Conclusion. These data suggest that OSM promotes angiogenesis and endothelial cell migration and potentiates the effects of IL-1 in promoting extracellular matrix turnover and human cartilage degradation. Furthermore, the induction of VEGF in cocultures supports the hypothesis of a link between angiogenesis and cartilage degradation.Rheumatoid arthritis (RA) is a chronic disease characterized by synovial tissue proliferation and articular cartilage degradation (1,2). In RA, angiogenesis is an early event required for pannus development, enabling activated monocytes to enter the synovium via endothelial cells by active recruitment (3). The new vessels support expansion of the synovial pannus over the cartilage, facilitating RA synovial fibroblast (RASF) invasion and cartilage degradation by proteolytic cleavage of both aggrecan and collagen (4). This process depends on cytokines and growth factors to stimulate cell survival, proliferation, and extracellular matrix (ECM) degradation (5). Erosion is characterized by a loss of ECM by overexpression of matrix metalloproteinSupported by the Health Research Board of Ireland.
Previous in vitro studies have identified a nuclear isoform of Cathepsin L. The aim of this study was to examine if nuclear Cathepsin L exists in vivo and examine its association with clinical, pathological and patient outcome data. Cellular localization (nuclear and cytoplasmic) and expression levels v of Cathespin L in 186 colorectal cancer cases using immunohistochemistry. The molecular weight and activity of nuclear and cytoplasmic Cathepsin L in vivo and in vitro were assessed by Western blotting and ELISA, respectively. Epithelial nuclear staining percentage (p 5 0.04) and intensity (p 5 0.006) increased with advancing tumor stage, whereas stromal cytoplasmic staining decreased (p 5 0.02). Using multivariate statistical analysis, survival was inversely associated with staining intensity in the epithelial cytoplasm (p 5 0.01) and stromal nuclei (p 5 0.007). In different colorectal cell lines and in vivo tumors, pro-and active Cathepsin L isoforms were present in both the cytoplasm and nuclear samples, with pro-Cathepsin L at 50 kDa and active Cathepsin L at 25 kDa. Purified nuclear and cytoplasmic fractions from cell lines and tumors showed active Cathepsin L activity. The identification of nuclear Cathepsin L may play an important prognostic role in colorectal disease progression and patient outcome. Moreover, these findings suggest that altering active nuclear Cathepsin L may significantly influence disease progression. ' UICCKey words: colorectal cancer; cathepsin L; disease progression; survival Colorectal cancer is one of the most common cancers in the Western World. Tumor invasion and metastasis are major causes of treatment failure 1 and this multi-step process involves penetration of host extracellular matrix (ECM) by cancer cells, which invade the host stroma and enter the circulation. The outcome of metastasis is dependent on the interaction between the intrinsic properties of the tumor cells and various host factors, and this balance may vary from patient to patient. 2,3 The ability of tumor cells to invade tissues and metastasize is thought to involve an increased expression and activity of proteases including cathepsins. 4,5 Tumor spread is also correlated with increased levels of these activated enzymes. 6 The cysteine protease, Cathepsin L, is thought to participate in tumor cell invasion, although its exact role remains unknown. 7 The Cathepsin L gene is activated by a variety of growth factors and oncogenes. 8 It is initially synthesized as a 334-amino acid precursor containing a 17-amino acid N-terminal signal peptide followed by a 96-amino acid propeptide. 9-11 Pro-Cathepsin L is an inactive precursor and is processed to a single chain form of mature Cathepsin L, which can be further cleaved to the two-chain forms, linked to a light-chain by disulfide bonds. 12,13 Pro-and active forms of Cathepsin L differ in size depending on the species, tissue and cell line investigated. Colorectal cancers have been profiled based on the levels of different cysteine proteases including Cathepsin L. 1...
Vegetable consumption is associated with a reduced risk of colorectal cancer, which is the second most common cancer after lung/breast cancer within Europe. Some putative protective phytochemicals are found in higher amounts in young sprouts than in mature plants. The effect of an extract of mixed cruciferous and legume sprouts on DNA damage induced by H2O2 was measured in HT29 cells using single cell microgelelectrophoresis (comet). Significant antigenotoxic effect (P ≤ 0.05) was observed when HT29 cells were pre-incubated with the extract (100 and 200 μL/mL) for 24 hours and then challenged with H2O2. A parallel design intervention study was carried out on 10 male and 10 female healthy adult volunteers (mean age = 25.5 years) fed 113 g of cruciferous and legume sprouts daily for 14 days. The effect of the supplementation was measured on a range of parameters, including DNA damage in lymphocytes (comet), the activity of various detoxifying enzymes (glutathione S-transferase, glutathione peroxidase, and superoxide dismutase), antioxidant status using the ferric reducing ability of plasma assay, plasma antioxidants (uric acid, ascorbic acid, and α-tocopherol), blood lipids, plasma levels of lutein, and lycopene. A significant antigenotoxic effect against H2O2-induced DNA damage was shown in peripheral blood lymphocytes of volunteers who consumed the supplemented diet when compared with the control diet (P = 0.04). No significant induction of detoxifying enzymes was observed during the study, neither were plasma antioxidant levels or activity altered. The results support the theory that consumption of cruciferous vegetables is linked to a reduced risk of cancer via decreased damage to DNA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.