The prospect of targeting T cell immunoglobulin and mucin-domain containing-3 in renal cell carcinoma immunotherapy.

Despite the advances in the diagnosis and treatment of renal cell carcinoma (RCC), it remains one of the most deadly urological cancers. At present, using immune checkpoint inhibition and their combination with antiangiogenic therapy is the standard of care in patients with advanced RCC. Unfortunately, a considerable part of tumour-bearing hosts does not benefit from this type of treatment. However, our knowledge about the detailed role of mucin-domain containing-3 (TIM-3) in the RCC cells is little, and further studies are required in this field, but its significant expression in the RCC microenvironment makes this receptor a promising target for designing new monoclonal antibodies alone or in combination with other checkpoint inhibitors for RCC immunotherapy.

The role of nutritional interventions in prostate cancer: A review.

The high prevalence rate in conjunction with the long latency period made prostate cancer (PCa) an attractive and reasonable candidate for preventive measures. So far, several dietary and nutritional interventions have been implemented and studied with the aim of preventing the development or delaying the progression of PCa. Calorie restriction accompanied by weight loss has been shown to be associated with decreased likelihood of aggressive PCa. Supplements have played a major role in nutritional interventions. While genistein and lycopene seemed promising as preventive agents, minerals such as zinc and selenium were shown to be devoid of protective effects. The role of vitamins has been widely studied, with special emphasis on vitamins with antioxidant properties. Data related to Vitamin A and Vitamin C were rather controversial and positive effects were of insignificant magnitude. Vitamin E was associated with a decreased risk of PCa in high-risk groups like smokers. However, when it comes to Vitamin D, the serum levels might affect the risk of PCa. While deficiency of this vitamin was associated with increased risk, high serum levels imposed the risk of aggressive disease. Despite the seemingly promising effects of dietary measures on PCa, no firm recommendation could be made due to the limitations of the studies and evidence. However, the majority of these advices could be followed by the patients with the intent of living a healthy lifestyle.

Global, Regional and National Burden of Bladder Cancer, 1990 to 2016: Results from the GBD Study 2016.

PURPOSE: Bladder cancer is among the leading causes of cancer death worldwide. Data on the bladder cancer burden are valuable for policy-making. We aimed to estimate the burden of bladder cancer by country, age group, gender and sociodemographic status between 1990 and 2016. MATERIALS AND METHODS: Data from vital registration systems and cancer registries were the input to estimate the bladder cancer burden. Mortality was estimated in an ensemble model approach, incidence was estimated by dividing mortality by the mortality-to-incidence ratio and prevalence was estimated using the mortality-to-incidence ratio as a surrogate for survival. We modeled the years lived with disability using disability weights of bladder cancer sequelae. Years of life lost were calculated by multiplying the number of deaths by age by the standard life expectancy at that age. Disability adjusted life-years were calculated by summing the years lived with disability and the years of life lost. Moreover, we also estimated the burden attributable to bladder cancer risk factors, smoking and high fasting plasma glucose using the comparative risk assessment framework of the Global Burden of Disease study. RESULTS: In 2016 there were 437,442 incident cases (95% UI 426,709-447,912) of bladder cancer with an age standardized incidence rate of 6.69/100,000 (95% UI 6.52-6.85). Bladder cancer led to 186,199 deaths (95% UI 180,453-191,686) in 2016 with an age standardized rate of 2.94/100,000 (95% UI 2.85-3.03). Bladder cancer was responsible for 3,315,186 disability adjusted life-years (95% UI 3,193,248-3,425,530) in 2016 with an age standardized rate of 49.45/100,000 (95% UI 47.68-51.11). Of bladder cancer deaths 26.84% (95% UI 19.78-33.91) and 7.29% (95% UI 1.49-16.19) were due to smoking and high fasting glucose, respectively, in 2016. CONCLUSIONS: Although the number of bladder cancer incident cases is growing globally, the age standardized incidence and number of deaths are decreasing, as mirrored by a decreasing smoking contribution.

Toll-like receptors: The role in bladder cancer development, progression and immunotherapy.

Bladder cancer is one of the leading causes of death worldwide. The main immune mechanisms which lead to bladder cancer development or treatment outcomes have yet to be elucidated. Toll-like receptors (TLRs) play key roles against cancer. TLRs are expressed both on immune cells and on tumour cells and drive immune responses in progression as well as treatment of cancer. Identification of signalling pathways via TLRs could revolutionize further improvement of therapeutic strategies against cancers in the future. According to the recent studies, TLRs agonists are effective immunostimulants and have important role in induction of immune responses with immunotherapeutic potential against several diseases including cancer. They play an important role in the bladder urothelium as a part of immune defence against uropathogens. On the other hand, decreased TLRs expression was found in bladder tumours, particularly in non-muscle-invasive ones. Bacillus Calmette-Guerin (BCG) (agonist of TLR2 and TLR4) is approved by US FDA for immunotherapy of bladder cancer. Despite high efficiency, immunotherapy with BCG may cause toxicity and adverse effects. Nowadays, in vitro and in vivo studies have been conducted to find alternative options for non-responder patients. Studies on TLR agonists for bladder cancer treatment have shown promising results. In this review, we discuss recent data about mechanisms played by TLRs in bladder cancer developments as well as therapeutic application of TLR agonists in cancer treatment.

Global, regional and national burden of testicular cancer, 1990-2016: results from the Global Burden of Disease Study 2016.

OBJECTIVE: To provide estimates of the global incidence, mortality and disability-adjusted life-years (DALYs) associated with testicular cancer (TCa) between 1990 and 2016, using findings from the Global Burden of Disease (GBD) 2016 study. MATERIALS AND METHODS: For the GBD 2016 study, cancer registry data and a vital registration system were used to estimate TCa mortality. Mortality to incidence ratios were used to transform mortality estimates to incidence, and to estimate survival, which was then used to estimate 10-year prevalence. Prevalence was weighted using disability weights to estimate years lived with disability (YLDs). Age-specific mortality and a reference life expectancy were used to estimate years of life lost (YLLs). DALYs are the sum of YLDs and YLLs. RESULTS: Global incidence of TCa showed a 1.80-fold increase from 37 231 (95% uncertainty interval [ UI] 36 116-38 515) in 1990 to 66 833 (95% UI 64 487-69 736) new cases in 2016. The age-standardized incidence rate also increased from 1.5 (95% UI 1.45-1.55) to 1.75 (95% UI 1.69-1.83) cases per 100 000. Deaths from TCa remained stable between 1990 and 2016 [1990: 8394 (95% UI 7980-8904), 2016: 8651 (95% UI 8292-9027)]. The TCa age-standardized death rate decreased between 1990 and 2016, from 0.39 (95% UI 0.37-0.41) to 0.25 (95% UI 0.24-0.26) per 100 000; however, the decreasing trend was not similar in all regions. Global TCa DALYs decreased by 2% and reached 391 816 (95% UI 372 360-412 031) DALYs in 2016. The age-standardized DALY rate also decreased globally between 1990 and 2016 (10.31 [95% UI 9.82-10.84]) per 100 000 in 2016). CONCLUSION: Although the mortality rate for TCa has decreased over recent decades, large disparities still exist in TCa mortality, probably as a result of lack of access to healthcare and oncological treatment. Timely diagnosis of this cancer, by improving general awareness, should be prioritized. In addition, improving access to effective therapies and trained healthcare workforces in developing and under-developed areas could be the next milestones.

Feasibility and Safety of Ultrasonography Guidance and Flank Position during Percutaneous Nephrolithotomy.

PURPOSE: Percutaneous nephrolithotomy is generally performed using fluoroscopy, which is associated with exposure to radiation. Another drawback of fluoroscopic guided percutaneous nephrolithotomy is the prone position, which is not suitable for all patients. In this study we evaluated the feasibility, safety and efficacy of ultrasound guided percutaneous nephrolithotomy with the patient in the flank position. MATERIALS AND METHODS: A total of 603 patients with a mean ± SD age of 50.9 ± 13 years were included in this study from December 2010 to July 2016. Access to the collecting system and tract dilation were performed under ultrasound guidance. Perioperative data on the stone-free rate, operative time, length of stay and complication rates were recorded. RESULTS: Successful access was achieved in all but 1 patient. Mean operative time was 56.6 ± 6.5 minutes. Complete stone clearance was achieved in 529 patients (87.7%) and Clavien-Dindo grade 3 complications were noted in 17 (2.8%). Blood transfusion was necessary in 43 patients (7.1%). However, bleeding was self-limited in all cases and did not require angioembolization. CONCLUSIONS: To our knowledge this is the largest series of ultrasound guided percutaneous nephrolithotomy with the patient in the flank position. Unlike in other studies we used this procedure in all patients irrespective of stone burden, renal anomaly and body habitus. Ultrasound guided percutaneous nephrolithotomy has outcomes comparable to those of conventional percutaneous nephrolithotomy and it is not associated with radiation exposure. Furthermore, anesthesia while in the flank position might be less harmful in some patients, including those with obesity or cardiopulmonary comorbidities.

Applying extender devices in patients with penile dysmorphophobia: assessment of tolerability, efficacy, and impact on erectile function.

INTRODUCTION: Most men seeking penile enhancement techniques have a normal penile size. They are either misinformed or suffer from penile dysmorphophobia and should be discouraged from undergoing invasive procedures. Less invasive techniques including penile extenders are not associated with major complications and may be beneficial from a psychological perspective. AIM: We conducted this study to assess the efficacy and safety of AndroPenis (Andromedical, Madrid, Spain) penile extender. METHODS: Between December 2010 and December 2013, 163 men presented to our institution complaining of small penile length and/or girth. All patients received structured psychosexual counseling. Fifty-four patients were willing to use the AndroPenis penile extender after counseling. Patients with major psychiatric disorders were excluded from enrollment. The patients were instructed to wear the device between 4 and 6 hours per day for 6 months. Penile dimensions including flaccid stretched and erected lengths were measured at baseline and after 1, 3, 6, and 9 months. Erectile function was assessed at baseline and 9 months after treatment using the simplified International Index of Erectile Function (IIEF-5). An institutional nonstandardized questionnaire was used to evaluate patient satisfaction at the end of study. MAIN OUTCOME MEASURES: Penile length and girth enhancement as well as satisfaction rate and improvement in erectile function were assessed during follow-up. RESULTS: At 6-month follow-up, a mean gain of 1.7 ± 0.8, 1.3 ± 0.4, and 1.2 ± 0.4 cm was noted for the flaccid, stretched, and erected penile lengths, respectively (all P values < 0.001). During the off treatment period, there were no significant changes in penile lengths. No effect on penile girth was observed. Patient satisfaction survey revealed modest satisfaction. From 13 patients with mild baseline erectile dysfunction, nine patients reported normal erectile function after 9 months. CONCLUSION: Penile extender as a minimally invasive technique is safe and provides modest benefits and patient satisfaction.

Molecular Characterization of KRAS, BRAF, and EGFR Genes in Cases with Prostatic Adenocarcinoma; Reporting Bioinformatics Description and Recurrent Mutations.

BACKGROUND: Prostate cancer is one of the most common cancers which develops by mutations and/or other genetic alterations in specific genes. Regarding the previous studies in literature predominant mutations take place in KRAS, BRAF, and EGFR genes in special types of cancers. In this research, we attempt to identify the prevalence and significant role of the possible mutations in EGFR exons 18-21, KRAS codon 12, 13, and 61, and BRAF codon 600 mutations in tumoral tissue specimens from patients with prostatic adenocarcinoma. Furthermore, in this research, it has been attempted to investigate the molecular characteristics of these genes in terms of bioinformatic aspects. METHODS: A total of 35 prostatic adenocarcinoma fresh tissue samples, enriched in neoplastic cells, were obtained from the Cancer Institute of Iran. The presence of mutations at codons 12, 13 and 61 of KRAS, codon 600 of BRAF and EGFR exons 18-21 were determined by direct Sanger sequencing. To evaluate the molecular features, structure, and post-translation modification of those genes, a bioinformatics survey was performed using the SWISS-MODEL (http://swissmodel.expasy.org) and NetPhos 2.0 (http://www.cbs.dtu.dk/services/NetPhos/) Server. Also, using bioinformatics software, the phylogeny tree of the mutations was drawn. RESULTS: Mutations of codons 12 and 13 of KRAS were found in 2 of the 35 prostatic adenocarcinomas. Two cases carried homozygous mutations on exon 2 in codon 12 (G12V) and codon 13 (G13D). Also, no mutation was detected at BRAF codon 600 and EGFR exons 18-21 in any of the samples. CONCLUSIONS: Based on the group of patients with prostate adenocarcinoma, our research shows that the mutations in codons 12 and 13 of KRAS are the most common in prostate carcinomas. Noting these results and the molecular pathway of this gene, there is a possible more perceptible role for this gene in the pathogenesis of prostatic carcinoma. However, according to our finding, as in previous studies, the role of BRAF and EGFR gene mutations in prostate adenocarcinoma are less than in the KRAS gene and, therefore, we assume that these common mutations of the KRAS gene can be used as an early determining marker for early diagnosis of prostate adenocarcinoma. In the future, due to the complexity of etiological parameters in prostate cancer development, the case specific tumor molecular identification and treatment for each affected subject are urgently needed.

Prevalence of lymph node metastasis in radical prostatectomy; a retrospective and multicenter study in iran.

Lymph node (LN) metastasis is considered an important prognostic factor in patients with prostate cancer. The aim of this study was to determine the rate of LN metastasis among an Iranian population who underwent radical prostatectomy (RP) with pelvic LN dissection (PLND). In a retrospective review of medical records, 450 RP cases were included and the data on LN metastasis were extracted from surgical pathology reports. Overall, 4.7% of the patients had LN metastasis. The rate of surgical stage T3 (50% vs. 13.5%; P=0.021) and pathological Gleason score ³7 (82.4% vs. 48.8%; P=0.002) was significantly higher among LN-positive patients. All patients with LN metastasis had a serum prostate specific antigen level >4 ng/ml. The diagnosis of prostate cancer is in an acceptable, but not ideal, stage of the disease; this may be due to screening examinations and tests.

Renal synovial sarcoma: Considerations for radical nephrectomy- a case report and literature review.

Synovial sarcoma, a rare soft tissue malignancy typically arising from synovial tissue, primarily manifests in the extremities but it may uncommonly present in other locations such as kidneys. Primary renal synovial sarcoma is an uncommon sarcoma with high mortality and recurrence rates. Here, we present a teenage boy with primary renal synovial sarcoma who was referred to our institution.

Prognostic Value of NLR, PLR, SII, and dNLR in Urothelial Bladder Cancer Following Radical Cystectomy.

BACKGROUND: Inflammation plays a crucial role in tumor development and progression, with inflammatory markers showing promise in predicting cancer prognosis. However, their significance in muscle-invasive bladder cancer (MIBC), especially in the context of neoadjuvant chemotherapy (NAC), remains poorly understood. This study aims to evaluate the prognostic utility of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and derived neutrophil-to-lymphocyte ratio (dNLR) for overall survival (OS) in bladder cancer (BC) patients undergoing radical cystectomy (RC) in the NAC era. PATIENTS AND METHODS: A retrospective review analyzed prospectively-collected data from our institutional BC registry, covering patients with MIBC undergoing RC with curative intent from March 1st, 2016, to December 31st, 2022. Blood samples were collected preoperatively to calculate NLR, PLR, SII, and dNLR. OS was defined from surgery to last follow-up or death. Statistical analyses included ROC curves, Kaplan-Meier Curves, and Cox proportional hazards regression models. RESULTS: A total of 187 patients with median duration follow-up of 14.7 month were included in this study and 50.8% experienced death. NAC was administered in 50.3% of cases. The ideal cut-off for dichotomizing NLR, PLR, SII, and dNLR was 1.76, 104.30, 410.66, and 1.30, respectively. In multivariable analysis each of these biomarkers emerged as an independent prognostic factor for predicting OS. The results showed a correlation between higher NLR, PLR, SII, and dNLR levels and a deterioration in OS. CONCLUSION: Elevated values of these inflammatory markers indicate poorer survival, highlighting their potential as indicators of disease aggressiveness. Identifying patients with elevated markers can help healthcare providers personalize treatment strategies, improving patient outcomes and survival rates.

A case report of a self-inserted foreign body in the urethra/bladder causing urinary calculus formation, and a review of the literature.

Several self-inserted foreign bodies have been reported in the lower genitourinary system. We report a 27-year-old man with suprapubic severe pain, purulent discharge from the urethra, and dribbling. He had a history of psychotic disorders and inserting an ink chamber of a pen into the urethra. Imaging showed hydronephrosis and a large urinary stone in the bladder with no sign of foreign body. During open cystotomy, we found that bladder stone was attached to a plastic tube that was extended into the patient's urethra. In such cases, timely surgery to prevent urinary retention and psychological support are required.

Log Odds of Positive Lymph Nodes (LODDS) as an Independent Predictor of Overall Survival Following Radical Cystectomy in Urothelial Bladder Cancer: Time to Rethink Conventional Node Staging.

BACKGROUND: Radical cystectomy (RC) with lymph node dissection is the mainstay of treatment for patients with muscle-invasive bladder cancer (MIBC) and high risk non-MIBC. The American Joint Committee on Cancer's (AJCC) node staging and lymph node ratio (LNR) systems are used in estimating prognosis; however, they do not directly factor in negative dissected nodes. In this study, we evaluated the log odds of positive lymph nodes (LODDS), a novel measure of nodal involvement, as a predictor of survival. PATIENTS AND METHODS: Eighty-three patients who underwent RC were retrospectively included and their demographic and clinical data were collected. Kaplan-Meier curve and Cox regression were used for survival analyses. RESULTS: Median number of dissected lymph nodes was 13 (range 3-45). ROC curve analysis indicated -0.92 as the optimal LODDS cutoff. LODDS > -0.92 was associated with higher T stage, lymphovascular invasion, and significantly worse overall survival (OS) (mean OS 18.6 vs. 45.1 months, P-value < .001). Furthermore, we evaluated AJCC node staging, LNR, and LODDS in three separate multivariable Cox regression models. Among 3 different measures of nodal disease burden, only LODDS was an independent predictor of OS (HR 2.71, 95% CI 1.28-5.73, P = .009). CONCLUSIONS: Our results show that LODDS is an independent predictor of OS and outperforms AJCC node staging and LNR in forecasting prognosis among patients with urothelial bladder cancer who undergo RC.

Evaluation of IGF2, KRT14, and KRT20 as Urinary Biomarkers in Patients with Bladder Cancer.

Background: Many researchers have tried to identify bladder cancer biomarkers to reduce the need for cystoscopy. The aim of this study was to identify and measure appropriate transcripts in patient urine to develop a non-invasive screening test. Methods: From February 2020 to May 2022, 49 samples were obtained from Velayat Hospital, Qazvin University of Medical Sciences, Qazvin, Iran. Twenty-two samples were obtained from bladder cancer patients and 27 from bladder cancer-free subjects. RNA was extracted from participant samples, quantitative RT-PCR was performed, and TNP plots were used to assess IGF2 (NCBI Gene ID: 3481), KRT14 (NCBI Gene ID: 3861) and KRT20 (NCBI Gene ID: 54474) expression. For UCSC Xena analysis, Dataset ID: TCGA-BLCA was used to compare transitional cell carcinoma (TCC) and normal samples for survival rates. Results: IGF and KRT14 were more greatly expressed in patient urine samples than in those of the normal group. However, KRT20 expression did not significantly differ between the two groups. IGF2 had 45.45 and 88.89% sensitivity and specificity, respectively, for detecting TCC in urine samples while KRT14 had 59 and 88.89% sensitivity and specificity, respectively. Also, these results infer that overexpression of IGF would be prognosticators of poor TCC outcomes. Conclusion: Our study showed that IGF2 and KRT14 are overexpressed in bladder cancer patient urine, and IGF2 could be a potential biomarker for poor prognoses in TCC.

Cardiovascular surgical experiences of IVC tumor and thrombus: Operative strategies Based on 51 consecutive patients.

BACKGROUND: The only beneficial treatment option for the management of inferior vena cava (IVC) tumor thrombus is complete tumor removal. The aim of this study was to report our experience in surgical and clinical outcomes in patients with tumor thrombosis in IVC. METHODS: A retrospective chart review of patients who underwent surgical resection of IVC tumor at our institution over the past 10 years was performed. The patients were identified using a prospectively maintained database. RESULTS: We identified 51 patients, the mean age was 53.4 ± 16.8 years, and 25.4% were female. They were divided into three groups based on tumor thrombosis level. Twenty patients (39.2%) required sternotomy, and cardiopulmonary bypass (CPB) was used in 19 (37.2%) patients, and 2 (3.9%) cases underwent coronary artery bypass graft. The perioperative complications were severe bleeding (3 patients), pulmonary embolism (2 patients), and duodenal perforation (1 patient). Three (5.8%) in-hospital deaths occurred, and all were due to severe abdominal bleeding. After a mean follow-up time of 46.5 ± 42.0 months, 29 (56.9%) patients were alive. The mean survival time was 75.2 ± 8.4 months. In multivariate analysis, higher age (p = 0.033) and male gender (p = 0.033) proved to be independent prognostic factors. CONCLUSIONS: Tumor thrombus extending to the IVC is a rare and challenging event. Although using CPB may be safe and result in long-term survival with acceptable function, excessive bleeding during surgery may limit the use of this method.

Genetic and Epigenetic Evaluation of Human Spermatogonial Stem Cells Isolated by MACS in Different Two and Three-Dimensional Culture Systems.

Objective: Epigenetic and genetic changes have important roles in stem cell achievements. Accordingly, the aim of this
study is the evaluation of the epigenetic and genetic alterations of different culture systems, considering their efficacy in
propagating human spermatogonial stem cells isolated by magnetic-activated cell sorting (MACS).
Materials and Methods: In this experimental study, obstructive azoospermia (OA) patient-derived spermatogonial cells were divided into two groups. The MACS enriched and non-enriched spermatogonial stem cells (SSCs) were cultured in the control and treated groups; co-culture of SSCs with Sertoli cells of men with OA, co-culture of SSCs with healthy Sertoli cells of fertile men, the culture of SSCs on PLA nanofiber and culture of testicular cell suspension. Gene-specific methylation by MSP, expression of pluripotency (NANOG, C-MYC and OCT-4), and germ cells specific genes (Integrin α6, Integrin ß1, PLZF) evaluated. Cultured SSCs from the optimized group were transplanted into the recipient azoospermic mouse.
Results: The use of MACS for the purification of human stem cells was effective at about 69% with the culture of the testicular suspension, being the best culture system. Upon purification, the germ-specific gene expression was significantly higher in testicular cell suspension and treated groups (P≤0.05). During the culture time, gene-specific methylation patterns of the examined genes did not show any changes. Our data from transplantation indicated the homing of the donor-derived cells and the presence of human functional sperm.
Conclusion: Our in vivo and in vitro results confirmed that culture of testicular cell suspension and selection of
spermatogonial cells could be effective ways for purification and enrichment of the functional human spermatogonial cells. The epigenetic patterns showed that the specific methylation of the evaluated genes at this stage remained constant with no alteration throughout the entire culture systems over time.

Association Between Preoperative De Ritis (AST/ALT) Ratio and Oncological Outcomes Following Radical Cystectomy in Patients With Urothelial Bladder Cancer.

BACKGROUND: Radical cystectomy in combination with neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (BC). However, response to treatment varies between patients. Considering the role of hepatic glucose metabolism in urothelial cancer, AST/ALT ratio (De Ritis ratio) has the potential to serve as a prognostic factor for bladder cancer and a predictor for treatment outcome. MATERIALS AND METHODS: We retrospectively analyzed patients who underwent radical cystectomy between March 2016 - March 2019. Patients were classified into 2 groups based on De Ritis ratio (< 1.3 [normal] vs. ≥ 1.3 [high]). Demographics, disease severity, treatment status, and disease outcome (90-day mortality and overall survival [OS]) were compared between 2 groups. RESULTS: A total of 89 patients were included, 62.9% of them having a De Ritis ratio of < 1.3 and 37.1% with a De Ritis ratio of ≥ 1.3. Mean OS was significantly higher in patients with normal De Ritis ratio (40.84 vs. 18.28 months, P < .001), and 90-day mortality rate was lower in these patients (8.9% vs. 36.4%, P = .001). Moreover, De Ritis ratio was the sole independent predictor of OS in multivariable regression analysis. CONCLUSION: De Ritis ratio is an independent prognostic factor in BC patients who underwent radical cystectomy. Furthermore, higher De Ritis ratio is associated with worse OS and a higher 90-day mortality rate after surgery, and therefore, has the potential to serve as a predictor of treatment outcome in BC patients.

Molecular Characteristics of Bladder Tumor: Increased Gene Expression of MAGE-A6 and MAGE-A11 with Decreased MicroRNA-34a and MicroRNA-125b.

Bladder cancer is recognized as one of the top ten most common cancers worldwide. Activation of oncogenes, inactivation of tumor suppressor genes, and dysregulation of androgen signaling pathways are three major pathophysiological causes in the development of bladder tumors. Discovering potential biomarkers is required for the management and immunotherapy of bladder cancer. Melanoma-associated antigen (MAGE)-A6 and MAGE-A11 are two cancer-testis antigens that are potential coregulators of androgen receptors. MicroRNAs, especially miR-34a and miR-125b are two important tumor suppressors that play a critical role in regulating different signaling pathways and inhibiting tumor development. Twenty-nine surgical tissue biopsies were collected from patients with no preoperative chemotherapy or radiotherapy (26 males and, 3 females, mean age±SD: 62.4±13.3 years). Seventeen adjacent uninvolved tissues with no abnormalities upon histological examination were considered normal controls (14 males and, 3 females, mean age±SD: 64.2±7.4 years) . Quantitative PCR was performed to evaluate the gene expression level of MAGE-A6, MAGE-A11, miR-34a, and miR-125b in bladder cancer biopsies. MAGE-A6 and MAGE-A11 expressions were significantly increased in bladder tumors compared with normal tissues. However, the expression levels of miR-34a and miR-125b were significantly downregulated in bladder tumor tissues. Interestingly, the expression level of all these genes was significantly associated with tumor grade, pathological stage (pT), and muscular invasion. MAGE-A6 and MAGE-A11 can be considered potential markers for the diagnosis and immunotherapy of bladder tumors. Furthermore, the modulation of miR-34a and miR-125b gene expression in association with increased MAGE-A6 and MAGE-A11 genes could open a new horizon in the improvement of bladder cancer.

The effect of Melatonin on Improving the benign Prostatic Hyperplasia Urinary Symptoms, a Randomized Clinical Trial.

PURPOSE: to investigate the effect of melatonin along with tamsulosin in improving BPH urinary symptoms. MATERIALS AND METHODS: A total of 108 men with BPH symptoms, age of ≥ 50 years, and International Prostate Symptom Score (IPSS) ≥ 8 entered into the parallel group randomized, double-blind clinical trial with balanced randomization. The treatment group received of 3mg melatonin plus 0.4mg tamsulosin and the control group received placebo plus 0.4mg tamsulosin. Patients and physicians were concealed by sealed and opaque envelopes. Symptoms were assessed at baseline and 1 month after treatment. Finally all scores at the initial and end of the study were compared and analyzed using SPSS software. RESULTS: This study showed that adding melatonin to the classic treatment of BPH patients with tamsulosin could significantly reduce the likelihood of nocturia by 2.39 times (95% CI: 1.07-5.32, OR = 2.39, p = 0.033) and could also reduce the frequency of urination by 2.59 times (95% CI: 1.15-5.84, OR = 2.59, p = 0.021). There was no statistically significant difference between the two groups in IPSS, intermittency, incomplete emptying, straining, urgency, and weak stream. CONCLUSION: Melatonin plus tamsulosin treatment is associated with a significant improvement of nocturia and frequency in patients with benign proststic hyperplasia. However, it is necessary to do more studies.

Diagnostic and Therapeutic Implications of Sortilin Expressed on the Surface of Bladder Carcinoma Cells.

Background & Objective: Cell surface expression of sortilin in different types of cancer signifies it as a therapeutic target for cancer therapy. The aim of this study was to detect sortilin expression in bladder cancer cells using an anti-sortilin monoclonal antibody (mAb) to evaluate sortilin as a target for developing diagnostic and therapeutic agents against bladder carcinoma. Methods: The protein expression of sortilin in bladder cancer tissues and cell lines (5637 and EJ138) was investigated by immunohistochemistry (IHC), immune-cytochemistry (ICC), and flow cytometry. Furthermore, the capability of anti-sortilin mAb in apoptosis induction in bladder cancer cells was evaluated. Results: A high expression level was observed in bladder carcinoma tissues (P≤0.001) and cell lines, using IHC and ICC, respectively. Flow cytometry results showed cell surface expression of 27.5±3% (P≤0.01), 74.4±7.8% (P≤0.001), and 4.2±0.4% of sortilin in EJ138, 5637, and HFFF cells, respectively. In EJ138 anti-sortilin mAb induced apoptosis in 25.2±11.5% (P≤0.05) (early) and 4.5±1.1% (P>0.05) (late) after 6 h incubation, while for 12 h, the values of 11.6±3.8% (P>0.05) and 20.7±4.4% (P≤0.05) were achieved. In 5637 cells, 6 h incubation resulted in 10.2±0.3% (P>0.05) and 6.6±1.4% (P>0.05) apoptosis induction, while these values were 12.1±0.8% (P>0.05) and 27.4±4.5% (P≤0.01) after 12 h. The HFFF cells did not show significant apoptosis. Conclusion: The overexpression of sortilin in bladder tumor cells and its potential in inducing apoptosis via directed targeting with the specific monoclonal antibody may represent this protein as a potential candidate of targeted therapy in bladder carcinoma.