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Biomedical subjects

I Spuzić

Publications and source records attributed to I Spuzić.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1994

Association among an autocrine parameter (EGF-R) and endocrine parameters (ER and PR) in locoregional breast cancer.

Sixty-three locoregional breast cancer biopsies were examined for association among epidermal growth factor receptors (as parameter of autocrine growth control), and estrogen and progesterone receptors (as endocrine parameters of estrogen responsiveness). In the tumor group with similar steroid receptor levels, low (0-50 fmol/mg), medium (50-100 fmol/mg) and high (above 100 fmol/mg), an inverse quantitative correlation between epidermal growth factor receptors and progesterone receptors was obtained (p < 0.05). In the tumor groups where estrogen receptor levels were higher or lower than progesterone receptor levels, epidermal growth factor receptors were correlated neither with estrogen nor with progesterone receptors (p > 0.05). It seemed that inverse correlation between endocrine and autocrine parameters obtained in previous studies might not be a common behaviour of all breast tumors.

Adult↗
PubMed1994

To the mechanism of spermine-FBS cytotoxicity toward K562 human myelogenous leukemia cells.

The effects of several compounds acting through adenylate cyclase system and/or influencing prostaglandin biosynthesis on spermine-FBS cytotoxicity to human myelogenous leukemia K562 cells were studied. Salbutamol, a beta 2-adrenoceptor agonist inhibited to a certain extent spermine-FBS cytotoxic action to K562 cells, and propranolol, a beta 2-adrenoceptor antagonist, did not affect this inhibition. Aminophylline, an inhibitor of cyclic nucleotide phosphodiesterase, acted suppressing spermine-FBS cytotoxicity to K562 cells. Pretreatment of the cells with dexamethasone did not significantly alter salbutamol-related inhibition of spermine-FBS cytotoxicity. Indomethacin, an inhibitor of cyclooxygenases directly involved in prostaglandin biosynthesis, did not interfere with protective terbutaline effects against spermine-FBS cytotoxicity to K562 cells during the 24-hour period.

Albuterol↗
PubMed1993

Enhancement of phytohemagglutinin-induced lymphoproliferative response by indomethacin, Thymex L or their combination in lung cancer patients.

Several studies showed that thymic factors and prostaglandin synthesis inhibitors enhance in vitro lymphoproliferative response (LPR) to mitogens in cancer patients. In this study we investigated whether indomethacin and thymic extract (Thymex L), applied in combination, may in a synergistic pattern influence phytohemagglutinin-induced LPR in lung cancer patients. The results demonstrate that the use of the investigated agents enhances LPR to a similar level in hyporeactive patients before, as well as after, therapy. However, this drug combination exerts an additive effect on LPR, but only in patients who underwent cytoreductive radiation therapy, indicating the potential usefulness of this drug combination as an adjuvant treatment of these patients.

Adjuvants, Immunologic↗
PubMed1993

Stage dependence of NK cell activity and its modulation by interleukin 2 in patients with breast cancer.

NK cell activity was evaluated in breast cancer patients with different clinical stages of disease prior to surgery. In 58 patients with Stages I-III of breast cancer the peripheral blood NK cell activity was significantly reduced as compared to controls, and NK activity of 11 patients with Stage IV and metastases was significantly reduced as compared to both controls and patients with locoregional disease. In vitro treatment of peripheral blood lymphocytes (PBL) in medium with 10% fetal bovine serum (FBS) alone significantly increased NK cell activity in patients with Stages I-III and Stage IV of disease, although the level of NK cell activity of patients with Stage IV remained below that for less advanced disease. In vitro treatment of PBL of some Stages I-III patients (n = 41) with interleukin 2 (IL 2) gave a significant, dose-dependent enhancement of their NK cell activity so that it was significantly higher than basic NK activity of healthy controls. The results showed decrease of NK cell activity in breast cancer patients especially in advanced disease and enhancement with IL 2 indicating the possibility of immunotherapy in this neoplasm.

Analysis of Variance↗
PubMed1992

In vitro effect of indomethacin on mitogen-induced lymphoproliferative response in lung cancer patients.

There is some evidence that prostaglandin (PGE)-secreting cells may have a role in immunosuppression in cancer patients. In this work we investigated the effects of indomethacin--a PGE synthesis inhibitor, on PHA-induced lymphoproliferative response in vitro. Twenty patients with lung cancer before therapy were included in this study. When compared to controls, the patients had significant decrease of T cell number and proliferative response to PHA (p less than 0.001) and increased number of mononuclear phagocyting cells (p less than 0.001). The degree of depression of lymphocyte response did not correlate with the number of mononuclear phagocytes. The presence of indomethacin in the culture induced significant (p less than 0.01) improvement of the reactivity in high percentage (75%) of patients with diminished lymphoproliferative response to PHA. In the patients with normal lymphocyte response, indomethacin did not change reactivity to PHA. These results indicate that PGE-secreting cells may contribute to the immune depression in lung cancer patients, and that indomethacin may have therapeutical potential in some patients.

Adult↗
PubMed1992

Evaluation of different effects of sera of breast cancer patients on the activity of natural killer cells.

In this study NK cell activity of 88 breast cancer patients in various stages of disease was investigated and a significantly lower activity in clinical stages I-III and especially in stage IV was found. Short term culture of peripheral blood lymphocytes (PBL) of these patients in medium RPMI 1640 with fetal calf serum (FCS) alone, gave a significant enhancement of NK cell activity and even more significantly if rhIL 2 was added to this medium. Considering the finding of diminished native NK cell activity in breast cancer patients and its augmentation by the above stated in vitro treatment, it was of interest to investigate the effect of sera of these patients, which represent the natural in vivo environment of NK cells, in order to see if the sera modulate the antitumor cytotoxic activity of these cells. In this sense, the in vitro treatment was performed on PBL of patients and controls with sera of patients with stages I-III (CaSa), stage IIIb (CaSb), stage IV (CaSm) and healthy control sera (HS). The results obtained for patients and controls show that compared to FCS all sera act in an inhibitory manner, but in contrast to HS, CaSa has a stimulative effect, while CaSb and CaSm give the greatest degree of NK cell inhibition of both controls and patients. Pooled metastatic sera (CaSp) and these sera after removal of molecules up to 8-10 kD by dyalisis (CaSd) show a similar degree of inhibition of NK cell activity of healthy controls and interfere in a reversible manner with NK cell activation by recombinant human interleukin 2 (rhIL 2). Analysis of soluble IL 2 receptor (s IL 2R) concentration, as a potential inhibitory factor in metastatic sera, rarely showed an increase. In conclusion, an impaired NK cell activity was found in patients with breast cancer. The impairment of NK cell activity progressed with the advancement of the disease. Along with this, the finding of a marked inhibitory effect of sera of breast cancer patients in advanced stage with metastases on the activity of NK cells and their activation by interleukin 2 may pose a problem for adjuvant immunotherapy with LAK cells and IL 2 and may indicate a need for prior plasmapheresis.

Breast Neoplasms↗
PubMed1992

Amine oxidase-mediated cytotoxicity of spermine and epinephrine to human myelogenous leukemia K562 cells.

The effects of spermine and beta-adrenoceptor agonists (epinephrine, terbutaline and orciprenaline) in the presence and in the absence of fetal bovine serum (FBS) on human myelogenous leukemia K562 cells viability (V) and survival (N/Nc) were examined. Spermine-FBS significantly decreased both V and N/Nc of K562 cells. Aminoguanidine (AG), an amine oxidase inhibitor, and reduced form of glutathione abolished this effect demonstrating that the spermine-FBS action was amine oxidase-mediated. Epinephrine expressed a strong cytotoxicity to K562 cells which was abolished by pargyline, a specific monoamine oxidase (MAO) inhibitor, as well as by reduced form of glutathione. Terbutaline and orciprenaline exerted no cytotoxic activity to K562 cells cultured in FBS-supplemented medium, independently on the presence of spermine. However, terbutaline at concentrations of over 1 mmol strongly inhibited the cytotoxic effect on spermine-FBS. The relationship between cytotoxicity and chemical structure of beta-adrenoceptor agonists was discussed especially with respect to their stability toward oxidation.

Amine Oxidase (Copper-Containing)↗
PubMed1992

Estrogen dependence of primary breast cancer--correlation with histologic type and grade.

The purpose of this study was to investigate whether histologic type and grade of primary breast cancer are related to the estrogen and progesterone receptors. Our results showed that histologic type influenced the estrogen dependence through histologic grade. There was no difference in the estrogen and progesterone receptor content, when corresponding grades of different histologic types and estrogen dependence were confirmed by quantitative non-parametric analysis. It showed a direct relationship between estrogen and progesterone receptor content in all the three histologic grades and further that histologic grade defines three different groups in regard to progesterone receptor content.

Breast Neoplasms↗
PubMed1991

The importance of the specific Z-DNA structure and polyamines in carcinogenesis: fact or fiction.

In this work some aspects of carcinogenesis are given. The importance of the emergence of Z or H DNA structure in the gene, or in the flanking gene sequences for the gene deletion and unusual gene recombination, is discussed. Some considerations on the role of selective pressure (of polyamines, of Mg2+, of the various levels of topoisomerase II, and of ATP) in the process of oncogene amplification, are given too.

Animals↗
PubMed1991

[Determination of T lymphocyte subpopulations in malignant lymphoproliferative diseases].

The aim of this work was to investigate T cell subset composition of peripheral blood cells in patients with acute myeloid leukaemia, acute lymphoblastic and chronic lymphocytic leukaemia, by enumerating T cells positive for receptors for sheep erythrocytes (E-RFC, A-RFC) using the method of E-rosette, and for CD3, CD4 and CD8 antigens, by indirect immunofluorescence technique, using the monoclonal antibodies of the OK series. The study was performed on 57 patients without therapy and 46 healthy persons. The results of enumeration of T cells and their subsets obtained in the stage of the disease when the total leukocyte count was below 20 x 10(9)/L, were markedly decreased in all three types of leukaemias. The most significant decrease of relative count of T cells and their subpopulations was obtained in CLL patients. Analysis of T cells subsets and their ratio in CLL patient in the stage of disease when the total leukocyte count as higher than 20 x 10(9)/L, demonstrated the most pronounced decrease of total T lymphocytes and CD4+ cells. The relative count of the "active" (A-RFC)T cells and CD8+ cells did not change, and was the same as in the patients suffering from CLL with a lower leukocyte count.

Humans↗
PubMed1991

[The effect of serum on NK cell activity].

In the immunosurveillance of the development and spread of tumors NK cells seem to have a major role. For this reason, the assessment of NK cell activity of patients with a malignant disease represents a significant immunological parameter. The results of our study indicate that for the group of 26 breast cancer patients basic NK cell activity is significantly below NK cell activity for healthy controls. In a previous set of experiments we found that a short term incubation of peripheral blood lymphocytes of these patients in medium, alone, gives a considerable augmentation of impaired basic NK activity, so we made an attempt to determine the influence of autologous serum on NK cell activity. Our data indicate that both healthy serum and autologous serum of breast cancer patients, in the early stage of disease, give a similar degree of inhibition of NK cell activity, after in vitro cultivation of PBL, when compared to PBL cultured in medium with FCS, and that only sera from breast cancer patients with advanced disease had a greater inhibiting effect. Incubation of PBL of healthy controls with autologous healthy sera showed a somewhat greater inhibitory effect on NK cell activity than sera from breast cancer patients in the early stage of disease. We consider that monitoring of NK cell activity after incubation with autologous serum may give not only a better assessment of NK cell activity of these patients in vivo, but also possibilities fro investigating factors which lead to serum-induced modulation of NK cell activity.

Blood Physiological Phenomena↗
PubMed1991

[The importance of hormone receptor determination in breast malignancies].

Estrogen and progesterone receptor phenotypes expressed as "positive" or "negative" are widely used for the determination of estrogen dependence of primary breast tumor. In our opinion the receptor phenotype, so important for biological and clinical behavior of tumor, should consider the quantitative values of receptor content. For this purpose, the correlation between quantitative estrogen versus progesterone receptor content and the distribution of the quantitative estrogen and progesterone receptor content within some parameters of tumor and tumor-host was analyzed. Our results show: There is the same range of correlation between estrogen versus progesterone receptor content in tubular tumor type, invasive ductal and lobular carcinomas, and in all three histologic grades; Histologic type influences the estrogen dependence through histologic grade. There is no difference in distribution of the quantitative estrogen and progesterone receptor content when corresponding grades of tubular tumor type, invasive ductal and lobular carcinomas are compared; In premenopause status histologic grade defines different groups with regard to the quantitative progesterone receptor content; In postmenopause status histologic grade defines different groups with regard to the quantitative estrogen and progesterone receptor content; In tumors with histologic grade I, transition of pre to postmenopause status is connected with a significant increase of the frequency of the high quantitative estrogen receptor content; In tumors with histologic grade III, transition of pre to postmenopause status is connected with a significant increase of the frequency of the low quantitative estrogen and progesterone receptor content.

Breast Neoplasms↗
PubMed1991

[Parameters of humoral immunity in patients with breast carcinoma during therapy with leukocyte interferon].

The values of parameters of humoral immunity, such as concentration of immunoglobulins IgG, IgA, and IgM, as well as the absorbance of patients serum at 450 nm (A4 5 0) in the presence of PEG 6000 (as a measure of the presence of immune complex in circulation, CIC) in a group of breast cancer patients stage T + N0 M0, after surgical tumor resection, and before and after various therapy phases with the leucocyte IFN therapy are given. The IFN (product of Torlak, Belgrade, or Immunological Department Zagreb) therapy was performed in four therapy phases. During the first month (first phase) 3.10(6) U IFN-alpha were administered i.m. every day, during the second month 3.10(6) U were administrated thrice weekly, during the third month 3.10(6) U IFN-alpha were administered i.m.twice weekly, and during the fourth month 3.10(6) U IFN were administered i.m. once a week. The average concentration of IgG, IgA, and IgM fall in the range of normal values during the therapy. Nevertheless, some mild stimulation of the IgG production and transient one for IgA can be noticed. The average value of A4 5 0 for patients was before therapy significantly (P less than 0.05) higher than normal value--at the end of the therapy it was in the range of normal A4 5 0.

Antigen-Antibody Complex↗