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Povzetek: 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.
Ključne besede: cysteine cathepsins, cathepsin X, colorectal cancer, prognosis, serum biomarker
Objavljeno v DiRROS: 21.03.2024; Ogledov: 276; Prenosov: 140
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Povzetek: 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.
Objavljeno v DiRROS: 18.03.2024; Ogledov: 297; Prenosov: 76
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Povzetek: 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.
Objavljeno v DiRROS: 31.01.2024; Ogledov: 302; Prenosov: 69
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Objavljeno v DiRROS: 31.01.2024; Ogledov: 269; Prenosov: 71
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Objavljeno v DiRROS: 31.01.2024; Ogledov: 475; Prenosov: 82
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