Type-1 Plasminogen Activator Inhibitor in Human Renal Cell Carcinoma

Wagner, Stephan N.; Atkinson, Michael J.; Thanner, Stephanie; Wilhelm, Olaf G.; Rotter, Michael C.; Höfler, Heinz

doi:10.1002/(sici)1096-9896(199605)179:1<95::aid-path534>3.0.co;2-z

Cited by 12 publications

(3 citation statements)

References 24 publications

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“…(p < 0.001) than in the 30 normal samples. None of the cancer samples exhibited an aberrant TPRII mRNA tran-PAI-1 and MMP9 are metastasis-promoting genes (12)(13)(14)(15)(16)(17)(18). Therefore we next determined PAI-1 and MMP9 expression in relation to TPRII mRNA levels.…”

Section: Tprii Expression In Human Pancreatic Tissuesmentioning

confidence: 99%

“…Inasmuch as the breakdown of extracellular matrix components is an essential step in tumor invasiveness and metastasis, the excessive expression of PAI-1 and MMP9 is believed to contribute in an important manner to both processes in vivo. Thus increased PAI-1 and MMP9 levels have been associated with increased metastatic potential and tumor aggressiveness in a variety of malignancies (12)(13)(14)(15)(16)(17)(18).…”

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confidence: 99%

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Enhanced Expression of the Type II Transforming Growth Factor-β Receptor Is Associated with Decreased Survival in Human Pancreatic Cancer

et al. 1999

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Transforming growth factor-Ps (TGF-Ps) bind to the type I1 TGF-P receptor (TPRII), which then heterodimerizes with the type I TGF-P receptor (TPRI), thereby initiating a signaling cascade. TGF-Ps are overexpressed in pancreatic cancer, and this overexpression is associated with more aggressive disease. Although TPRII also is overexpressed in pancreatic ductal adenocarcinoma cells in vivo, the biologic significance of this overexpression is not completely known. Therefore in this study, we characterized TPRII expression by Northern blot analysis in 32 normal and 42 cancerous pancreatic tissues and correlated the survival of the cancer patients with TPRII messenger RNA (mRNA) levels. Northern blot analysis revealed that, by comparison with the normal controls, TPRII expression was increased in 19 (45%) of 42 cancer samples. Densitometric analysis of all the pancreatic tissues revealed a 3.4-fold increase (p c 0.01) in TPRII mRNA levels in the cancer tissues by comparison with normal controls. There was a strong correlation between the expression of TPRII and the levels of two invasion-promoting genes, plasminogenactivator-inhibitor-1 (PAI-1) and matrix-metalloproteinase-9 (MMP9). Log-rank analysis of the Kaplan-Meier survival curves indicated that patients whose tumors overexpressed TPRII had a significantly shorter survival period than did patients whose cancers expressed low levels of TPRII. It is suggested that TPRII overexpression may be a marker that correlates with disease progression in pancreatic ductal adenocarcinoma. Key Words: TGF-P receptor type II-PAI-1-MMP9-Pancreatic cancer.Pancreatic ductal adenocarcinoma is a devastating disease that is the fifth leading cause of cancer death in the Western world (1,2). The l-year overall survival rate in this disorder is only 12%, and >98% of the patients are dead within 5 years (1.2). The diagnosis of pancreatic cancer is often established at an advanced stage when the tumor has already metastasized, precluding patients from undergoing a curative resection. Furthermore, nonsurgical treatments for pancreatic cancer are often ineffective because of the resistance of pancreatic cancer cells to cytotoxic agents and the failure of radiation therapy to arrest tumor spread (3,4). Although the reasons for the aggressiveness of pancreatic cancer and the molecular mechanisms that contribute to its propensity to metasta-

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Section: Tprii Expression In Human Pancreatic Tissuesmentioning

confidence: 99%

mentioning

confidence: 99%

Enhanced Expression of the Type II Transforming Growth Factor-β Receptor Is Associated with Decreased Survival in Human Pancreatic Cancer

et al. 1999

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“…Furthermore, it has been suggested that PAI-1 can either enhance or inhibit tumour growth and angiogenesis depending on its concentration [5]. In several carcinomas PAI-1 expression has been found to be higher than in normal cells and associated with tumour growth, invasion, and metastasis [6,7]. Divergent results have also been reported about the clinical significance of the urokinase-type plasminogen activator (u-PA) system in renal cell carcinoma (RCC) [5,6,8-10].…”

Section: Introductionmentioning

confidence: 99%

Type 1 plasminogen activator inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC) and its impact on angiogenesis, progression and patient survival after radical nephrectomy

et al. 2010

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BackgroundTo examine the expression of type 1 plasminogen inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC), and its possible association with microvessel density (MVD), the expression of thrombospondin-1 (TSP-1), nuclear grade, tumour stage, continuously coded tumour size (CCTS) and to assess the value of PAI as a prognostic marker in 162 patients with CCRCC treated with radical nephrectomy.MethodsA total of 172 consecutive patients with CCRCC treated with radical nephrectomy were enrolled in the study. The expression of PAI-1, TSP-1 and factor VIII were analysed on formalin-fixed, paraffin-embedded tissues without knowledge of the clinical outcome. Ten cases, where PAI-1 immunohistochemistry was not possible due to technical problems and lack of material, were excluded. Sixty-nine patients (43%) died of RCC, while 47 patients (29%) died of other diseases. Median follow-up was 13.8 years for the surviving 46 patients (28%).ResultsNine percent of the tumours showed PAI-1 positivity. High expression of PAI-1 was significantly inversely correlated with TSP-1 (p = 0.046) and directly with advanced stage (p = 0.008), high NG (3+4) (p = 0.002), tumour size (p = 0.011), microvessel density (p = 0.049) and disease progression (p = 0.002). In univariate analysis PAI-1 was a significant prognosticator of cancer-specific survival (CSS) (p < 0.001). Multivariate analysis revealed that TNM stage (p < 0.001), PAI-1 (p = 0.020), TSP-1 (p < 0.001) and MVD (p = 0.007) were independent predictors of CSS.ConclusionsPAI-1 was found to be an independently significant prognosticator of CSS and a promoter of tumour angiogenesis, aggressiveness and progression in CCRCC.

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Urokinase gene expression indicates early invasive growth in squamous cell lesions of the uterine cervix

Riethdorf

Petersen

Bauer³

et al. 1999

J. Pathol.

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Type-1 Plasminogen Activator Inhibitor in Human Renal Cell Carcinoma

Cited by 12 publications

References 24 publications

Enhanced Expression of the Type II Transforming Growth Factor-β Receptor Is Associated with Decreased Survival in Human Pancreatic Cancer

Enhanced Expression of the Type II Transforming Growth Factor-β Receptor Is Associated with Decreased Survival in Human Pancreatic Cancer

Type 1 plasminogen activator inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC) and its impact on angiogenesis, progression and patient survival after radical nephrectomy

Urokinase gene expression indicates early invasive growth in squamous cell lesions of the uterine cervix

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