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.

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.

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.

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.

FruHis significantly increases the anti-benign prostatic hyperplasia effect of lycopene: A double-blinded randomized controlled clinical trial.

Background: For decades, lycopene was considered the main compound of tomato protecting benign prostatic hyperplasia (BPH). Recent animal studies suggest that a newly discovered compound "FruHis" boosts lycopene for its action. This study aimed to determine whether FruHis enhances the action of lycopene to modify the laboratory parameters and clinical outcomes of patients with BPH. Materials and methods: Current study was conducted on 52 BPH patients, who were randomly assigned into four groups of treatments: lycopene plus FruHis (n = 11, 25 mg/day lycopene and 10 mg/day FruHis), lycopene (n = 12, 25 mg/day lycopene), FruHis (n = 12, 10 mg/day FruHis), and placebo (n = 13). Patients received these supplements for 8 weeks. Results: FruHis intake strengthened the reducing effects of lycopene on insulin-like growth factor-1 (IGF-1) (-54.47 ± 28.36 ng/mL in the lycopene + FruHis group vs. -30.24 ± 46.69 ng/mL in the lycopene group), total prostate-specific antigen (TPSA) (-1.49 ± 4.78 ng/mL in the lycopene + FruHis group vs. -0.64 ± 2.02 ng/mL in the lycopene group), and symptom score (-4.45 ± 4.03 in the lycopene + FruHis group vs. -1.66 ± 5.41 in the lycopene group) in BPH patients. Such findings were also seen for body mass index (BMI) and waist circumference (WC). However, except for IGF-1, these reductions were not statistically significant compared with the placebo, and the intakes of lycopene and FruHis alone, however, were clinically important. Such effects of lycopene and FruHis were not seen for free PSA (FPSA) and FPSA/TPSA ratio. Conclusion: Despite the non-significant effects of lycopene and FruHis, it seems that FruHis intake strengthens the beneficial effects of lycopene on IGF-1, TPSA, and symptom scores among BPH patients. Clinical trial registration: [www.irct.ir], identifier [IRCT20190522043669N1].

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.

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.

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.

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.

Opium use and risk of bladder cancer: a multi-centre case-referent study in Iran.

BACKGROUND: Bladder cancer (BC) is the 10th most common type of cancer worldwide and the fourth most common type of cancer in Iran. Opium use is considered as one of the risk factors for BC. We aim to assess the association between various parameters of opium use, which in Iran is mainly ingested or smoked in various forms, and the risk of BC. METHOD: In this multi-centre case-referent study in Iran, 717 BC cases and 3477 referents were recruited to the study from May 2017 until July 2020. Detailed histories of opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure adjusted odds ratio (OR) and 95% confidence intervals (CI). The ORs were adjusted for age, gender, place of residence and pack-years of cigarette smoking. RESULTS: Regular opium consumption was associated with an increased risk of BC (OR 3.5, 95% CI: 2.8, 4.3) compared with subjects who never used opium. Compared with continuous users, the risk decreased to one-third for those who stopped opium more than 10 years ago. The adjusted OR for those who used both crude opium (teriak) and opium juice was 7.4 (95% CI: 4.1, 13.3). There was a joint effect of opium and tobacco (OR for users of both opium and tobacco 7.7, 95% CI: 6.0, 9.7). CONCLUSIONS: Regular opium use is associated with an approximately 4-fold risk for BC. The OR decreases along with the increasing time since stopping opium use.

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.

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.

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.

A possible protective role for Bacillus Calmette-Guérin therapy in urinary bladder cancer in the era of COVID-19: a brief report.

Given the systemic immunogenic effects of Bacillus Calmette-Guérin (BCG) therapy in patients with bladder cancer and its non-specific immunogenic effects in viral respiratory diseases, we aimed to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in bladder cancer patients with a history of BCG therapy. In the present study, all bladder cancer survivors with a history of BCG therapy were identified and included in the study according to the data recovered from the UORC (Uro-Oncology Research Center) registry database. These patients were followed up in terms of acquiring coronavirus disease 2019 (COVID-19). Among the studied patients, 102 eligible bladder cancer patients with a history of BCG therapy entered the study. The males constituted the majority of the patients (86.3%), and more than half of the study population (55.9%) were above 65 years old. Among the understudy patients, 12.7% were confirmed for COVID-19. The study results did not show a statistically significant association between the time and number of BCG therapy courses and SARS-CoV-2 infection. Although no statistically significant association was observed between receiving BCG therapy and developing COVID-19, the infection rate in patients who had recently received BCG therapy was lower than those who had received therapy more than a year ago.

The Association of Cell Surface Fibromodulin Expression and Bladder Carcinoma.

BACKGROUND: Fibromodulin (FMOD) is a secretory protein which is considered a major component of extracellular matrix. Its dysregulation in different types of cancer implies it as a promising target for cancer therapy. Within the scope of its rather wide expression in different tumors, we studied expression of FMOD and effect of anti-FMOD antibody in bladder cancer cells in order to identify new target for diagnostic and therapeutic interventions. We report here for the first time the expression of FMOD in bladder cancer cell lines in comparison to the normal cell line and tissues. METHODS: A peptide-based produced anti-FMOD murine monoclonal antibody (mAb) (clone 2C2-A1) was applied for evaluation of FMOD expression in bladder cancer and normal tissues by immunohistochemistry (IHC) staining. Furthermore, the expression of FMOD was examined in human bladder cell lines, 5637 and EJ138, as well as a non-cancerous human cell line, human fetal foreskin fibroblast (HFFF), by immunocytochemistry (ICC) and flow cytometry. The apoptosis induction of anti-FMOD mAb was also evaluated in bladder cancer cells. RESULTS: IHC and ICC analyses revealed that the qualitative expression of FMOD in bladder cancer tissues and cell lines is higher than in normal tissues and cell lines. Flow cytometry analyses revealed that 2C2-A1 mAb could recognize FMOD expression in 84.05 ± 1.85%, 46.1 ± .4% , and 2.56 ± 1.26% of 5637, EJ138, and HFFF cells, respectively. An effective apoptosis induction was detected in 5637 and EJ138 cells with no significant effect on HFFF cell. CONCLUSION: To our knowledge, this is for the first time reporting surface expression of FMOD in bladder cancer. This significant surface expression of FMOD in bladder cancer with no expression in normal bladder tissues and the capacity of inducing apoptosis through directed targeting of FMOD with specific monoclonal antibody might candidates FMOD as a diagnostic marker as well as a potential immunotargeting with monoclonal antibody.

Primary squamous cell carcinoma of renal parenchyma: Case report and review of literature.

Primary squamous cell carcinoma (SCC) of renal parenchyma is very rare and until now only a few cases have been reported. We report a unique SCC case in terms of aggressive nature and metastatic pattern. Renal rubber consistency and pasty keratin secretions were important findings in our patient. The patient underwent radical nephrectomy and lymphadenectomy and received 4 cycles of chemotherapy with cisplatin and gemcitabine. Eight month later, she succumbed the disease after developing ovary metastasis and not responding to chemotherapy. Also, our study showed that SCC may be present in pyelonephritic kidneys without a specific radiologic finding.

The Potential of T Cell Immunoglobulin and Mucin-Domain Containing-3 (Tim-3) in Designing Novel Immunotherapy for Bladder Cancer.

Targeting inhibitory receptors on T cells in the tumor sites can promote effective anti-tumor immunity in bladder cancer. Unfortunately, the main dilemma is that a large number of patients remain refractory to CTLA-4, PD-1, and PD-L1 blockade therapies. T-cell immunoglobulin and mucin domain 3 (Tim-3) is an inhibitory receptor expressed on T cells and innate immune cells. Both in vivo and in vitro data from patients with advanced cancers support the role of Tim-3 inhibition in satisfactory anti-tumor immunity. In bladder cancer, the expression level of Tim-3 significantly increases with advanced pathological grade and T stage. Therefore, rationality implies that designing novel monoclonal antibodies reactive with Tim-3 alone or in combination with other checkpoint inhibitors may indicate a favorable response in bladder cancer. Here, we aimed to investigate the possibility of targeting Tim-3 as a novel anti-cancer treatment for bladder cancer.

The Epigenetic Assessment of Human Spermatogenic Cells Derived from Obstructive Azoospermic Patients in Different Culture Systems.

PURPOSE: Generating functional gametes for patients with male infertility is of great interest. We investigated different cultural systems for proliferation of SSCs derived from obstructive azoospermic patients. MATERIALS AND METHODS: Testicular cells were obtained from men with obstructive azoospermia. After enzymatic digestion process, cells were assigned to various groups: culture of SSCs in the dish without cover (control group), co-culture of SSCs with infertile Sertoli cells (I), co-culture of SSCs with fertile Sertoli cells (II), culture of SSCs on nanofiber (covered with laminin) (III), culture of testicular cell suspension (IV). Then cells were cultured and colony formation, gene-specific methylation (by MSP), quantitative genes expression of pluripotency (Nanog, C-Myc, Oct-4) and specific germ cell (Integrin α6, Integrin ß1, PLZF) genes were evaluated in five different culture systems. RESULTS: Our findings indicate a significant increase in the number and diameter of colonies in IV group in compare to control group and other groups. Expression of germ specific genes in IV group were significantly increased (P ≤ 0.05) and levels of expression of pluripotency genes were significantly decreased in this group (P ≤ 0.05) compared with other groups. Gene-specific pattern of methylation of examined genes showed no changes in culture systems during the culture era. CONCLUSION: A microenvironment capable of controlling the proliferation of cell colonies can be restored by testicular cell suspension.