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Query: "author" (Barbara Jezeršek Novaković) .

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

Abstract: 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.
Keywords: diffuse large B-cell lymphoma, R-CHOP, treatment result, routine treatments
Published in DiRROS: 21.03.2024; Views: 58; Downloads: 24
.pdf Full text (621,34 KB)

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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, original scientific article

Abstract: 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.
Published in DiRROS: 22.02.2024; Views: 125; Downloads: 30
.pdf Full text (232,23 KB)

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Rituximab affects the prognosis of patients with nonHodgkin's lymphomas
Barbara Jezeršek Novaković, Marjeta Vovk, Simona Borštnar, Radka Tomšič, 2004, original scientific article

Abstract: Backround. Rituximab - the most widely used monoclonal antibody in the B cell lymphoid malignancies has been applied successfully in the treatment of relapsed and refractory indolent CD20 positive B cell lymphomas and more recently, also in the treatment of aggressive lymphomas in combination with standard chemotherapy. Albeit the chemo-immunotherapy has a wide range of potential applications, there are still several issues that have to be resolved: (1) the optimal scheduling of antibody-chemotherapy combinations, (2) the most active of these combinations, as well as (3) the predictors of response to rituximab. Patients and methods. To facilitate addressing the first two questions, we performed an analysis in 25 patients with different histological types of CD20 positive nonHodgkin's lymphomas (10 aggressive and 15 indolent). Seventeen patients were treated with chemo-immunotherapy for a relapse, and just in 8 patients rituximab was added to first line chemotherapy. Most of the responders received the CHOP regimen, but also otherregimens (FC, BVCPP) were effective in combination with rituximab. Results. The overall response rate was 76%, with 68% complete remissions. The median response duration has not been reached yet. The response was markedly better in the group of previously untreated patients, where the overall response rate reached 100%, with 7 patients in complete and 1 patient in partial remission. Most of the treatment failures occurred in heavily pretreated patients with aggressive lymphomas. No serious adverse effects wereobserved. Conclusion The chemo-immunotherapy improves the treatment outcomes in patients with untreated and relapsed CD20 positive nonHodgkin's lymphomas in comparison to chemotherapy alone. The combined treatment is the most effective when used as soon as possible (preferably as the first line treatment). (Abstract truncated at 2000 characters).
Published in DiRROS: 07.02.2024; Views: 147; Downloads: 33
.pdf Full text (4,61 MB)

6.
A brief overview of the tumor vaccines through the last decade
Srdjan Novaković, Barbara Jezeršek Novaković, 2002, review article

Abstract: How to destroy cancer cells without damaging the normal cells? How to make conventional methods of systemic cancer treatment that predominantly comprise cytotoxic drugs more selective and prevent the development of drug resistance?There is an abundance of such guestions that do not have simple answers. If, a few years ago, unselective cytotoxic drugs were the method of choice for the treatment of cancer, in the last 25 years we are witnessing therapid transition of immunotherapy from the laboratories to the clinics. Among the most attractive and promising immunotherapies for cancer, a special place is reserved for tumor vaccines. Exploiting the latest knowledge in immunology, tumor physiology, as well as in molecular biology, many outstanding approaches for the creation of tumor vaccines have been developed.With no intention to be comprehensive, in the present article some of those approaches are reviewed.
Published in DiRROS: 31.01.2024; Views: 131; Downloads: 28
.pdf Full text (97,46 KB)

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Antibodies to p53 - can they serve as tumor markers in patients with malignantlymphomas?
Barbara Jezeršek Novaković, Srdjan Novaković, 2000, original scientific article

Abstract: Background. Tumor suppressor gene p53 is mutated in approximately 21% of patients with nonHodgkin's lymphomas (the percentage varying from 0 up to 67% depending upon the histological type). Most of the mutations are point missense mutations resulting in nuclear accumulation of altered protein. Roughly one third of patients with overexpression of p53 protein develop circulating anti p53 antibodies. The present study was aimed at defining the usefulness of serial serological determinations of autoantibodies to p53 for clinical follow up of NHL patients. Patients and methods. Serum levels of antibodies to p53 were determined in various time intervals in three lymphoma patients (who had elevated serum levels at the time of diagnosis) for maximum two years using the commercially available ELISA kit p53-Autoantikoerper ELISA2. Generation. Results. In all three cases the temporal patterns of anti p53 antibodies reflected accurately disease progression or regression, and even foretold a relapse ten months in advance. The reflection of disease regression by autoantibodies lagged approximately three months behind the morphological disappearance of the disease due to a long half life of the antibodies. Conclusion. Our results confirmed the usefulness of antibodies to p53 as tumor markers for follow up of lymphoma patients, yet the subset of patients that could be appropriately followed up with this method is very limited due to the low proportion of patients that develop immune response to p53 protein.
Published in DiRROS: 25.01.2024; Views: 149; Downloads: 32
.pdf Full text (397,81 KB)

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p53 - the paradigm of tumor-suppresor genes?
Barbara Jezeršek Novaković, Srdjan Novaković, 1998, review article

Abstract: p53 is a tumor-suppressor gene the alterations of which are among the most frequent genetic changes detected in human neoplasms. Its product - p53 protein is a component of several biochemical pathways that are central to carcinogenesis: DNA transcription, genomic stability, DNA repair, cell cycle control, and apoptosis. The analysis of the spectrum of p53 mutations and insight into the p53 mediated biochemical pathways of programmed cell death and cell cycle arrest, provide clues to understanding of molecular pathogenesis of cancer of mechanisms related to p53 mediated tumor suppression. The purpose of the resent article is to summarise the most important facts concerning p53 since understanding of the above listed processes might provide the potential molecular targets for the development ofa rational cancer treatment.
Published in DiRROS: 19.01.2024; Views: 128; Downloads: 38
.pdf Full text (482,88 KB)

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Simple but extremely effective autologous tumor vaccines
Srdjan Novaković, Barbara Jezeršek Novaković, 1998, original scientific article

Published in DiRROS: 19.01.2024; Views: 142; Downloads: 38
.pdf Full text (428,08 KB)

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