荧光原位杂交在膀胱癌检测中的应用进展

膀胱癌是我国泌尿系统最常见的恶性肿瘤.目前膀胱癌的治疗效果不容乐观,因此肿瘤的早期诊断、早期治疗显得尤为重要.本文介绍了荧光原位杂交技术在膀胱癌早期诊断及预后监测应用中的研究进展.     

膀胱癌FGFR3基因突变及靶向药物治疗研究进展

膀胱癌是泌尿系统常见的恶性肿瘤,目前治疗手段多为外科手术治疗辅以化疗,但当前的化疗方案存在不足。成纤维细胞生长因子受体3 (fibroblast growth factor receptor 3, FGFR3)属于酪氨酸激酶受体家族,是膀胱癌中最常见的突变基因之一。研究表明,该基因突变可作为膀胱癌治疗的靶点。该文概述膀胱癌中常见的FGFR3基因突变及相关信号通路的改变,总结了针对FGFR3的靶向药物的研究进展。     

MicroRNA与膀胱癌

MicroRNA(miRNA)是一类21～23个核苷酸长度的单链非编码小分子RNA,在转录后水平调节基因表达,从而实现对组织发生、个体发育及肿瘤发生等生理病理过程的调节作用。膀胱癌是国人泌尿系统中最常见的肿瘤。研究表明,miRNA参与了膀胱癌的发生、发展,一些差异表达miRNA有望成为膀胱癌诊断、治疗的靶点。该文就miRNA在膀胱癌发病机理、诊断、治疗等方面的研究进展作一综述。     

膀胱癌术后卡介苗灌注的护理配合

膀胱癌是泌尿系统常见的肿瘤,确诊后应首选手术治疗.据资料记载,手术切除肿瘤或膀胱部分切除术后,约有2/3患者肿瘤复发,故一般术后采用膀胱内药物灌注治疗以防复发[1].我院自1995年以来对32例膀胱癌患者术后采用卡介苗(BCG)灌注治疗,疗效好,副作用少,现就护理体会总结如下.     

非肌层侵润性膀胱癌的治疗

膀胱癌是一种全球性疾病。在我国泌尿外科肿瘤中的发病率和死亡率均占首位,非肌层侵润性膀胱癌占初发膀胱肿瘤的70%。对膀胱癌的研究已成为目前学术界的热点话题。目前学界对于非肌层侵润性膀胱癌主要采用以外科手术为主的综合治疗方案。为探讨该类肿瘤的治疗方法,本文就近年来对非肌层侵润性膀胱癌的各种治疗措施进行了比较系统的阐述。我们希望能尽可能的找到高效低风险并且经济的方法,为膀胱癌的诊断和治疗提供新途径。     

非肌层侵润性膀胱癌的治疗

膀胱癌是一种全球性疾病。在我国泌尿外科肿瘤中的发病率和死亡率均占首位,非肌层侵润性膀胱癌占初发膀胱肿瘤的70%。对膀胱癌的研究已成为目前学术界的热点话题。目前学界对于非肌层侵润性膀胱癌主要采用以外科手术为主的综合治疗方案。为探讨该类肿瘤的治疗方法,本文就近年来对非肌层侵润性膀胱癌的各种治疗措施进行了比较系统的阐述。我们希望能尽可能的找到高效低风险并且经济的方法,为膀胱癌的诊断和治疗提供新途径。     

膀胱灌注吡柔比星治疗膀胱癌的护理

膀胱癌是泌尿系统最常见的肿瘤,其中70%~80%为表浅性膀胱癌[1]。据文献报道,经尿道膀胱肿瘤电切(TUR)术后膀胱肿瘤复发率达50%~70%,其中10%~30%的复发病例伴有恶性程度增高或浸润能力增强[2]。术后膀胱内灌注药物治疗可降低和延缓肿瘤复发,防止肿瘤发生浸润,提高患者生存率和生     

膀胱癌尿液生物标记物的现状与展望

膀胱癌是世界上最常见的肿瘤之一,膀胱肿瘤的早期检测对改善病人预后至关重要。目前检测和监视膀胱肿瘤的常规方法是膀胱镜检查联合应用尿细胞学检查,但其局限性已经表明膀胱癌需要更好的诊断方法。理想中的诊断方法应该是非侵袭性的,既能够诊断,也能监测疾病的复发,并且能够为治疗提供依据。因此,以尿液为基础的非侵袭性方法将会给患者和医院带来福音。本文综述了近年来报道的膀胱癌尿液生物标记物及相关新技术。     

细胞角蛋白20在膀胱癌中的研究进展

膀胱肿瘤是最常见的泌尿系统肿瘤,其中上皮性肿瘤占95％以上,绝大多数为尿路移行上皮细胞癌。膀胱癌的早期症状不明显,复发率较高,早期诊断和治疗对提高其疗效非常重要。近年来,诊断膀胱肿瘤的新方法不断出现,显著提高了膀胱肿瘤诊断及预后预测水平。其中,膀胱肿瘤标记物检测已成为膀胱肿瘤的诊断新方法,具有十分重要的临床意义。研究发现,细胞角蛋白20fcytokeratin20,CK20）是中间纤维家族成员之一,在正常膀胱组织中特异性表达于伞细胞,在膀胱癌中特异性表达于膀胱移行细胞癌,其诊断膀胱肿瘤的特异性和灵敏性均较高,且与膀胱肿瘤的临床分级、病理分期和转移均密切相关,因此可作为辅助诊断膀胱肿瘤的检测标志物及治疗和预后评估指标。本文将就其在膀胱癌中的研究进展综述如下。     

细胞角蛋白20 在膀胱癌中的研究进展

膀胱肿瘤是最常见的泌尿系统肿瘤,其中上皮性肿瘤占95%以上,绝大多数为尿路移行上皮细胞癌。膀胱癌的早期症状不 明显,复发率较高,早期诊断和治疗对提高其疗效非常重要。近年来,诊断膀胱肿瘤的新方法不断出现,显著提高了膀胱肿瘤诊断 及预后预测水平。其中,膀胱肿瘤标记物检测已成为膀胱肿瘤的诊断新方法,具有十分重要的临床意义。研究发现,细胞角蛋白20 (cytokeratin 20,CK20)是中间纤维家族成员之一,在正常膀胱组织中特异性表达于伞细胞,在膀胱癌中特异性表达于膀胱移行细 胞癌,其诊断膀胱肿瘤的特异性和灵敏性均较高,且与膀胱肿瘤的临床分级、病理分期和转移均密切相关,因此可作为辅助诊断 膀胱肿瘤的检测标志物及治疗和预后评估指标。本文将就其在膀胱癌中的研究进展综述如下。     

Mammalian Target of Rapamycin Complex 2 (mTORC2) Is a Critical Determinant of Bladder Cancer Invasion

Bladder cancer is the fourth most common cause of cancer in males in the United States. Invasive behavior is a major determinant of prognosis. In this study, we identified mammalian target of rapamycin complex 2 (mTORC2) as a central regulator of bladder cancer cell migration and invasion. mTORC2 activity was assessed by the extent of phosphorylation of Ser473 in AKT and determined to be approximately 5-fold higher in specimens of invasive human bladder cancer as opposed to non-invasive human bladder cancer. The immortalized malignant bladder cell lines, UMUC-3, J82 and T24 demonstrated higher baseline mTORC2 activity relative to the benign bladder papilloma-derived cell line RT4 and the normal urothelial cell line HU1. The malignant bladder cancer cells also demonstrated increased migration in transwell and denudation assays, increased invasion of matrigel, and increased capacity to invade human bladder specimens. Gene silencing of rictor, a critical component of mTORC2, substantially inhibited bladder cancer cell migration and invasion. This was accompanied by a significant decrease in Rac1 activation and paxillin phosphorylation. These studies identify mTORC2 as a major target for neutralizing bladder cancer invasion.     

FAM83H-AS1 is associated with clinical progression and modulates cell proliferation,migration, and invasion in bladder cancer

FAM83H-AS1, also known as oncogenic long noncoding RNA (lncRNA)-3, is a novel lncRNA that has been suggested to be dysregulated in a variety of human cancers. However, the expression status and function of FAM83H-AS1 in bladder cancer are still unknown. The object of our study is to explore the clinical value of FAM83H-AS1 in patients with bladder cancer and the biological function of FAM83H-AS1 in bladder cancer cells. In our results, the expression of FAM83H-AS1 was obviously elevated in bladder cancer tissue samples and bladder cancer cell lines compared with adjacent normal tissue samples and normal bladder epithelial cell lines, respectively. In addition, high expression of FAM83H-AS1 was associated with advanced clinical stage and the presence of muscularis invasion and served as an independent poor prognostic factor for overall survival in patients with bladder cancer. The loss-of-function study showed that silencing FAM83H-AS1 expression suppressed cell proliferation, migration, and invasion and induced cycle arrest at G0/G1 phase. In conclusion, FAM83H-AS1 is involved in the progression of bladder cancer and serves as a prognostic biomarker and potential therapeutic target for patients with bladder cancer.     

用组织光学特性鉴别诊断人离体的正常膀胱和膀胱癌组织

研究正常人膀胱和膀胱癌组织在Kube lka-Munk二流模型下对476.5 nm,514.5 nm和808 nm波长的激光的光学特性的差异。采用双积分球系统和Kube lka-Munk二流模型进行测量研究。实验结果表明,正常膀胱和膀胱癌组织在Kube lka-Munk二流模型下对476.5 nm,514.5 nm和808 nm波长的每一个波长的激光的吸收、散射、总衰减、有效衰减系数都有非常显著性的差异(P<0.01)。膀胱癌组织对476.5 nm,514.5 nm和808nm波长的激光的吸收系数明显地较正常膀胱组织对相应波长的激光的吸收系数要大(P<0.01),膀胱癌组织对476.5 nm和514.5 nm波长的激光的散射系数明显地较正常膀胱组织对相应波长的激光的散射系数要小(P<0.01),而膀胱癌组织对808 nm波长的激光的散射系数明显地较正常膀胱组织对同一波长的激光的散射系数要大(P<0.01)。膀胱癌组织对476.5 nm,514.5 nm和808 nm波长的激光的总衰减系数明显地较正常膀胱组织对相应波长的激光的总衰减系数要大(P<0.01),膀胱癌组织对476.5 nm,514.5 nm和808 nm波长的激光的有效衰减系数明显地较正常膀胱组织对相应波长的激光的有效衰减系数要大(P<0.01)。提示使用双积分球系统和Kube lka-Munk二流模型来确定离体的正常膀胱组织和膀胱癌组织对476.5 nm,514.5 nm和808nm波长的激光的光学特性的差异鉴别诊断病变的膀胱组织是一个有效的方法。     

Synthesis and evaluation of a radioiodinated bladder cancer specific peptide

Bladder cancer is the second most common cancer of the urinary tract, however the invasive cystoscopy is still the standard technique for diagnosis and surveillance of bladder cancer. Herein, we radiolabel bladder cancer specific peptide with radioactive iodine ((131/124)I) and evaluate its potential as a new radiopharmaceutical for the non-invasive diagnosis of bladder cancer. A 9-mer bladder cancer specific peptide (BP) was conjugated with tyrosine and cyclized by disulfide bond formation to give Y-BP, which was further radioiodinated to give [(131/124)I]Y-BP in good radiochemical yield. The biodistribution data showed the high selectivity of [(124)I]Y-BP in HT1376 human bladder cancer xenograft models with a tumor-to-muscle ratio of 6.2. This tumor targeting was not observed in control B16F10 melanoma tumor models. In microPET studies, while the control scrambled peptide, [(124)I]Y-sBP, did not accumulate in either the bladder cancer or melanoma, [(124)I]Y-BP showed high tumor uptake only in animals with HT1376 bladder cancer cells. Furthermore, [(124)I]Y-BP showed superior bladder cancer uptake even compared to most commonly used cancer imaging tracer, [(18)F]FDG. The experimental results suggest the potential of [(124)I]Y-BP as a new radiopharmaceutical for the non-invasive diagnosis of bladder cancer with high binding affinity and selectivity.     

CircHIPK3 sponges miR‐558 to suppress heparanase expression in bladder cancer cells

Increasing evidences suggest that circular RNAs (circRNAs) exert crucial functions in regulating gene expression. In this study, we perform RNA‐seq and identify 6,154 distinct circRNAs from human bladder cancer and normal bladder tissues. We find that hundreds of circRNAs are significantly dysregulated in human bladder cancer tissues. We further show that circHIPK3, also named bladder cancer‐related circular RNA‐2 (BCRC‐2), is significantly down‐regulated in bladder cancer tissues and cell lines, and negatively correlates with bladder cancer grade, invasion as well as lymph node metastasis, respectively. Over‐expression of circHIPK3 effectively inhibits migration, invasion, and angiogenesis of bladder cancer cells in vitro and suppresses bladder cancer growth and metastasis in vivo. Mechanistic studies reveal that circHIPK3 contains two critical binding sites for the microRNA miR‐558 and can abundantly sponge miR‐558 to suppress the expression of heparanase (HPSE). Taken together, our findings provide evidence that circRNAs act as “microRNA sponges”, and suggest a new therapeutic target for the treatment of bladder cancer.     

Bladder Polypoid Cystitis-Derived A20 Associates with Tumorigenesis

Bladder chronic inflammation is associated with the pathogenesis of bladder cancer; the underlying mechanism is unclear. The PT53 gene is an important anticancer gene in the body, which is suppressed in cancer. The ubiquitin E3 ligase A20 (A20) plays a role in regulating the activities of epithelial cells. This study was designed to investigate the correlation between A20 and the pathogenesis of bladder cancer. The biopsy tissues of human bladder cancer, bladder polypoid cystitis, and chronic inflammation were collected; the levels of A20 and p53 were analyzed by quantitative real-time RT-PCR, Western blotting, and immune precipitation. HEK293 cells were employed to test the role of overexpression of A20 in the suppression of the p53 gene in the cells. Fifty-six patients with bladder cancer, 48 patients with bladder polypoid cystitis, and 16 patients with bladder chronic inflammation were recruited into this study. Human bladder cancer tissue and the polypoid tissue showed high levels of A20, which had a positive correlation with the tumorigenesis in the bladder; 12 out of 46 (26.1 %) patients with bladder polypoid cystitis were diagnosed as bladder cancer. A20 bound to p53 to form complexes in bladder cancer tissue and bladder polypoid tissue. The overexpression of A20 suppresses p53 protein levels in HEK293 cells. A20 has a positive correlation in the tumorigenesis of bladder polypoid disorders.     

Circular RNA circMTO1 suppresses bladder cancer metastasis by sponging miR-221 and inhibiting epithelial-to-mesenchymal transition

Bladder cancer remains a leading cause of cancer-related death because of its distant metastasis and high recurrence rates. Deregulation of circular RNAs (circRNAs) can act either as tumor suppressors or oncogenes to control cell proliferation, migration, and metastasis. The role of circMTO1 in bladder cancer remain unknown. In this study, we investigated whether circMTO1 could use as a biomarker and therapeutic target for bladder cancer treatment. We first demonstrated that circMTO1 was an important circRNA frequently downregulated in bladder cancer tissue, and lower circMTO1 levels were positively correlated with bladder cancer patients' metastasis and poorer survival. Ectopic expression of circMTO1 in bladder cancer cells inhibited cell's epithelial-to-mesenchymal transition (EMT) and metastasis. In addition, we also revealed that circMTO1 was able to sponge miR-221 and overexpression of circMTO1 negatively regulated the E-cadherin/N-cadherin pathway to inhibit bladder cancer cells' EMT by competing for miR-221. In conclusion, our findings provide comprehensive evidences that circMTO1 is a prognostic biomarker in bladder cancer and suggest that circMTO1 may function as a novel therapeutic target in human bladder cancer.     

Tyrosine kinase ETK/BMX is up-regulated in bladder cancer and predicts poor prognosis in patients with cystectomy

Deregulation of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors. In this report, we demonstrated that ETK expression is progressively increased during bladder cancer progression. We found that down-regulation of ETK in bladder cancer cells attenuated STAT3 and AKT activity whereas exogenous overexpression of ETK had opposite effects, suggesting that deregulation of ETK may attribute to the elevated activity of STAT3 and AKT frequently detected in bladder cancer. The survival, migration and invasion of bladder cancer cells were significantly compromised when ETK expression was knocked down by a specific shRNA. In addition, we showed that ETK localizes to mitochondria in bladder cancer cells through interacting with Bcl-XL and regulating ROS production and drug sensitivity. Therefore, ETK may play an important role in regulating survival, migration and invasion by modulating multiple signaling pathways in bladder cancer cells. Immunohistochemistry analysis on tissue microarrays containing 619 human bladder tissue samples shows that ETK is significantly upregulated during bladder cancer development and progression and ETK expression level predicts the survival rate of patients with cystectomy. Taken together, our results suggest that ETK may potentially serve as a new drug target for bladder cancer treatment as well as a biomarker which could be used to identify patients with higher mortality risk, who may be benefited from therapeutics targeting ETK activity.     

UHRF1在膀胱尿路上皮癌中对HIF1α-VEGF通路的调控作用

目的:本文研究旨在探讨UHRF1对膀胱癌早期诊断和预后的价值.方法:本文研究收集26例膀胱癌病人的癌旁组织和癌症组织,同时用人BCa细胞T24细胞作为体外模型.CCK-8分析、TUNEL染色、LDH活性和Caspase 3/8/9蛋白表活性达水平被用于检测UHRF1的作用.qRT-PCR检测、基因芯片和Western ...