Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urokinase-type plasminogen activator has been administered by other investigators to patients with small cell carcinoma of the lung (SCCL) in an attempt to induce lysis of fibrin that is known to exist in the connective tissue stroma of this tumour type and that may support tumour growth. To study the fate of infused urokinase in this disease, a biopsy of a scalp metastasis was obtained from a patient with SCCL (entered on a phase I clinical trial of urokinase plus combination chemotherapy) immediately following urokinase infusion during the fourth course of therapy a time when this tumour mass had decreased to approximately 25% of its original size. Immunohistochemical procedures revealed abundant stromal fibrin in accord with previous observations from this laboratory. By contrast, urokinase, that is not a feature of small cell tumour cells, was present on the tumour cells in this specimen. Urokinase infusion was associated with a rapid increase in the amount of this enzyme associated with isolated peripheral blood monocytes. These results are consistent with uptake of infused urokinase onto monocytes and possibly tumour cells. It is postulated that substantial tumour fibrinolysis may not accompany such therapy and that urokinase, or its amino terminal fragment that bears the growth factor domain of this molecule, may bind to and alter the growth of the tumour cells.
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PMID:Studies of possible mechanisms for the effect of urokinase therapy in small cell carcinoma of the lung. 760 74

We sought to determine if urokinase expression is regulated at the post-transcriptional level in cultured lung epithelial cells. We also sought to determine if differences in urokinase expression by cultured human lung carcinoma and non-malignant lung epithelial subtypes were attributable to post-transcriptional regulatory mechanisms. Urokinase was expressed by phenotypically diverse lung carcinoma cell lines as well as non-malignant small airway epithelial cells and bronchial epithelial cells. Using gel mobility shift and UV cross-linking assays, we identified a 30-kDa urokinase mRNA-binding protein that selectively bound to a 66-nucleotide protein-binding fragment of urokinase mRNA. The urokinase mRNA-binding protein is found in the cytosolic but not nuclear extracts of non-malignant lung epithelial cells; whereas, it is found in the nuclear but not cytosolic extracts of selected malignant carcinoma-derived cells that express relatively large amounts of urokinase. Chimeric beta-globin/urokinase cDNA containing the urokinase mRNA-binding protein binding sequence destabilized otherwise stable beta-globin mRNA. Our results demonstrate that urokinase gene expression in lung epithelial and lung carcinoma-derived cells is regulated at the post-transcriptional level. The mechanism involves an interaction between a 66-nucleotide sequence of the urokinase mRNA 3'-untranslated region with a newly recognized urokinase mRNA-binding protein to regulate urokinase mRNA stability.
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PMID:Post-transcriptional regulation of urokinase mRNA. Identification of a novel urokinase mRNA-binding protein in human lung epithelial cells in vitro. 1078 98