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It has previously been shown that high PAI plasma values were significantly but not strongly associated with poor prognosis in univariate analysis of the same patient material, whereas there was no significant association in multivariate analysis. These results may suggest that these endogenous proteinase inhibitors may serve a similar function.Including PAI in the present multivariate model showed that high values of TIMP were still associated with poor prognosis. This apparent interaction is poorly understood at present, although it is highly significant.However, additional studies are needed to elucidate the biological significance of TIMP in cancer progression as well as the potential clinical use of plasma TIMP measurements.Click on Request Permissions which will take you to the Copyright Clearance Centers Downloaded from clincancerres.aacrjournals.org on April. American Association for Cancer Research. A common scenario for miRNA expression in carcinogenesis is emerging that shows that impaired miRNA production andor downregulation of these transcripts occurs in many neoplasms.In human cancer, miRNA expression proles differ between normal tissues, derived tumors, and tumor types. Importantly, an miRNA expression prole of human tumors has emerged that is characterized by a defect in miRNA production and global miRNA downregulation. Despite the enormous potential that a small molecule that enhances RNA interference might have for cancer therapeutic purposes, the effects of enoxacin in tumor proliferation have not been characterized.Thus, we rst analyzed whether enoxacin could predominantly act as a cancer growth inhibitor by examining the effects of the drug in a panel of cancer cell lines from seven common malignancies.Freely available online Flunisolide through the PNAS open access option.We observed a great decrease in cell viability, measured by the MTT assay, in all cancer cell lines compared with carrier. Most importantly, when we treated two types of normal cells, broblast lines and six primary cultures of normal peripheral blood lymphomononuclear cells derived from healthy donors, we did not observe any effect on cell viability in any of these cells upon enoxacin treatment, suggesting a cancerspecic growthsuppressive activity.The antiproliferative effects of enoxacin were reinforced by the nding that the clonogenic assay capacity of all of the adherent cancer cell lines was signicantly inhibited by drug treatment. Of the cellular biological explanations for the observed growth inhibition effect, the induction of Thujone cellcycle arrest andor apoptosis is the most likely.Thus, we assessed the cellcycle patterns by ow cytometry in the colorectal cancer cell lines HCT and RKO.We found that after hof enoxacin treatment, both cancer cell lines exhibited cellcycle arrest in the GM phase. One critical matter to address is the characterization of the molecular pathways involved in the observed cancer growthinhibitor phenotype mediated by enoxacin.Enoxacin has been characterized as an enhancer of RNA interference, although this mechanism is not naturally used by human cells to silence gene expression posttranscriptionally.We also analyzed the global miRNA expression prole of RKO cells upon enoxacin treatment by using a comprehensive expression miRNA microarray platform. We decided to investigate an additional link between enoxacin, TRBP protein, miRNA processing, and cellular growth by taking advantage of human cancer cells harboring genetic defects in the TARBP gene that encodes the TRBP protein.

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