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V Jović

Publications and source records attributed to V Jović.

6 recordsLinked to original sources

[Correlation between functional capability and phenotypic characteristics of peripheral blood lymphocytes in patients with malignant melanoma].

Malignant melanoma is well known for its poor response to chemotherapy, radiotherapy and its susceptibility to immunotherapy. Considering that dacarbazine (DTIC) and interferon alpha (IFNalpha) are among the most frequently used agents in the treatment of melanoma, the aim of this study was to evaluate the kinetics of immunological changes during adjuvant treatment of melanoma patients with DTIC or with IFNalpha monotherapy, as well as with their combination in metastatic disease. Pre-therapy values of immunological parameters showed significantly decreased NK cell activity, altered in vitro production of TNFalpha, IL-2 and proliferative response of peripheral blood lymphocytes (PBL), while percentage of PBL subpopulations was unchanged. During therapy, NK cell activity was significantly increased after the 1st cycle of combined chemoimmunotherapy (DTIC + IFNalpha), followed by a significant decrease after the 2nd cycle of therapy. Furthermore, in this group, there was a significant increase in CD4+ T helper cell percentage after the 1st cycle of therapy. Serial monitoring of activation antigens also showed a significant increase in the expression of CD38 on CD8+ cytotoxic T cells, after the 1st and 2nd cycle in combined chemoimmunotherapy group and, after 30 days, in the group of patients treated with IFNalpha, only. The increase in the expression of HLA-DR activation antigen on CD3+ and CD8+ T cells had a gradual increase and significant rise after the 2nd cycle of combine chemoimmunotherapy, only. The dynamic of immunological changes, mostly observed in combined chemoimmunotherapy, and rarely in IFNalpha monotherapy gives valuable insight into induced immunomodulation, suggesting early, but transient favourable changes, that could be prolonged by timely introduction of other immunotherapeutic agents.

Adult↗

Therapeutic implications of the kinetics of immunomodulation during single or combined treatment of melanoma patients with dacarbazine and interferon-alpha.

The therapy of metastatic melanoma has not given satisfactory results. Single chemo- or immunotherapeutic agents in the adjuvant setting or combined chemoimmunotherapy for metastatic disease have generally been evaluated only in terms of clinical benefit. Considering that dacarbazine (DTIC) and interferon-alpha (IFN-alpha) are among the most frequently used agents in the treatment of melanoma, the aim of this study was to evaluate the kinetics of immunological changes during adjuvant treatment of melanoma patients with DTIC or with IFN-alpha monotherapy, as well as by their combination in metastatic disease. The evaluated immunological parameters showed significant early increase in the activity of NK (natural killer) cells, CD4/CD8 ratio, CD4+ T cell number in patients treated with combined chemoimmunotherapy and an increase in expression of the early activation antigen CD38 on CD8+ cytotoxic T cells, both, in patients treated with combined chemoimmunotherapy and with IFN-alpha alone, while, no significant change in any one parameter was detected in the group of patients receiving DTIC. The kinetics of the observed immunological changes, restricted to combined chemoimmunotherapy, indicate that the engagement of antitumor immune response appears early but is short-lived and that this favorable effect should be augmented and prolonged by the timely introduction of additional immunomodulating agents.

ADP-ribosyl Cyclase↗

Selenium status in soils in Yugoslavia.

In the last 8 years, a number of data on selenium (Se) content and distribution in the soil of Yugoslavia (Serbia and Montenegro) became available. The Se content of the soil in Yugoslavia varies in a broad range 39 to 440 microg/kg (mean value 230 microg/kg; n = 284). The soil clay fraction is rich in Se (range 146 to 586 microg/kg) in relation to sand and silt fractions. The available Se content (after extraction with ammonium acetate and EDTA) varies in the range of 1.2 to 28.2% of the total Se content. The speciation of Se is shown for the soils derived from volcanic rocks in Serbia. In addition, the influence of some soil properties on the Se content, as well as its content in the rocks, sediment, and wild plants in Yugoslavia, is discussed. The geographical distribution of Se in the soil of Yugoslavia shows that it is found in inadequate amounts in many agricultural regions. Its low content in soil has been thought to be associated with a higher incidence of some diseases. The Se content of the soil in Yugoslavia is not fully known. There is a great need to make a systematic geochemical mapping for Se and other trace elements in the soil.

Chemical Phenomena↗

Selenium in soil, grass, and human serum in the Zlatibor mountain area (Serbia): geomedical aspects.

The Zlatibor district in Serbia has lower mortality rates of malignant and cardiovascular diseases (CVD) compared with other regions in Serbia. To better understand the influence of the geochemical environment, we collected and analyzed soil from various bedrocks and the grass growing on them. We also analyzed spring and stream waters, including large water supply accumulations, for major chemical elements and examined the serum of healthy adults in the large area of Zlatibor for selenium (Se) and magnesium (Mg). Our studies included villages, small towns, and the town of Uzice. Our results showed a variable Se content in the soil over different bedrocks. In general, soil in this area has a higher Se content than in other regions of Serbia. The Se content of the grass is influenced by bedrock and soil mineralogy, but mostly by soil pH and the date of collection. For example, in late summer, grass contains twice as much Se than in spring. Mg2+HCO3(-)-type waters occur in the ultramafic massif of Zlatibor in a concentration of 44 to 68 mgMg/L. The serum Se values were higher in the Zlatibor area than in other regions of Serbia (62.6 +/- 14.9 microgSe/L; n = 158). The serum Mg content (22.7 +/- 2.2 mg/L; n = 158) was in the uppermost part of the reference range. Taking into account their biological role, the Se and Mg levels in the human population in the Zlatibor area could influence the lower mortality rates of cancer and CVD in this region compared with other regions in Serbia.

Adult↗

Selenium deficiency in Yugoslavia.

Data on selenium (Se) deficiency in Yugoslavia are presented. The results include Se content of soil, cereal crops, and garlic grown in these soils, and human serum and scalp hair from several towns and regions. All data indicate a serious Se deficiency: soil (n = 140), the mean value of 200 +/- 69.6 micrograms/kg Se; wheat, (58) mean = 20.5 +/- 12.4 micrograms/kg; corn, (79) mean = 13.7 +/- 13.6 micrograms/kg; and garlic, (66) mean = 13.7 +/- 17.1 micrograms/kg Se. Analyses of human tissue show a very low Se status of the Yugoslav population: serum, (n = 875) mean = 50.0 +/- 18.0 micrograms/L and scalp hair, (388) mean = 94 +/- 16 micrograms/kg Se. In some regions, Se contents of grain, garlic, and human serum and hair are approaching those in the low-Se belt in China. It is assumed that very low Se status of a human population could be a risk factor in the development of Balkan Endemic Nephropathy (BEN) and in a high incidence of urinary tract tumors (UTT) in endemic areas.

Balkan Nephropathy↗

Impaired perforin-dependent NK cell cytotoxicity and proliferative activity of peripheral blood T cells is associated with metastatic melanoma.

AIMS AND BACKGROUND: Patients with metastatic melanoma often have defects in the percentage and function of peripheral blood NK cells, which are involved in the non-specific innate antitumor immune response, and T cells, which participate in the specific acquired antitumor immune response. The aim of this study was to investigate in more detail not only the percentage but also the activation status and function of NK and T cells in patients with metastatic melanoma prior to therapy. METHODS: The percentage of peripheral blood CD56+ NK cells, CD3+ T cells and their CD4+ and CD8+ subsets, as well as the expression of the activation antigens CD69, CD38 and HLA-DR were analyzed by flow cytometry. The functional capacity of NK cells was evaluated by the 51-chromium release cytotoxicity assay, while the proliferative activity of T cells was estimated by the lymphocyte transformation test to mitogen phytohemagglutinin. RESULTS: The results obtained in this study have revealed a new aspect of NK and T cell dysfunction that is not, as commonly reported, associated with a decrease in their percentage. Moreover, a significant number of the investigated patients had a higher percentage of NK cells that did not lead to improved NK cell cytotoxicity as a result of the detected defect in the NK cell perforin-mediated cytotoxic mechanism of tumor cell lysis. The impaired proliferative response of T cells was associated with a decreased expression of the activation antigen HLA-DR. CONCLUSION: The novel finding in this study of melanoma patients with metastatic disease is the impaired perforin-dependent NK cell cytotoxic mechanism, which was recently shown to be primarily responsible for preventing metastasis. Another interesting finding was the generally hyporeactive status of T cells, possibly resulting from persistent antigenic stimulation. The observed dysfunction of NK and T cells in patients with metastatic melanoma prior to therapy point to the need to supplement chemotherapy with appropriate immunotherapeutic agents in order to overcome the immunosuppression associated with advanced malignancy.

Adult↗