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I Spuzić

Publications and source records attributed to I Spuzić.

At least 19 recordsLinked to original sources
PubMed2004

The comparison of spontaneous LDH release activity from cultured PBMC with sera LDH activity in non-Hodgkin's lymphoma patients.

Based on the fact that lactate dehydrogenase (LDH) enzyme is a very sensitive indicator of the cellular metabolic state, aerobic or anaerobic direction of glycolysis, activation status, and malignant transformation, in this study we compared values of the spontaneous LDH release from circulating PBMC with sera LDH activity in 53 different subtypes of non-Hodgkin's lymphoma (NHL) patients. Results shows that serum LDH was significantly (p < 0.05) elevated in comparison to the range values only in the advance clinical stage (III and IV) in all investigated subtypes of NHL according to The Working and REAL classification. On the other hand, the spontaneous LDH release from cultures PBMC is significantly (p < 0.01) elevated in early and advanced stage in all investigated forms of NHL in comparison to healthy controls. Based on consideration that an increase in spontaneous LDH release appears before elevated sera LDH activity, we conclude that determination of spontaneous LDH release by microassay from cultured cells together with other findings may help in the diagnosis of NHL patients, especially in patients with early stage of disease.

Adolescent↗
PubMed2002

[Accomplishments and perspectives in tumor diagnostics and treatment].

In contemporary medicine cancer has an exceptionally important role, even though it is not a new disease. Tumors are found in all animals and plants, and today are more frequent than before, when they were found predominantly in advanced ages. The frequency occurrence depends of many factors, and it is more frequent in countries with higher degree of civilization, what is the consequence of irradiation of other diseases as well as more pronounced industrialization, leading to in proper nourishment, many sources of intoxication with carcinogenic factors arising from environmental pollution, and even by the use of some diagnostic and therapeutic procedures. Cancer is the result of disturbance in cell growth and differentiation. In the appearance and spreading of tumors many factors are involved. In the Department of Experimental and Clinical Oncology of the Institute for Oncology and Radiology, we in the first place investigated the role of immunity, hormones and central nervous system, predominantly in experimental conditions, based on the investigations on animals, the in vitro investigations is tissue cultures and some disturbances which are found in blood of patients with tumors. As in the processes of carcinogenesis the immune system has in important role, in the immunological investigations we primarily investigated parameters of the status of the immune system in patients with malignant processes. The number and function of particular cell subsets of the immune system was investigated, namely T and B lymphocytes and their subclasses, NK cells and monocytes-macrophages. In the majority of analyzed patients with breast and lung cancer, lymphoproliferative diseases and other malignancies, it was shown that the majority of them had a decreased number of immune cells that correlated with the clinical advances of disease and applied cytostatic therapy. However, it was shown that the function of these cells, primarily NK, but also of T lymphocytes, was markedly decreased even before changes in the cell number, indicating that a functional impairment is present even before the cell number decrease and proportional to the advancement of the disease. As the results of exploring of investigation of the immunological status indicate the concrete defects in the function of the separate components of the immune system, these findings make it possible to direct immunotherapy for the correction of existing defects. The activity and pathways of mechanisms of NK cells and the possibility of their modulation were also investigated. Also, the possibility of the application of mAbs in the precise diagnostics of some malignancies was explored. The role in carcinogenesis was investigated in tumors whose appearance, growth and spreading is hormone-dependent. One of the hormone-dependent tumors is breast cancer. It was shown that they are significantly dependent on estrogen and growth factor presence, steroid-receptor content, and that these characteristics can change during the disease and do not have to be identical in their metastasis. Numerous investigations that we performed were in the in vitro conditions, i.e. in cell cultures. The obtained data show how some tumor cells react to applied agents, cytostatical and biological. However their effect in vivo is very often different, as in the in vivo conditions many other factors are involved, suggesting a need for further investigations of these factors. The role of the central nervous system neurotransmiters in carcinogenesis in experimental animals exposed to chemical cancerogen (5-methylcholantrene) with simultaneous treatment of the monoamine system was investigated. It was shown that monoamines expressed their influence on carcinogenesis by regulating the brain homeostasis, as well as by direct influence on the intracellular processes during cell development and differentiation. The obtained results will direct our further investigations toward obtaining mAbs for receptors for TNFalpha and IFNgamma, transfection of suppressor gene into tumor cell cultures and genes for IL-2 and TNFalpha. At the same time we will work on isolation of malignant melanoma tumor antigen and construction of a vaccine using some epitopes and adjuvantes. We will try to introduce appropriate immunotherapy in the advancedehZAD.

Animals↗
PubMed2002

[The possibilities of modulation of NK cell activity].

The immune system has an important role in tumor appearance and spreading. One of the most efficient subpopulations of cytotoxic cells in the destruction of tumors are NK cells. NK cells are activated and increase their cytotoxic potential and modulate their cytokine production after treatment with IFNgamma, IL-12, TNFalpha and IL-2. The investigation of the activity of NK cells was performed on peripheral blood lymphocytes (PBL) of 16 healthy controls and of 40 patients with metastatic breast carcinoma. Modulation of NK cells was performed with IL-2, IL-7, IL-12, TNFalpha, monoclonal antibodies (mAb) for TNFalpha and TNFalpha receptors type I and II, as well as with sera of healthy controls and patients with breast cancer in different clinical stages. Modulating effect of the applied factors after in vitro treatment of PBL was evaluated by the cytotoxic assay using 51chromium. Our results indicate that IL-2 significantly increased the activity of NK cells of controls and breast cancer patients. The sera of patients with advanced breast cancer significantly reduced NK cell activity. IL-7, IL-12 and mAb for TNFalpha do not significantly change the activity of NK cells. The presence of anti-TNFalpha mAb did not change the inhibitory effect of the sera of breast cancer patients with advanced disease on the activity of NK cells of controls and patients with breast cancer. Blocking of TNFalpha Rcs with mAbs decrease the reactivity of NK cells for IL-2. The treatment of breast cancer patients with advanced clinical stage of breast cancer with IL-2, as an additional therapy, could be advantageous, as NK cells after this treatment increase their cytotoxic activity against tumor cells and can improve therapeutical results.

Antibodies, Monoclonal↗
PubMed2002

[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↗
PubMed2002

[Lactate dehydrogenase (LDH) in peripheral blood lymphocytes (PBL) of patients with solid tumors].

Serum LDH level is a prognostic factor in different malignancies as its increase reflects tumor mass and response to therapy. Serum LDH is the consequence of the disruption of the cell membrane of a large fraction of dividing malignant cells whose metabolic hallmark is anaerobic glycolysis that leads to increased LDH enzyme activity. Moreover, as we have previously shown that spontaneous LDH release from cells represents a measure of cell membrane damage, and this parameter is used for the estimation of cell destruction in cytotoxic assays, the aim of this study was to evaluate the characteristics of LDH activity of PBMC of patients with different solid tumors (non-Hodgkin's lymphomas--NHL, n=47; Hodgkin's disease--HD, n=45; ovarian cancer--OvCa, n=6; breast cancer--BrCa, n=34; thyroid cancer--TyCa, n=3; cancer of PVU--CaPVU, n=4 and head & neck--H&N, n=6) in all clinical stages of NHL and HD and in advanced clinical stages of disease for BrCa, OvCa, CaPVU and H&N. Spontaneous LDH release from PBMC was determined by the spectrophotometric method from supernatants of 8 x 10(6)/ml PBMC cultured for 2 h in RPMI 1640 without phenol red using and LDH substrate mixture. The total LDH activity was determined after lysis of PBMC by ultrasound. The obtained results indicate that PBMC in all the investigated malignancies, compared to control PBMC, demonstrate a significant increase (p<0.01) in spontaneous LDH release act, which correlates with advanced clinical stage in all malignancies except in Hodgkin's disease, in which the spontaneous LDH release was increased in all clinical stages. Contrary to this, the total LDH activity was not increased in PBMC in all investigated tumors. However, the "percent of spontaneous LDH release" was always increased, regardless of the total LDH activity, indicating that spontaneous LDH release is the consequence of PBMC membrane damage present in advanced stages of different solid tumors.

Humans↗
PubMed2001

Association of NK cell dysfunction with changes in LDH characteristics of peripheral blood lymphocytes (PBL) in breast cancer patients.

The cytotoxic activity of NK (natural killer) cells is very important in immunological surveillance against the appearance and especially the spread of malignant disease. The aim of this study was to investigate the function of this subpopulation of cells in breast cancer patients in different clinical stages of disease prior to therapy. NK cell activity was determined in breast cancer patients and healthy controls by three different methods: standard 51-chromium-release assay and by the original colorimetric uncorrected and corrected lactate dehydrogenase (LDH) release assay. A discrepancy was shown between the assays, as the uncorrected LDH assay showed, not only, much higher values, but no stage-dependent depression in NK cell activity compared to the chromium-release assay. Further analyses of separately cultured peripheral blood lymphocytes (PBL) revealed that this difference arose from an increasing, clinical stage-dependent, spontaneous LDH release from PBL of breast cancer patients. Furthermore, a stage-dependent increase in intracellular LDH activity of PBL was found, although without difference in LDH-H and LDH-M isotype ratio, compared to controls. Increased spontaneous LDH release and intracellular LDH activity was more evident in young patients, under 40 years. Correction of the original LDH-release assay for the spontaneous LDH release activity from PBL present in the assay, gave values of NK cell activity comparable to those determined by the chromium assay and indicated that breast cancer patients have a significant depression in NK cell activity which correlates with the stage-dependent increase in spontaneous LDH release. Moreover, as both assays measure the secretory, perforin-mediated, NK cell cytotoxic pathway against tumor cells, it can be concluded that the appearance of spontaneous LDH release is an indicator of cell membrane damage which not only allows the loss of LDH, but also of the components of the secretory killing pathway, resulting in NK cell dysfunction with the progression of disease. The novel findings obtained in this work reveal the association of PBL membrane damage with clinical stage of breast cancer that can, aside from reflecting NK cell depression, underlie the defect in other PBL subsets and subsequently facilitate progression of the malignant process.

Adult↗
PubMed2001

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↗
PubMed2000

Different alterations in lactate dehydrogenase activity and profile of peripheral blood mononuclear cells in Hodgkin's and non-Hodgkin's lymphomas.

The enzyme lactate dehydrogenase (LDH) activity of peripheral blood mononuclear cells (PBMC), LDH isotype H and M pattern and PBMC spontaneous LDH release activity were examined in 55 non-Hodgkin's lymphoma (NHL) patients, 46 Hodgkin's disease (HD) patients and 47 controls. The intracellular LDH and M isotype activity of PBMC, their spontaneous LDH release activity significantly increase (p < 0.01) in NHL with progressing histological grade of malignancy. Contrary to this, all classical HD patients have a significant elevation (p < 0.05) of each of these parameters. Furthermore, unlike HD, in NHL clinical stage is associated with significant (p < 0.05) increase in the level of spontaneous LDH release activity in each histological form. It is also shown that spontaneous LDH release activity of PBMC for HD and NHL patients demonstrates significant positive correlation (p < 0.005) with serum LDH level, although elevation of spontaneous LDH release precedes serum LDH increase in both diseases. The results obtained regarding alterations in intracellular, isotype and spontaneously released LDH activity of circulating PBMC show that these parameters are dependent, in NHL patients, on the grade of malignancy and tumor burden, while they are persistently present in HD patients.

Hodgkin Disease↗
PubMed2000

Content of epidermal growth factor receptor in metastatic breast cancer: its role in endocrine sensitivity prediction.

Epidermal growth factor receptor (EGF-R) is known as an indicator of endocrine independence of breast cancer. However, a small proportion of EGF-R expressing tumors was found to respond to endocrine treatments. On the other side, a cut-off point of EGF-R positivity is not yet defined. In the aim to find out whether there exists a cut-off value that sharply discriminate the endocrine sensitive and endocrine insensitive breast cancers, the quantitative EGF-R content was analyzed in a group of 42 female patients with metastatic disease, being routinely treated with chemo-, chemo-endocrine, or endocrine therapy alone. Steroid receptors (SR) and EGF-R were determined by biochemical methods in tissue samples of an unselected group of patients. Patients with metastatic disease, either at diagnosis, or developed after the treatment of operable or locally advanced breast cancer, were included in the present analysis. According to the treatments used, and their therapeutic response, all patients were divided in endocrine sensitive or resistant, and chemo-sensitive or resistant. The SR and EGF-R status and content was analyzed in relation to the sensitivity to both systemic treatments. The EGF-R content was significantly lower in responders to endocrine treatments, compared to non-responders, while there was no difference in EGF-R level, in relation to the sensitivity to chemotherapy. In addition, the EGF-R content was significantly higher in chemo-sensitive tumors, than in endocrine sensitive. On the contrary, ER content was significantly higher in endocrine sensitive, than in endocrine resistant, and in chemo sensitive patients, as well. Similar differences were found in PR content, but they were less pronounced. While the individual ER contents in endocrine sensitive and endocrine resistant tumors overlapped, the EGF-R ranges were different: no one endocrine sensitive tumor exceeded the EGF-R content of 26 fmol/mg, thus suggesting the EGF-R cut-off point of endocrine sensitivity. The clinical use of EGF-R, with the cut-off point of 26 fmol/mg, in addition to clinical criteria of endocrine sensitivity and SRs, would significantly improve the correct endocrine sensitivity prediction (from 52 to 78%). In conclusion, in a group of metastatic breast cancer patients, treated routinely by systemic therapies it was found, that the use of higher cut-off point for EGF-R positivity can improve the prediction of endocrine sensitivity. The prognostic relevance of this cut-off value remains to be analyzed.

Adult↗
PubMed1999

A comparison of the NK cell cytotoxicity with effects of TNF-alpha against K-562 cells, determined by LDH release assay.

Effects of r h TNF-alpha as a single cytotoxic mediator against K-562 cells was examined by LDH release and compared with NK cell cytotoxicity. The mean values of the percentage of LDH release (x = 6.25 +/- 3.68%, for ten individual experiments) from K-562 cells cultured for 2 h with r h TNF-alpha 100 U/ml of culture medium did not give significant difference in comparison with mean values of percentage LDH release (x = 6.43 +/- 2.97%, for 37 individual experiments) from K-562 cells which were cultured without r h TNF-alpha (Student's t-test, P > 0.05). The results also showed, that in the presence of increasing concentrations of r h TNF-alpha there was no significant increase of LDH release through the cell membrane in these short term incubations. However, significant difference in LDH release from K-562 cells was found after 6 h between cultures treated for 30 min with or without r h TNF-alpha (Mann-Whitney test, P < 0.05). Since TNF-alpha alone shows a lower degree of K-562 cell membrane damage than NK effectors, this suggested that TNF-alpha is neither an only nor a major mediator of cell destruction, based on determination of LDH release.

Adult↗
PubMed1999

The difference in NK-cell activity between patients with non-Hodgkin's lymphomas and Hodgkin's disease.

Natural killer (NK) cells play an important role in immune surveillance against malignant diseases. Considering the lymphoid origin of malignant lymphomas, as well as scarce data concerning NK-cell function in these neoplasms, we evaluated NK-cell activity in 49 patients with non-Hodgkin's lymphomas (NHL) and 47 patients with Hodgkin's disease (HD), prior to therapy. Using the recommended International Working Formulation and the Ann Arbor staging system for classification of lymphomas we found, by the LDH release cytotoxicity assay, that decreased NK-cell activity (P < 0.05) in NHL patients was essentially related to unfavourable histology (13 indolent lymphomas, 25 intermediate and 11 very aggressive lymphomas were included), but that within these categories clinical stage of the disease also contributed to the degree of NK-cell dysfunction. In contrast, in HD, NK-cell activity was persistently decreased (P< 0.05), compared to controls, irrespective of histological type and clinical stage. It is of interest also that the most profound NK-cell dysfunction that is present and persistent from the onset of HD, and which appears in very aggressive NHL was associated with the phenomenon of increased spontaneous lactate acid dehydrogenase (LDH) release activity from the separated PBMC of these patients. The difference in the level of NK-cell impairment between patients with various histological grades of malignancy in NHL and HD suggests different initial participation of innate immune reactions in these diseases.

Cytotoxicity, Immunologic↗
PubMed1999

Expression of epidermal growth factor receptor in breast cancer, from early stages to advanced disease.

Epidermal growth factor receptor was determined in 106 newly diagnosed breast cancer patients, using the biochemical method. The group consisted of 58 patients in stage I-II, and 48 patients in stage III-IV. Although a significant inverse correlation was found between EGF-R status, and ER or PR status, quantitative content of EGF-R did not correlate either with quantitative ER, or PR levels. The ER/PR content was similar in all clinical stages, suggesting their stability during the clinical course of the disease. EGF-R content was significantly higher in stage IV, compared to stage I, while intermediate clinical stages and all substages did not differ according to the EGF-R content. EGF-R was confirmed as a weak prognostic factor within clinical stages. However, in a whole group, the overall survival was significantly better in patients whose tumors EGF-R content was lower than 26 fmol/mg, compared to those with higher ERF-R content. EGF-R content was highly predictive for the response to systemic endocrine treatment, in metastatic breast cancer patients. In locally advanced breast cancer a trend towards higher levels of EGF-R was found in inflammatory breast cancers, compared to non-inflammatory ones. Slightly higher levels were found in responders to local non-endocrine primary treatments (radiotherapy with or without chemotherapy), compared to non-responders, suggesting the possible predictive role of EGF-R for the response to such treatments. Our results emphasized the usefulness of quantitative receptor determination suggesting the relative stability of EGF-R content during the clinical course of breast cancer, its independence from ER, its significant predictive and weak prognostic values, and a possible correlation with the aggressiveness of the disease, and response to non-endocrine treatments.

Aged↗
PubMed1995

Estrogen and progesterone receptor content in bilateral breast cancer.

Estrogen and progesterone receptor content was determined in 34 patients with synchronous and 23 patients with asynchronous bilateral breast cancer. Steroid receptor content was measured quantitatively by DCC method. It was shown that progesterone receptor content could not be predicted, as well as, that steroid receptor content of the second tumor significantly influenced the development of asynchronous bilateral breast cancer. The high discordance rate concerning histologic type between two tumors within synchronous as well as asynchronous biopsies was observed. The obtained results indicate that both synchronous and asynchronous bilateral breast tumors may be considered as biologically different tumors whose both steroid receptor levels should be determined whenever possible.

Adult↗
PubMed1995

Reactivity of monoclonal antibodies OK-CLL (anti-CD5) with peripheral blood cells of patients with B cell lymphoproliferative disorders.

Reactivity of OK-CLL monoclonal antibodies that can identify CD5 antigen on peripheral blood mononuclear cells, was investigated in 172 patients with B cell chronic lymphocytic leukemia (B-CLL) in clinical stages RAI O-I and RAI II-IV and in patients with non-Hodgkin's lymphomas, classified according to the Working formulation into high and low grade histologic type. The OK-CLL reactivity with B-CLLs in the initial (RAI O-I), as well as in advanced stages of disease (RAI II-IV) was significantly higher than in controls. Peripheral blood cells of lymphoma patients, regardless of histological type, showed a much lower values of the CD5 positive population than chronic lymphocytic leukemia (CLL) patients, and a non significant discrepancy between the number of cells stained with anti-CD5 and those stained with other T cell markers. In spite of the showed considerable decrease of CD5 positive cells in CLL patients during therapy, elevated number of this population compared to normal individuals, after chemotherapy, was found. However, in lymphoma patients of both types of malignancies, CD5 positive population increased concomitantly with therapy. These results may suggest that analysis of CD5 antigen expression on peripheral blood cells of patients with B cell lymphoproliferative malignancies may have diagnostic, or, in correlation with some relevant clinical parameters, a potential predictive value in the treatment of those patients.

Adult↗
PubMed1994

[Effect of interferon alpha on immunologic parameters in patients with carcinoma of the renal parenchyma].

A wide range of immunological abnormalities have been described in renal-cell carcinoma (RCC). The only constant one was the decrease of CD4/CD8 ratio, reversible following radical nephrectomy in the absence of metastases. Alpha-interferon was administered with variable benefit to patients with metastatic RCC. The aim of this study was to document whether the treatment of patients with metastatic RCC, with unpurified human alpha-interferon, induced any change in the number and functional properties of peripheral blood T lymphocytes and monocytes. Fifteen patients were included in the study; all were treated with IFN 2,000,000 IJ/24h x 15 days, with an intercycle interval of 15 days during at least 4 cycles. The immunological analyses included the percentage and absolute number of E-rosette forming cells, CD3+, CD4+, CD8+ and CD4/CD8 ratio as well as the percentage and absolute number of monocytes and their phagocytic index toward the yeast particles. The analyses were done before the treatment and after the 4th cycle of the IFN therapy and compared toward the same analyses done in 22 healthy controls. Following IFN treatment two significant changes were noted: a decrease in CD4/CD8 ratio (mean 1.050 fall for 19% to 44%, mean 27.25% from the initial value) as well as a marked decrease in monocyte phagocytic index (p < 0.005). These data point to either disease-related or treatment-related decrease in the phagocytic properties of monocytes and the decrease of CD4/CD8 ratio.

CD4-CD8 Ratio↗
PubMed1994

[The effect of interferon alfa-2b therapy on titers of isohemagglutinins and anti-Forssman antibodies in patients with malignant melanoma].

According to experimental data, administration of interferon in mice before contact with antigen reduced antibody response, while its presence after antigen load enhanced them. The aim of this study was to detect possible immunomodulatory effects of unpurified human alpha-interferon on izohemagglutinin (IZO), and anti-Forssman antibody (AFA) serum levels during a treatment in patients with malignant melanoma. Fifty-two patients treated with the same chemotherapy regimen (ADM-VCR-CPM-DTIC-PCB) entered the study; 30 received INF 1.000.000 U/24 h x 10 during each cycle, intercycle interval 4 weeks. Twenty-two did not receive interferon. Initial IZO titers were 1/4-1/256, median 1/64, and for AFA 0-1/14, median 1/7. Following 4 cycles, values for IZO titers were: in the IFN group 1/32-1/262.144, median 1/128; in the non-IFN group range 1/8-1/512, median 1/32. The values for AFA titers were: in the INF group 0-1/442, median between 1/28 and 1/56; in control group 0-1/112, median 1/14. The difference between both median values for the INF group and initial median values was statistically significant. Initial elevation of titers was reversed during a few cycles with both A and B substances and the Forssman antigen, immunisation of humans is permanent. It would be of interest to ascertain effects of interferons on antibody response to others antigens, especially bacterial and viral, during aggressive chemotherapy. In any case, both experimentally observed phenomena seem to occur in vivo during interferon treatment of metastatic melanoma.

Antibodies↗
PubMed1994

[Immunomodulatory effect of serum on NK cells in vitro in healthy individuals].

The regulatory role of the immune system in malignancies is realized through cytotoxic cells. The main cytotoxic cells that destroy tumor cells are NK cells. Considering this, the activity and regulation of NK cell function is of significance in malignant diseases. Our previous studies showed that different sera had a profound effect on the NK activity of breast cancer patients. In this work we tried to investigate these effects on the NK cell activity of healthy individuals. Our data indicate that the FCS has a profound stimulative effect on the activity of NK cells of healthy donors. We also found that healthy control serum induces a significant inhibition of NK cell activity of these donors. Compared to this effect of healthy sera, sera of breast cancer patients with early clinical stage I-III induced a significant activation of NK cell activity while sera of patients with advanced breast cancer, stage IV with generalized metastases, gave a significant decrease of the NK cell activity of healthy individuals. In this study several sera of patients with stage IV of the disease without metastases gave the greatest inhibition of the NK cell activity which were not found in our previous more extensive investigations of this type of sera. We confirmed that the investigated sera displayed the same effects on the activity of NK cells of healthy persons as they did on NK cells of breast cancer patients. These findings not only indicate the cause of the impaired NK cell activity in patients with malignant disease but also give an indication for immunotherapeutic approaches.

Breast Neoplasms↗