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Ključne besede: internistična onkologija, CAR-T terapija, kemoterapija
Objavljeno v DiRROS: 19.04.2024; Ogledov: 32; Prenosov: 4
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Povzetek: Gene electrotransfer (GET) of plasmids encoding interleukin 12 (IL-12) has already been used for the treatment of various types of tumors in human oncology and as an adjuvant in DNA vaccines. In recent years, we have developed a plasmid encoding human IL-12 (phIL12) that is currently in a phase I clinical study. The aim was to confirm the results of a non-clinical study in mice on pharmacokinetic characteristics and safety in a porcine model that better resembled human skin. The GET of phIL12 in the skin was performed on nine pigs using different concentrations of plasmid phIL12 and invasive (needle) or noninvasive (plate) types of electrodes. The results of our study demonstrate that the GET of phIL-12 with needle electrodes induced the highest expression of IL-12 at the protein level on day 7 after the procedure. The plasmid was distributed to all tested organs; however, its amount decreased over time and was at a minimum 28 days after GET. Based on plasmid copy number and expression results, together with blood analysis, we showed that IL-12 GET is safe in a porcine animal model. Furthermore, we demonstrated that pigs are a valuable model for human gene therapy safety studies.
Ključne besede: interleukin 12, gene electrotransfer, immunotherapy
Objavljeno v DiRROS: 18.04.2024; Ogledov: 20; Prenosov: 13
Celotno besedilo (16,83 MB)
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Povzetek: Background: There is a concern that terminally ill cancer patients may be aggressively treated due to the rapidly growing possibilities of anticancer treatment. The aim of this study was to evaluate the use of anticancer treatment at the end of life (EoL). Materials and methods: This retrospective study included adult patients with advanced solid cancers who were treated at the Institute of Oncology Ljubljana and died of cancer between January 2015 and December 2019. A multiple logistic regression model was used to assess an association between the aggressiveness of anticancer treatment (i.e. systemic therapy, radiotherapy and surgery) in the last 2 weeks of life and year of death, age at death, sex, prognosis of cancer and enrolment into the specialist palliative care (SPC). Results: We included 1736 patients in our analysis. Overall, 13.7% of patients were enrolled into the SPC and 14.4% received anticancer treatment in the last 2 weeks of life. The odds of receiving anticancer treatment significantly increased over time [odds ratio (OR) 1.15, 95% confidence interval (CI) 1.04-1.27]. There was an increased use of novel systemic therapy (e.g. small-molecule targeted therapy and immunotherapy) at the EoL. Older patients had significantly lower odds to receive anticancer treatment in the last 2 weeks of life as compared to younger patients (OR 0.96, 95% CI 0.95-0.98). As compared to patients receiving only a standard oncology care, those also enrolled into the SPC had significantly lower odds for anticancer treatment in the last 2 weeks of life (OR 0.22, 95% CI 0.12-0.43). Conclusions: Terminally ill cancer patients have increased odds for receiving anticancer treatment, especially novel systemic therapies, in the last 2 weeks of life. Younger patients and those not enrolled into the SPC are at particular risk for anticancer treatment at the EoL
Ključne besede: systemic therapy, aggressive treatment, anticancer drugs, palliative care
Objavljeno v DiRROS: 18.04.2024; Ogledov: 25; Prenosov: 14
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Povzetek: Background. Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients. Patients and methods. 606 primary breast cancer patients were enrolled in the prospective study in the Department of gynaecological oncology and breast oncology at the University Medical Centre Maribor between the years 2004 and 2010. We evaluated the traditional prognostic factors (age, menopausal status, tumour size, pathohistological type, histologic grade, lymph node status, lymphovascular invasion and hormone receptor status), together with uPA and PAI-1. We used Spearman%s rank correlation, Mann Whitney U test and X2 test for statistical analysis. Results. Our findings indicate a positive correlation between uPA and tumour size (p < 0.001), grade (p < 0.001), histological type (p < 0.001), lymphovascular invasion (p = 0.01) and a negative correlation between uPA and hormone receptor status (p < 0.001). They also indicate a positive correlation between PAI-1 and tumour size (p = 0.004), grade (p < 0.001), pathohistological type (p < 0.001) and negative correlation between PAI-1 and hormone receptor status (p = 0.002). Conclusions. Our study showed a relationship between uPA and PAI-1 and traditional prognostic factors. Their role as prognostic and predictive factors remains to be further evaluated.
Ključne besede: urokinase plasminogen activator, plasminogen activator inhibitor, breast cancer
Objavljeno v DiRROS: 17.04.2024; Ogledov: 47; Prenosov: 23
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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: 56; Prenosov: 12
Celotno besedilo (730,95 KB)