Natural Killer Cell Subsets in Tumor Draining Lymph Nodes of Patients with Bladder Cancer and Their Clinical Implications.

Background: Natural killer (NK) cells are crucial innate components in anti-tumor immunity. However, the clinical impacts and their phenotypes in bladder cancer (BC) remain unclear. Objective: To assess the clinical significance of NK cell subsets in tumor-draining lymph nodes of patients with BC. Methods: In a cross-sectional study, pelvic lymph nodes were obtained from 49 untreated patients with BC. Mononuclear cells were isolated and immunophenotyped using CD3, CD56, CD16, CD27, and CD11b markers. NK cells were then classified based on their expression patterns of CD56/CD16 (conventional) and CD27/CD11b (new). Results: On average, NK cells constituted 2.99±1.44% of the total lymphocytes in the draining lymph node of patients with BC. The CD56dim and regulatory NK subsets (CD27+CD11b+/-) were the predominant old and new NK, respectively. The NK cells significantly increased in patients with at least one involved node (LN+) compared with those with free nodes (LN-; p=0.022). Conversely, CD56dimCD16- subset significantly decreased in higher stages (p=0.032) and in tumors with muscle invasion (p=0.038). Significant variations were also observed in different T-stages (p<0.05). Regarding new classification, the frequency of CD11b+ regulatory NK cells was significantly lower in node-positive patients (p=0.025). Conclusion: These findings emphasize the dynamic nature of NK cell subsets in bladder cancer and their potential relevance in disease progression and management, suggesting potential implications for therapeutic strategies targeting these specific subsets.

Sudden cardiovascular collapse during the TUL procedure: A case series.

Although ureteroscopy is a minimally invasive procedure, there have been reports of some minor and major complications, from self-limited to complicated events such as ureteral avulsion, urosepsis, and even death due to cerebrovascular accidents and deep vein thrombosis. Herein, we aim to report seven patients who presented with cardiovascular collapse during ureteroscopy in a 19-year period from January 2002 to January 2021.

Comparative proteomics analysis in different stages of urothelial bladder cancer for identification of potential biomarkers: highlighted role for antioxidant activity.

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) has a high recurrence rate and muscle-invasive bladder cancer (MIBC) has unfavorable outcomes in urothelial bladder cancer (UBC) patients. Complex UBC-related protein biomarkers for outcome prediction may provide a more efficient management approach with an improved clinical outcome. The aim of this study is to recognize tumor-associated proteins, which are differentially expressed in different stages of UBC patients compared non-cancerous tissues. METHODS: The proteome of tissue samples of 42 UBC patients (NMIBC n = 25 and MIBC n = 17) was subjected to two-dimensional electrophoresis (2-DE) combined with Liquid chromatography-mass spectrometry (LC-MS) system to identify differentially expressed proteins. The intensity of protein spots was quantified and compared with Prodigy SameSpots software. Functional, pathway, and interaction analyses of identified proteins were performed using geneontology (GO), PANTHER, Reactome, Gene MANIA, and STRING databases. RESULTS: Twelve proteins identified by LC-MS showed differential expression (over 1.5-fold, p < 0.05) by LC-MS, including 9 up-regulated in NMIBC and 3 up-regulated in MIBC patients. Proteins involved in the detoxification of reactive oxygen species and cellular responses to oxidative stress showed the most significant changes in UBC patients. Additionally, the most potential functions related to these detected proteins were associated with peroxidase, oxidoreductase, and antioxidant activity. CONCLUSION: We identified several alterations in protein expression involved in canonical pathways which were correlated with the clinical outcomes suggested might be useful as promising biomarkers for early detection, monitoring, and prognosis of UBC.

Penile Girth Enhancement Using Amniotic Membrane in a Rabbit Model: A stereological study.

Objectives: This study aimed to evaluate the efficacy of penile girth enhancement (PGE) using amniotic membrane (AM) as a graft in a rabbit model. Additionally, quantitative histological data of the structure of the penis were obtained by stereological studies. Methods: This study was conducted at the Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. In this study, 20 adult male rabbits of similar age and weight were allocated to two groups: sham surgery and surgery+AM. Both groups underwent surgery in which a longitudinal I-shaped midline incision was made in the tunica albuginea on the dorsal surface of the penis. The surgery+AM group underwent PGE using AM as a graft. The penile length and mid circumference were measured using a vernier caliper before and two months after the surgery. Results: The mean total volume and diameter of the penis significantly increased in the surgery+AM group (P <0.03 and P <0.04, respectively). On stereological evaluation, a significant increase in the mean volumes of the tunica albuginea and corpora cavernosa was observed in the surgery+AM group compared to the sham group (P <0.01 and P <0.03, respectively). Additionally, the mean volume densities of the collagen bundles, muscle fibres, cavernous sinuses, and the total number of fibroblasts and smooth muscle cells increased in the surgery+AM group compared to the sham group (P <0.05 each). No infections, bleeding or other complications were observed. Conclusion: The use of AM as a graft is a method that shows promising results for material use in penile enhancement. Thus, it may be considered for PGE in the future.

The impact of killer cell immunoglobulin-like receptor (KIR) genes and human leukocyte antigen (HLA) class I ligands on predisposition or protection against prostate cancer.

Natural killer (NK) cell development largely depends on killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands. In the current study, we investigated the role of KIR genes, HLA ligands, and KIR-HLA combinations in vulnerability or protection against prostate cancer (PC). To analyze the frequency of 16 KIR genes and 5 HLA ligands, polymerase chain reaction with sequence-specific primers (PCR-SSP) was conducted in 150 PC patients and 200 healthy controls (CNs). KIR2DL5 (p = 0.0346, OR = 0.606, CI = 0.3916-0.9336), KIR2DS5 (p = 0.0227, OR = 0.587, CI = 0.3793-0.9139), HLA-B Bw4Thr80 (p = 0.0401, OR = 0.3552, CI = 0.1466-0.9059), HLA Bw4 (p = 0.0190, OR = 0.4744, CI = 0.2656-0.8521), and T4 gene cluster (including KIR2DS5-2DL5-3DS1-2DS1 genes) (p = 0.0194, OR = 0.5575, CI = 0.3449-0.8938) had a lower frequency in the PC patients compared to the control group. Moreover, a lower frequency of the genotypes contacting activating KIR (aKIR) > inhibitory KIR (iKIR) (p = 0.0298, OR = 0.5291, CI = 0.3056-0.9174) and iKIR + HLA < aKIR + HLA (p = 0.0183, OR = 0.2197, CI = 0.0672-0.7001) in PC patients compared to the CNs implies a protective role for aKIR genes. In the case of KIR-HLA interactions, we detected a significant association between KIR3DS1+ + HLA-A Bw4+ (p = 0.0113, OR = 0.5093, CI = 0.3124-0.8416) and KIR3DL1- + HLA-A Bw4+ (p = 0.0306, OR = 0.1153, CI = 0.0106-0.6537) combinations and resistance to prostate cancer. In contrast, the presence of KIR3DL1 in the absence of HLA-A Bw4 (p = 0.0040, OR = 2.00, CI = 1.264-3.111), HLA Bw4 (p = 0.0296, OR = 2.066, CI = 1.094-3.906), and HLA-Bw4Thr80 (p = 0.0071, OR = 2.505, CI = 1.319-4.703) genes probably predisposes to prostate cancer. Carrying the CxT4 genotype in PC patients was positively associated with lower tumor grades (Gleason score ≤ 6) (p = 0.0331, OR = 3.290, and CI = 1.181-8.395). Altogether, our data suggest a protective role for aKIRs, HLA-B Bw4Thr80, and HLA Bw4 ligands as well as a predisposing role for certain KIR-HLA combinations in prostate cancer. The findings of this study offer new insight into the population's risk assessment for prostate cancer in men. Additionally, predicting immunotherapy response based on KIR-HLA combinations aids in implementing the most effective therapeutic approach in the early stages of the disease.

Expression analysis of hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, and hsa_circ_0006990 in renal cell carcinoma.

Renal cell carcinoma (RCC) is a prevalent heterogeneous kidney cancer. So far, different genes have been reported for RCC development. However, its particular molecular mechanism remains unclear. Circular RNAs (circRNAs), a class of non-coding RNAs, are involved in numerous biological processes in different malignancies such as RCC. This study aims to assess the expression and underlying mechanism of four circRNAs (hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, hsa_circ_0006990) with possible new roles in RCC. In the experimental step, we investigated the expression of these four circRNAs in our RCC samples using quantitative real-time polymerase chain reaction. In the bioinformatics step, the differential expressed mRNAs (DEmRNAs), and miRNAs (DEmiRNAs) were obtained from the GEO datasets using the GEO2R tool. A protein-protein interaction network was constructed using the STRING database, and hub genes were identified by Cytoscape. Molecular pathways associated with hub genes were detected using KEGG pathway enrichment analysis. Then, we utilized the ToppGene database to detect the relationships between DEmiRNAs and hub genes. Furthermore, interactions between circRNAs and DEmiRNAs were predicted by the StarBase and circinteractome databases. Finally, a circRNA-DEmiRNA-hub gene triple network was constructed. Our results revealed that the expression of hsa_circ_0020397, hsa_circ_0005986, and hsa_circ_0006990 was downregulated in RCC tissues. Moreover, these circRNAs had a significantly lower expression in patients with a history of kidney disease. Furthermore, hsa_circ_0003028 and hsa_circ_0006990 showed higher expression in the tumor of participants with Lymphovascular/perineural invasion and oncocytoma type, respectively. Based on bioinformatic results, 15 circRNA-DEmiRNA-hub gene ceRNA regulatory axes were predicted, which included three hub genes, five miRNAs, and four selected circRNAs. In conclusion, the current work is the first to emphasize the expression of the hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, and hsa_circ_0006990 in RCC patients presents a novel perspective on the molecular processes underlying the pathogenic mechanisms of RCC.

Concordance between Gleason score of prostate biopsies and radical prostatectomy specimens and its predictive factors.

OBJECTIVE: The Gleason score is an essential factor for making decisions about prostate cancer management and its prognosis. Thus, we conducted this research to discover the histologic-grading accuracy of needle biopsy specimens, and to identify preoperative clinical and pathological factors that predict upgrading and downgrading from biopsy to radical prostatectomy specimen. PATIENTS AND METHODS: This study was performed on 570 patients who were referred to the medical centers affiliated with Shiraz University of Medical Sciences and underwent radical prostatectomy from 2013 to 2017. Concordance was evaluated between the Gleason score of needle biopsy and radical prostatectomy specimens. Predictors of upgrades and downgrades were assessed in univariate and multivariate logistic regression analyses. RESULTS: Scores were the same in 50% of cases, downgraded in 26%, and upgraded in 24%. The variables predicting a Gleason score upgrade were higher Prostate specific antigen level, larger tumors, and older age. Lower tumor volume, lower Prostate specific antigen, and low maximum percentage of cancer in cores were predictors of downgrading from Gleason score>6 to ⩽6. Also, Body mass index>30, smaller tumor size, and negative lymph nodes were predictors of downgrading from Gleason score>7 to 7. CONCLUSION: The correlation between biopsy and Radical prostatectomy Gleason scores was only 50%. After dividing them into the new grading groups, this coordination increased by only 5.6%. Physicians need to consider possible limitations of the Gleason score of biopsy and factors that can be predictive of upgrading to high-risk prostate cancer before making treatment decisions.

Inflammatory Myofibroblastic Tumor of the Right Kidney Mimicking a Locally Advanced Renal Carcinoma: A Case Report.

An inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with an unclear origin that can arise anywhere on the body. It contains spindle cells (myofibroblasts) with different inflammatory elements. Primary IMT of the kidney is a clinically rare disease and is difficult to differentiate from other renal malignancies. We reported a 49-year-old male who presented with right flank pain in the past year. A computed tomography scan showed a mixed density with slight heterogeneous enhancement mass in the upper pole of the right kidney, two small hypodense nodules invading the liver, and another mass in the lateral aspect of inferior vena cava. The patient underwent right radical nephrectomy and metastasectomy. IMT was confirmed by both postoperative histopathological examination and immunohistochemical assay. The patient recovered well after the operation, and no recurrence or metastasis was noted during the 12-month follow-up.

Prognostic significance of immunoscore related markers in bladder cancer.

BACKGROUND: The significance of total and specific subpopulations of tumor-infiltrating lymphocytes (TILs) in cancer is now well-documented. In the present study, we investigated the relevance of CD3+, CD8 +, CD45RO +, and FOXP3 + TILs to the prognosis and survival of patients with bladder cancer and the disease's clinical-pathological parameters. METHODS: Infiltration of each subset was immunohistochemically evaluated in both stromal and intratumoral regions of tumor tissues from 85 patients with urothelial cell carcinoma of the bladder, with known survival. RESULTS: Our results indicated that intratumoral CD45RO+ lymphocytes were significantly higher in high-grade tumors than in low-grade ones (P = 0.028). The frequencies of intratumoral CD3+ (P = 0.002), CD8 + (P = 0.008), intratumoral (P = 0.002), and stromal (P = 0.017) CD45RO+ lymphocytes were also higher in patients with muscular invasion than those without invasion. The frequencies of intratumoral CD3+ (P = 0.043), CD8+ (P = 0.003), CD45RO+ (P = 0.023), and total CD45RO+ (P = 0.015), showed variation in patients with different T-stage, as well; mostly increased in T2 versus Ta and T1. Comparing patients in different stages revealed an increase in the frequencies of total CD3+ (P = 0.011), intratumoral CD3+ (P = 0.006), total CD8+ (P = 0.012), intratumoral CD8+ (P = 0.009) and stromal CD8+ (P = 0.034), as well as total and stromal CD45RO+ lymphocytes (P = 0.01 and P = 0.034, respectively) in stage II comparing to stage I, while the frequencies of stromal CD3+ (P = 0.077) and CD8+ (P = 0.053) cells tended to be decreased in stage III compared to stage II. CONCLUSIONS: We collectively observed that the frequency of immune cells, especially CD45RO+, CD3+, and CD8+ lymphocytes, were significantly higher in early-progressed tumors. This observation could be explained by continuous and prolonged stimulation of immune cells with tumor antigens during tumor progression or an increase in the recruiting factors, especially in the early stages, to eliminate tumor cells. However, with tumor progression to the late stages, the inhibitory microenvironment provided by tumor cells suppresses or changes the functionality of the effector and memory immune cells to help tumor growth. However, more functional studies with larger sample sizes are needed to reveal the real status of the immune system in patients with bladder cancer.

Retinal Vessel Segmentation, a Review of Classic and Deep Methods.

Retinal illnesses such as diabetic retinopathy (DR) are the main causes of vision loss. In the early recognition of eye diseases, the segmentation of blood vessels in retina images plays an important role. Different symptoms of ocular diseases can be identified by the geometric features of ocular arteries. However, due to the complex construction of the blood vessels and their different thicknesses, segmenting the retina image is a challenging task. There are a number of algorithms that helped the detection of retinal diseases. This paper presents an overview of papers from 2016 to 2022 that discuss machine learning and deep learning methods for automatic vessel segmentation. The methods are divided into two groups: Deep learning-based, and classic methods. Algorithms, classifiers, pre-processing and specific techniques of each group is described, comprehensively. The performances of recent works are compared based on their achieved accuracy in different datasets in inclusive tables. A survey of most popular datasets like DRIVE, STARE, HRF and CHASE_DB1 is also given in this paper. Finally, a list of findings from this review is presented in the conclusion section.

Intrapelvic malignant nerve sheath tumors presenting as acute urinary retention: A case report and literature review.

Malignant nerve sheath tumors (MPNSTs) are rare sarcomas tumors which rarely present as intrapelvic mass and are hard to diagnose clinically. We present a 29-year-old male patient presented with acute urinary retention and was diagnosed with large intrapelvic mass. After complete surgical resection, the histopathology confirmed the diagnosis of low MPNST.

Relationship of Clinical and Ultrasonographic Grading of Varicocele with Semen Analysis Profile and Testicular Volume.

Background: Varicoceles are a major cause of infertility. The purpose of this study was to determine the relationship of the clinical and ultrasonographic grades of varicocele with the semen analysis profile and testicular volume among men undergoing scrotal ultrasonography. Methods: This cross-sectional analytical study involved 109 males undergoing scrotal ultrasonography for various indications in Shiraz, Iran, between January 2019 and January 2020. Varicoceles were graded with color Doppler ultrasonography (CDU) by an expert radiologist (Sarteschi's criteria) before an experienced urologist determined the clinical grade (Dubin and Amelar criteria) and requested further investigations. Next, the demographics, reasons for referral, testicular volumes, and semen analysis profiles across the different clinical/ultrasonographic grades were compared. Key statistical measures included Cohen's kappa coefficient, the Mann-Whitney and Kruskal-Wallis tests, and Spearman correlation. Data were analyzed using SPSS v. 21 with p-values <0.05 indicating statistical significance. Results: Ultrasonographic grades 1 and 2 provided the highest correlation with subclinical cases, while ultrasonographic grades 3, 4, and 5 corresponded with clinical grades 1, 2, and 3, respectively. Further comparisons were made between subclinical and clinical cases, which were similar in terms of reason for referral, total testicular volume, testicular volume differential, and semen analysis profile. Notably, total testicular volumes below 30 ml were associated with oligoasthenoteratospermia. Conclusion: The present study showed a relatively high correlation between varicocele grading based on clinical evaluation and CDU. However, the grades were similar in testicular volume parameters and semen analysis indices. Hence, decision-making should be guided by the infertility history, testicular atrophy, and abnormal semen analysis.

The effect of retroperitonealization of ureteroileal anastomosis on perioperative complications of radical cystectomy with ileal conduit urinary diversion.

BACKGROUND: Radical cystectomy (RC) has been considered the standard management of muscle-invasive bladder cancer. Despite the improvements in surgical techniques and perioperative care, RC is still associated with high perioperative morbidity and mortality. OBJECTIVE: This study aims to evaluate the effect of retroperitonealization of ureteroileal anastomosis on perioperative complications of RC with ileal conduit urinary diversion. PATIENTS AND METHODS: This is a retrospective cohort study. We reviewed medical charts of 876 patients who underwent RC between 2016 and 2021. Based on the inclusion and exclusion criteria, 748 patients entered the study. According to retroperitonealization of the ureteroileal anastomosis, patients were categorized into two groups (group I without retroperitonealization of the ureteroileal anastomosis and group II with retroperitonealization of the ureteroileal anastomosis). Patients' characteristics and occurrences of any complications and high-grade complications were compared between these groups. RESULTS: In comparing the complication categories between the two groups, fewer patients in group II suffered from gastrointestinal, urinary, and cardiac events (p values were 0.018, 0.021, and 0.013, respectively). Moreover, fewer patients in group II experienced any complications and high-grade complications (p values were < 0.001 and < 0.001, respectively). The length of hospital stay was also significantly shorter in group II (p < 0.001). CONCLUSIONS: RC is associated with comparatively high perioperative morbidity and mortality. In the present study, 61% of the patients experienced at least one complication postoperatively. Retroperitonealization of the ureterointestinal anastomosis may decrease perioperative adverse events of RC with ileal conduit urinary diversion.

Primary Rhabdomyosarcoma of Kidney with Local Recurrence and Liver Metastasis in Adults: A Case Report.

Primary rhabdomyosarcoma (RMS) of the kidney in an adult is rare, with only a few cases published in the literature. It is a mesenchymal tumor associated with an aggressive and rapid clinical progression course. We present a case of primary renal RMS in a 58-year-old female who presented with intermittent abdominal pain in the past year. The computed tomography (CT) scan revealed a 20×25×8 cm heterogeneous solid mass in the middle pole extended to the lower pole of the right kidney. Therefore, the patient underwent a right radical nephroureterectomy. Histopathology examination and immunohistochemistry studies confirmed the diagnosis of RMS with pleomorphic components. Postoperatively, the patient was discharged without any complications and was referred to an oncologist for chemotherapy. However, a follow-up CT scan in 2 months showed widespread liver metastasis and local recurrence. The patient received Gemcitabine and Docetaxel, but her condition worsened, and she passed away 5 months later. Primary renal RMS is rare in adults. In addition, liver metastasis is uncommon and poorly understood. Hence, we describe the clinicopathologic characteristics, including clinical follow-up of our case, focusing on the disease progression, treatment, and outcome.

Elevated IL-37 Serum Levels in Patients with Transitional Cell Carcinoma of Bladder.

BACKGROUND: Interleukin-37 (IL-37) is a recently described cytokine that emerges as a natural inhibitor of inflammatory and immune responses. However, IL-37 has not yet been investigated in bladder cancer, and its biological role is unknown. OBJECTIVE: The purpose of this study was to investigate IL-37 serum levels in patients with bladder cancer and determine whether they were linked to the patients' pathological characteristics. METHODS: IL-37 serum levels were measured using a commercial ELISA kit in 60 patients with transitional cell carcinoma (TCC) of the bladder (mean age: 64.55±12.93) and 50 healthy controls (mean age: 62.94±12.69). Non-parametric tests were used for statistical comparisons, and the Cohen's d effect size was calculated to evaluate the practical and clinical significance of the results. RESULTS: Our findings indicated an increasing trend in IL-37 serum levels in patients with TCC (42.77±3.36 pg/ml) in comparison with controls (40.51±7.32 pg/ml, p=0.09). However, IL-37 serum levels were found to be significantly higher in male patients (44.72±3.81 pg/ml) and patients aged ≥70 (46.92±6.77 pg/ml) in comparison with male controls (29.96±3.30 pg/ml, p=0.026) and controls aged ≥70 (23.62±4.43 pg/ml, p=0.009). In comparison to similar controls, Cohen's d effect size for patients aged ≥70 years was found to be 0.90. CONCLUSION: The findings reveal a higher serum level of IL-37 in patients with TCC, which might be clinically associated with immunosuppression and tumor growth. However, this is a preliminary study, and more research on the biological role of IL-37 and its potential therapeutic effects in bladder cancer is required.

Upregulation of Cytotoxic T-Lymphocyte-Associated Protein 4 and Forkhead Box P3 Transcripts in Peripheral Blood of Patients with Bladder Cancer.

Background: Regulatory T cells (Tregs) play a key role in the progression of tumors. These cells express forkhead box P3 (FOXP3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), which are the potential targets for cancer immunotherapy. The present study aimed to evaluate FOXP3 and CTLA4 transcripts in patients with bladder cancer (BC) compared with healthy individuals. Methods: Transcripts of CTLA4 and FOXP3 genes in the peripheral blood mononuclear cells (PBMCs) of 50 patients with histologically confirmed BC and 50 healthy individuals were assessed at the Institute for Cancer Research, Shiraz University of Medical Sciences (Shiraz, Iran) during 2014-2016. RNA was extracted from PBMCs, then cDNA was synthesized and subjected to quantitative real-time PCR (qRT-PCR) using appropriate primers. Statistical analysis was performed using SPSS software (version 21.0). Results: Significantly higher amounts of CTLA4 and FOXP3 gene transcripts were found in the peripheral blood of BC patients compared with healthy individuals. The expression of both genes was significantly higher in patients with non-invasive and grade I/II BC. The median of CTLA4 and FOXP3 transcript expressions was 3.74 and 5.39, respectively, in non-invasive BC patients, which was significant compared with the control group (P=0.0016 and P=0.009, respectively). The median of target gene mRNA expression in grade I/II BC patients was 2.9 for CTLA4 and 6.61 for FOXP3, which was significant compared with the controls (P=0.013 and P=0.0037, respectively). Conclusion: This study highlights the functional activity of Tregs in early stages of bladder cancer and showed the importance of CTLA4 and FOXP3, when it comes to screening BC.

GM-CSF-producing lymphocytes in tumor-draining lymph nodes of patients with bladder cancer.

Bladder cancer (BC) is the tenth common cancer worldwide. Despite progress in treatment and the use of chemotherapoeutic drugs, the survival rate of BC patients is still low. Manipulation of the immune system was recently introduced as an interesting alternative treatment for this immunogenic cancer with fewer side effects. Accordingly, in the present study, we assessed the frequency of GM-CSF-producing lymphocytes in tumor-draining lymph nodes (TDLNs) of BC patients and evaluated their relationship with clinicopathological factors and survival rate. Fifty-four patients with BC who had received no treatment were recruited. Mononuclear cells were isolated from fresh homogenized lymph nodes by centrifugation over Ficoll-Hypaque, activated and subsequently analyzed by flow cytometry for the cell surface expression of CD4 and CD8 and the intracellular production of GM-CSF. Flow cytometric analysis revealed that 4.97 ± 2.7% of lymphocytes in TDLNs of patients with BC produced GM-CSF. The mean frequency of GM-CSF-producing cells was 5.5% among CD4+ lymphocytes and 11.7% in the CD8+ population. Elevated frequencies of GM-CSF-producing lymphocytes, as well as a higher production of GM-CSF by CD4+ lymphocytes was observed in the patients with tumor-free lymph nodes, as compared to those with at least one tumor-infiltrated lymph node (p < 0.05). On the other hand, the lower frequency of GM-CSF-producing CD4+ lymphocytes (ThGM) was associated with improved overall, but not one-year, survival. No other significant relationship was observed between clinicopathological parameters and the frequency of GM-CSF-producing subsets. Collectively, our findings suggest a protective role for GM-CSF in the early stages of BC; however, the unfavorable association of ThGM frequency with survival rate may imply a more complex role for this cytokine in BC.

The Effect of Daily Intake of Selenium, Vitamin E and Folic Acid on Sperm Parameters in Males with Idiopathic Infertility: A Single-Blind Randomized Controlled Clinical Trial.

BACKGROUND: Male infertility may originate from a wide spectrum of conditions while in 30-40 percent of cases, no significant reason can be identified. Thereby, it is recognized as male idiopathic infertility. This study was undertaken to investigate the effect of daily intake of selenium, vitamin E and folic acid on sperm parameters in males with idiopathic infertility. MATERIALS AND METHODS: Seventy infertile men were selected to participate in this single-blind, randomized controlled clinical trial using convenience sampling. They were equally divided into two groups via permuted block randomization method. The intervention group received selenium tablet (200 µg per day, oral), vitamin E capsule (400 IU per day, oral) and folic acid tablet (5 mg per day, oral).The placebo group received matching placebo for three months. Semen volume, total sperm motility, sperm concentration, progressive sperm motility, normal sperm morphology, sperm motility index (SMI) and functional sperm concentration (FSC) were assessed by sperm quality analyzer-v (SQAV) before and after the intervention. Paired t test, and independent t test were used to compare the results within and between the groups, respectively. The IBM SPSS V.16.005 was used for data analysis. A P<0.05 was considered statistically significant. RESULTS: After three months, according to within-group analysis, a significant difference was found in mean SMI (P=0.007) and FSC (P=0.001) in the intervention group. According to between-group analysis, no significant difference was found in mean semen volume (P=0.610), sperm concentration (P=0.126), total sperm motility (P=0.765), progressive sperm motility (P=0.767), normal sperm morph (P=0.403), SMI (P=0.556) or FSC (P=0.706) between the groups. CONCLUSION: Consumption of selenium, vitamin E and folic acid in infertile men with asthenozoospermia was not effective (Registration number: IRCT2017012432153N1).

An Investigation of the Pathology Report of Bladder Cancer Patients with Radical Cystectomy in Southern Iran, 2013-2018: A Cross-Sectional Study.

Background: The oncological outcomes of bladder cancer are directly associated with disease pathology and surgical technique. Therefore, we investigated the pathologic factors of radical cystectomy (RC) specimens. Methods: In this retrospective study, 365 patients who underwent RC between March 2013 to March 2018 in hospitals affiliated to Shiraz University were enrolled. The patients' clinicopathological parameters, such as tumor type, tumor grade, carcinoma in situ, lymph node (LN) involvement, lymphovascular invasion (LVI), perineural invasion (PNI), and age, were recorded from their pathology reports. For comparison of variables, an independent t test was used. P < 0.05 was regarded as significant. The statistical software SPSS version 22 was used to examine the data. Results: The participants' mean age was 64.52 ± 11.54 years, and 320 (87.7%) patients were men and 45 (12.3%) were women. The mean dissected LN was 9.69 ± 8.70 nodes and 1.06 ±3.49 of the dissected LNs were involved by tumor. PNI and perivesical invasion were presented in 148 (40.5%) and 96 (26.3%) patients, respectively. Ureteral, urethral, and prostate involvements were seen in 23 (6.3%), 50 (13.7%), and 66 (18.1%) patients. Most patients had pathologic tumor stage 2 (36.4%). Factors such as LVI, PNI, perivesical invasion, and prostate involvement, were strongly correlated with positive LN (P ≤ 0.05). Conclusion: The examination of the RC specimen is critical for patient care, outcome, and justification of adjuvant therapy. Factors such as LVI, perineural invasion, perivesical invasion, and prostate involvement were strongly correlated with positive LN.

Establishment of a bladder cancer cell line expressing both mesenchymal and epithelial lineage-associated markers.

Several experimental models including patient biopsies, animal models, and cell lines have been recommended to study the mechanism of bladder cancer development. After several passages in culture, cell lines lose some original features, and no longer resemble the cells of their original tumor. This makes it necessary to establish various cell lines. In an attempt to establish a new cell line for bladder cancer, JAM-ICR (RRID: CVCL_A9QB) was derived from a 64-year-old man diagnosed with a high-grade tumor. This cell line was characterized in multiple experiments involving morphological studies, immunophenotyping (by immunohistochemistry and flow cytometry), karyotyping, short tandem repeat analysis, colony-forming assays, migration and invasion assays, and chemosensitivity to anti-cancer drugs. JAM-ICR cells are pale with an irregular polygonal shape, and show some similarities to mesenchymal stem cells but with a wider shape and shorter arms. Phenotypic assessment demonstrated the simultaneous expression of mesenchymal-(vimentin, desmin, CD29, CD90, and CD106) and epithelial lineage (pan-cytokeratin) markers, which supports a phenotype similar to epithelial-mesenchymal transition for this cell line. JAM-ICR displayed high metastatic potential and stem-like properties, i.e., self-renewal, colony forming, and the coexpression of TRA-1 with CD44 and CD166. Furthermore, this cell line was significantly more resistant to doxorubicin in comparison to the 5637 cell line. These features make JAM-ICR a new bladder cancer cell line with metastatic potential and stem-like properties, which may be potentially useful as a model to elucidate the molecular and cellular mechanisms of bladder cancer pathogenesis or evaluate new drugs.