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Biospecifična protitelesa : struktura, princip delovanja, neželeni učinki
Barbara Jezeršek Novaković, 2024, objavljeni strokovni prispevek na konferenci

Ključne besede: internistična onkologija, biospecifična protitelesa, kemoterapija
Objavljeno v DiRROS: 19.04.2024; Ogledov: 15; Prenosov: 4
.pdf Celotno besedilo (812,93 KB)

Do double-expressor high-grade B-cell lymphomas really need intensified treatment : a report from the real-life series of high-grade B-cell lymphomas treated with different therapeutic protocols at the Institute of Oncology Ljubljana
Lučka Boltežar, Samo Rožman, Gorana Gašljević, Biljana Grčar-Kuzmanov, Barbara Jezeršek Novaković, 2024, izvirni znanstveni članek

Povzetek: High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are known for their aggressive clinical course and so are the ones with MYC and BCL2 protein overexpression. The optimal therapy for these lymphomas remains to be elucidated. A retrospective analysis of all diffuse large B-cell lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements diagnosed between 2017 and 2021 at the Institute of Oncology Ljubljana, Slovenia, has been performed. Only patients with double-expressor lymphoma (DEL), double-hit lymphoma (DHL), or triple-hit lymphoma (THL) were included. Demographic and clinical parameters were assessed, as well as progression-free survival (PFS) and overall survival (OS). In total, 161 cases out of 309 (161/309; 52,1%) were classified as DEL. Sixteen patients had DHL, MYC/BCL2 rearrangement was observed in eleven patients, and MYC/BCL6 rearrangement was observed in five patients. Five patients were diagnosed with THL. Out of 154 patients (according to inclusion/exclusion criteria) included in further evaluation, one-hundred and thirty-five patients had double-expressor lymphoma (DEL), sixteen patients had DHL, and three patients had THL. In total, 169 patients were treated with R-CHOP, 10 with R-CHOP and intermediate-dose methotrexate, 19 with R-DA-EPOCH, and 16 with other regimens. The median follow-up was 22 months. The 5-year OS for the whole DEL group was 57.1% (95% CI 45.9–68.3%) and the 5-year PFS was 76.5% (95% CI 72.6–80.4%). The log-rank test disclosed no differences in survival between treatment groups (p = 0.712) while the high-risk international prognostic index (IPI) carried a significantly higher risk of death (HR 7.68, 95% CI 2.32–25.49, p = 0.001). The 5-year OS for DHL patients was 32.4% (95% CI 16.6–48.2%) while all three TH patients were deceased or lost to follow-up. Our analyses of real-life data disclose that the R-CHOP protocol with CNS prophylaxis is a successful and curative treatment for a substantial proportion of DEL patients.
Ključne besede: lymphoma, double-expressor lymphoma, oncology
Objavljeno v DiRROS: 18.04.2024; Ogledov: 41; Prenosov: 11
.pdf Celotno besedilo (1004,13 KB)
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Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer : correlation with traditional prognostic factors
Maja Lampelj, Darja Arko, Nina Čas-Sikošek, Rajko Kavalar, Maja Ravnik, Barbara Jezeršek Novaković, Sarah Dobnik, Nina Fokter Dovnik, Iztok Takač, 2015, izvirni znanstveni članek

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: 44; Prenosov: 23
.pdf Celotno besedilo (571,67 KB)
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Clonality analysis of lymphoid proliferations using the BIOMED-2 clonality assays : a single institution experience
Ira Koković, Barbara Jezeršek Novaković, Petra Škerl, Srdjan Novaković, 2014, izvirni znanstveni članek

Povzetek: Background. Clonality determination in patients with lymphoproliferative disorders can improve the final diagnosis.The aim of our study was to evaluate the applicative value of standardized BIOMED-2 gene clonality assay protocolsfor the analysis of clonality of lymphocytes in a group of different lymphoid proliferations.Materials and methods. With this purpose, 121 specimens from 91 patients with suspected lymphoproliferationssubmitted for routine diagnostics from January to December 2011 were retrospectively analyzed. According to thefinal diagnosis, our series comprised 32 cases of B-cell lymphomas, 38 cases of non-Hodgkins T-cell lymphomas and51 cases of reactive lymphoid proliferations. Clonality testing was performed using the BIOMED-2 clonality assays.Results. The determined sensitivity of the TCR assay was 91.9%, while the sensitivity of the IGH assay was 74.2%. Thedetermined specificity of the IGH assay was 73.3% in the group of lymphomas and 87.2% in the group of reactivelesions. The determined specificity of the TCR assay was 62.5% in the group of lymphomas and 54.3% in the group ofreactive lesions.Conclusions. In the present study, we confirmed the utility of standardized BIOMED-2 clonality assays for the detectionof clonality in a routine diagnostical setting of non-Hodgkins lymphomas. Reactions for the detection of thecomplete IGH rearrangements and reactions for the detection of the TCR rearrangements are a good choice forclonality testing of a wide range of lymphoid proliferations and specimen types while the reactions for the detectionof incomplete IGH rearrangements have not shown any additional diagnostic value.
Ključne besede: Biomed-2, clonality analysis, lymphomas, IGH rearrangement, TCR rearrangement
Objavljeno v DiRROS: 11.04.2024; Ogledov: 55; Prenosov: 17
.pdf Celotno besedilo (622,10 KB)

Dnevi internistične onkologije 2024 : inovativna zdravila v onkologiji
2024, zbornik strokovnih ali nerecenziranih znanstvenih prispevkov na konferenci

Objavljeno v DiRROS: 04.04.2024; Ogledov: 84; Prenosov: 30
.pdf Celotno besedilo (9,80 MB)

The diffuse large B-cell lymphoma - where do we stand now in everyday clinical practice
Brigita Gregorič, Vesna Zadnik, Barbara Jezeršek Novaković, 2012, izvirni znanstveni članek

Povzetek: Background. Due to superior results observed with the addition of rituximab into treatment of patients with the diffuse large B-cell lymphoma (DLBCL),the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen and its variants became the standard initial treatment of these patients. However, the treatment recommendations are based on resultsof clinical studies while the conditions of routine treatment are far different from the ones in clinical studies. The aim of this retrospective study was therefore to compare the treatment results of routinelz treated patients with the DLBCL to results reported by some larger studies. Patients and methods. Two hundred and ninety five patients with the DLBCL were treated between 2004 and 2008 according to the then protocol with R-CHOP or R-CHOP-like regimens at the Institute of Oncology Ljubljana. Treatment response was evaluated according to Chesonʼs criteria and the disease-free andoverall survival by means of Kaplan Meier survival curves. Results. Response to treatment in our evaluation diverged from the reported one predominately in the low risk group (international prognostic index [IPI] categorisation) and in the very good prognosis group (revised international prognostic index (R-IPI) categorisation). The determined complete response (CR) rates in other IPI and R-IPI groups were generally within expectations. Also in the disease-free survival the largest discrepancy occurred in the low-risk patient group (3 year disease-free survival rate of 75%) and in the very good prognosis group (4 year disease-free survival rate of 59%). In all other IPI risk groups, the disease-free survival at 3 zears (low intermediate risk 76%, high intermediate risk group 57%, and high risk group 53%) agreed verz well with the quoted ones. Slightly worse was the compliance of the 4 year disease-free survival rates (72% in the good prognosis and 51% in the poor prognosis group) with the results from the literature. The 3 year overall survival rates (low risk patients 87%, high intermediate risk 61% and high risk patients 51%) were somewhat worse than the reported ones in all IPI subgroups except in the low intermediate risk group (82%). On the other hand, the 4 year overall survival rates of the R-IPI categories (94% in the very good prognosis group, 80% in the good prognosis group, 56% in the poor prognosis group) were much better correlated with the data from the literature. Conclusions. In total, the treatment outcomes of routinely treatedpatient with the DLBCL at our institute are quite encouraging when compared to results of some larger studies. There are probably no dilemmas about how to treat young good prognosis patients and patients aged over 60 years at present. However, the 5 year overall survival rate of 76% for the young poor prognosis group is unsatisfying and needs to be improved. At present, quite a few studies are underway to clarify which of the regimens will perform best in this population.
Ključne besede: diffuse large B-cell lymphoma, R-CHOP, treatment result, routine treatments
Objavljeno v DiRROS: 21.03.2024; Ogledov: 80; Prenosov: 29
.pdf Celotno besedilo (621,34 KB)

Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphoma
Barbara Jezeršek Novaković, Vladimir Kotnik, Tanja Južnič Šetina, Marjeta Vovk, Srdjan Novaković, 2007, izvirni znanstveni članek

Povzetek: Background. Rituximab has been applied successfully in the treatment of indolent and aggressive CD20 positive B cell lymphomas, yet the exact in vivo mechanisms of its action have not been unambiguously explained. This study wastherefore aimed to confirm the presumed major mechanisms of action of rituximab and concomitantly to assess the effectiveness of first-line chemoimmunotherapy in high-risk patients with aggressive CD20 lymphomas. Patients, materials and methods. The activity of rituximab was tested in vitroon Raji and SU-DHL-4 cells using the cell proliferation assay and flow cytometry. In the clinical part of the study, 20 high-risk patients with aggressive CD 20 lymphomas were treated with R-CHOP. Results. Only complement-mediated cytotoxicity was observed under the in vitro applied experimental conditions. Neither the direct apoptotic effect nor the antibody-dependent cell-mediated cytotoxicity was detected probably due to a too low concentration of rituximab and a too low ratio of cytotoxic lymphocytes to tumor cells. The treatment outcome in patients was excellent since complete remissions were achieved in 90% of poor-risk patients at the end of primary treatment and 80% of patients were disease free at 18.5 months median observation period. Conclusions. According to our results, the complement-dependent cytotoxicity is an important mechanism of rituximab action in vitro. To achieve direct apoptosis, higher concentrations than 20 micro g/ml of rituximab should be used, while for an effective antibody-dependent cell-mediated cytotoxicity, the ratio of cytotoxic lymphocytes to tumor cells should be higher than 1:1. In the high- risk patients with aggressive CD20 lymphomas, the addition of rituximab to CHOP substantially improves the therapeutic results.
Objavljeno v DiRROS: 22.02.2024; Ogledov: 136; Prenosov: 36
.pdf Celotno besedilo (232,23 KB)

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