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Query: "author" (Srdjan 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, 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: 97; Downloads: 26
.pdf Full text (232,23 KB)

4.
Rapid detection of most frequent Slovenian germ-line mutations in BRCA1 gene using real-time PCR and melting curve analysis
Srdjan Novaković, Vida Stegel, 2005, original scientific article

Abstract: Background. Detection of inherited mutations in cancer susceptibility genes isof great importance in some types of cancers including the colorectal cancer(mutations of APC gene in familial adenomatous polyposis -FAP, mutationsin mismatch repair genes in hereditary nonpolyposis colorectal cancer- HNPCC), malignant melanoma (mutations in CDKN2A and CDK4 genes) and breast cancer (mutations in BRCA1 and BRCA2 genes). Methods. This article presents the technical data for the detection of five mutations in BRCA1 gene in breast cancer patients and their relatives. The mutations - 1806C>T, 300T>G, 300T>A, 310G>A, 5382insC -were determined by the real-time PCR and themelting curve analysis. Results and conclusion. In comparison to direct sequencing, this method proved to be sensitive and rapid enough for the routine daily determination of mutations in DNA isolated from the peripheral blood.
Published in DiRROS: 14.02.2024; Views: 99; Downloads: 27
.pdf Full text (254,79 KB)

5.
Tumor markers in clinical oncology
Srdjan Novaković, 2004, review article

Abstract: The subtle differences between normal and tumor cells are exploited in the detection and treatment of cancer. These differences are designated as tumor markers and can be either qualitative or quantitative in their nature. That means that both the structures that are produced by tumor cells as well as thestructures that are produced in excessive amounts by host tissues under theinfluence of tumor cells can function as tumor markers. Speaking in general, the tumor markers are the specific molecules appearing in the blood or tissues and the occurrence of which is associated with cancer. According totheir application, tumor markers can be roughly divided as markers in clinical oncology and markers in pathology. In this review, only tumor markersin clinical oncology are going to be discussed. Current tumor markers in clinical oncology include (i) oncofetal antigens, (ii) placental proteins, (iii) hormones, (iv) enzymes, (v) tumor-associated antigens, (vi) special serum proteins, (vii) catecholamine metabolites, and (viii) miscellaneous markers. As to the literature, an ideal tumor marker should fulfil certain criteria - when using it as a test for detection of cancer disease: (1) posirive results should occur in the early stages of the disease, (2) positiveresults should occur only in the patients with a specific type of malignancy, (3) positive results should occur in all patients with the same malignancy, (4) the measured values should correlate with the stage of the disease, (5) the measured values should correlate to the response to treatment, (6) the marker should be easy to measure. Most tumor markers available today meet several, but not all criteria. As a consequence of that, some criteria were chosen for the validation and proper selection of the most appropriate marker in a particular malignancy, and these are: (1) markers' sensitivity, (2) specificity, and (3) predictive values. (Abstract truncated at 2000 characters).
Published in DiRROS: 13.02.2024; Views: 77; Downloads: 16
.pdf Full text (117,07 KB)

6.
Tumor markers in clinical oncology
Srdjan Novaković, 2004, review article

Abstract: The subtle differences between normal and tumor cells are exploited in the detection and treatment of cancer. These differences are designated as tumor markers and can be either qualitative or quantitative in their nature. That means that both the structures that are produced by tumor cells as well as thestructures that are produced in excessive amounts by host tissues under theinfluence of tumor cells can function as tumor markers. Speaking in general, the tumor markers are the specific molecules appearing in the blood or tissues and the occurrence of which is associated with cancer. According totheir application, tumor markers can be roughly divided as markers in clinical oncology and markers in pathology. In this review, only tumor markersin clinical oncology are going to be discussed. Current tumor markers in clinical oncology include (i) oncofetal antigens, (ii) placental proteins, (iii) hormones, (iv) enzymes, (v) tumor-associated antigens, (vi) special serum proteins, (vii) catecholamine metabolites, and (viii) miscellaneous markers. As to the literature, an ideal tumor marker should fulfil certain criteria - when using it as a test for detection of cancer disease: (1) posirive results should occur in the early stages of the disease, (2) positiveresults should occur only in the patients with a specific type of malignancy, (3) positive results should occur in all patients with the same malignancy, (4) the measured values should correlate with the stage of the disease, (5) the measured values should correlate to the response to treatment, (6) the marker should be easy to measure. Most tumor markers available today meet several, but not all criteria. As a consequence of that, some criteria were chosen for the validation and proper selection of the most appropriate marker in a particular malignancy, and these are: (1) markers' sensitivity, (2) specificity, and (3) predictive values. (Abstract truncated at 2000 characters).
Published in DiRROS: 13.02.2024; Views: 114; Downloads: 0

7.
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: 128; Downloads: 28
.pdf Full text (97,46 KB)

8.
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: 131; Downloads: 30
.pdf Full text (397,81 KB)

9.
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: 109; Downloads: 36
.pdf Full text (482,88 KB)

10.
Simple but extremely effective autologous tumor vaccines
Srdjan Novaković, Barbara Jezeršek Novaković, 1998, original scientific article

Published in DiRROS: 19.01.2024; Views: 122; Downloads: 36
.pdf Full text (428,08 KB)

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