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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: 131; Prenosov: 28
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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: 166; Prenosov: 40
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Objavljeno v DiRROS: 31.01.2024; Ogledov: 148; Prenosov: 38
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Objavljeno v DiRROS: 31.01.2024; Ogledov: 201; Prenosov: 36
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Povzetek: The aim of the retrospective study was to evaluate the efficacy of radiosynovectomy (with yttrium 90) mainly in patients with rheumatoid arthritis, less with some other rheumatic diseases. The evaluation period varied from half to nine years. The procedure was performed in 273 patients (225 females, 48 males) or in 463 joints (402 knees, 61 shoulders and ankles).The effects was evaluated by change in degree of morning stiffiness, pain and swelling (score from 0 to 9). Very good results were obtained in 69 (15%), good in 142 (30.5%), moderate in 197 (42.5%) and no effect in 55 (12%) joints. Six months after the procedure 38 joints (8%), half to two years after221 joint (48%) were in good remission, after 3 to 4 years 95 joints (20%), after 5 to 6 years 57 joints (12%) were well, 7 to 9 years later 52 joints (11%) showed no signs of arthritis. Joint pain and swelling were the most frequent procedure complications (5.6%). In two patients with additional immunomodulating therapy chronic myeloid and lymphocityc leukaemia were diagnosed. Radiosynovectomy is considered to be an effective and safe treatment for synovitis indifferent rheumatic diseases.
Objavljeno v DiRROS: 18.01.2024; Ogledov: 212; Prenosov: 42
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