[This retracts the article DOI: 10.1039/C5RA12373A.].

Objective: This study set out to analyze the value of TPA (tissue polypeptide antigen), TPS (tissue polypeptide specific antigen), and CA242 single and combined tests in diagnosing renal carcinoma (RC). Methods: A total of 126 RC patients and 102 healthy subjects were selected as a research group (RG) and a control group (CG) respectively. The TPS, TPA and CA242 expression levels were determined, and the diagnostic value of the three for RC as well as the diagnostic effects of TPS combined with CA242 and TPA combined with CA242 were analyzed. The relationships among TPS, TPA, CA242, and the pathological features of RC were observed, and the effects of the three on the prognosis of RC patients were analyzed. Results: The TPS, TPA, and CA242 expression levels in the RG were higher than those in the CG (P < 0.05). TPA, TPS, and CA242 alone have a good diagnostic value for RC, but TPS combined with CA242 and TPA combined with CA242 each have a better diagnostic efficacy than a single test. TPS, TPA, and CA242 are relevant to the clinical stage, lymph metastasis, invasion depth, distant metastasis, differentiation degree, and tumor diameter (P < 0.05). TPA, TPA, and CA242 are closely linked to patient prognosis. Conclusion: TPS, TPA, and CA242 are highly expressed in RC patients. The combined quantifications of TPS and CA242 as well as TPA and CA242 have a good diagnostic effect for RC's occurrence and are relevant to its prognosis. It may be an excellent potential indicator for RC's future diagnosis and treatment.

目的:探讨MTA1和XIAP蛋白表达与前列腺癌临床病理特征和预后的关系.方法:应用免疫组化技术检测53例前列腺癌(PCa)和20例前列腺增生(BPH)组织中MTA1和XIAP蛋白表达,并结合肿瘤的病理学行为和临床随访资料进行分析.结果:在PCa组织中MTA1和XIAP阳性表达率分别为81.1％、75.5％,均显著高于BPH组织(P＜0.05).MTA1和XIAP表达与肿瘤分化程度、周围淋巴结转移、远处转移、预后密切相关(P＜0.05).MTA1和XIAP蛋白表达呈显著正相关(r=0.369,P=0.004).结论:MTA1和XIAP蛋白表达与PCa发生、转移和患者生存期密切相关,联合检测可以对PCa的发生、发展、预后及药物治疗提供重要依据.

Rationale: Malignant pheochromocytoma is a rare disease and surgical resection is the only curative treatment. Patient concerns: An 81-year-old man of Chinese ethnicity was found to have a giant retroperitoneal tumor. Diagnoses: B-scan ultrasonography and CT scan presented a mass above the left kidney, measuring 13.5 × 10 .6 × 9.8 cm. Subsequent analysis of 24-h urinary catecholamines and vanillylmandelic acid, as well as of blood catecholamines and blood cortisol, showed no elevated levels. Interventions: The patient was treated with surgery. Outcomes: The result from immunohistochemical staining confirmed the presence of malignant pheochromocytoma. After three months follow-up, the blood pressure and serum potassium were all within normal limits, no post-operative complications, no tumor recurrence and metastasis were found. Lessons: This is the oldest patient known to have histologic documentation of this disease. Giant malignant pheochromocytomas are rare entities requiring clinical suspicion coupled with strategic diagnostic evaluation to confirm the diagnosis, personalized therapeutic treatment is required, particularly among elderly population.

Renal cell carcinoma (RCC) is characterized by robust angiogenesis during tumor development. Various therapies are not able completely eradicated tumor relapse. The present study targeted angiogenesis and developed a recombinant adeno-associated virus (rAAV) vector containing human endostatin gene for human kidney cancer gene therapy. Prophylactic and therapeutic RCC models were established in nude mice by subcutaneous inoculation of RCC cells and intra-muscular or intra-tumor injection of rAAV-Endostatin. The growth of xenograft tumors was evaluated by tumor volume and weight. The microvessel density (MVD) was used to measure the anti-angiogenesis effect of rAAV-Endostatin. The toxic effect of rAAV-Endostatin was also examined. In the therapeutic model, tumor-bearing mice with rAAV-Endostatin intra-tumor injection demonstrated slow tumor growth (32.63±9.75) compared with control groups with intratumoral rAAV-enhanced yellow florescent protein (EYFP) injections (21.50±11.42) and the RPMI-1640 group (21.75±10.48 days, for tumors to reach ~300 mm3). MVD of the xenografts treated with rAAV-Endostatin was 8.30±3.14/0.739 mm2 whereas that of control groups was 13.87±4.09/0.739 mm2 (rAVV-EYFP) and 13.76±3.50/0.739 mm2 (RPMI-1640). No significant side effects associated with rAAV-endostatin use were identified in the vital organs. rAAV-Endostatin demonstrated significant anti-angiogenesis and antitumor activities. It may serve as an effective agent for renal cancer gene therapy.

Immune checkpoint blockade therapy (ICBT) uses drugs to interrupt signaling pathways that inhibit antitumor immune responses. Although ICBT has provided clinical benefits in certain cancer patients, a large number of patients do not respond to ICBT. Therefore, it is necessary to find other efficient targets to promote the effects of ICBT. Renal cell carcinoma (RCC) is one of the leading causes of cancer-associated mortality worldwide. To date, there is no efficient treatment for patients with advanced RCC. The present study aimed to evaluate the prognostic value of CD103+ cells in patients with RCC and their potential role in enhancing the effect of ICBT in RCC. A total of 200 tumor tissue samples were collected from patients with RCC. The CD103+ cell count and survival of these patients was assessed, and the role of CD103+ cells in combination with ICBT was evaluated in an RCC mouse model. It was identified that a high CD103+ cell count was an independent favorable prognosticator in patients with RCC. The expansion of CD103+ cells promoted the effects of ICBT in the RCC xenograft mouse model, while depletion of CD103+ cells had the opposite effect. Furthermore, the expansion of CD103+ cells enhanced the count and activation of tumor infiltrating CD8+ T cells in RCC tumor tissue. These results indicate that a high CD103+ cell count is an independent favorable prognosticator in RCC patients. Thus, the expansion of CD103+ cells may increase the efficacy of ICBT in patients with RCC.

Background and aim: High levels of peripheral plasma fibrinogen have recently been revealed that related to poor clinical prognosis in various types of malignant tumors. The purpose of this research was to identify the prognostic significance of the preoperative peripheral serum fibrinogen level in patients with penile cell carcinoma. Methods: This retrospective research included 72 penile cancer patients with date about their serum fibrinogen value before surgery who undergone either partial or radical penectomy at The 2nd Hospital of Tianjin Medical University between January 2002 to January 2012. They had a mean follow-up of 30.8 months. To determine the factors that were significant in predicting a patient's prognosis, univariate and multivariate analyses were performed according to the Cox proportional hazards regression model. Results: The 5-year cancer specific survival (CSS) rate was 62.4% of patients with preoperative fibrinogen levels below 340 mg/dl and 41.9% for those with higher levels (p = 0.001). Multivariate analysis revealed that the pathological T stage (p < 0.001), tumor grade (p = 0.036), postoperative chemotherapy (p = 0.041), nodal metastasis(p < 0.001), pathological type (p < 0.001) and fibrinogen (p = 0.023) were independent prognostic factors for survival. Patients with low fibrinogen level (<340mg/dl) had significantly longer CSS and the different survival rate were defined using the log-rank test. Conclusions: The high preoperative peripheral serum fibrinogen level was related to poor survival in penile cancer patients. Fibrinogen may serve as a powerful predictor of CSS in penile cancer patients.

Even though standard treatment options are available for prostate cancer patients, prostate cancer is still a leading cause of death in many Western countries due to drug resistance and recurrence. Immune checkpoint blockade therapy has been proved to be very effective in some melanoma patients, which might dependent on the preconditioned immune system. Here we explored the effect of chemotherapy (oxaliplatin) in combination with immune checkpoint blockade therapy (anti‑PD‑1 treatment) in prostate cancer cell lines and pre‑clinical animal models. We found that oxaliplatin is effective in castration‑resistant cells and enhanced the response of prostate cancer to anti‑PD‑1 antibody treatment. Oxaliplatin stimulated the immunogenic potential and established a pro‑immune microenvironment in prostate cancer. In conclusion, oxaliplatin sensitized anti‑PD‑1 treatment in prostate cancer and this combination may be an option for castration‑resistant prostate cancer patients.

Introduction: The aim of this study was to explore if the preoperative neutrophil-lymphocyte ratio (NLR) and fibrinogen level can help in distinguishing between muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Methods: We identified 669 patients who underwent surgery at our institution, and evaluated their preoperative NLRs and fibrinogen levels. Patients were divided into two groups, NMIBC (group-I) and MIBC (group-II), according to the postoperative pathology. For the intergroup comparison, data obtained from the two groups were evaluated using independent samples t-test. The cutoff value of the NLR, fibrinogen level, and integrated NLR and fibrinogen level was determined with receiver operating characteristic (ROC) curve. Results: The mean NLRs of group-I and group-II were found as 2.71 +/- 2.46 and 4.66 +/- 8.00, respectively (P<0.001). The fibrinogen levels of the two groups were similar to 3.13 +/- 0.70 g/L and 3.41 +/- 0.84 g/L, respectively (P=0.001). Whether the NLR, fibrinogen level, and integrated NLR and fibrinogen level can help in distinguishing between MIBC and NMIBC was evaluated with ROC curve. The cutoff value of NLR was estimated as 2.01 according to the Youden index. With this value, sensitivity was found as 67.1%, specificity was 52.7%, and area under receiver operating characteristic (ROC) curve (AUC) was 0.601 (P=0.031). The cutoff value of fibrinogen level was estimated as 3.17 g/L according to the Youden index. Accordingly, sensitivity was found as 58%, specificity was 58%, and AUC was 0.60 (P=0.001). The cutoff value of integrated NLR and fibrinogen level was found as 0.166; the sensitivity was found as 86%, specificity was 42%, and AUC was 0.801 (P=0.01). Conclusion: The data obtained in this study suggested that 67.1% of Ta-T1 tumors were likely to be invasive if the NLR was >2.01 and 58% were likely to be invasive if the fibrinogen level was >3.17 g/L. When we used both the NLR and fibrinogen level to distinguish between the MIBC and NMIBC, sensitivity was found to be 86%, and specificity was 42%.

BACKGROUND:Survivin has been reported to play a role in the diagnosis and prognosis of renal cell carcinoma (RCC); however, published data on this subject are conflicting. AIM:To conduct a meta-analysis to evaluate the impact of survivin as a prognostic marker and its association with clinicopathological variables in patients with RCC. METHOD:Comprehensive searches of electronic databases (PubMed, ISI Web of Knowledge Embase, Google Scholar Web and the Cochrane Library) were updated to June 2016 to retrieve eligible studies. The association strength was measured with relative risks (RRs) and pooled HRs with 95% CIs, which were extracted and pooled to determine the association between survivin expression and patient survival and clinicopathological features. RESULTS:Ten studies with 1063 cases of RCC were included. Positive survivin expression in RCC was associated with the TNM stage (pooled RR 1.49; 95% CI 1.07 to 2.07) or Fuhrman grade (pooled RR 1.63; 95% CI 1.15 to 2.32) in patients. The correlation between survivin expression and gender was not significant (pooled RR 0.97; 95% CI 0.83 to 1.15). In addition, a considerable association was found between survivin expression and overall survival for patients with RCC (pooled HR 1.94; 95% CI 1.24 to 3.05 (multivariate model) and 5.41; 95% CI 4.08 to 7.17 (univariate model)). CONCLUSIONS:Our results indicate that survivin is of prognostic significance in patients with RCC.

目的:了解重组hIFN-α-2b-BCG (rBCG)体外抗肿瘤的作用效果和作用机制.方法:体外共培养后,透射电镜观察不同时间点rBCG对人膀胱肿瘤EJ细胞的影响.吖啶橙染色观察各组肿瘤细胞形态.MTr法检测rBCG对肿瘤细胞生长抑制率.ELISA检测rBCG作用后淋巴细胞分泌Th1型细胞因子水平.LDH释放试验检测rBCG激活的淋巴细胞对肿瘤细胞杀伤效应.结果:BCG和rBCG作用后的肿瘤细胞在透射电镜下和吖啶橙染色后均有显著变化.MTT显示rBCG的生长抑制率显著高于BCG和BCG+IFN-α-2b组.rBCG对淋巴细胞分泌Th1型细胞因子有影响,同时rBCG激活的淋巴细胞对膀胱肿瘤细胞有杀伤作用.结论:重组BCG在体外有优于BCG的免疫调节特性、抗肿瘤作用和直接细胞毒作用.

Background: In recent years, bladder stones are increasing in China. However, a giant bladder stone is rarely found nowadays. Methods: A case of a 54-year-old man who presented with a >9-year history of urinary frequency and urgency and macrohematuria for the past 3 days, was examined by ultrasound scan, kidney-ureter-bladder x-ray, and computed tomography. Then, the patient received a cystolithotomy. Results: His suprapubic area was hard when palpated. An ultrasound scan showed hydronephrosis of both kidneys and expanded ureters. A kidney-ureter-bladder x-ray showed a large stone within the bladder, and computed tomography revealed that the stone occupied most of the bladder. A large bladder stone composed of magnesium ammonium phosphate, weighing 1048g, and measuring 13.3*8.0*9.7cm in size was removed. Conclusion: This rare case is, to the best of our knowledge, the largest bladder stone case reported to date in China. For patients with only Lower urinary tract symptoms, bladder stone should be taken into consideration when other signs occur, such as recurrent urinary tract infection and hematuria.

目的：研究单核细胞趋化蛋白（ MCP）－1与血管内皮生长因子（ VEGF）在膀胱癌组织中的表达及作用机制。方法选择接受手术治疗的35例膀胱癌患者保存完好的癌组织石蜡标本为观察组，另选同期35例在医院接受前列腺增生电切手术时同时切取的少量膀胱黏膜标本为对照组，通过免疫组织化学法检测两组MCP－1与VEGF的阳性表达情况，另通过双抗体夹心（ ELISA）法检测两组组织中 MCP－1与 VEGF 表达，分析MCP－1、VEGF与膀胱癌临床病理分级的关系及两指标的相关性。结果 MCP－1与VEGF在膀胱癌组织中的阳性表达率分别是91．43％、85．71％，均明显高于在正常膀胱组织中的（11．43％、20．00％，P＜0．05）；MCP－1与 VEGF在膀胱癌组织中的表达水平均分别高于在正常膀胱组织（ P＜0．05）；MCP－1及VEGF阳性表达与临床分级及病理分级有关（ P＜0．05）。 Pearson相关性分析可知，膀胱癌组织中 MCP－1的表达与 VEGF 呈正相关，同时MCP－1及VEGF阳性表达与临床分期及病理分级均呈正相关。结论 MCP－1及VEGF在膀胱癌组织中高表达且与患者临床及病理分级密切相关，同时二者呈正相关联系并共同参与膀胱癌病情进展。

In mouse testes, Musashi-1 (Msi-1) was predominantly expressed in the cytoplasm and nuclei of Sertoli cells. Here we demonstrate that knockdown of Msi-1 in Sertoli cells altered the levels and distribution of blood-testis barrier (BTB)-associated proteins. Moreover, Msi-1 knockdown in vivo disrupted BTB functional structure and spermatogenesis. In addition, we report a novel role of Msi-1 in regulating Sertoli cells survival following heat-induced injury. Endogenous Msi-1 protein in heat-treated Sertoli cells was recruited to stress granules. The formation of stress granules was considerably disrupted, and apoptosis was significantly up-regulated in Msi-1-knockdown Sertoli cells after heat treatment. p-ERK1/2 acted downstream of stress granule formation, and inhibition of p-ERK1/2 signaling triggered Sertoli cell apoptosis upon heat stress. In conclusion, we demonstrate that Msi-1 is critical for constructing a functional BTB structure and maintaining spermatogenesis. We also note a role for Msi-1 in regulating Sertoli cell fate following heat-induced injury, likely through the induction of stress granule formation and subsequent activation of p-ERK1/2 signaling.

A sensitive biosensor for miRNA quantification was fabricated by using a graphene oxide/DNA-decorated electrode.

Bacillus Calmette-Guérin (BCG) reduces the recurrence and progression of non-muscle invasive bladder cancer. The present study aimed to investigate the impact of a recombinant hIFN-α2b-secreting BCG (rBCG) on the mouse bladder MB49 cell line and an orthotopic mouse model of bladder cancer. MB49 cells were cultivated in the presence or absence of rBCG, BCG or BCG+hIFN-α2b. Cellular morphology and viability were assessed by microscopy and CCK-8 assay, respectively. Apoptosis was assessed by acridine orange, Hoechst 33258 staining and flow cytometry. MHC-I expression was assessed by flow cytometry. MB49 cells were transplanted into the bladders of C57BL/6 mice administered BCG, rBCG or BCG+hIFN-α2b. Local tissue Fas expression and T cell subsets were assessed by immunohistochemistry. Peripheral blood TNF-α and IL-12 levels were measured by ELISA, and circulating T lymphocyte subsets by flow cytometry. BCG, rBCG and BCG+hIFN-α2b increased the distortion and death of MB49 cells, yet rBCG reduced the proliferation and enhanced apoptosis most substantially. Apoptosis was increased after a 24-h co-culture with rBCG or BCG+hIFN-α2b. Mice administered rBCG survived longer than mice administered BCG (p<0.001), yet this result was not significantly different from mice administered BCG+hIFN-α2b. The average bladder weight was reduced by administration of rBCG (p<0.001). Fas expression and peripheral blood mTNF-α and mIL-12, cell counts of polymorphonuclear leukocytes, monocytes, T lymphocytes and CD4+/CD8+ ratios were significantly increased by all BCG treatments (p≤0.05), yet monocyte and T lymphocyte counts were higher in mice administered rBCG than in mice treated with BCG or BCG+hIFN-α2b (p=0.000). These results indicate that in an orthotopic murine bladder cancer model rBCG possesses superior antitumor activity to BCG+hIFN-α2b.

We fabricate a sensitive biosensor for miRNA quantification using a graphene oxide/DNA-decorated electrode. AgNPs are modified on DNA probe, which is the complementary sequence of target miRNA. Since the hybridization between DNA and miRNA releases DNA, electrochemical signals from AgNPs are declined, which indicates the concentration of miRNA.

Bladder cancer is the second most common urological malignancy around the world and is by far the most frequent urological malignancy in China. The abnormal expression of sphingosine kinase 2 (SphK2) is associated with tumor progression and a poor patient survival rate, however, the effect of SphK2 on the bladder cancer cells remains unclear. The aim of the paper was to study the expression of SphK2 in bladder cancer and the role of SphK2 on the cell proliferation, metastasis, and apoptosis in bladder cancer in vitro. Our results showed that SphK2 is up-regulated in bladder cancer tissues compared with the corresponding adjacent non-neoplastic tissues, and the expression level of SphK2 was significantly higher in human bladder cancer cells in comparison with normal bladder epithelial cells. Silencing of SphK2 could inhibit the proliferation ability of T24 cells in vitro. In addition, SphK2 knockdown could induce a significant increase in the number of apoptotic cells. Furthermore, the transwell assay also showed significant cell migration inhibition in SphK2 siRNA transfectant compared with cell lines transfected with NC. Thus, this study suggested that SphK2 inhibition may provide a promising treatment for bladder cancer patients.

We fabricate a sensitive biosensor for miRNA quantification using a graphene oxide/DNA-decorated electrode. AgNPs are modified on DNA probe, which is the complementary sequence of target miRNA. Since the hybridization between DNA and miRNA releases DNA, electrochemical signals from AgNPs are declined, which indicates the concentration of miRNA.

[目的]研究重组分泌型内皮抑素腺相关病毒(rAAV-Endostatin,rAAV-ES)的抗肿瘤血管生成及抑制肾细胞癌进展的作用.[方法]应用rAAV-ES转染肾癌细胞,ELISA法测定上清液中重组内皮抑素的浓度并检测其对血管内皮细胞趋化运动的抑制作用；建立裸鼠肿瘤模型,检测肾癌细胞被感染后的成瘤率及全身应用rAAV-ES后抑制肿瘤发展的作用及其毒副作用.[结果]RCC细胞感染rAAV-ES后上清液中重组内皮抑素浓度为52.67 ng/ml,对血管内皮细胞趋化运动的抑制率为38.13％;转染rAAV-ES后的肾癌细胞成瘤率为对照组的60％,体内实验证实全身应用rAAV-ES后血清中内皮抑素长期高效表达,肿瘤生长速度减慢,瘤体微血管密度变低,心脑组织检查未见缺血和其他病理改变.[结论]rAAV-ES无毒副作用,可有效地抑制肿瘤的血管生成,从而抑制肾细胞癌的发生和发展.