autophagy flux in PCa. Our results suggest that LLGL2 is a novel target for alleviating PCa via the regulation of autophagy.

A cross-sectional study of ERG expression and the relationship with clinicopathological features of Prostate cancer in Southwestern Uganda.

BACKGROUND: Prostate cancer is the leading cause of cancer-related death and the second most commonly diagnosed cancer among men in Uganda and most countries in Sub-Saharan Africa (SSA). The TMPRSS2-ERG fusion gene is the most common genetic alteration seen among prostate cancer patients. There are several contradicting reports about the association of ERG protein with poor prognosis, high PSA, and Gleason score. This study determined the prevalence of ERG expression and the relationship with PSA, Gleason score, and Age of prostate cancer patients in Southwestern Uganda. METHODS: We reviewed 130 archived prostate biopsy (needle and TURP) specimens from patients of age ≥ 50 years who had a histological diagnosis of prostate cancer. We obtained their biodata, and preoperative PSA, from the archived records. We did Immunohistochemistry (IHC) to determine the prevalence of ERG expression. RESULTS: The mean patient age in our study was 74.64 ± 10.19 years. Pre-operative PSA levels had been done for 79.2% of the participants. Most cancers (58.46%) were of high grade (grade group 3-5). ERG expression prevalence was 75.4% and its expression was independent of age, re-operative PSA, and Gleason score. CONCLUSION: There is a significantly higher prevalence of ERG expression in our study compared to what is reported in other African-based studies. The expression of the ERG is independent of age, Gleason score, and serum PSA levels. A high proportion of our prostate cancer has high-grade disease at the time of diagnosis.

Homologous Recombination Repair Deficiency in Metastatic Prostate Cancer: New Therapeutic Opportunities.

More than 20% of metastatic prostate cancer carries genomic defects involving DNA damage repair pathways, mainly in homologous recombination repair-related genes. The recent approval of olaparib has paved the way to precision medicine for the treatment of metastatic prostate cancer with PARP inhibitors in this subset of patients, especially in the case of BRCA1 or BRCA2 pathogenic/likely pathogenic variants. In face of this new therapeutic opportunity, many issues remain unsolved. This narrative review aims to describe the relationship between homologous recombination repair deficiency and prostate cancer, the techniques used to determine homologous recombination repair status in prostate cancer, the crosstalk between homologous recombination repair and the androgen receptor pathway, the current evidence on PARP inhibitors activity in metastatic prostate cancer also in homologous recombination repair-proficient tumors, as well as emerging mechanisms of resistance to PARP inhibitors. The possibility of combination therapies including a PARP inhibitor is an attractive option, and more robust data are awaited from ongoing phase II and phase III trials outlined in this manuscript.

CYP7B1 as a Biomarker for Prostate Cancer Risk and Progression: Metabolic and Oncogenic Signatures (Diagnostic Immunohistochemistry Analysis by Tissue Microarray in Prostate Cancer Patients-Diamond Study).

We aimed to analyze the association between CYP7B1 and prostate cancer, along with its association with proteins involved in cancer and metabolic processes. A retrospective analysis was performed on 390 patients with prostate cancer (PC) or benign prostatic hyperplasia (BPH). We investigated the interactions between CYP7B1 expression and proteins associated with PC and metabolic processes, followed by an analysis of the risk of biochemical recurrence based on CYP7B1 expression. Of the 139 patients with elevated CYP7B1 expression, 92.8% had prostate cancer. Overall, no increased risk of biochemical recurrence was associated with CYP7B1 expression. However, in a non-diabetic subgroup analysis, higher CYP7B1 expression indicated a higher risk of biochemical recurrence, with an HR of 1.78 (CI: 1.0-3.2, p = 0.05). PC is associated with elevated CYP7B1 expression. In a subgroup analysis of non-diabetic patients, elevated CYP7B1 expression was associated with an increased risk of biochemical recurrence, suggesting increased cancer aggressiveness.

Unveiling the Genomic Landscape of Intraductal Carcinoma of the Prostate Using Spatial Gene Expression Analysis.

Intraductal carcinoma of the prostate (IDCP) has recently attracted increasing interest owing to its unfavorable prognoses. To effectively identify the IDCP-specific gene expression profile, we took a novel approach of characterizing a typical IDCP case using spatial gene expression analysis. A formalin-fixed, paraffin-embedded sample was subjected to Visium CytAssist Spatial Gene Expression analysis. IDCP within invasive prostate cancer sites was recognized as a distinct cluster separate from other invasive cancer clusters. Highly expressed genes defining the IDCP cluster, such as MUC6, MYO16, NPY, and KLK12, reflected the aggressive nature of high-grade prostate cancer. IDCP sites also showed increased hypoxia markers HIF1A, BNIP3L, PDK1, and POGLUT1; decreased fibroblast markers COL1A2, DCN, and LUM; and decreased immune cell markers CCR5 and FCGR3A. Overall, these findings indicate that the hypoxic tumor microenvironment and reduced recruitment of fibroblasts and immune cells, which reflect morphological features of IDCP, may influence the aggressiveness of high-grade prostate cancer.

Recent advances in flavonoid compounds for the treatment of prostate cancer.

Prostate cancer is a malignant epithelial tumor of the prostate gland and is the most common malignant tumor of the male genitourinary system. Pharmacological therapies, including chemotherapy and androgen deprivation therapy, play a key role in the treatment of prostate cancer. However, drug resistance and side effects limit the use of these drugs and so there is a need for new drug therapies for prostate cancer patients. Flavonoids, with their wide range of sources and diverse biological activities, have attracted much attention in the field of anti-tumor drug screening. In 2016, at least 58 flavonoids were reported to have anti-prostate cancer activity. In recent years, six additional flavonoid compounds have been found to have anti-prostate cancer potential. In this review, we have collected a large amount of evidence on the anti-prostate cancer effects of these six flavonoids, including a large number of cellular experiments and a small number of preclinical animal experiments. In addition, we predicted their drug-forming properties using Schrödinger's QikProp software and ADMETlab due to the lack of in vivo pharmacokinetic data for the six compounds. In conclusion, this review has fully confirmed the anti-prostate cancer effects of these six flavonoids, summarized their mechanisms of action and predicted their druggability. It provides a reference for the further development of these compounds into anti-prostate cancer drugs.

Associations between knowledge of health issues and health care satisfaction and propensity to complain: a cross-sectional survey of adult men in Denmark.

OBJECTIVES: The objective of this study was to investigate associations between knowledge of health issues and healthcare satisfaction and propensity to complain including the association between knowledge and greater patient involvement. DESIGN: The present study is a secondary analysis of a larger cross-sectional case vignette survey. SETTING: Survey conducted in adult Danish men. PARTICIPANTS: Participants included 6755 men aged 45-70 years. INTERVENTIONS: Participants responded to a survey with scenarios illustrating prostate-specific antigen (PSA) testing and different information provision. PRIMARY AND SECONDARY OUTCOME MEASURES: Using Likert scales (scored 1-5), participants rated their satisfaction with the care described and their inclination to complain and responded to a short quiz (scored 0-3) assessing their knowledge about the PSA test. RESULTS: Satisfaction with healthcare increased with better quiz performance (Likert difference 0.13 (95% CI .07 to 0.20), p <0.001, totally correct vs totally incorrect responders) and correspondingly, the desire to complain significantly decreased (Likert difference -0.34 (95% CI 0.40 to -0.27), p <0.001). Respondents with higher education performed better (mean quiz score difference 0.59 (95% CI 0.50 to 0.67), p <0.001, most educated vs least educated). Responders who received information about the PSA test generally performed better (quiz score difference 0.41 (95% CI 0.35 to 0.47), p<0.001, neutral vs no information). Overestimation of PSA merits was more common than underestimation (7.9% vs 3.8%). CONCLUSIONS: Mens' knowledge of the benefits of screening varies with education, predicts satisfaction with care and the desire to complain, and may be improved through greater involvement in decision-making.

The role of androgen deprivation therapy prior to radical prostatectomy in high-risk prostate cancer: a systematic review.

INTRODUCTION: Patients with high-risk prostate cancer (HRPCa) are prone to have worse pathological features, resulting in early biochemical recurrence after radical prostatectomy (RP). There is an urgent need to develop novel treatment strategies for this group of patients to optimize their outcomes. The purpose of this study is to perform a systematic review of the role of neoadjuvant hormonal therapy (NHT) followed by RP in HRPCa patients. EVIDENCE ACQUISITION: We performed a systematic review of the following databases, MEDLINE (PubMed), EMBASE, Cochrane Library, and clinical Trial.gov; between January 2007 and August 2023, following the PRISMA guidelines. EVIDENCE SYNTHESIS: After screening and deduplication, we included ten studies from an initial pool of 1275. The risk of bias was low in observational studies but ranged from moderate to low in controlled trials. Five studies utilized traditional androgen deprivation treatments (ADT), revealing favorable pathological outcomes but inconsistency in evaluating oncological results. Additionally, four studies focused on RP combined with androgen receptor pathway inhibitors (ARPIs) in the NHT setting, all showing primarily positive pathological outcome, with no clear evidence of an oncological benefit. Limited long-term follow-up data and a shortage of randomized controlled trials were evident among all the studies included in this review, regardless of the type of hormonal treatment used. CONCLUSIONS: Different hormonal treatments, including traditional ADT and ARPIs, yield positive pathology outcomes. Oncological evidence remains limited, echoing older findings predating ARPIs. Definitive conclusions require longer follow-ups and precise patient selection. Currently, insufficient evidence support ARPIs' superiority over conventional therapy before RP.

PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility.

BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a lethal subset of prostate cancer which is characterized by neuroendocrine differentiation and loss of androgen receptor (AR) signaling. Growing evidence reveals that cell lineage plasticity is crucial in the failure of NEPC therapies. Although studies suggest the involvement of the neural transcription factor PAX6 in drug resistance, its specific role in NEPC remains unclear. METHODS: The expression of PAX6 in NEPC was identified via bioinformatics and immunohistochemistry. CCK8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay were used to illustrate the key role of PAX6 in the progression of in vitro. ChIP and Dual-luciferase reporter assays were conducted to confirm the binding sequences of AR in the promoter region of PAX6, as well as the binding sequences of PAX6 in the promoter regions of STAT5A and MET. For in vivo validation, the xenograft model representing NEPC subtype underwent pathological analysis to verify the significant role of PAX6 in disease progression. Complementary diagnoses were established through public clinical datasets and transcriptome sequencing of specific cell lines. ATAC-seq was used to detect the chromatin accessibility of specific cell lines. RESULTS: PAX6 expression was significantly elevated in NEPC and negatively regulated by AR signaling. Activation of PAX6 in non-NEPC cells led to NE trans-differentiation, while knock-down of PAX6 in NEPC cells inhibited the development and progression of NEPC. Importantly, loss of AR resulted in an enhanced expression of PAX6, which reprogramed the lineage plasticity of prostate cancer cells to develop NE phenotypes through the MET/STAT5A signaling pathway. Through ATAC-seq, we found that a high expression level of PAX6 elicited enhanced chromatin accessibility, mainly through attenuation of H4K20me3, which typically causes chromatin silence in cancer cells. CONCLUSION: This study reveals a novel neural transcription factor PAX6 could drive NEPC progression and suggest that it might serve as a potential therapeutic target for the management of NEPC.

Analysis of 3D pathology samples using weakly supervised AI.

Human tissue, which is inherently three-dimensional (3D), is traditionally examined through standard-of-care histopathology as limited two-dimensional (2D) cross-sections that can insufficiently represent the tissue due to sampling bias. To holistically characterize histomorphology, 3D imaging modalities have been developed, but clinical translation is hampered by complex manual evaluation and lack of computational platforms to distill clinical insights from large, high-resolution datasets. We present TriPath, a deep-learning platform for processing tissue volumes and efficiently predicting clinical outcomes based on 3D morphological features. Recurrence risk-stratification models were trained on prostate cancer specimens imaged with open-top light-sheet microscopy or microcomputed tomography. By comprehensively capturing 3D morphologies, 3D volume-based prognostication achieves superior performance to traditional 2D slice-based approaches, including clinical/histopathological baselines from six certified genitourinary pathologists. Incorporating greater tissue volume improves prognostic performance and mitigates risk prediction variability from sampling bias, further emphasizing the value of capturing larger extents of heterogeneous morphology.

Comparison of perioperative and functional outcomes of single-incision versus standard multi-incision robot-assisted laparoscopic radical prostatectomy: a prospective, controlled, nonrandomized trial.

To compare perioperative and functional outcomes between improved (port-free) single-site robot-assisted laparoscopic radical prostatectomy (pf-ssRARP) and standard multi-port robot-assisted radical prostatectomy (MPRARP). A total of 372 consecutive patients underwent RARAP using the da Vinci Si® robotic surgical system. Group I (n = 210) included patients undergoing pf-ssRARP and Group II (n = 162) included patients undergoing MPRARP. Demographics and perioperative data including postoperative recovery outcomes were recorded and compared between the two groups. Overall mean operative time was significantly shorter with the pf-ssRARP compared to the MPRARP (p < 0.05). The length of hospitalization after the pf-ssRARP was shorter (p < 0.05). In Group I, the positive surgical margin rate was 15.2%; while in Group II, the positive margin rate was 33.3% (p < 0.05). The rate of instant urinary continence was significantly higher in Group I than in Group II (p < 0.05). The percentage of urinary continence was higher in the pf-ssRARP than in the MPRARP, at 6 months post-surgery (p < 0.05) and 9 months post-surgery (p < 0.05). There was no significant difference in the proportion of erectile function in the pf-ssRARP and MPRARP groups at the time of reaching the endpoint of this study (p > 0.05). The two groups were comparable in terms of total hospitalization costs (p < 0.05). The improved (port-free) single-site robot-assisted laparoscopic radical prostatectomy is a practical and easy technique to implement in clinical practice. Extraperitoneal implementation of the modified technique requires only a small incision, no special PORT, no additional auxiliary foramen creation, increased postoperative aesthetics and reduced hospitalization costs, and a high percentage of early postoperative urinary control recovery.

Nanocarrier - Mediated Salinomycin Delivery Induces Apoptosis and Alters EMT Phenomenon in Prostate Adenocarcinoma.

Salinomycin (Sal) has been recently discovered as a novel chemotherapeutic agent against various cancers including prostate cancer which is one of the most commonly diagnosed cancers affecting male populations worldwide. Herein we designed salinomycin nanocarrier (Sal-NPs) to extend its systemic circulation and to increase its anticancer potential. Prepared nanoform showed high encapsulation and sustained release profile for salinomycin. The present study elucidated the cytotoxicity and mechanism of apoptotic cell death of Sal-NPs against prostate cancer both in vitro and in vivo. At all measured concentrations, Sal-NPs showed more significant cytotoxicity to DU145 and PC3 cells than Sal alone. This effect was mediated by apoptosis, as confirmed by ROS generation, loss of MMP and cell cycle arrest at the G1 phase in both cells. Sal-NPs efficiently inhibited migration of PC3 and DU145 cells via effectively downregulating the epithelial mesenchymal transition. Also, the results confirmed that Sal-NPs can effectively inhibit the induction of Prostate adenocarcinoma in male Wistar rats. Sal-NPs treatment exhibited a decrease in tumour sizes, a reduction in prostate weight, and an increase in body weight, which suggests that Sal-NPs is more effective than salinomycin alone. Our results suggest that the molecular mechanism underlying the Sal-NPs anticancer effect may lead to the development of a potential therapeutic strategy for treating prostate adenocarcinoma.

Increasing the radiation-induced cytotoxicity by silver nanoparticles and docetaxel in prostate cancer cells.

BACKGROUND: Radiation therapy is utilized for treatment of localized prostate cancer. Nevertheless, cancerous cells frequently develop radiation resistance. While higher radiation doses have not always been effective, radiosensitizers have been extensively studied for their ability to enhance the cytotoxic effects of radiation. So, this study aims to evaluate the possible radiosensitization effects of docetaxel (DTX) and silver nanoparticles (SNP) in LNCaP cells. METHODS: The cytotoxic effects of DTX, SNP and 2 Gy of X-Ray radiation treatments were assessed in human LNCaP cell line using the MTT test after 24 h. Moreover, the effects of DTX, SNP and radiation on Epidermal growth factor (EGF), Caspase 3, inducible nitric oxide synthase and E-cadherin gene expression were analyzed using the Real-time PCR method. The level of Hydrogen peroxide (H2O2), an oxidative stress marker, was also detected 24 h after various single and combined treatments. RESULTS: The combinations of SNP (in low toxic concentration) and/or DTX (0.25× IC50 and 0.5 × IC50 concentrations for triple and double combinations respectively) with radiation induced significant cytotoxicity in LNCaP cells in comparison to monotherapies. These cytotoxic effects were associated with the downregulation of EGF mRNA. Additionally, H2O2 levels increased after Radiation + SNP + DTX triple combination and double combinations including Radiation + SNP and Radiation + DTX versus single treatments. The triple combination treatment also increased Caspase 3 and and E-cadherin mRNA levels in compared to single treatments in LNCaP cells. CONCLUSION: Our results indicate that the combination of SNP and DTX with radiation induces significant anti-cancer effects. Upregulation of Caspase 3 and E-cadherin gene expression, and decreased mRNA expression level of EGF may be exerted specifically by use of this combination versus single treatments.