Human cytomegalovirus infection in Iranian glioma patients correlates with aging and tumor aggressiveness.

Human cytomegalovirus (HCMV), as a ubiquitous and opportunistic virus, is a matter for consideration in broad-spectrum diseases, specifically in immunocompromised individuals. In recent decades, many studies that have evaluated the role of HCMV in inflammation and malignancies, especially in high-grade gliomas, have reported inconsistent results. Thus, this study was conducted to analyze 97 primary gliomas for human CMV UL83 gene and protein through TaqMan real-time polymerase chain reaction and immunohistochemistry, respectively. The results were positive for the UL83 gene and pp65 protein in 71% and 24% of samples, respectively. The frequency of HCMV was significantly higher in glioblastomas than other glioma grades (P < .01 and P < .05 for the UL83 gene and protein, respectively). In addition, the association between the prevalence of HCMV and aging strengthened the virus reactivation hypothesis in gliomas. In conclusion, a high frequency of HCMV infection was found in gliomas that correlated with tumor aggressiveness and age. This study recommends a thorough investigation to determine HCMV infection in gliomas to improve the existing knowledge of its role in glial tumors, its prognostic value, and possible efficient antiviral target therapy.

Bone morphogenetic protein-7 incorporated polycaprolactone scaffold has a great potential to improve survival and proliferation rate of the human embryonic kidney cells.

Renal failures treatment has been faced with several problems during the last decades. Kidney tissue engineering has been created many hopes to improve treatment procedures with scaffold fabrication that can modulate kidney cells/stem cells migration to the lesion site and increase the survival of these cells at that site with imitating the role of the kidney extracellular matrix. In this study, bone morphogenetic protein-7 (BMP7) as a vital factor for kidney development and regeneration was incorporated in the polycaprolactone (PCL) nanofibers and after morphological, mechanical, and biocompatible characterization, proliferation, and survival of the human embryonic kidney cells (HEK) were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and gene expression while cultured on scaffolds. Mechanical properties of the PCL nanofibers modulated after combining with BMP7 and hydration degree, protein adsorption and cell adhesion were enhanced in PCL-BMP7 compared to the pure PCL. Proliferation rate and growth increased significantly in HEK cells cultured on PCL-BMP7 when compared with that of PCL and tissue culture plate, whereas these data were also confirmed via significant decrease in apoptotic genes expression level in HEK cell cultured on PCL-BMP7. According to the results, PCL-BMP7 demonstrated positive effects on the survival and proliferation rate of the kidney cells and showed has also a great potential to use as a bioimplant for kidney tissue engineering applications.

N-acetylcysteine decreases urinary level of neutrophil gelatinase-associated lipocalin in deceased-donor renal transplant recipients: a randomized clinical trial.

CONTEXT: Acute kidney injury (AKI) is a common complication after kidney transplantation (KT), especially in recipients from deceased donors. Urinary neutrophil gelatinase-associated lipocalin (u-NGAL) is an early and sensitive marker of AKI after transplantation. OBJECTIVES: We assessed the renoprotective effect of N-acetylcysteine (NAC) on u-NGAL levels as an early prognostic marker of graft function immediately after transplantation. MATERIALS AND METHODS: A double-blind, randomized, placebo-controlled trial was conducted on 70 deceased-donor KT recipients ( www.irct.ir , trial registration number: IRCT2014090214693N4). Patients received 600 mg oral NAC or placebo twice daily from day 0 to 5 and urine samples were taken before, and on the first and fifth days after transplantation. U-NGAL and early graft function were compared between the two groups. RESULTS: NAC significantly reduced u-NGAL levels compared to placebo (p value = 0.02), while improvement in early graft function with NAC did not reach statistical significance. CONCLUSIONS: This study showed that NAC administration in deceased-donor KT recipients can reduce tubular kidney injury, evidenced by u-NGAL measurements. Improvement in early graft function needs a larger sample size to reach a statistical conclusion.

Prevalence of virulence determinants and antibiotic resistance patterns of Enterococcus faecalis strains in patients with community-acquired urinary tract infections in Iran.

The aim of this study was to characterize virulence factors and antibiotic resistance patterns in E. faecalis strains obtained from community-acquired urinary tract infections. A total of 70 E. faecalis isolates from Labbafinejad Hospital in Tehran were collected. Antibiotic resistance and virulence determinants were examined by phenotypic and molecular methods. Among 70 E. faecalis isolates, efba (97.1%), ace (95.7%), and gelE (94.3%) were the most prevalent virulence genes. The most common antibiotic resistance pattern was tetracycline (88.6%) and minocycline (87.1%). Multi-drug resistant phenotype was detected among 10% of them. Our results showed capability of E. faecalis strains for infection of the urinary tract in community. Involvement of virulence determinants in the pathogenesis of community acquired E. faecalis strains was proposed due to their high prevalence rates. Food producing animals were proposed as their environmental reservoirs, due to dominance of tetracycline resistance phenotype among them.

1 H NMR-based metabolomics study for identifying urinary biomarkers and perturbed metabolic pathways associated with severity of IgA nephropathy: a pilot study.

The severity of IgA nephropathy (IgAN), the most common primary glomerulonephritis, is judged on the basis of histologic and clinical features. A limited number of studies have considered molecular signature of IgAN for this issue, and no reliable biomarkers have been presented non-invasively for use in patient evaluations. This study aims to identify metabolite markers excreted in the urine and impaired pathways that are associated with a known marker of severity (proteinuria) to predict mild and severe stages of IgAN. Urine samples were analysed using nuclear magnetic resonance from biopsy-proven IgAN patients at mild and severe stages. Multivariate statistical analysis and pathway analysis were performed. The most changed metabolites were acetoacetate, hypotaurine, homocysteine, L-kynurenine and phenylalanine. Nine metabolites were positively correlated with proteinuria, including mesaconic acid, trans-cinnamic acid, fumaric acid, 5-thymidylic acid, anthranilic acid, indole, deoxyguanosine triphosphate, 13-cis-retinoic acid and nicotinamide riboside, while three metabolites were negatively correlated with proteinuria including acetoacetate, hypotaurine and hexanal. 'Phenylalanine metabolism' was the most significant pathway which was impaired in severe stage in comparison to mild stage of IgAN. This study indicates that nuclear magnetic resonance is a versatile technique that is capable of detecting metabolite biomarkers in combination with advanced multivariate statistical analysis. Copyright © 2017 John Wiley & Sons, Ltd.

1 H NMR-based metabolomics exploring urinary biomarkers correlated with proteinuria in focal segmental glomerulosclerosis: a pilot study.

Focal segmental glomerulosclerosis (FSGS) is a common glomerulonephritis, and its rates of occurrence are increasing worldwide. Proteinuria is a clinical defining feature of FSGS which correlates with the severity of podocyte injury in patients with nephrotic-range protein excretion. Metabolite biomarkers corresponding with the level of proteinuria could be considered as non-invasive complementary prognostic factors to proteinuria. The urine samples of 15 patients (n = 6 women and n = 9 men) with biopsy-proven FSGS were collected and subjected to nuclear magnetic resonance (NMR) analysis for metabolite profiling. Multivariate statistical analyses, including principal component analysis and orthogonal projection to latent structure discriminant analysis, were applied to construct a predictive model based on patients with proteinuria >3000 mg/day and <3000 mg/day. In addition, random forest was performed to predict differential metabolites, and pathway analysis was performed to find the defective pathways responsible for proteinuria. Ten metabolites, significant in both statistical methods (orthogonal projection to latent structure discriminant analysis and random forest), were considered as prognostic biomarkers for FSGS: citrulline, dimethylamine, proline, acetoacetate, alpha-ketoisovaleric acid, valine, isobutyrate, D-Palmitylcarnitine, histidine, and N-methylnicotinamide. Pathway analysis revealed impairment of the branched-chain amino acid degradation pathways in patients with massive proteinuria. This study shows that metabolomics can reveal the molecular changes corresponding with disease progression in patients with FSGS and provide a new insight for pathogenic pathways. Copyright © 2016 John Wiley & Sons, Ltd.

Urinary lithogenic risk profile in recurrent stone formers with hyperoxaluria: a randomized controlled trial comparing DASH (Dietary Approaches to Stop Hypertension)-style and low-oxalate diets.

BACKGROUND: Patients with nephrolithiasis and hyperoxaluria generally are advised to follow a low-oxalate diet. However, most people do not eat isolated nutrients, but meals consisting of a variety of foods with complex combinations of nutrients. A more rational approach to nephrolithiasis prevention would be to base dietary advice on the cumulative effects of foods and different dietary patterns rather than single nutrients. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: Recurrent stone formers with hyperoxaluria (urine oxalate > 40 mg/d). INTERVENTION: The intervention group was asked to follow a calorie-controlled Dietary Approaches to Stop Hypertension (DASH)-style diet (a diet high in fruit, vegetables, whole grains, and low-fat dairy products and low in saturated fat, total fat, cholesterol, refined grains, sweets, and meat), whereas the control group was prescribed a low-oxalate diet. Study length was 8 weeks. OUTCOMES: Primary: change in urinary calcium oxalate supersaturation. SECONDARY: Changes in 24-hour urinary composition. RESULTS: 57 participants were randomly assigned (DASH group, 29; low-oxalate group, 28). 41 participants completed the trial (DASH group, 21; low-oxalate group, 20). As-treated analysis showed a trend for urinary oxalate excretion to increase in the DASH versus the low-oxalate group (point estimate of difference, 9.0mg/d; 95% CI, -1.1 to 19.1mg/d; P=0.08). However, there was a trend for calcium oxalate supersaturation to decrease in the DASH versus the low-oxalate group (point estimate of difference, -1.24; 95% CI, -2.80 to 0.32; P=0.08) in association with an increase in magnesium and citrate excretion and urine pH in the DASH versus low-oxalate group. LIMITATIONS: Limited sample size, as-treated analysis, nonsignificant results. CONCLUSIONS: The DASH diet might be an effective alternative to the low-oxalate diet in reducing calcium oxalate supersaturation and should be studied more.

Postmortem Histopathologic Findings and SARS-CoV-2 Detection in Autopsy Kidneys of Patients With COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to investigate the prevalence of postmortem kidney histopathologic features of patients with coronavirus disease 2019 (COVID-19) in addition to the rate of renal tropism in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We searched Web of Science, PubMed, Embase, and Scopus up to September 2022 to identify eligible studies. A random-effects model was used to estimate the pooled prevalence. Cochran Q test and Higgins I2 were used to assess evidence of heterogeneity. RESULTS: In total, 39 studies were included in the systematic review. The meta-analysis included 35 studies consisting of a total of 954 patients, with an average age of 67.1 years. The pooled prevalence of acute tubular injury (ATI)-related changes was the predominant finding (85% [95% confidence interval, 71%-95%]), followed by arteriosclerosis (80%), vascular congestion (66%), and glomerulosclerosis (40%). Endotheliitis (7%), fibrin microthrombi (12%), focal segmental glomerulosclerosis (1%), and calcium crystal deposits (1%) were seen in a smaller number of autopsies. The overall average rate of virus detection was 47.79% in the pooled data of 21 studies (272 samples). CONCLUSIONS: The main finding-ATI-correlated to clinical COVID-19-associated acute kidney injury. The presence of SARS-CoV-2 in kidney samples in addition to vascular lesions in kidneys can be linked to direct kidney invasion by the virus.

The relationship between CT value and clinical outcomes in renal patients with COVID-19.

PURPOSE: Concomitant kidney diseases raise the mortality rate due to the SARS-CoV-2 virus as an independent factor. Although a qualitative PCR test's result is sufficient for diagnosis, Cycle threshold value may present relevant information to the physicians in providing faster treatment in patients with chronic conditions, including kidney diseases, to prevent morbidity and subsequent mortality. Thus, the present study was conducted to determine the relationship between the Cycle threshold value and clinical outcomes in renal patients with the coronavirus 2019. METHODS: This retrospective study was conducted on renal patients with the coronavirus 2019 infection admitted to Labbafinejad Hospital in Tehran, the capital of Iran, within a period of one year, from late February 2020 to February 2021. Data were collected per the prepared checklist. Cycle threshold values were measured by performing PCR on nasopharynx and oropharynx swab samples of patients. RESULTS: According to the adjusted analysis, having high viral load increased the odds of in-hospital mortality (aOR = 11.65, 95% CI 3.93-34.54), ICU admission (aOR = 5.49, 95% CI 2.16-13.97), and invasive ventilation (aOR = 7.18, 95% CI 2.61-19.74). Having high viral load also increased the odds of O2 therapy (aOR = 3.08, 95% CI 0.79-12.01), although the difference was not statistically significant (P = 0.105). CONCLUSION: Cycle threshold value was a significant predictor of mortality in renal patients. Nevertheless, further studies are required on how to render optimal use of the Cycle threshold value, given that the quality of the test sample and the different groups of patients under study affect the effectiveness of this marker in predicting disease severity.

Comparison of different urinary diversions after radical cystectomy in Iran: Assessment of health-related quality of life and financial burden in a Middle Eastern country.

OBJECTIVES: To compare health-related quality of life (HRQOL), cost-effectiveness, and survival among different types of urinary diversion (UD) utilized after radical cystectomy (RC) for bladder cancer with consideration of the unique economic and cultural context in Iran. PATIENTS AND METHODS: In this retrospective study, we examined all patients who underwent RC from May 2017 to December 2021 at two specialized centers by the same surgical team. Patients were grouped based on their UD. Post-surgical HRQOL (obtained from EORTC QLQ-C30 and QLQBLM-30), financial burden, surgical complications, and survival were compared. Kruskal-Wallis H test, One-way ANOVA, and Kaplan-Meier analyses were utilized; accordingly. RESULTS AND LIMITATIONS: In total 187 patients were identified-orthotopic neobladder (ONB) (N = 75), ileal conduit (IC) (N = 57), and cutaneous ureterostomy (CU) (N = 55)-and were followed for a median 17.5 (Interquartile range: 7.0, 47.0) months. ONB was associated with better HRQOL, especially in the domains addressing physical, role and social functioning (p = 0.003, 0.011, 0.045) as well as better body image (p < 0.001), lower short- and long-term financial burden (p = 0.034 and <0.001, respectively), marginally lower complication rate (p = 0.049), and better 5-year overall survival (p < 0.001), in comparison with other UDs. Patients who underwent CU had the lowest HRQOL and worst survival. Limitations were retrospective design and possibility of selection bias. CONCLUSIONS: In this first study that assesses a Middle Eastern collective; ONB seems to be the UD of choice with regard to HRQOL and economic burden when there is no contraindication.

Renal mucormycosis following transurethral resection of prostate in the time of COVID-19: Unique imaging features resembling emphysematous pyelonephritis.

We report a case of isolated renal mucormycosis 2 weeks following transurethral resection of prostate. The patient also mentioned history of admission for COVID-19, two months earlier. Symptoms progressed and patient underwent urgent nephrectomy. CT scan resembled imaging features of emphysematous pyelonephritis and therefore, patient did not receive timely treatment with amphotericin B in addition to nephrectomy and succumbed to the disease.

Antibody-mediated Rejection of Kidney Allografts Following COVID-19: A Report of Two Cases.

Increased risk of graft rejection could be the consequence of COVID-19 in kidney transplant recipients (KTRs). We report two cases of kidney transplant (KT) with stable graft function who experienced antibody-mediated rejection (ABMR) following recovery from COVID-19. It seems that reduced immunosuppression during the acute illness, is the main explanation for post-COVID-19 ABMR. However, the inflammatory state associated with COVID-19, as well as direct cytopathic effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can predispose the kidney allograft to rejection. There is no definite guideline for the modification of immunosuppressives during COVID-19 in kidney transplant recipients. However, re-institution of full-dose immunosuppressives soon after recovery from COVID-19 and frequent outpatient follow-up visits are recommended.  DOI: 10.52547/ijkd.7176.

Combination of T-DM1 and platinum-based chemotherapy in patient-derived xenograft models of muscle-invasive bladder cancer.

Objectives: To assess the efficacy and safety of T-DM1, as an anti-HER2 antibody-drug conjugate (ADC), alone and in combination with two platinum-based chemotherapy regimens in patient-derived xenografts (PDXs) of muscle-invasive bladder cancer (MIBC) established in immunodeficient mice. Materials and Methods: After treatment initiation, tumor size was measured twice a week. Percent of tumor growth inhibition (TGI) and tumor response rates were calculated as efficacy endpoints. To evaluate treatment toxicity, relative body weight (RBW) was calculated for each group. For comparison of TGIs between treatment groups, the Kruskal-Wallis test was used. Also, the significance of the overall response (OR) rate between placebo groups with treatment groups was analyzed using Fisher's exact test. Immunohistochemistry and fluorescence in situ hybridization techniques were used to evaluate the level of HER2 expression. Results: Our data showed that T-DM1 alone induced a moderate antitumor activity. While chemotherapy regimens induced a slight TGI when administered alone, interestingly, they showed strong antitumor activity when administered combined with T-DM1. The OR rates were higher when T-DM1 was combined with chemotherapy regimens than T-DM1 alone. When compared with the placebo group, the OR rates of combination groups were statistically significant. Our data also showed that the administered dose of each drug was well tolerated in mice. Conclusion: The combination of T-DM1 and platinum-based chemotherapy may represent a new treatment option for bladder tumors with even low HER2 expression, and could also provide substantial novel insight into tackling the challenges of MIBC management.

An assessment of parathyroid hormone, calcitonin, 1,25 (OH)2 vitamin D3, estradiol and testosterone in men with active calcium stone disease and evaluation of its biochemical risk factors.

The aim of this study is to investigate the serum levels of parathyroid hormone (PTH), calcitonin, 1,25 (OH)(2) vitamin D3, estradiol and testosterone in male patients with active renal calcium stone disease compared with controls and investigate their relationship with serum/urinary biochemistry. Male active renal calcium stone formers (ASF) were enrolled from December 2008 to April 2009. Controls were selected from age and sex matched individuals. Two 24-h urine samples and a blood sample were withdrawn from each participant while they were on free diet. Serum 1,25 (OH)(2) vitamin D3 levels in the ASF and control groups were 127 ± 40 and 93 ± 35 pmol/l (p < 0.001). Serum levels of PTH, calcitonin, estradiol and testosterone were not statistically different between the ASF and control groups (all p > 0.05). Serum 1,25 (OH)(2) vitamin D3 was associated with higher urinary excretion of calcium and phosphorus in ASF patients. Serum levels of calcitonin were related to less urinary excretion of calcium in the control group. Serum testosterone was related to higher urinary excretion of uric acid in ASF patients and to higher urinary excretion of oxalate in the control group. 1,25 (OH)(2) Vitamin D3 is an important hormone in the pathogenesis of recurrent renal calcium stone disease and could increase renal stone risk by increasing the urinary excretion of calcium and phosphorus. There is a possibility of testosterone involvement in the pathogenesis of renal stones through higher urinary uric acid and oxalate excretion.

The role of human papillomavirus infection in prostate carcinoma.

Human papillomavirus (HPV) infections are associated with benign and malignant lesions of the female and male anogenital tract. Currently the possible role of HPV infections in prostate carcinogenesis is a subject of great controversy. In this study we aimed to investigate the role of HPV infection in prostate carcinoma (PCa). The study included formalin-fixed paraffin-embedded tissue samples of 104 primary prostate adenocarcinoma cases and 104 control tissues of benign prostatic hyperplasia (BPH). HPV-DNA was purified and amplified through MY09/MY11 and GP5(+)/GP6(+) primers and subsequently subjected to sequencing. HPV-DNA was found in 13 of 104 (12.5%) PCa and 8 of 104 (7.7%) BPH samples. High-risk HPVs were detected in 10 of 13 (76.9%) PCa and 5 of 8 (62.5%) BPH samples with positive HPV-DNA. Low-risk HPVs were detected in 3 of 13 (23.1%) PCa and 3 of 8 (37.5%) BPH specimens with positive HPV-DNA. There was no significant difference between PCa and BPH specimens regarding HPV-DNA presence or the detection of high-risk and low-risk types of HPV. Our data do not support the role of HPV infection in prostate carcinoma. Further studies are required to elucidate the role of HPV infection in human prostate carcinogenesis.

The Prevalence of Vitamin D Deficiency, Its Predisposing Factors and Association with 24-hour Urine Metabolites Among Iranian Kidney Stone Formers.

INTRODUCTION: To study the prevalence of vitamin D deficiency in kidney stone formers and its predisposing factors and to assess the relationship between serum 25-Hydroxyvitamin D and urine metabolites. METHODS: Kidney stone formers were selected from the records of the kidney stone prevention clinic in Labbafinejad hospital, Tehran, Iran. Vitamin D deficiency was defined as 25-Hydroxyvitamin D < 20 ng/mL. The association between vitamin D deficiency and predisposing factors, serum, and urine metabolites was evaluated. RESULTS: In 1005 patients (66.4% men and 33.6% women), the prevalence of vitamin D deficiency was 44.8%. Vitamin D deficiency was more prevalent in patients under 50 years (P < .001) and patients with hyperparathyroidism (P < .05). The lowest prevalence of hyperparathyroidism was in the 25-Hydroxyvitamin D range of 40 to 49.9 ng/mL, followed by the range of 30 to 39.9 and 20 to 29.9 ng/mL. Patients with vitamin D deficiency had lower serum creatinine (P < .02), lower 24-hour urine calcium (P < .01), and lower 24-hour urine oxalate (P < .05). CONCLUSION: Iranian kidney stone formers have a relatively high prevalence of vitamin D deficiency. Our population seems to have different predisposing factors for vitamin D deficiency, i.e., higher prevalence among younger patients and no association between obesity and gender with vitamin D status. According to the parathyroid hormone, the favorable serum 25-Hydroxyvitamin D level was 20 to 49.9 ng/mL in our kidney stone formers.

Development and immunohistochemical characterization of patient-derived xenograft models for muscle invasive bladder cancer.

Objectives: Patient-derived xenograft (PDX) models have become a valuable tool to evaluate chemotherapeutics and investigate personalized cancer treatment options. The role of PDXs in the study of bladder cancer, especially for improvement of novel targeted therapies, continues to expand. In this study, we aimed to establish autochthonous PDX models of muscle-invasive bladder cancer (MIBC) to provide a useful tool to conduct research on personalized therapy. Materials and Methods: Tumors from MIBC patients undergoing radical cystectomy were subcutaneously transplanted into immunodeficient mice. The tumor size was measured by a caliper twice a week for up to five months. After the first growth in mice, they were serially passaged. Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) of 11 markers (Ki67, P63, GATA3, KRT5/6, KRT20, E-cadherin, 34ßE12, PD-L1, EGFR, Nectin4, and HER2) were used to evaluate phenotype maintenance of original tumors. Results: From 10 MIBC patients, two PDX models (P8X20 and P8X26) were successfully established (20% success rate). These models mostly retained primary tumor characteristics including histology, morphology, and molecular nature of the original cancer tissues. IHC analysis showed that the expression level of 7 markers for the model P8X20, and 8 markers for the model P8X26 was exactly similar between the patient tumor and the next generations. Conclusion: We developed the first autochthonous PDX models of MIBC in Iran. Our data suggested that the established MIBC PDX models reserved mostly histopathological characteristics of primary cancer and could provide a new tool to evaluate novel biomarkers, therapeutic targets, and drug combinations.

Data-Driven Discovery of Molecular Targets for Antibody-Drug Conjugates in Cancer Treatment.

Antibody-drug conjugate therapy has attracted considerable attention in recent years. Since the selection of appropriate targets is a critical aspect of antibody-drug conjugate research and development, a big data research for discovery of candidate targets per tumor type is outstanding and of high interest. Thus, the purpose of this study was to identify and prioritize candidate antibody-drug conjugate targets with translational potential across common types of cancer by mining the Human Protein Atlas, as a unique big data resource. To perform a multifaceted screening process, XML and TSV files including immunohistochemistry expression data for 45 normal tissues and 20 tumor types were downloaded from the Human Protein Atlas website. For genes without high protein expression across critical normal tissues, a quasi H-score (range, 0-300) was computed per tumor type. All genes with a quasi H - score ≥ 150 were extracted. Of these, genes with cell surface localization were selected and included in a multilevel validation process. Among 19670 genes that encode proteins, 5520 membrane protein-coding genes were included in this study. During a multistep data mining procedure, 332 potential targets were identified based on the level of the protein expression across critical normal tissues and 20 tumor types. After validation, 23 cell surface proteins were identified and prioritized as candidate antibody-drug conjugate targets of which two have interestingly been approved by the FDA for use in solid tumors, one has been approved for lymphoma, and four have currently been entered in clinical trials. In conclusion, we identified and prioritized several candidate targets with translational potential, which may yield new clinically effective and safe antibody-drug conjugates. This large-scale antibody-based proteomic study allows us to go beyond the RNA-seq studies, facilitates bench-to-clinic research of targeted anticancer therapeutics, and offers valuable insights into the development of new antibody-drug conjugates.

Female Urethral Cavernous Hemangioma, A Rare Entity: Two Case Reports and Review of The Literature.

Genitourinary hemangiomas are very rare. To our knowledge few cases of female urethral hemangiomas have been reported and presenting cases are the first reports in Iran.They should be considered as differential diagnosis of any female patient with microscopic or gross hematuria or bloody urethral discharge, especially when other parts of urinary system are radiologically intact. Thorough physical examination of genital area is highly recommended in order not to miss any urethral lesions. Herein we report two cases of female urethral cavernous hemangioma, their management and a review of literature.