1. The cost of systemic therapy for metastatic colorectal carcinoma in Slovenia : discrepancy analysis between cost and reimbursementTanja Mesti, Biljana Mileva Boshkoska, Mitja Kos, Metka Tekavčič, Janja Ocvirk, 2015, izvirni znanstveni članek Povzetek: The aim of the study was to estimate the direct medical costs of metastatic colorectal cancer (mCRC) treated at the Institute of Oncology Ljubljana and to question the healthcare payment system in Slovenia. Methods. Using an internal patient database, the costs of mCRC patients were estimated in 2009 by examining (1) mCRC direct medical related costs, and (2) the cost difference between payment received by Slovenian health insurance and actual mCRC costs. Costs were analysed in the treatment phase of the disease by assessing the direct medical costs of hospital treatment with systemic therapy together with hospital treatment of side effects, without assessing radiotherapy or surgical treatment. Follow-up costs, indirect medical costs, and nonmedical costs were not included. Results. A total of 209 mCRC patients met all eligibility criteria. The direct medical costs of mCRC hospitalization with systemic therapy in Slovenia for 2009 were estimated as the cost of medications (cost of systemic therapy + cost of drugs for premedication) + labor cost (the cost of carrying out systemic treatment) + cost of lab tests + cost of imaging tests + KRAS testing cost + cost of hospital treatment due to side effects of mCRC treatment, and amounted to %3,914,697. The difference between the cost paid by health insurance and actual costs, estimated as direct medical costs of hospitalization of mCRC patients treated with systemic therapy at the Institute of Oncology Ljubljana in 2009, was %1,900,757.80. Conclusions. The costs paid to the Institute of Oncology Ljubljana by health insurance for treating mCRC with systemic therapy do not match the actual cost of treatment. In fact, the difference between the payment and the actual cost estimated as direct medical costs of hospitalization of mCRC patients treated with systemic therapy at the Institute of Oncology Ljubljana in 2009 was %1,900,757.80. The model Australian Refined Diagnosis Related Groups (AR-DRG) for cost assessment in oncology being currently used is probably one of the reasons for the discrepancy between pay-outs and actual costs. We propose new method for more precise cost assessment in oncology.
Ključne besede: cost of treatment, metastatic colorectal cancer, cost of targeted therapy, monitoring costs
Objavljeno v DiRROS: 17.04.2024; Ogledov: 48; Prenosov: 10
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2. Inhibition of cathepsin X enzyme influences the immune response of THP-1 cells and dendritic cells infected with Helicobacter pyloriMiha Skvarč, David Štubljar, Andreja Nataša Kopitar, Samo Jeverica, Bojan Tepeš, Janko Kos, Alojz Ihan, 2013, izvirni znanstveni članek Povzetek: Background. The immune response to Helicobacter pylori importantly determines the outcome of infection as well as the success of eradication therapy. We demonstrate the role of a cysteine protease cathepsin X in the immune response to H. pylori infection. Materials and methods. We analysed how the inhibition of cathepsin X influenced the immune response in experiments when THP-1 cells or dendritic cells isolated from patients were stimulated with 48 strains of H. pylori isolated from gastric biopsy samples of patients which had problems with the eradication of bacteria. Results. The experiments, performed with the help of a flow cytometer, showed that the expression of Toll-like receptors (TLRs), especially TLR-4 molecules, on the membranes of THP-1 cells or dendritic cells was higher when we stimulated cells with H. pylori together with inhibitor of cathepsin X 2F12 compared to THP-1 cells or dendritic cells stimulated with H. pylori only, and also in comparison with negative control samples. We also demonstrated that when we inhibited the action of cathepsin X in THP-1 cells, the concentrations of pro-inflammatory cytokines were lower than when THP-1 cell were stimulated with H. pylori only. Conclusions. We demonstrated that inhibition of cathepsin X influences the internalization of TLR-2 and TLR-4. TLR-2 and TLR-4 redistribution to intra-cytoplasmic compartments is hampered if cathepsin X is blocked. The beginning of a successful immune response against H. pylori in the case of cathepsin X inhibition is delayed.
Ključne besede: cathepsin X, macrophage, dendritic cells
Objavljeno v DiRROS: 22.03.2024; Ogledov: 74; Prenosov: 40
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4. Cathepsin X in serum from patients with colorectal cancer: relation to prognosisTjaša Vižin, Ib Jarle Christensen, Hans Jørgen Nielsen, Janko Kos, 2012, izvirni znanstveni članek 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: 70; Prenosov: 42
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5. Cathepsin H indirectly regulates morphogenetic protein-4 (BMP-4) in various human cell linesMatija Rojnik, Zala Jevnikar, Bojana Mirković, Damjan Janeš, Nace Zidar, Danijel Kikelj, Janko Kos, 2011, izvirni znanstveni članek 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: 83; Prenosov: 43
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6. Cathepsin H indirectly regulates morphogenetic protein-4 (BMP-4) in various human cell linesMatija Rojnik, Zala Jevnikar, Bojana Mirković, Damjan Janeš, Nace Zidar, Danijel Kikelj, Janko Kos, 2011, izvirni znanstveni članek 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: 88; Prenosov: 17
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8. Cysteine proteinase inhibitors stefin A and stefin B in operable carcinoma of the head and neck : Inhibitorji cisteinskih proteinaz stefin A in stefin B pri operabilnem karcinomu glave in vratuPrimož Strojan, Marjan Budihna, Alojz Šmid, Branka Svetic, Ivan Vrhovec, Janko Kos, Janez Škrk, 2002, izvirni znanstveni članek 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: 139; Prenosov: 34
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