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Biomedical subjects

I Spuzić

Publications and source records attributed to I Spuzić.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1990

[The effect of hormones on tumor growth].

It is well documented that estrogen influences the growth of mammary carcinoma. Estrogen-induced response of target tissue includes protein-biosynthesis as well as stimulation of cell proliferation. Estrogen stimulates tumor cell proliferation in vitro in a dose-related manner by shortening the cell cycle time primarily at the G1 duration and by increasing the number of dividing cells per cycle. The mechanisms of estrogen action on target cell proliferation are not understood well and because of controversial experimental results the role of functional estrogen receptors in estrogen-induced proliferation is not yet clear. In this work, we studied the effect of estrogen on the growth of cells derived from primary tumors (N = 4) and malignant pleural effusions (N = 6) from patients with histopathologically verified breast cancer. We correlated steroid receptor content of malignant tissue used with results obtained for estrogen-induced cell proliferation. It was shown that there was a positive correlation between steroid receptor content and effect of estrogen on cell proliferation in most of the cases studied (7/10). Our study also confirms the possibility of positive and negative influences of estrogen on modulation of tumor cell growth.

Breast Neoplasms↗
PubMed1990

[The significance of determination of NK cell activity in malignant diseases].

It is considered that NK cells have a major role in the immunosurveillance of the development and spread of tumors so it is of interest to try to determine, not only the basic NK activity of patients with malignant diseases, but also factors that lead to its impairment, as well as therapeutic means of augmentation of NK activity. The results of our study indicate that NK cell activity of breast cancer patients, following surgery, was significantly below NK cell activity of healthy controls. The impaired NK cell activity of breast cancer patients, as our data indicate, could be significantly augmented by, short term, in vitro, cultivation of PBL with low doses of rIL 2. We further found that both healthy sera and autologous sera of breast cancer patients showed a similar degree of inhibition of NK cell activity, after in vitro cultivation of PBL, when compared to PBL cultivated in medium with FCS, and only sera from breast cancer patients with advanced disease had a greater inhibiting effect. We consider that monitoring of NK cell activity after incubation in autologous serum can give a better assessment of NK cell activity of these patients in vivo, and also possibilities of investigating factors which lead to serum-induced modulation of NK cell activity and that preincubation of PBL with immunomodulators, such as IL 2, in in vitro conditions, could give an indication as to whether it is worthwhile proceeding, in the case of each individual patient, with the application of specific immunotherapy.

Breast Neoplasms↗
PubMed1990

[Hereditary factors in the etiology of chronic lymphocytic leukemia].

Leukocyte counts, hemoglobin concentration, PAS positivity index in lymphocytes, leukocyte alkaline phosphatase, karyotype, HLA phenotype as wall as the quality of the cellular and humoral immunity have been studied in 45 patients with chronic lymphocytic leukemia (CLL) and in 103 their closest relatives (sibs, parents). The aim was to detect the possible preleukemic condition in the relatives as a strong propensity towards developing has been previously established in families of patients with CLL. In the CLL patients our studies have confirmed the results of the determination of similar parameters by other authors, namely a higher percentage of PAS+ lymphocytes than normal together with a variety of humoral and cellular immunity disturbances. Regarding the morphological and cytochemical changes in lymphocytes in family members of the CLL patients a higher frequency of PAS+ lymphocytes have been observed: it has been established in over 10 per cent lymphocytes (normally 4-8 per cent) in 31 (30%) examinees and in 14 (13.5%) of these persons the percentage of PAS positivity was equal to that found in CLL patients. Cellular immunity examinations established that in one third of examined E rossete counts counts were lower and in 2 persons the degree of this decrease corresponded to the decrease observed in CLL patients. In one fifth of the examined family members T4:T8 ratio was reduced. In the 13 per cent of the examined M rossete counts were increased, a fact which supports the notion that immunity of B cells exists in relatives of CLL patients. The authors contend that the increased percentage of PAS+ lymphocytes and inadequate functional maturity of the T and B cells in a relatively large number of family members of the CLL patients, intimates that a hereditary disturbance in the lymphocyte make up and their role in the immunity pathways exists and could possibly represent one of the factors implicated in a high frequency of CLL in some families.

Aged↗