1. Dendritic cell profiles in the inflamed colonic mucosa predict the responses to tumor necrosis factor alpha inhibitors in inflammatory bowel diseaseNataša 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: 202; Downloads: 106
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2. Dynamic susceptibility contrast enhanced (DSC) MRI perfusion and plasma cytokine levels in patients after tonic-clonic seizuresTatjana Filipovič, Katarina Šurlan Popović, Alojz Ihan, David B. Vodušek, 2017, original scientific article Abstract: Background Inflammatory events in brain parenchyma and glial tissue are involved in epileptogenesis. Blood concentration of cytokines is shown to be elevated after tonic-clonic seizures. As a result of inflammation, blood-brain barrier leakage occurs. This can be documented by imaging techniques, such is dynamic susceptibility contrast enhanced (DSC) MRI perfusion. Our aim was to check for postictal brain inflammation by studying DSC MRI perfusion and plasma level of cytokines. We looked for correlations between number and type of introducing seizures, postictal plasma level of cytokines and parameters of DSC MRI perfusion. Furthermore, we looked for correlation of those parameters and course of the disease over one year follow up. Patients and methods We prospectively enrolled 30 patients, 8%24 hours after single or repeated tonic-clonic seizures. Results 25 of them had normal perfusion parameters, while 5 had hyperperfusion. Patients with hyperperfusion were tested again, 3 months later. Two of 5 had hyperperfusion also on control measurements. Number of index seizures negatively correlated with concentration of proinflammatory cytokines IL-10, IFN-[gamma] and TNF-[alpha] in a whole cohort. In patients with hyperperfusion, there were significantly lower concentrations of antiinflammatory cytokine IL-4 and higher concentrations of proinflammatory TNF-[alpha]. Conclusions Long lasting blood- brain barrier disruption may be crucial for epileptogenesis in selected patients. Keywords: cytokines, blood-brain barrier, tonic-clonic seizures Published in DiRROS: 03.06.2024; Views: 244; Downloads: 171
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3. Perioperative increase in neutrophil CD64 expression is an indicator for intra-abdominal infection after colorectal cancer surgeryMilena Kerin-Povšič, Bojana Beović, Alojz Ihan, 2017, original scientific article Abstract: Colorectal surgery is associated with a high incidence of postoperative infections. Early clinical signs are difficult to distinguish from the systemic inflammatory response related to surgical trauma. Timely diagnosis may significantly improve the outcome. The objective of this study was to compare a new biomarker index CD64 for neutrophils (iCD64n) with standard biomarkers, white blood cell (WBC) count, neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP) and procalcitonin (PCT) for the early detection of postoperative infection. Methods. The prospective study included 200 consecutive patients with elective colorectal cancer surgery. Postoperative values of biomarkers from the postoperative day (POD) 1 to POD5 were analysed by the receiver operating characteristic (ROC) analysis to predict infection. The Cox regression model and the Kaplan-Meier method were used to assess prognostic factors and survival. Results. The increase of index CD64n (iCD64n) after surgery, expressed as the ratio iCD64n after/before surgery was a better predictor of infection than its absolute value. The best 30-day predictors of all infections were CRP on POD4 (AUC 0.72, 99% CI 0.61%0.83) and NLR on POD5 (AUC 0.69, 99% CI 0.57%0.80). The best 15-day predictors of organ/ space surgical site infection (SSI) were the ratio iCD64n on POD1 (AUC 0.72, 99% CI 0.58%0.86), POD3 (AUC 0.73, 99% CI 0.59%0.87) and CRP on POD3 (AUC 0.72, 99% CI 0.57%0.86), POD4 (AUC 0.79, 99% CI 0.64%0.93). In a multivariate analysis independent risk factors for infections were duration of surgery and perioperative transfusion while the infection itself was identified as a risk factor for a worse long-term survival. Conclusions. The ratio iCD64n on POD1 is the best early predictor of intra-abdominal infection after colorectal cancer surgery. CRP predicts the infection with the same predictive value on POD3. Keywords: colorectal surgery, index CD64n, postoperative infection Published in DiRROS: 10.05.2024; Views: 339; Downloads: 140
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4. The influence of cytokine gene polymorphisms on the risk of developing gastric cancer in patients with Helicobacter pylori infectionDavid Štubljar, Samo Jeverica, Tomislav Jukić, Miha Skvarč, Tadeja Pintar, Bojan Tepeš, Rajko Kavalar, Borut Štabuc, Alojz Ihan, 2015, original scientific article Keywords: cytokine gene, gastric cancer, Helicobacter pylori infection Published in DiRROS: 16.04.2024; Views: 311; Downloads: 95
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5. 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, original scientific article Abstract: 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. Keywords: cathepsin X, macrophage, dendritic cells Published in DiRROS: 22.03.2024; Views: 290; Downloads: 154
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6. Influence of surgical treatment and radiotherapy of the advanced intraoral cancers on complete blood count, body mass index, liver enzymes and leukocyte CD64 expressionTadej Dovšak, Alojz Ihan, Vojislav Didanovič, Andrej Kansky, Nataša Ihan Hren, 2009, original scientific article Abstract: Background. The aim of our study was to evaluate the influence of the surgery and radiotherapy of the advanced oral squamous cell carcinoma on the complete blood count, body mass index (BMI), acute inflam-matory response, liver enzymes and expression of the CD64 index on leukocytes in the peripheral blood. Patients and method. Venous blood was obtained from 16 patients with advanced oral squamous cell carcinomas treated with radical surgery and external beam radiotherapy. Blood samples were collected prior to surgery (T1), after surgery (T2) and after radiotherapy (T3). Blood samples were analyzed for whole blood count, immunoglobulin G levels, liver enzymes (transaminases (ALT and AST) and gammaglutamyl trasferase (?-GT)), inflammatory response markers (C-reactive protein, erythrocyte sedimentation rate, albumin, white blood count, leukocyte count and CD64 expression on leukocytes). Assessment of nutrition was done by calculating the body mass index.Results. Surgery caused anaemia, trombocytosis, leukocytosis, lymphopenia, rise in acute phase proteins, elevation of CD64 expression on monocytes and neutrophyls, elevation of liver transaminases and lowering of ?-GT, albumin, protein and bilirubin levels. After radiotherapy haemoglobin, leukocytes, C-reactive protein, erythrocyte sedimentation rate, liver transferases, albumin, bilirubin and proteins returned almost to T1 levels, levels of lymphocytes, ?-GT and body mass index lowered. IgG levels remained almost unchanged at T2 and T3. Levels of the CD64 expression on monocytes and neutrophyls also elevated after radiotherapy.Conclusions. Surgery caused a significantly larger acute phase response than radiotherapy, while radiotherapy worsened the already present lymphopenia. Published in DiRROS: 08.03.2024; Views: 360; Downloads: 85
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7. Tumor vaccinesMojca Frank Bertoncelj, Alojz Ihan, 2006, review article Abstract: Tumor vaccines have several potential advantages over standard anticancer regirrcents. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tccmor aaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which imrrtune tolerance exists. That is why the population of tumor-specific lymphocytes is represented by a small number of low-affinity T-lymphocytes that induce weak antitumor immune response. Simultaneously, tumors evolve many mechanisms to actively evade immune system,what makes them poorly immunogenic or even tolerogenic. Novel irrtmunotherapeutic strategies are directed toward breaking immune tolerance to tumor antigens, enhancing immunogenicity of tumor vaccines and overcoming mechanisms of tumor escape. There are several approaches, unfortunately, all of them still far away from an ideal tumor vaccine that would reject a tumor. Difficulties in the activation of antitumor immune response by tumor vaccines have led to the development of alternative immunotherapeutic strategies that directly focus on effector mechanisms of immune system (adoptive tumor-specific T-lymphocyte transfer and tumor specific monoclonal antibodies). Published in DiRROS: 15.02.2024; Views: 304; Downloads: 83
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8. A correlation of NK cytolitic test and BLT esterase test in determining activity of NK cells, stimulated by tumor target cellsAlojz Ihan, 1999, original scientific article Abstract: We examined the granule exocytosis in natural killer (NK) cells by measuring N-benzyloxycarboxy-L-lysine esterase activity. As a source of NK cells we usedbuffy-coat isolated NK cells or peripheral blood lymphocytes (PBL). The exocytosis was triggered by incubating cells with ionomycin/PMA or by NK cell susceptible tumour target cells K562. When we stimulated purified NK cells with tumour target cells, a close correlation (Corr=0.84) of cytolitic NK testresults and BLT test results was obtained. We may conclude that BLT test can provide a valuable tool to discriminate further NK cell deficiency in patients with low cytolitic NK test results. Published in DiRROS: 22.01.2024; Views: 313; Downloads: 102
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9. Flow cytometric pitfalls in immunophenotyping of lymphomasAlojz Ihan, 1998, review article Abstract: Flow cytometry has been introduced as the most reliable method for the analysis of lymphocyte subsets. The advantage of flow cytometry is that it enables application of virtually all monoclonal antibodies (native cells), a quantitative estimation of different lymphoid cells, and that cell can be simultaneously analysed for multiple marker expression. The usage of flow cytometers requiers considerable knowledge of physics and its technical application. Moreover, several problems arise from the complexity of the biolocal systems investigated. Published in DiRROS: 19.01.2024; Views: 325; Downloads: 98
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10. The rate of natural killer cells and their cytotoxic activity in patients with advances pharyngeal and laryngeal cancerAlojz Šmid, Miha Žargi, B. Rok, Avgust Župevc, Vladimir Kotnik, Alojz Ihan, Mirela Rode, 1993, original scientific article Keywords: rak (medicina), žrelo, požiralnik, fiziologija Published in DiRROS: 10.01.2024; Views: 392; Downloads: 100
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