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Iskalni niz: "avtor" (Barbara Jezeršek Novaković) .

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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, 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: 97; Prenosov: 26
.pdf Celotno besedilo (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, izvirni znanstveni članek

Povzetek: 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).
Objavljeno v DiRROS: 07.02.2024; Ogledov: 138; Prenosov: 32
.pdf Celotno besedilo (4,61 MB)

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A brief overview of the tumor vaccines through the last decade
Srdjan Novaković, Barbara Jezeršek Novaković, 2002, pregledni znanstveni članek

Povzetek: 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.
Objavljeno v DiRROS: 31.01.2024; Ogledov: 128; Prenosov: 28
.pdf Celotno besedilo (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, izvirni znanstveni članek

Povzetek: 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.
Objavljeno v DiRROS: 25.01.2024; Ogledov: 131; Prenosov: 30
.pdf Celotno besedilo (397,81 KB)

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p53 - the paradigm of tumor-suppresor genes?
Barbara Jezeršek Novaković, Srdjan Novaković, 1998, pregledni znanstveni članek

Povzetek: 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.
Objavljeno v DiRROS: 19.01.2024; Ogledov: 109; Prenosov: 36
.pdf Celotno besedilo (482,88 KB)

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Simple but extremely effective autologous tumor vaccines
Srdjan Novaković, Barbara Jezeršek Novaković, 1998, izvirni znanstveni članek

Objavljeno v DiRROS: 19.01.2024; Ogledov: 122; Prenosov: 36
.pdf Celotno besedilo (428,08 KB)

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Tumor necrosis factor-alpha (TNF-alpha): biological activities and mechanisms of action
Srdjan Novaković, Barbara Jezeršek Novaković, 1995, pregledni znanstveni članek

Objavljeno v DiRROS: 15.01.2024; Ogledov: 112; Prenosov: 33
.pdf Celotno besedilo (1,03 MB)

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