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Query: "author" (Borut Štabuc) .

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Sorafenib for the treatment of hepatocellular carcinoma : a single-centre real-world study
Jurij Hanžel, Tajda Božič, Borut Štabuc, Rado Janša, 2020, original scientific article

Abstract: Background Sorafenib is an oral multi-kinase inhibitor used for the treatment of hepatocellular carcinoma. Its efficacy in randomised controlled trials was demonstrated in patients with well-preserved liver function and good functional status. In the real-world setting, treatment is often offered to patients outside these criteria. We therefore performed a single-centre real-world cohort study on the efficacy of sorafenib in patients with hepatocellular carcinoma. Patients and methods We identified all patients with hepatocellular carcinoma initiating treatment with sorafenib between January 2015 and January 2018. The primary endpoint was overall survival (OS) since starting sorafenib. Clinical and demographic variables associated with survival were studied. Results The median OS was 13.4 months (95% CI 8.2%18.6). Multivariable Cox%s regression identified worse ECOG performance status (HR 2.21; 95% CI 1.56%3.16; P < 0.0001), Child-Pugh class C (HR 52.4; 95% CI 3.20%859; P = 0.005) and absence of prior locoregional treatment (HR 2.30; 95% CI 1.37%3.86; P = 0.002) to be associated with increased mortality. Conclusions Careful selection of patients for treatment with sorafenib is of paramount importance to optimize outcomes.
Keywords: hepatocellular carcinoma, survival, sorafenib
Published in DiRROS: 12.07.2024; Views: 66; Downloads: 40
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Dendritic cell profiles in the inflamed colonic mucosa predict the responses to tumor necrosis factor alpha inhibitors in inflammatory bowel disease
Nataša Smrekar, David Drobne, Lojze Šmid, Ivan Ferkolj, Borut Štabuc, Alojz Ihan, Andreja Nataša Kopitar, 2018, original scientific article

Abstract: Background Dendritic cells play crucial roles in the control of inflammation and immune tolerance in the gut. We aimed to investigate the effects of tumor necrosis factor alpha (TNFa) inhibitors on intestinal dendritic cells in patients with inflammatory bowel disease and the potential role of intestinal dendritic cells in predicting the response to treatment. Patients and methods Intestinal biopsies were obtained from 30 patients with inflammatory bowel disease before and after treatment with TNFa inhibitors. The proportions of lamina propria dendritic cell phenotypes were analysed using flow cytometry. Disease activity was endoscopically assessed at baseline and after the induction treatment. Results At baseline, the proportion of conventional dendritic cells was higher in the inflamed mucosa (7.8%) compared to the uninflamed mucosa (4.5%) (p = 0.003), and the proportion of CD103+ dendritic cells was lower in the inflamed mucosa (47.1%) versus the uninflamed mucosa (57.3%) (p = 0.03). After 12 weeks of treatment, the proportion of conventional dendritic cells in the inflamed mucosa decreased from 7.8% to 4.5% (p = 0.014), whereas the proportion of CD103+ dendritic cells remained unchanged. Eighteen out of 30 (60%) patients responded to their treatment by week 12. Responders had a significantly higher proportion of conventional dendritic cells (9.16% vs 4.4%, p < 0.01) with higher expression of HLA-DR (median fluorescent intensity [MFI] 12152 vs 8837, p = 0.038) in the inflamed mucosa before treatment compared to nonresponders. Conclusions A proportion of conventional dendritic cells above 7% in the inflamed inflammatory bowel disease mucosa before treatment predicts an endoscopic response to TNFa inhibitors.
Keywords: inflammatory bowel disease, dendritic cells, colon cancer
Published in DiRROS: 02.07.2024; Views: 140; Downloads: 68
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Microsatellite instability in colorectal cancer
Matej Horvat, Borut Štabuc, 2011, review article

Abstract: Background. Colorectal cancer (CRC) is the third most common cancer in the world. In 75% CRC develops sporadically, in 25% hereditary or as a consequenceof inflammatory bowel disease. CRC carcinogenesis develops over many years. The cause of CRC in 85% is chromosomal instability (CIN) and in 15% microsatellite instability (MSI-H), where hereditary nonpolyposis colorectal cancer (HNPCC) represents 10-20%. Microsatellite sequences (MS) arerepeated sequences of short stretches of DNA all over the genome. Microsatellite stability (MSS) means MS are the same in each cell of an individual, whereas microsatellite instability (MSI-H) means MS differ in normal and cancer cells of an individual. The cause of MSI-H is a damaged mismatch repair mechanism (MMR), with the most important MMR proteins being MSH2, MLH1 and MSH6. Conclusions. MSI-H seems to be an important prognostic factor in CRC and an important predictive factor of CRC chemotherapeutic treatment efficacy. Clinical trials conducted until now have shown contradictory findings in different chemotherapeutic settings, adjuvant and palliative; therefore MSI-H is going to be the object of the future research. The future of cancer treatment is in the individualized therapy based on molecular characteristics of the tumour, such as MSI-H in CRC.
Published in DiRROS: 19.03.2024; Views: 275; Downloads: 114
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The urokinase plasminogen activator and its inhibitors PAI-1 nad PAI-2 in primary cutaneous melanoma
Jasmina Markovič Božič, Borut Štabuc, 2003, original scientific article

Abstract: Background. We investigated the differences in urokinase plasminogen activator(uPA) and its inhibitors type-1 and 2 (PAI-1/2) concentrations in clinically suspected nevi, primary cutaneous melanoma and normal skin and correlations with histopathological prognostic factors of primary melanoma. Patients and methods. Fifty-one patients were enrolled. The tissue concentrations of uPA, PAI 1 and PAI2 were quantified by enzyme-linked immunosorbent assay (ELISA). Results. Mean uPA and PAI-1 concentrations in melanomas were higher than in normal surrounding skin (uPA: 1.08; vs. 0.48 ng/mgp; PAI-1: 14.07 vs. 2.07 ng/mgp; p < 0.001), uPA and PAI-1 concentrationswere higher in melanomas than in nevi, and higher in nevi than in normal surrounding skin (uPA: p > 0.05; PAI-1: p = 0.02). PAI-2 concentration was higher in normal surrounding skin than in nevi and melanomas(p > 0.05). Melanoma uPA, PAI-1 and PAI-2 concentrations correlated significantly with normal skin (r= 0.73, 0.54, 0.38 respectively). PAI 1 was significantly lower in melanomas of Breslow thickness < 0.75 mm, Clark invasion of O+I, without microscopic ulceration, without vascular invasion (p < 0.01) than in melanomas of Breslow thickness > 0.75 mm, Clark invasion > II,with ulceration and vascular invasion. Conclusions. Determination of uPA and PAI-1 can provide significant additional prognostic information for melanoma patients.
Published in DiRROS: 06.02.2024; Views: 260; Downloads: 61
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Assessment of renal function from creatinine clearance measurement and 131I-hippuran renography in cancer patients before chemotherapy
Borut Štabuc, Tine Hajdinjak, Tomaž Edvard Cizej, 1999, original scientific article

Abstract: Background. Serum creatinine and endogenous creatinine clearance (CrCl) are widely used measures of renal function before prescribing nephrotoxic chemotherapy. This study compares the precision and bias in glomerular filtration rate (GFR) estimation without the need to collect urine by using Cockcroft-Gault formula on a single serum creatinine concentration (CrCo) and 131I- hippuran clearance (HC) determined from the renographic curves. Patientsand methods. Fourty-seven patients aged between 27 and 73 years were studied. In all patients, we determined serum creatinine concentration, CrCl, CrCo and HC simultaneously before treatment by combined chemotherapy with cisplatin (CDDP) and in 31 patients, before the third cycle. Serum and urine creatinine concentrations were determined with a Hitachi 911, an automated biochemical analyser CrCl was calculated from the urine flow, from the ratio between the serum and urine creatinine concentrations and was standardized forthe body surface area. Serum creatinine was used to estimate CrCo using a Cockcroft and Gault formula. HC was determined from 131I-hippuran uptake by both kidneys, results were compared to our Nuclear Medicine Department normal values with regard to the age of each patient. For the evaluation of results, Pearson's correlation coefficient and t-test with 95 % confidence interval were used. Results. The sensitivity of serum creatinine, CrCo and HC to predict CrCl<78 mL/min/1.73m2 was 41 %, 68% and 46% and specificity was 95%, 71 % and 76% respectively. Value of CoCr for prediction of reduced CrCl (sensitivity) was statistically significantly better than the HC (p=0.03). Value of CoCr fnr prediction of normal CrCl (specificity) was as good as HC (p=0.3). Conclusions. CrCl for the GFR estimation in the patients treated withnephrotoxic chemotherapy cannot be changed by CrCo and/or HC.
Published in DiRROS: 22.01.2024; Views: 302; Downloads: 77
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Phase II study of fluorouracil, leucovorin and interferon alpha-2a in patients with advanced colon cancer
Borut Štabuc, Aleksandra Markovič, Erik Brecelj, Samir Bešlija, Tomaž-Edvard Cizej, 1998, original scientific article

Abstract: Based on in viro studies that have demonstrated synergy between fluorouracil (5-FU) and leucovorin (LV) as well as between 5-FU and recombinant alpha-2a interferon (IFN) against colon cancer cell lines a phase II study was carried out to evaluate the toxicity and clinical activity of 5-FU modulated with LV and IFN in patients with metastatic colon cancer. Twenty-two chemotherapy naive patients with measurable metastases of colon cancer have been treated with daily doses of 5-FU 600 mg/m2 in 6-hr intravenous infusion, and of LV 20 mg/m2 intravenously and IFN 6 MU subcutaneously, for 5 days every 4 weeks. Median age was 60 years, median PS (ECOG) was 1 (range 0-2). Liver, soft tissue and lung metastases were found in 12, 5 and 8 patients, respectively. Nineteen patients had a single metastatic site, two double, whereas one had more than two metastatic sites. Patients had 2-9 (mean 5) cycles of treatment.Objective response was observed in 7 patients (32%), and stable disease in 7 patients (32%). Overall median survival was 12.5 months, and for responders 14.4 months. Responses were generally short and median time for progression was 5.5 months. The most frequent adverse reactions were flu-like syndrome (50%), nausea/vomiting (36%), diarhoea (13Č), stomatitis (27%) and leucopenia (13%). This regimen of 5-FU with LV and IFN administration does notappear to be superior to previously published shedules of 5-FU with IFN or 5-FU with LV.
Published in DiRROS: 19.01.2024; Views: 294; Downloads: 90
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