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Clear cell renal cell carcinoma (ccRCC) is one of the most common cancer types worldwide, and its incidence is increasing year by year. Endoplasmic reticulum stress (ERS) caused by protein misfolding has broad and profound effects on the progression and metastasis of various cancers. Accumulating evidence suggests that ERS-related genes are closely related to the occurrence and progression of ccRCC. This study aimed to identify ERS-related signature genes for evaluating the prognosis of ccRCC patients. Transcriptomic expression profiles of patients with ccRCC from public databases Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) and survival data and clinical phenotype data of patients in the TCGA database were used. Then the GeneCards database was used to identify the differentially expressed genes related to ERS. We obtained 11 signature genes, and then used the Lasso regression method to establish a diagnostic model, univariate and multivariate Cox analysis was used to analyze the correlation between the expression levels of the signature genes and the clinical characteristics, and finally 5 signature genes were associated with poor prognosis (TNFSF13B, APOL1, COL5A3, CDH5）. In summary, this study suggests that these genes may have potential as prognostic biomarkers in ccRCC and may provide new evidence to support targeted therapy in ccRCC.

Purpose-Natural killer (NK) cells play a potent role in antitumor immunity via spontaneously eliminating tumor directly. However, some tumors such as prostate cancer constantly escape this immune response by down-regulating cell surface molecule recognition and/or secreting immune impressive cytokines. Pterostilbene, a dietary compound primarily found in blueberries, exhibits a potential anti-tumor activities and immunoregulation function. However, whether it could affect NK cells immune response against prostate cancer is not clear.Methods-NK cell cytotoxicity against prostate cancer cells was analyzed using the CytoTox 96 cytotoxicity assay kit. Flow cytometry was used to detected NK cell degranulation, NK cell-surface and intracellular protein expression. The effects of pterostilbene on TGF-β1 secretion were determined by Enzyme-linked immunosorbent assay. The candidate target gene of miR-20a was determined by luciferase reporter assay and the expression of major histocompatibility complex class I chain-related proteins A and B (MICA/B) was detected by quantitative real-time polymerase chain reaction.Results-We found pterostilbene could enhance expression of MICA/B on prostate cancer cells surface, which are ligands of the natural killer group 2 member D (NKG2D) expressed by NK cells, and inhibit TGF-β1 secretion by prostate cancer cells. Further, we discovered that these effects were caused by inhibition of miR-20a in prostate cancer cells by pterostilbene. MiR-20a could target the 3’ untranslated region (UTR) of MICA/B, resulting in their expression down-regulation. Inhibition of TGF-β1 function by its specific antibody attenuated its impairment to NKG2D on NK cells. Finally, we observed that pterostilbene-treated prostate cancer cells were more easily to be killed by NK cells.Conclusions-Our findings demonstrated inhibition of miR-20a by pterostilbene in prostate cancer cells could increase MICA/B expression and decrease TGF-β1 secretion, which enhanced NK cell-mediated cytotoxicity againt prostate cancer cells, suggesting a potential approach for increasing anti-prostate cancer immune.

Prostate cancer (PCa) is the most common malignant tumor for men. But the mechanism is unclear. EIF3C was shown to be overexpressed in PCa tissues and cell lines. EIF3C overexpression was correlated to age and tumor stage in PCa patients and indicated poor survival. The proliferation, migration, and invasiveness of PC3 cells were all inhibited after EIF3C knockdown. Additionally, the phosphorylation level of PI3K and Akt was downregulated while total NF-κB and Myc decreased after EIF3C knockdown. But the expression of IκB increased reversely. Therefore, EIF3C at least partially regulates the activity of PI3K/Akt/NF-κB signaling pathway in PC3 cells.

Rab23 is a member of Ras-related small GTPase family, which plays a critical role in the progression of wide range of tumors. However, its biological function in hepatocellular carcinoma still remains unclear. Here, we investigated the effects of Rab23 on proliferation and migration in hepatocellular carcinoma cell and its potential mechanisms. We found over-expression of Rab23 promoted the Hep3B hepatocellular carcinoma cell migration, which could be reversed by Rab23 silencing. Rab23 induced Rac1 activation and followed progression of epithelial-mesenchymal transition (EMT) along with upregulation of N-cadherin, snail as well as vimentin and downregulation of E-cadherin via upregulating Transforming Growth Factor-β (TGF-β). Silencing Rac1 significantly attenuated Rab23-induced HepG2 migration and TGF-β. Moreover, knockdown of TGF-β effectively attenuated Rab23-induced EMT. Taken together, we demonstrated a mechanistic cascade of Rab23 enhangcing Rac1 activation and subsequent TGF-β expression, leading to hepatocellular carcinoma cell migration.

Prostate cancer is one of the most common malignancies in older men. Recent evidence has demonstrated microRNA (miRNA) Let-7a expression decreased in prostate cancer, while the expression of CC chemokine receptor type 7 (CCR7) increased. In this study, we investigated whether CCR7 overexpression was associated with a decrease in the expression of miRNA Let-7a in invasion and metastasis of prostate cancer cell. Synthetic Let-7a mimics and Let-7a inhibitors were transfected into prostate cancer PC-3 cells, respectively. Then Western blot was used to detect the expression of CCR7, ERK, p38, MMP-9, and Epithelial-Mesenchymal Transition (EMT)-related proteins. Matrigel invasion assays were performed to assess the migratory and invasive activities of PC3 cells. To confirm the fact that 3'UTR of CCR7 is a direct target of Let-7a, a luciferase assay for the reporter gene expressing the Let-7a binding sites of CCR7 3'UTR was used. Synthetic Let-7a mimics decreased prostate cancer cell migration and invasion, as well as the expression of CCR7, phospho-p38, phospho-ERK1/2, MMP-9, N-cadherin, and Snail in PC-3 cells. The Let-7a inhibitors reversed the effects of Let-7a on PC-3 cells. The 3'UTR of CCR7 was confirmed as a direct target of Let-7a by using the luciferase assay. All findings demonstrated that Let-7a/CCR7 axis regulated EMT progress in prostate cancer cells and mediated the tumor cell invasion and migration process via activation of P38/ERK signal pathway. Our results suggested that the therapeutic potential of Let-7a as an antitumor and antimetastatic manager in prostate cancer and CCR7 may be regarded as a therapeutic target for the prostate cancer treatment.

Rationale: Bladder paraganglioma is characterized by headache, palpitations, hypertension, blurred vision, or sweating during voiding. Transurethral holmium laser resection is a safe and efficacious alternative method for the resection of bladder neoplasms. Patient concerns: A 24-year-old female had a 2-year history of intermittent headaches, palpitation, and sweating during micturition. Diagnosis: Physical examination revealed a rise in the patient's blood pressure to 180/90 mmHg after micturition. Laboratory examination found that the blood catecholamine metabolites were significantly increased. Abdominal ultrasound and computed tomography (CT) scan indicated a 37 mm × 31 mm paraganglioma situated at the right anterolateral wall of the bladder. A diagnosis of bladder paraganglioma was considered based on a comprehensive evaluation of the physical examination, laboratory examination, ultrasound and computerized tomography scan. Interventions: Preoperative oral administration of a nonselective α-adrenergic receptor antagonist (phenoxybenzamine, 10 mg three times a day,) accompanied by a high-sodium diet and generous fluid intake, was initiated 2 weeks before the surgery to stabilize intraoperative hemodynamics. As the patient was newly married and nulligravid, management with transurethral resection was considered superior to open or partial cystectomy and was selected as the treatment method. Outcomes: Transurethral holmium resection of the bladder paraganglioma was successfully performed with blood loss less than 20 ml and well-controlled intraoperative blood pressure. The 1-year follow-up results demonstrated well-controlled symptoms. Cystoscopy and evaluation of blood catecholamine metabolites revealed no disease recurrence. Lessons: Transurethral holmium laser resection is a good alternative approach for the resection of bladder paraganglioma, given its advantages of safety and efficacy.

Prostate cancer (PCa) is the most common malignant tumor for men. But the mechanism is unclear.

There currently exists no satisfactory treatment for patients with prostate cancer with local evolution and distant metastasis. Previous studies have confirmed the importance of CC chemokine receptor 7 (CCR7) in the invasion and metastasis of prostate cancer. And increasing evidence prove that Notch1 can play diametrically opposite roles in the development and progression of different tumors. To demonstrate the correlation between CCR7 and Notch1, PC-3 cells were transfected with pcDNA3.1-CCR7 or CCR7 si-RNA, respectively. Then Western blot analysis was used to detect the expressions of Notch1, ERK, P38, JNK, NF-κB, MMP-9, and epithelial-mesenchymal transition (EMT)-related proteins. Moreover, matrigel invasion assays were performed to assess the migratory and invasive activities of PC-3 cells. PcDNA3.1-CCR7 increased the expression of Notch1, phospho-MAPK, phospho-P65, MMP-9, N-cadherin, and Snail in PC-3 cells, but decreased the expression of E-cadherin. PcDNA3.1-CCR7 also promoted the migration and invasion of PC-3 cells. However, CCR7 si-RNA reversed the effect of pcDNA3.1-CCR7 in PC-3 cells. And MAPK and NF-κB pathway inhibitors were used to testify that activation of Notch1 induces EMT through MAPK and NF-κB pathway. All these results indicate that upregulation of Notch1 by CCR7 can accelerate the evolution of EMT and develop the invasion and metastasis in prostate cancer cells by activating MAPK and NF-κB signaling pathways in prostate cancer cells, which provides a new molecular evidence for targeted therapy in metastatic prostate cancer.

Cystadenomas of the seminal vesicles are extremely rare. Here, we report a large seminal vesicle cystadenoma. A 37-year-old man presented a 6-month history of haemospermia, 10 days of Lower Urinary Tract symptoms (LUTSs) and gross haematuria. Transabdominal ultrasonography, computed tomography and magnetic resonance imaging were performed and revealed a large solid-cystic pelvic mass morphometrically measured 7.0 cm × 11.9 cm × 8.6 cm on the right seminal vesicle, which caused hydronephrosis of the right kidney. The prostate-specific antigen of the patient was 27.860 ng/dl. Laparoscopic exploration found the capsule of tumour was complete and the tumour came from the right seminal vesicle, in addition, the mass had a certain space with the bladder and prostate, which could be separated. So a nerve-sparing Laparoscopic Vesiculectomy was performed at last, even though the intraoperative frozen section analysis could not make sure the nature of the tumour either. The postoperative pathology revealed cystadenoma of the seminal vesicle.

Transplantation of mesenchymal stem cells (MSCs) for the treatment of diabetic erectile dysfunction (ED) is hampered by apoptosis of the transplanted cells. In diabetic ED, there is increased oxidative stress and decreased NO in the corpora cavernosa, and reactive oxygen species (ROS) induce apoptosis of the transplanted cells. In this study we examined whether and how autophagy was involved in ROS-induced apoptosis of MSCs. Mouse C3H10 MSCs were treated with H2O2 to simulate the high oxidative condition in diabetic ED. Cell viability was measured using MTT assay. Apoptosis was analyzed by flow cytometry. Apoptosis- and autophagy-related proteins were detected with Western blot assays. Intracellular autophagosome accumulation was studied using transmission electron microscopy. Treatment of MSCs with H2O2 (50–400 μmol/L) inhibited the cell viability in concentration- and time-dependent manners. Furthermore, H2O2 (300 μmol/L) induced apoptosis, as well as activated autophagy in MSCs. Pretreatment with lysosome inhibitor chloroquine (10 μmol/L) or PI3K inhibitor 3-methyladenine (5 mmol/L) significantly enhanced H2O2-induced cell death. Pretreatment with JNK inhibitor SP600125 (10 μmol/L) abrogated H2O2-induced accumulation of LC3-II, and attenuated H2O2-induced reduction of Bcl-2 levels in MSCs. ROS induce autophagy to counteract apoptosis in MSCs by activation of JNK. Thus, augmentation of autophagy may reduce apoptosis, prolonging MSC survival and improving MSC-based therapeutic efficacy for diabetic ED.

Background Ischemia–reperfusion (IR) causes various damages in renal tissues, which is exacerbated by hypoxia-induced excessive inflammation and deteriorates the prognosis of patients after kidney surgery. Celastrol is a potent inflammation inhibitor that has little toxicity. In this report, we investigated whether celastrol protects against IR-induced renal injury in rats. Materials and methods Renal IR injury was induced by occlusion of the bilateral renal pedicles for 45 min followed by reperfusion for 6 h. Celastrol or vehicle solution was intraperitoneally injected 30 min before renal ischemia, respectively. Renal histology, function, and pro-inflammatory cytokines and mediators were assessed. The effect of celastrol on nuclear translocation of nuclear factor kappa B (NF-κB) was also measured. Results Celastrol significantly suppressed elevation of the renal function markers and the lipid peroxidation level, alleviated renal tubular damage, and decreased the levels of tumor necrosis factor-α, interleukin-1β, and monocyte chemotactic protein-1 (MCP-1) messenger RNA in kidney caused by IR. Moreover, celastrol prevented IR-induced expression of pro-inflammatory mediators, which was associated with suppression of nuclear translocation of NF-κB subunit p65. Conclusions Celastrol ameliorated the acute kidney injury caused by IR, which was associated with inhibiting local NF-κB activation and inflammation. Our findings suggest that celastrol could be useful for preventing IR-induced renal injury.