1. Clonality analysis of lymphoid proliferations using the BIOMED-2 clonality assays : a single institution experienceIra Koković, Barbara Jezeršek Novaković, Petra Škerl, Srdjan Novaković, 2014, original scientific article Abstract: 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.
Keywords: Biomed-2, clonality analysis, lymphomas, IGH rearrangement, TCR rearrangement
Published in DiRROS: 11.04.2024; Views: 55; Downloads: 17
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2. Clonality analysis of lymphoid proliferations using BIOMED-2 clonality assays : a single institution experienceIra Kokovič, Barbara Jezeršek Novaković, Petra Škerl, Srdjan Novaković, 2014, professional article Keywords: onkologija, rak (medicina), limfom, diagnostika, analiza, molekularne metode, molekularna diagnostika
Published in DiRROS: 10.04.2024; Views: 65; Downloads: 14
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3. Breast cancer risk prediction using Tyrer-Cuzick algorithm with an 18-SNPs polygenic risk score in a European population with below-average breast cancer incidenceTjaša Oblak, Petra Škerl, Benjamin J. Narang, Rok Blagus, Mateja Krajc, Srdjan Novaković, Janez Žgajnar, 2023, original scientific article Abstract: Goals: To determine whether an 18 single nucleotide polymorphisms (SNPs) polygenic risk score (PRS18) improves breast cancer (BC) risk prediction for women at above-average risk of BC, aged 40-49, in a Central European population with BC incidence below EU average. Methods: 502 women aged 40-49 years at the time of BC diagnosis completed a questionnaire on BC risk factors (as per Tyrer-Cuzick algorithm) with data known at age 40 and before BC diagnosis. Blood samples were collected for DNA isolation. 250 DNA samples from healthy women aged 50 served as a control cohort. 18 BC-associated SNPs were genotyped in both groups and PRS18 was calculated. The predictive power of PRS18 to detect BC was evaluated using a ROC curve. 10-year BC risk was calculated using the Tyrer-Cuzick algorithm adapted to the Slovenian incidence rate (S-IBIS): first based on questionnaire-based risk factors and, second, including PRS18. Results: The AUC for PRS18 was 0.613 (95 % CI 0.570-0.657). 83.3 % of women were classified at above-average risk for BC with S-IBIS without PRS18 and 80.7 % when PRS18 was included. Conclusion: BC risk prediction models and SNPs panels should not be automatically used in clinical practice in different populations without prior population-based validation. In our population the addition of an 18SNPs PRS to questionnaire-based risk factors in the Tyrer-Cuzick algorithm in general did not improve BC risk stratification, however, some improvements were observed at higher BC risk scores and could be valuable in distinguishing women at intermediate and high risk of BC.
Keywords: early breast cancer, polygenic risk score, risk prediction
Published in DiRROS: 21.03.2024; Views: 73; Downloads: 26
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4. Efficacy of first-line systemic treatment in correlation with BRAF V600E and different KRAS mutations in metastatic colorectal cancer : a single institution retrospective analysisMartina Reberšek, Marko Boc, Petra Škerl, Jernej Benedik, Zvezdana Hlebanja, Neva Volk, Srdjan Novaković, Janja Ocvirk, 2011, original scientific article Keywords: rak (medicina), debelo črevo, danka, zdravljenje
Published in DiRROS: 18.03.2024; Views: 72; Downloads: 27
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5. Genotyping of BRCA1, BRCA2, p53, CDKN2A, MLH1 and MSH2 genes in a male patient with secondary breast cancerAna Lina Vodušek, Srdjan Novaković, Vida Stegel, Berta Jereb, 2011, original scientific article Published in DiRROS: 18.03.2024; Views: 69; Downloads: 28
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6. Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphomaBarbara 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: 133; Downloads: 33
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7. Rapid detection of most frequent Slovenian germ-line mutations in BRCA1 gene using real-time PCR and melting curve analysisSrdjan 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: 131; Downloads: 34
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8. Tumor markers in clinical oncologySrdjan 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: 103; Downloads: 21
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9. Tumor markers in clinical oncologySrdjan 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: 150; Downloads: 0 |
10. A brief overview of the tumor vaccines through the last decadeSrdjan 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: 147; Downloads: 32
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