Atypical Recurrent Renal Cell Carcinoma of the Ipsilateral Ureter Showing Typical Symptoms of Upper Urinary Tract Urothelial Carcinoma: A Case Report and Literature Review.

BACKGROUND: Ureteral metastasis is a rare phenomenon. Synchronous recurrence in both the pelvis and ureter with symptoms that are typical of upper urinary tract urothelial carcinoma (UTUC) has not been reported previously. METHODS: We present a case of metastasis of clear cell renal cell carcinoma (ccRCC) to the ipsilateral pelvis and ureter in a 37-year-old man who underwent open partial nephrectomy (PN) after laparoscopic exploration 20 months after surgery. We suspected painless hematuria with clots and upper UTUC based on the imagological diagnosis. We performed complete transperitoneal laparoscopic nephroureterectomy in a single position. We also searched PubMed for studies with the keywords "renal cell carcinoma" and "ureteral metastasis" that had been published since 2000. RESULTS: Postoperative pathology demonstrated ccRCC in the left pelvis that had spread along the ureter. The patient was discharged 1 week after surgery, without a drainage tube, and free to eat and perform normal activities. We identified 10 cases from nine studies that had been published since 2000. Nephrectomy was performed in all 10 cases, and nine of the patients had hematuria. Open ureterectomy was performed on two patients who had ipsilateral ureteral metastasis. CONCLUSIONS: Recurrent ccRCC in the ureter is rare. Due to the difficulty in distinguishing it from ipsilateral upper UTUC, complete transperitoneal laparoscopic nephroureterectomy in a single position is a safe and feasible treatment option in this situation.

Endometriosis derived exosomal miR-301a-3p mediates macrophage polarization via regulating PTEN-PI3K axis.

This study aimed to explore the effects of endometriosis (EMS)-derived exosomes and miR-301a-3p on the polarization of macrophages and investigate the involved molecular mechanism. The exosomes were isolated from ectopic endometrial tissues of EMS patients and normal human serum (NHS). Results of transmission electron microscope and Nanoparticle Tracking Analysis showed that both EMS-exosomes and NHS-exosomes are about 80 nm microvesicles. Exosomal markers CD63 and TSG101 were abundantly expressed in both EMS-exosomes and NHS-exosomes. No negative marker Calnexin was detected in NHS-exosomes. A small amount of Calnexin was detected in EMS-exosomes. THP-1 cells differentiatee to macrophages by incubating with phorbol-12-myristate-13-acetate. Effects of the exosomes on the phagocytosis and polarization of macrophages were evaluated by PKH26 fluorescent labeling and flow cytometry, respectively. Compared with the NHS-exosomes group, the phagocytic capacity of macrophages was reduced and the polarization of macrophages to M2 macrophages was promoted after EMS-exosomes treatment. Results of western blot showed that compared with the NHS-exosomes group, the EMS-exosomes treatment significantly up-regulated the expression of phosphatidylinositol 3-kinase (PI3K) and down-regulated the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN). miR-301a-3p mimic, negative control (NC) mimic, miR-301a-3p inhibitor and NC inhibitor were transfected into cells. Transfection efficiency was confirmed by RT-qPCR. Effects of the miR-301a-3p expression on the macrophages polarization and the expression of Arg-1, PTEN and PI3K in the macrophages were evaluated by flow cytometry and western blot, respectively. miR-301a-3p overexpression significantly enhanced the ability of EMS-exosomes-inducing M2 transformation of macrophages, promoted the expression of Arg-1 and PI3K, and inhibited the PTEN expression. miR-301a-3p inhibitor significantly reduced the expression of Arg-1 and PI3K and promoted the PTEN expression. In conclusion, EMS derived exosomal miR-301a-3p mediated macrophage polarization via regulating PTEN-PI3K axis.

Detection of Prostate Cancer Antigen 3 and Prostate Cancer Susceptibility Candidate in Non-DRE Urine Improves Diagnosis of Prostate Cancer in Chinese Population.

Although prostate biopsy is the gold standard for the diagnosis of prostate cancer, it also leads to high incidence of negative biopsies and the diagnosis of clinically low-risk prostate cancer and the subsequent overtreatment. It remains an unmet need to discover new biomarkers in order to defer the unnecessary biopsies in clinical practice. In this study, we described a new method, LBXexo score, to measure the urine exosomal PCA3/PRAC expression from non-DRE urine as a noninvasive diagnosis to improve the detection rate in Chinese population with a low serum PSA level. First-voided urine samples were collected to isolate exosomes, and exosomal RNAs of PCA3 and PRAC were measured by quantitative reverse transcription PCR. A significant increase in exoPCA3/PRAC was observed in both any-grade and high-grade prostate cancer groups when compared with the biopsy-negative group. Receiver-operating characteristic curve analyses showed that the LBXexo score significantly improved diagnostic performance in predicting biopsy results, with AUCs of 0.723 (p=0.017) and 0.736 (p=0.038) for any-grade and high-grade (GS ≥ 7) prostate cancer, respectively. For high-grade cancer, LBXexo had the negative and positive predictive values of 100% and 27.59%, respectively, and could potentially avoid unnecessary biopsy. This is the first report in Chinese population that demonstrates the predictive value of the exosomal expression of PCA3 and PRAC derived from non-DRE urine in predicting prostate biopsy outcomes. It could be used in clinical practice to make a better informed biopsy decision and avoid unnecessary biopsies in Chinese population.

BiodMHC: an online server for the prediction of MHC class II-peptide binding affinity.

Effective identification of major histocompatibility complex (MHC) molecules restricted peptides is a critical step in discovering immune epitopes. Although many online servers have been built to predict class II MHC-peptide binding affinity, they have been trained on different datasets, and thus fail in providing a unified comparison of various methods. In this paper, we present our implementation of seven popular predictive methods, namely SMM-align, ARB, SVR-pairwise, Gibbs sampler, ProPred, LP-top2, and MHCPred, on a single web server named BiodMHC (http://biod.whu.edu.cn/BiodMHC/index.html, the software is available upon request). Using a standard measure of AUC (Area Under the receiver operating characteristic Curves), we compare these methods by means of not only cross validation but also prediction on independent test datasets. We find that SMM-align, ProPred, SVR-pairwise, ARB, and Gibbs sampler are the five best-performing methods. For the binding affinity prediction of class II MHC-peptide, BiodMHC provides a convenient online platform for researchers to obtain binding information simultaneously using various methods.