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BACKGROUND: The activation of Fas/Fas ligand (FasL) and DR4-DR5/tumor necrosis factor-related-apoptosis-inducing ligand (TRAIL) pathways in cancer cells triggers apoptosis. The objective of this study was to investigate the prognostic value of soluble FasL (sFasL) and soluble (sTRAIL) in the serum of patients with bladder cancer. METHODS: The sFasL and sTRAIL levels in the sera of patients with bladder cancer or healthy donors were determined using the enzyme-linked immunosorbent assay. Micro-culture tetrazolium viability assay and Western blot were used to analyze cell cytotoxicity and death receptors protein expression respectively. RESULTS: Whether no difference in sTRAIL levels was seen between patients and controls, the level of sFasL was higher in patients than that in healthy donors. According to, sFasL level was the highest in the serum of patients with superficial stage or low- and medium-grade cancer. Moreover, sFasL in patients with superficial noninvasive bladder tumors or low- and medium-grade cancers was higher than that in patients with invasive carcinomas and high-grade cancers. Patients with high levels of sFasL survive longer than those with low levels, probably related to the cytotoxic potential of FasL preserved in its soluble form. CONCLUSION: The data suggest that monitoring the level of sFasL and its cytotoxic activity could be a prognostic marker in the follow-up of patients with bladder cancer.
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Carcinoma de Células de Transição/sangue , Proteína Ligante Fas/sangue , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Neoplasias da Bexiga Urinária/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Tunísia , Bexiga Urinária/patologiaRESUMO
BACKGROUND: Her2/neu is an oncogene that plays an important role in the pathogenesis of many cancer types. In bladder carcinoma (BC), the clinical significance of Her2/neu status remains under-investigated and poorly linked to the patients' clinic-pathological features and survival status. Thus, the current study was conducted to assess Her2/neu status in a cohort of patients' in Saudi Arabia, and to explore its prognostic value in BC. METHODS: A total of 160 consent patients of transitional cell carcinoma (TCC) of bladder were arranged on a tissue microarray (TMA) and stained by immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) methods. The intensity of Her2/neu protein receptor immunostaining was evaluated, correlated to Her2/neu gene amplification status in TCC and assessed for potential clinical value by correlation measures. RESULTS: IHC data demonstrated that Her2/neu protein is expressed in 60 % (2+ and 3+) of our TCC patient's cohort from Saudi Arabia. Her2/neu gene amplification is detected in 25 % by BDISH. There was a strong association between Her2/neu protein levels and lymph node invasion (p = 0.04), tumor stage (p = 0.002), vascular invasion and borderline significance with distant metastasis (p = 0.07). Amplification of Her2/neu gene was associated with tumor grade (p = 0.03) and poor disease-specific survival (p = 0.02), in that, patients with non-amplified Her2/neu gene live longer. Interestingly, there was a reasonable concordance rate (71 %) between IHC and BDISH data in the analyzed cohort. CONCLUSION: The study showed that 25 % of our patients' cohort has Her2/neu over-expression. This Her2/neu (over-expression/amplification) status was concordant using either IHC or BDISH and significantly associated with disease aggressiveness and poor outcome. These findings suggested a potential impact of anti-Her2 targeted therapy in the treatment of bladder cancer with amplified/overexpressed HER2 that needs further investigation.
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Carcinoma de Células de Transição/patologia , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Receptor ErbB-2/metabolismo , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/metabolismo , Feminino , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Gradação de Tumores , Invasividade Neoplásica , Prognóstico , Análise de Sobrevida , Análise Serial de Tecidos/métodos , Neoplasias da Bexiga Urinária/metabolismo , Adulto JovemRESUMO
Synchronous presentation of Multiple Primary Malignant neoplasms in genitourinary system is not a common event. Absolute majority of reported cases are concurrent outbreak of clear cell type renal cell carcinoma in the kidney and transitional cell carcinoma in ipsilateral renal pelvic. We reported concurrent presenting of two separate primary malignancies, urothelial cell carcinoma of bladder and papillary renal cell carcinoma Type 2 in kidney in a 59-year-old man for the first time.
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The association between dermatomyositis (DMS) and various types of malignancies has been reported in several studies, with an estimated frequency of 20-25%. DMS may precede, accompany or follow the diagnosis of malignancy. In the present report, we have discussed three cases of dermatomyositis associated with malignancy. In the first case, DMS preceded the diagnosis of gastric adenocarcinoma while in the second and third cases, it followed the diagnosis of ductal carcinoma of the breast and transitional cell carcinoma of the bladder respectively. In all three patients, cutaneous and musculoskeletal features of DMS showed very good response to the treatment, irrespective of the course of malignancy.
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The thyroid gland is a rare site for cancer metastasis. We report a 75-year-old man who was referred with a history of hematuria and generalized bone pain for the past few months. He had a past history of partial left lobe thyroidectomy for follicular adenoma. Subsequently he was referred for a thyroid mass and a subtotal thyroidectomy showed a poorly-differentiated carcinoma. On the latest admission, the patient underwent resection of a bladder tumour with malignant histology and an immunohistochemical profile of CK7+/CK20+/34 Beta E12+/CEA-/PSA-. Re-examination of thyroid sections with immunohistochemical stains revealed the malignant cells to be CK7+/CK20+/34 Beta E12+/CEA-/TTF1-. The findings were compatible with metastasis of the bladder transitional cell carcinoma to the thyroid gland.Scans revealed multiple liver and bone metastases. The patient died 2 months after the diagnosis.
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Objective To asses the value of fluorescence in situ hybridization (FISH) in diagnosis of transitional cell carcinoma of bladder in the urine using directly labeled DNA probes to the pericentromeric regions of chromosomes 3 , 7 and 17 and to the region of P16 tumor suppressor gene. Methods Chromosomal and gene abnormalities were detected using directly labeled DNA probes to the pericentromeric regions of chromosomes 3 , 7, and 17 and to the region of P16 tumor suppressor gene. The sensitivity of FISH and Cytology in diagnosing transitional cell carcinoma of bladder was also compared. Results The sensitivity of FISH and Cytology in diagnosing the disease was 85.5% and 34.2%, respectively. The sensitivity of FISH was prior to that of Cytology( P <0.05 ) and increased with increasing tumor pathologic grade but not clinical staging. Conclusions High sensitivity of FISH in diagnosing transitional cell carcinoma of bladder was obtained and it might be a potent method to diagnose bladder cancer in Chinese people in the future.
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Objective:To explore the relation of the abnormal condition of centrosome and p53 genetic mutation of bladder cancer cells,its effect on the onset and progress of the transitional cell carcinoma of bladder because of p53 genetic mutation. Methods: 76 transitional cell carcinoma of bladder were examined.The centrosome was stained by indirect immunofluorescence methods,and the primary antibody was monoclonal antibody against pericentrin.The p53 was stained by SP immunohistochemical methods and the primary antibody was monoclonal antibody against p53.Results: Through statistical analysis,detection of CH or p53 expression was useful in providing prognostic information in bladder cancer. There existed a positive correlated(r=0.707,P
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Objective:To explore the effect of gene hepaCAM transfection on the proliferation in human bladder carcinoma cell line. Methods: Plasmid pEGFP-N2-hepaCAM was transfected into T24 cells by Lipofectamine2000, and the T24 cell stably expressing hepaCAM gene was established by G4l8 selection.The expression of hepaCAM mRNA and protein was detected by RT-PCR and Western blot assays. The effects of hepaCAM on cell proliferation were measured by MTT and colony formation assays. The cell cycle progression were measured by flow cytometry. The expression of CyclinD1 mRNA was detected by RT-PCR. Results:Expression of hepaCAM gene and protein were proved by RT-PCR and Western blot assays. The MTT assay showed cell growth in the T24/hepaCAM-GFP group was significantly slow when compared with non-transfection and mock-vehicle groups whereas the rates of clonal formation were greatly decreased(P
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Objective To explore the Activation function of the bifidobacterium adolescence cell wall(BCW)on macrophage in abdominal cavity of mice and tumor-inhibition of BCW on human transitional cell carcinoma of bladder(BTCC)in vitro.Methods ①Twenty KM mice were randomly divided into two groups:control group(n=10)and BCW injection group(n=10).BCW was distilled by ultrasonic cell disintegrator.Then the BCW was injected into abdominal cavity of the BCW injection group mice,physiological saline was injected into the control group mice,then all the mice were killled,macrophage in abdominal cavity was collected under the condition of asepsis,the level of IL-2 and IFN-? which produced by macrophage was determined by ELISA reagent box;②The role of tumor-inhibition of BCW on human transitional cell carcinoma of bladder(BTCC,T24)in vitro was determined by MTT method:The cell of T24 in the stage of logarithmic growth was digested,inoculated in cell raise board,cultivated after 24 hours,different concentration of BCW were added into each hole,cultivated continually,replaced nutrient fluid on 1th day,3th day,5th day,MTT was added into each hole too,cultivated continually,DMSO was added into each hole,vibrated,shaked up,determined the A value at 490nm by ELIASA,calculated the tumor-inhibition rate;Observed the growth state under microscope:The cell of T24 in the stage of logarithmic growth was inoculated in cell raise board that comprise microscope slides,cultivated after 24 hours,BCW were added into each hole,cultivated continually,took out two slides after 24 hours,72 hours,120 hours,stained,observed the change of the shape of T24 under microscope,changed the culture liquid only on control group.each time.Results The level of IL-2 and IFN-? of BCW injection group was higher than of control group(P
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0. 05) . The sensitivity and specificity of NMP-,2 in diagnosing transitional cell carcinoma of bladder were 85. 7% and 60% when the cut-off was set 10 u/ml, In contrast, the sensitivity and specificity of urinec cytology were 32. 1% and 100%. Conclusions: Urinary NMP22 can be used to screen and follow up transitional cell carcinomas of bladder with high sensitivity and high specificity.
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Objective To observe the effects of E cadherin (ECD) on bladder cancer cell growth and invasion using gene transfection technique. Methods Human E cadherin gene was transfected into a highly invasive and metastatic bladder cancer cell line Ts3L. Cell growth curves, clone formation rate, in vitro tumor cell infiltrating ability, and cell cycle distribution were determined, respectively. Results Speed of bladder cancer cell growth decreased significantly to 35 7% after ECD gene transfection. Apoptotic cell rate in ECD transfected cells was markedly higher than that of the control cells. The percentage of superploid cells in Ts3L/ECD cells was significantly reduced than that in the control cells. Clone formation rate of ECD transfected cells, detected by soft agarose gel clone formation test, was significantly decreased as compared with that of the control cells ( P
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To determine whether the dysfunction of p53 caused either by mutation of the p53 gene itself or by binding to E6 protein of oncogenic HPVs is involved in the transitional cell carcinomas (TCCs) of the bladder, we analyzed 23 TCCs of the bladder. DNA was extracted from each paraffin embedded tissue of TCCs of bladder and polymerase chain reaction (PCR)/single strand conformation polymorphism (SSCP) analysis were performed to screen mutations in p53 tumor suppressor gene, then PCR/dot blot hybridization were performed to detect infection of HPVs. We found that p53 gene mutation was found in 3 cases and oncogenic HPV infection was detected in 8 cases and thus, the overall incidence of possible p53 dysfunction was 47.8% on DNA analysis (If the results of immunohistochemistry to detect overexpression of p53 protein were included, the incidence was 60.9%). Therefore, we concluded that dysfunction of p53 plays a major role in the development of TCCs of bladder in Korean patients.