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Abstract: Background. Up-regulation of lysosomal cysteine protease cathepsin X (Cat X) is associated with disorders of the immune system and neurodegenerative diseases, while its role in the development and progression of cancer is less understood. Enhanced secretion of pro-Cat X was observed in malignant processes, and therefore, the level of total serum Cat X rather than the active enzyme may better reflect the tumour status. Patients and methods. Seventy-seven patients with colorectal cancer (CRC) were included in a retrospective study. Blood samples were collected prior to therapy. Using ELISA, the values of total Cat X were measured in serum. Groups of healthy persons (n=77), patients with adenomas (n=77) and patients with non-neoplastic findings (n=77) were included. Results. Significant differences between the group of colorectal patients and the groups of healthy persons, adenoma patients and patients with non-malignant findings could not be shown (p=0.89). Within the group of CRC, higher levels of total Cat X significantly correlated to shorter overall survival (HR=2.08, 95% CI:1.07-4.05, p=0.028). Conclusions. Total serum Cat X could be a useful prognostic indicator for determining survival of patients with CRC. Increased serum levels of total CatX may reflect more aggressive tumour cell phenotypes and suggest the involvement of Cat X in processes involved in later stages of tumour progression.
Keywords: cysteine cathepsins, cathepsin X, colorectal cancer, prognosis, serum biomarker
Published in DiRROS: 21.03.2024; Views: 142; Downloads: 78
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Abstract: Background. Cathepsin H is a cysteine protease considered to play a major role in tumor progression, however, its precise function in tumorigenesis is unclear. Cathepsin H was recently proposed to be involved in processing of bone morphogenetic protein 4 (BMP-4) in mice. In order to clarify whether cathepsin H also regulates BMP-4 in humans, its impact on BMP-4 expression, processing and degradation was investigated in prostate cancer (PC-3), osteosarcoma (HOS) and pro-monocytic (U937) human cell lines. Materials and methods. BMP-4 expression was founded to be regulated by cathepsin H using PCR array technology and confirmed by real time PCR. Immunoassays including Western blot and confocal microscopy were used to evaluate the influence of cathepsin H on BMP-4 processing. Results. In contrast to HOS, the expression of BMP-4 mRNA in U937 and PC3 cells was significantly decreased by cathepsin H. The different regulation of BMP-4 synthesis could be associated with the absence of the mature 28 kDa cathepsin H form in HOS cells, where only the intermediate 30 kDa form was observed. No co-localization of BMP-4 and cathepsin H was observed in human cell lines and the multistep processing of BMP-4 was not altered in the presence of specific cathepsin H inhibitor. Isolated cathepsin H does not cleave mature recombinant BMP-4, neither with its amino- nor its endopeptidase activity. Conclusions. Our results exclude direct proteolytic processing of BMP-4 by cathepsin H, however, they provide support for its involvement in the regulation of BMP-4 expression.
Published in DiRROS: 18.03.2024; Views: 170; Downloads: 30
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Abstract: Purpose. To evaluate the significance of cysteine proteinase inhibitors stefins (Stefs) A and B for a treatment decision and prognosis in operable squamous cell carcinoma of the head and neck (SCCHN). Patients and methods. Stefs A and B concentrations were determined immunobiochemically using ELISAs in cytosols prepared from the tumor and adjacent normal mucosa from 91 patients with operable SCCHN. The median follow-up period of patients alive atthe close-out date was 5.8 years (range, 5-9.3 years). Results. Stef A concentrations were significantly higher in tumor compared to normal mucosa (FM.05). When a subgroup with clinically palpable nodes) at presentation was taken into consideration (n=57), a significant difference in Stef A (P=0.03) and Stef B (P=0.02) concentrations between those with negative and positive necks, as determined on histopathological examination, was observed. On the univariate survival analysis, higher Stefsć concentrations turned to be prognostically advantageous. Stef A proved its independent prognostic significance also on multivariate setting. Conclusions. With the capability todifferentiate between the pN0- and pN+-stages of the disease in the patientsoriginally presented as node-positive, Stefs A and B could be useful markers when deciding on the extent of neck surgery. In addition, both Stefs proved to be reliable prognosticators for survival in patients with operable SCCHN.
Published in DiRROS: 31.01.2024; Views: 180; Downloads: 45
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Published in DiRROS: 31.01.2024; Views: 156; Downloads: 40
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Published in DiRROS: 31.01.2024; Views: 239; Downloads: 40
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