1. Electrochemotherapy with bleomycin is effective in BRAF mutated melanoma cells and interacts with BRAF inhibitorsTanja Jesenko, Lara Prosen, Maja Čemažar, Tjaša Potočnik, Gregor Serša, 2016, original scientific article Abstract: The aim of the study was to explore the effectiveness of electrochemotherapy (ECT) during the treatment of melanoma patients with BRAF inhibitors. Its effectiveness was tested on BRAF mutated and non-mutated melanoma cells in vitro and in combination with BRAF inhibitors. Materials and methods. ECT with bleomycin was performed on two human melanoma cell lines, with (SK-MEL-28) or without (CHL-1) BRAF V600E mutation. Cell survival was determined using clonogenic assay to determine the effectiveness of ECT in melanoma cells of different mutation status. Furthermore, the effectiveness of ECT in concomitant treatment with BRAF inhibitor vemurafenib was also determined in BRAF mutated cells SK-MEL-28 with clonogenic assay. Results. The survival of BRAF V600E mutated melanoma cells was even lower than non-mutated cells, indicating that ECT is effective regardless of the mutational status of melanoma cells. Furthermore, the synergistic interaction between vemurafenib and ECT with bleomycin was demonstrated in the BRAF V600E mutated melanoma cells. Conclusions. The effectiveness of ECT in BRAF mutated melanoma cells as well as potentiation of its effectiveness during the treatment with vemurafenib in vitro implies on clinical applicability of ECT in melanoma patients with BRAF mutation and/or during the treatment with BRAF inhibitors.
Keywords: electrochemotherapy, BRAF inhibitors, vemurafenib, melanoma
Published in DiRROS: 30.04.2024; Views: 16; Downloads: 2
 Full text (642,09 KB) |
2. Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer : single center experienceJanja Ocvirk, Maja Ebert Moltara, Tanja Mesti, Marko Boc, Martina Reberšek, Neva Volk, Jernej Benedik, Zvezdana Hlebanja, 2016, original scientific article Abstract: Metastatic colorectal cancer (mCRC) is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients% register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer. Patients and methods. The registry of patients with mCRC was designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy as well as selection of patients in routine clinical practice. Patient baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected, evaluated and compared according to the age categories. Results. Between January 2008 and December 2010, 210 patients with mCRC (median age 63, male 61.4%) started bevacizumab-containing therapy in the 1st line setting. Majority of the 210 patients received irinotecan-based chemotherapy (68%) as 1st line treatment and 105 patients (50%) received bevacizumab maintenance therapy. Elderly (% 70 years) patients presented 22.9% of all patients and they had worse performance status (PS 1/2, 62.4%) than patients in < 70 years group (PS 1/2, 35.8%). Difference in disease control rate was mainly due to inability to assess response in elderly group (64.6% in elderly and 77.8% in < 70 years group, p = 0.066). The median progression free survival was 10.2 (95% CI, 6.7%16.2) and 11.3 (95% CI, 10.2%12.6) months in elderly and < 70 years group, respectively (p = 0.58). The median overall survival was 18.5 (95% CI, 12.4%28.9) and 27.4 (95% CI, 22.7%31.9) months for elderly and < 70 years group, respectively (p = 0.03). Three-year survival rate was 26% and 37.6% in elderly vs. < 70 years group (p = 0.03). Overall rates of bevacizumab-related adverse events were similar in both groups: proteinuria 21/22 %, hypertension 25/19 %, haemorrhage 2/4 % and thromboembolic events 10/6 %, for elderly and < 70 years group, respectively. Conclusions. In routine clinical practice, the combination of bevacizumab and chemotherapy is effective and welltolerated regimen in elderly patients with metastatic colorectal cancer.
Keywords: metastatic colorectal cancer, bevacizumab, chemotherapy, elderly
Published in DiRROS: 30.04.2024; Views: 18; Downloads: 2
Full text (620,74 KB) |
3. Malignant gliomas : old and new systemic treatment approachesTanja Mesti, Janja Ocvirk, 2016, review article Abstract: Malignant (high-grade) gliomas are rapidly progressive brain tumours with very high morbidity and mortality. Until recently, treatment options for patients with malignant gliomas were limited and mainly the same for all subtypes of malignant gliomas. The treatment included surgery and radiotherapy. Chemotherapy used as an adjuvant treatment or at recurrence had a marginal role. Conclusions. Nowadays, the treatment of malignant gliomas requires a multidisciplinary approach. The treatment includes surgery, radiotherapy and chemotherapy. The chosen approach is more complex and individually adjusted. By that, the effect on the survival and quality of life is notable higher.
Keywords: malignant gliomas, systemic treatment, multidisciplinary, survival
Published in DiRROS: 30.04.2024; Views: 13; Downloads: 4
Full text (696,05 KB) |
4. Cerebral toxoplasmosis in a diffuse large B cell lymphoma patientLina Savšek, Tanja Roš-Opaškar, 2016, original scientific article Abstract: Toxoplasmosis is an opportunistic protozoal infection that has, until now, probably been an underestimated cause of encephalitis in patients with hematological malignancies, independent of stem cell or bone marrow transplant. T and B cell depleting regimens are probably an important risk factor for reactivation of a latent toxoplasma infection in these patients. Case report. We describe a 62-year-old HIV-negative right-handed Caucasian female with systemic diffuse large B cell lymphoma who presented with sudden onset of high fever, headache, altered mental status, ataxia and findings of pancytopenia, a few days after receiving her final, 8th cycle of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone (R-CHOP) chemotherapy regimen. A progression of lymphoma to the central nervous system was suspected. MRI of the head revealed multiple on T2 and fluid attenuated inversion recovery (FLAIR) hyperintense parenchymal lesions with mild surrounding edema, located in both cerebral and cerebellar hemispheres that demonstrated moderate gadolinium enhancement. The polymerase chain reaction on cerebrospinal fluid (CSF PCR) was positive for Toxoplasma gondii. The patient was diagnosed with toxoplasmic encephalitis and successfully treated with sulfadiazine, pyrimethamine and folic acid. Due to the need for maintenance therapy with rituximab for lymphoma remission, the patient now continues with secondary prophylaxis of toxoplasmosis. Conclusions. With this case report, we wish to emphasize the need to consider cerebral toxoplasmosis in patients with hematological malignancies on immunosuppressive therapy when presenting with new neurologic deficits. In such patients, there are numerous differential diagnoses for cerebral toxoplasmosis, and the CNS lymphoma is the most difficult among all to distinguish it from. If left untreated, cerebral toxoplasmosis has a high mortality rate; therefore early recognition and treatment are of essential importance.
Keywords: toxoplasmosis, cerebral, lymphoma, rituximab
Published in DiRROS: 30.04.2024; Views: 11; Downloads: 5
Full text (648,57 KB)
This document has many files! More... |
5. The prognostic value of whole blood SOX2, NANOG and OCT4 mRNA expression in advanced small-cell lung cancerEva Sodja, Matija Rijavec, Ana Koren, Aleksander Sadikov, Peter Korošec, Tanja Čufer, 2016, original scientific article Abstract: The data on expression and clinical impact of cancer stem cell markers SOX2, NANOG and OCT4 in lung cancer is still lacking. The aim of our study was to compare SOX2, NANOG and OCT4 mRNA expression levels in whole blood between advanced small-cell lung cancer (SCLC) patients and healthy controls, and to correlate mRNA expression with progression-free survival (PFS) after first-line chemotherapy and overall survival (OS) in advanced SCLC patients. Patients and methods. 50 advanced SCLC patients treated with standard chemotherapy and followed at University Clinic Golnik, Slovenia, between 2009 and 2013 were prospectively included. SOX2, NANOG and OCT4 mRNA expression levels were determined using TaqMan qPCR in whole blood collected prior to chemotherapy. Whole blood of 34 matched healthy individuals with no cancerous disease was also tested. Results. SOX2 mRNA expression was significantly higher in whole blood of SCLC patients compared to healthy controls (p = 0.006). Significant correlation between SOX2 mRNA expression levels and the number of distant metastatic sites was established (p = 0.027). In survival analysis, patients with high SOX2 expression had shorter OS (p = 0.017) and PFS (p = 0.046). In multivariate Cox analysis, an independent value of high SOX2 expression for shorter OS (p = 0.002), but not PFS was confirmed. No significant differences were observed for NANOG or OCT4 expression levels when comparing SCLC patients and healthy controls neither when analysing survival outcomes in SCLC patients. Conclusions. SOX2 mRNA expression in whole blood might be a promising non-invasive marker for molecular screening of SCLC and important prognostic marker in advanced chemotherapy-treated SCLC patients, altogether indicating important role of cancer stem-like cell (CSC) regulators in cancer spread. Further evaluation of SOX2 as a possible screening/prognostic marker and a therapeutic target of SCLC is warranted.
Keywords: small-cell lung cancer, cancer stem cell markers, prognosis
Published in DiRROS: 30.04.2024; Views: 18; Downloads: 2
Full text (944,93 KB) |
6. Towards the development of a landslide activity map in SloveniaMateja Jemec Auflič, Krištof Oštir, Tanja Grabrijan, Matjaž Ivačič, Tina Peternel, Ela Šegina, 2024, original scientific article Abstract: To create the landslide activity map, we implemented and tested the procedure to fully utilise the 6-day repeatability of the Sentinel-1 constellation in three pilot areas in Slovenia for the observation period from 2017 to 2021. The interferometric processing of the Sentinel-1 images was carried out with ENVI SARScape, while the interpretation of the persistent scatterers InSAR data was done in three steps. In the first step, a preliminary interpretation of the landslide areas was performed by integrating the PS InSAR data into a GIS environment with information that could be relevant to explain the movement patterns of the PS InSAR points. In the second step, a field validation was performed to check the PS InSAR in the field and record the potential damage to the objects indicating the slope mass movements. In the third step, the deformations were identified, and areas of significant movement were determined, consisting of clusters of at least 3 persistent scatterers (PS) with a maximum spacing of 10 m. The landslide activity map was created based on the landslide areas categorised into four classes based on the geotechnical analyses, yearly velocity data obtained by PS InSAR, and validation of annual velocity data obtained by in-situ and GNSS monitoring and field observation. A total of 21 polygons with different landslide activities were identified in three study areas. The overall methodology will help stakeholders in the early mapping and monitoring of landslides to increase the urban resilience.
Keywords: landslides, EO data, sentinel, time series, methodology, Slovenia
Published in DiRROS: 30.04.2024; Views: 19; Downloads: 2
Full text (73,45 MB) |
7. Febrile neutropenia in chemotherapy treated small-cell lung cancer patientsRenata Režonja, Iztok Grabnar, Tomaž Vovk, Aleš Mrhar, Viljem Kovač, Tanja Čufer, 2015, original scientific article Abstract: Chemotherapy with platinum agent and etoposide for small-cell lung cancer (SCLC) is supposed to be associated with intermediate risk (10-20%) of febrileneutropenia. Primary prophylaxis with granulocyte colonystimulating factors (G-CSFs) is not routinely recommended by the treatment guidelines. However, in clinical practice febrile neutropenia is often observed with standard etoposide/platinum regimen. The aim of this analysis was to evaluate the frequency of neutropenia and febrile neutropenia in advanced SCLC patients in the first cycle of standard chemotherapy. Furthermore, we explored the association between severe neutropenia and etoposide peak plasma levels inthe same patients. The case series based analysis of 17 patients with advanced SCLC treated with standard platinum/etoposide chemotherapy, already included in the pharmacokinetics study with etoposide, was performed. Grade 3/4 neutropenia and febrile neutropenia, observed after the first cycle are reported. The neutrophil counts were determined on day one of the second cycle unless symptoms potentially related to neutropenia occurred. Adverse events were classified according to Common Toxicity Criteria 4.0. Additionally, association between severe neutropenia and etoposide peak plasma concentrations, which were measured in the scope of pharmacokinetic study, was explored. Two out of 17 patients received primary GCS-F prophylaxis. In 15 patient who did not receive primary prophylaxis the rates of both grade 3/4 neutropenia and febrile neutropenia were high (8/15 (53.3%) and 2/15 (13.3%), respectively), already in the first cycle of chemotherapy. One patient died due to febrile neutropenia related pneumonia. Neutropenic events are assumed to be related to increased etoposide plasma concentrations after a standard etoposide and cisplatin dose. While the mean etoposide peak plasma concentration in the first cycle of chemotherapy was 17.6 mg/l, the highest levels of 27.07 and 27.49 mg/l were determined in two patients with febrile neutropenia. Our study indicates that there is a need to reduce the risk of neutropenic events in chemotherapy treated advanced SCLC, starting in the first cycle. Mandatory use of primary G-CSF prophylaxis might be considered. Alternatively, use of improved risk models for identification of patients with increased risk for neutropenia and individualization of primary prophylaxis based on not only clinical characteristics but also on etoposide plasma concentration measurement, could be a new, promising options that deserves further evaluation.
Keywords: small cell lung cancer, platinum-etoposide chemotherapy, etoposide, febrile neutropenia, plasma drug concentration
Published in DiRROS: 22.04.2024; Views: 45; Downloads: 32
Full text (568,43 KB)
This document has many files! More... |
8. |
9. |
10. |
