Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer is the most common neoplasm affecting women in the Western world with approximately 1 in 11 developing the malignancy and 1 in 30 dying from the disease. For optimum management of these patients, assay of certain biochemical markers is necessary. Clinically, the most useful markers in breast cancer are the estrogen and progesterone receptors that are used to predict response to hormone therapy. Both American and European Expert Panels have recommended routine determination of these steroid hormone receptors in all patients with breast cancer. For surveillance of patients with diagnosed breast cancer, both CA 15-3 and BR 27.29 can be used. Serial determinations of these markers have the potential to preclinically detect recurrent disease and monitor the treatment of advanced disease. However, the benefit of this monitoring on patient outcome or quality of life is not clear. New or potentially new markers for breast cancer include BRCA1 and BRCA2 for selecting patients at high risk of developing breast cancer, urokinase plasminogen activator and PA1-1 for assessing prognosis and HER-2 for predicting response to the therapeutic antibody, Herceptin.
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PMID:Biochemical markers in breast cancer: which ones are clinically useful? 1152 69

In breast cancer, about 35% of patients without any clinical signs of overt distant metastases already have disseminated tumor cells in bone marrow aspirates at the time of primary therapy. A significant prognostic impact of these disseminated tumor cells has been shown by many international studies: patients with tumor cells in their bone marrow have a significantly worse prognosis than those without them. Even in malignancies where the skeletal system is not a preferred location for distant metastasis, such as ovarian cancer, early presence of minimal residual disease (MRD) is correlated with poor patient outcome. Thus, besides analysis of the primary tumor, detection of MRD can be used for assessment of patient prognosis and for prediction or monitoring of response to systemic therapy. Disseminated tumor cells are also the targets for novel tumor biological therapy approaches such as specific antibody-based therapies against target cell-surface antigens such as HER2, Ep-CAM (17-1A), and uPA-R. In breast cancer, a first antibody-based tumor therapy against HER2 (Herceptin) has already been approved for clinical use in recurrent disease. However, patient selection for such tumor biological therapies becomes rather difficult due to phenotype changes, which may manifest themselves as differences between primary lesion and disseminated tumor cells. Therefore, not only identification of disseminated tumor cells but even more so their characterization at the protein and gene levels have become increasingly important. In conclusion, characterization of tumor biological properties of disseminated tumor cells allows identification of patients with breast cancer or gynecological malignancies at risk for relapse who are likely to benefit from systemic treatment and/or novel tumor biological therapy approaches.
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PMID:Minimal residual disease in breast cancer and gynecological malignancies: phenotype and clinical relevance. 1279 Mar 24

The vectors PAI2, C595 and Herceptin target the membrane-bound uPA, MUC1 and HER2 antigens expressed by cancer cells, respectively. The expression of these receptors was tested in the ovarian cancer cell line OVCAR-3; MUC-1 was strongly expressed (3+), uPA moderately expressed (2+), but HER2 was negative (-). The alpha-emitting radionuclide Bismuth-213 was chelated with these targeting vectors to form alpha conjugates (ACs), the cytotoxicity of which were tested with OVCAR-3 cells. The PAI2 and C595 ACs are highly cytotoxic to the ovarian monolayer cancer cells and cell clusters in a concentration-dependent fashion and cause morphological changes of treated cancer cells, inducing apoptosis. These ACs are potential candidates for the control of ovarian cancer at the minimum residual disease (MRD) stage.
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PMID:Cytotoxicity of PAI2, C595 and Herceptin vectors labeled with the alpha-emitting radioisotope Bismuth-213 for ovarian cancer cell monolayers and clusters. 1596 Dec 20

Breast cancer is the most common neoplasm affecting women in the Western world. Many studies are still conducted with the purpose of finding markers that could be used for early diagnosis and/or serve as possible reliable prognostic or predictive parameters, but with conflicting results. At present, no markers are available for an early diagnosis of breast cancer For surveillance of patients with diagnosed breast cancer the most widely used serum markers are CA 15-3 and CEA which, in combination with other clinical parameters, could have clinical significance. The most useful and clinically important tissue-based markers in breast cancer are estrogen and progesterone receptors, used as a basis for hormonal therapy, and HER-2 receptors, essential in selecting patients for the treatment with Herceptin. New or potentially new markers for breast cancer include BRCA1 and BRCA2 genes for selecting patients at high risk of developing hereditary breast cancer, as well as urokinase plasminogen activator and inhibitor for assessing prognosis in lymph node-negative patients. Results of tumor and patient genetic analyses including their clinical evaluation will enable application of more individualized and personalized approach in diagnosis and therapy of breast cancer patients.
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PMID:Tumor markers in breast cancer--evaluation of their clinical usefulness. 2166 78