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Biomedical subjects

C C Zielinski

Publications and source records attributed to C C Zielinski.

At least 19 recordsLinked to original sources
PubMed1997

Decreased expression of ICAM-1 and its induction by tumor necrosis factor on breast-cancer cells in vitro.

In order to study adhesion-molecule expression and its consequences for cellular recognition, the presence of adhesion molecules ICAM-1, VCAM-1, VLA-4, LFA-1, alpha, LFA-1 beta, LFA-3, beta1-integrin and beta3-integrin was studied on specimens from breast tissue by immunohistochemistry and on cells from breast cell lines propagated in vitro. Breast-cancer tissue and the breast-cancer cell lines MCF-7, SK-BR-3 and ZR-75-1 showed expression of ICAM-1 and VLA-4 significantly lower than that of benign breast cells or normal breast epithelium. Of various cytokines tested, including recombinant human (rh) interleukin-6 (IL-6), rh tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), granulocyte/macrophage-colony-stimulating-factor (GM-CSF), interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma), only TNF was able to re-induce expression of ICAM-1 on cells from MCF-7, SK-BR-3 and ZR-75-1. Further, the ability of either unstimulated or lymphokine-stimulated killer (LAK) cells to recognize and lyse native or TNF-stimulated breast-cancer cells was studied. Whereas neither unstimulated lymphocytes or LAK cells were able to lyse untreated breast-cancer cells deficient for ICAM-1 expression, pre-treatment of tumor cells with TNF led to increased tumor-cell lysis. Anti-ICAM-1 antibodies, and pre-treatment of tumor cells with anti-TNF-receptor antibodies, abrogated these findings, corroborating their specificity. We thus conclude that the defective expression of ICAM-1 in our model might constitute a mechanism by which breast-cancer cells escape immunologic recognition and lysis by appropriate effector cells.

Antibodies↗
PubMed1996

Impaired hemorheology in patients with postmastectomy lymphedema.

Lymphedema of the arm is one of the most disabling and serious complications of breast cancer. Apart from tumor infiltration or fibrosis of lymphatic pathways, little is known about factors favoring the development of lymphedema. In the present study, we investigated the impact of rheologic parameters, e.g. red cell aggregation (EA) and plasma viscosity (PV), and of capillary morphology and capillary flow in patients with breast cancer with (n = 18) and without (n = 18) lymphedema. Patients with lymphedema showed a significant increase of red cell aggregation (p < 0.001) that indicates a systemic component of lymphedema and might offer a possibility of prevention and therapy of this condition. A hitherto unclassified protein factor favoring red cell aggregation and lymphedema might be postulated.

Aged↗
PubMed1996

Effect of estrogen replacement therapy on natural killer cell activity in postmenopausal women.

OBJECTIVE: To evaluate the impact of menopause and estradiol substitution on natural killer cell activity. METHODS: Natural killer cell activity and antibody-dependent cellular cytotoxicity were measured in peripheral blood of 53 postmenopausal and 20 premenopausal women in an interval of 3 weeks. Postmenopausal patients were randomly assigned to receive either estradiol valerate (2 mg daily) orally (n = 18), estradiol (50 micrograms/24 h) transcutaneously (n = 18) or no substitution (n = 17), and the testing was repeated 3 weeks later. RESULTS: Natural killer cell activity but not antibody-dependent cellular cytotoxicity was significantly (P < 0.01) higher in unsubstituted postmenopausal compared to premenopausal subjects. Natural killer cell activity decreased both in orally and transcutaneously estradiol-treated patients (mean [S.D.] before vs. after 3 weeks; oral: 60.8 [9.2]% vs. 52.8 [8.2]% P < 0.01; transcutaneous: 61.5 [10.6]% vs. 54.3 [9.1]% P < 0.01; no substitution: 60.6 [10.6]% vs. 59.3 [8.9]% P > 0.1), whereas antibody-dependent cellular cytotoxicity showed no changes. The addition of 0.1 to 10 ng/ml estradiol to peripheral blood mononuclear cells of untreated postmenopausal women in vitro had no influence upon natural killer cell activity. CONCLUSION: Postmenopausal women receiving no estrogen replacement exhibited an increased natural killer cell activity which decreased during estrogen substitution.

Administration, Cutaneous↗
PubMed1995

Natural killer cell activity in long-term survivors of testicular cancer. Influence of cytostatic therapy and initial stage of disease.

BACKGROUND: Patients with testicular cancer can be cured by cisplatin-based chemotherapy in many cases. Thus, concern about possible late toxicities of treatment is warranted. METHODS: In this investigation, the absolute number of natural killer (NK) cells according to their CD56+ phenotype, NK cell activity, and antibody dependent cellular cytotoxicity (ADCC) were investigated in 29 patients with seminomas or nonseminomatous germ cell tumors (NSGCT) a median of 31 months (range, 5-73 months) after termination of chemotherapeutic treatment. RESULTS: No difference in the absolute number of NK cells, NK cell activity, and ADCC was found between patients with testicular cancer after either standard polychemotherapy consisting of bleomycin, etoposide, and cisplatin (BEP) or monotherapy with carboplatin and healthy control subjects. When patients were analyzed further using multivariate analysis, a significant (P < 0.05) detrimental influence of BEP polychemotherapy versus carboplatin monotherapy on NK cell activity was found. Moreover, NK cell activity also depended significantly (P < 0.05) on the time elapsed after chemotherapy was administered, but normalized with time. Because the absolute number of NK cells was not affected, is was assumed that polychemotherapy induced a functional defect. In a subanalysis of patients with NSGCTs, metastases at diagnosis resulted in a significant (p < 0.05) and persistent stimulation of NK cell activity but not of ADCC. CONCLUSION: Cytostatic chemotherapy in patients with testicular cancer did not lead to compromised lytic effector cell function as assessed by NK cell activity and ADCC. However, a short, time-dependent reduction was found that also depended on the intensity of chemotherapeutic treatment. This finding related to the observation of a long-lasting stimulus of NK cell activity by initial metastases in patients with NSGCTs.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1995

Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer: a prospective longitudinal study.

Immunosuppression has been often associated with the course of malignant diseases. In the present study, the proliferation of peripheral blood mononuclear cells (PBMCs) in response to mitogenic stimulation with phytohaemagglutinin (PHA) was assessed prospectively in 90 patients with stage I-III breast cancer. Whereas PHA-induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals (P < 0.001), the degree of the defect in PHA-induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement (P < 0.003 in each case). PHA-induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) after an observation period of 6 months (P < 0.01), but not in patients under adjuvant treatment with tamoxifen only. After an additional 6 months (i.e. 12 months after surgery), PHA-induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment (P > 0.1), but in all patients still significantly decreased as compared with healthy controls (P < 0.001). When data obtained preoperatively and after 12 months were compared, it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA-induced proliferation, 14 (61%) had developed metastatic disease within the subsequent 24 months (i.e. 36 months after surgery). In contrast, out of 59 patients whose PBMCs showed an increase in their PHA-induced proliferation within the first 12 months after surgery, only one (2%) presented with disease progression. We thus conclude that PHA-induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

In vivo administration of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor increases neutrophil oxidative burst activity.

The influence of CSF therapy on the superoxide (O2-) releasing capacity in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) of neutrophils from 32 patients with testicular cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) was assessed: 8 patients were treated as control group without CSF therapy, 12 patients received GM-CSF, and 12 patients received G-CSF. To monitor the kinetics of the respiratory burst, leukocytes were collected before initiation of chemotherapy and ABMT, during CSF administration on days 1 and 3 after leukocyte recovery, and 7 days after leukocyte recovery (controls) or 3 days after the end of CSF therapy. Neutrophils from patients who received GM-CSF showed a significantly higher superoxide anion release compared with control patients (p < 0.001). O2- production in these patients was higher than that achieved by in vitro preincubation of neutrophils from control patients. Increased burst activity was seen only during infusion of GM-CSF and returned to pretherapeutic values after the end of GM-CSF administration. A similar but less pronounced increase was seen in patients who received G-CSF. In vitro preincubation of neutrophils from the same patients with GM-CSF, G-CSF, or TNF showed that O2- production by neutrophils from patients receiving GM-CSF could not be further enhanced, whereas O2- production by neutrophils derived from patients receiving G-CSF could be further augmented by TNF but not by GM-CSF. Interestingly, neutrophils from patients treated with GM-CSF but not those with G-CSF therapy retained a higher response to in vitro stimulation with GM-CSF or TNF after the end of CSF administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1995

Influence of in vivo administration of GM-CSF and G-CSF on monocyte cytotoxicity.

The influence of colony-stimulating factors (CSFs) on the monocyte functions of 32 patients with refractory testicular cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) was tested. Eight patients were treated as a control group without CSF therapy, 12 patients received recombinant human granulocyte-macrophage-CSF (rhGM-CSF), and 12 patients received recombinant human granulocyte-CSF (rhG-CSF). For the assessment of monocyte activation induced by CSF expression of major histocompatibility complex (MHC) class I and II antigens, production of tumor necrosis factor (TNF) and monocyte-mediated cytotoxicity against tumor cell targets were chosen. Monocytes from patients with GM-CSF therapy showed a significant increase in MHC class I and II antigen expression as compared to patients without CSF treatment (p < 0.001). A significant increase in the expression of MHC class I was seen in monocytes from patients under G-CSF treatment, whereas no change of class II antigens was noticed. Production of TNF and monocyte-mediated cytotoxicity against U937 tumor cells was significantly increased in monocytes derived from patients receiving GM-CSF, as compared to those from the control group, while no effect was detectable in monocytes from patients with G-CSF therapy. However, after in vitro stimulation with interferon-gamma (IFN-gamma), monocytes derived from GM-CSF as well as from G-CSF treated patients responded with a significantly higher TNF-production and cytotoxicity than monocytes from control patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[The significance of adhesion molecules in oncology].

Adhesion molecules are membrane proteins responsible for the complex functions of cell adhesion and cellular recognition and are thus of importance in inflammatory as well as neoplastic diseases. Adhesion molecules seem to play a significant role at each level of the metastatic cascade, including the destruction of normal cell-cell as well as cell-substrate cohesion, the penetration of tumor cells into the vascular system and the further spread into distant organs. In this summary an overview of subtypes, structure and function of the major groups of adhesion molecules is given and their possible role in the development, propagation and metastatic spread of malignancies discussed. Cell adhesion and its defects may be of importance in the behaviour of tumor cells and their spread. A better understanding of their function and possible manipulation of their expression, e.g., by cytokines could provide new therapeutic approaches in clinical oncology.

Cell Adhesion↗
PubMed1994

Effect of elevated growth hormone concentrations on the phenotype and functions of human lymphocytes and natural killer cells.

Over the past decades, strong evidence has accumulated that growth hormone (GH) has immunostimulatory properties. Therefore, an investigation was conducted on 10 acromegalic patients and 9 age- and sex-matched healthy controls to determine whether plasma GH concentrations correlate with changes in several immune parameters, including serum concentrations of immunoglobulins, lymphocyte subsets, lymphocyte transformation with phytohemagglutinin (PHA), natural killer (NK) cell activity as well as phagocytic and metabolic burst activity. While NK cell activity, serum concentrations of immunoglobulins (IgG, IgM, IgA) and metabolic burst activity were within the normal range in both groups, a significantly enhanced phagocytic activity was observed in the acromegalic patients. Surface markers on T lymphocytes (CD3, CD4, CD8), B lymphocytes (CD19) and NK cells (CD16/56) were normal in both groups; however, in the acromegalic subjects, CD4+ and CD8+ cells showed a significant higher expression of transferrin receptors (CD71), indicating enhanced T-cell activity. The lymphocyte transformation response to PHA at the highest concentration tested showed a tendency to be elevated in acromegalics; however, the difference failed to be significant. Long-lasting and pronounced elevation of GH in acromegaly induces significantly enhanced phagocytic activity, but only negligible changes in most patients in lymphocyte phenotype and in the lymphocyte response to PHA.

Acromegaly↗
PubMed1993

Reduced production of immunoreactive interleukin-1 by peripheral blood monocytes of patients with acute and chronic viral hepatitis.

The in vitro production of interleukin-1 beta by peripheral blood monocytes derived from patients with various liver diseases was studied. An impaired production of immunoreactive interleukin-1 (IL-1) (mean +/- SEM) by monocytes stimulated with an optimal dose (100 ng/ml) of lipopolysaccharide was observed in patients with chronic hepatitis B (N = 13; 32 +/- 6 pg/ml) or chronic hepatitis C (N = 13; 61 +/- 12 pg/ml) as compared to those of healthy control individuals (N = 35; 166 +/- 24 pg/ml; P = 0.0003 and P = 0.015, respectively), whereas an unaltered IL-1 production was seen in patients with alcoholic cirrhosis (N = 23; 125 +/- 28 pg/ml) and primary biliary cirrhosis (N = 6; 111 +/- 33 pg/ml). Similar to the situation seen in chronic viral hepatitis, lipopolysaccharide-stimulated monocytes from patients with acute hepatitis also showed a decreased IL-1 production in the first week after onset of jaundice (N = 17; 55 +/- 20 pg/ml; P = 0.001) and a return to normal in the second and third week. An impaired production of IL-1 in chronic as well as acute viral hepatitis is a further example of the known disturbed immunoregulation in this disease.

Acute Disease↗
PubMed1993

[Combined therapy with cyclosporin A and cortisone in endocrine Basedow endocrine orbitopathy: successful use in compressive optic neuropathy].

This study reports our experience with a combined treatment with cyclosporin A (Cy A) and cortisone in patients with Graves' ophthalmopathy (GO), all of whom had compressive optic nerve disease (CON). The therapy was performed in 8 patients (6 females, age range: 40 to 76 years) with normal liver and kidney function and classical Graves' disease, except for 1 male, who had normal thyroid function and no detectable thyroid antibodies. 5 patients were euthyroid on methimazole, 2 patients were off thyrostatic treatment for 5 and 2 years. 3 patients have had high-dose cortisone (100 mg/die) treatment for GO before the study. Visual field defects were reported by the patients 1 week before start of therapy and evaluated by computerized visual field measurements (CVFM). The treatment consisted of Cy A in a dose which aimed at through levels between 100 and 300 ng/ml (RIA method) for 2 to 6 months and of methylprednisolone in a starting dose of 1 mg/kg body weight, tapered gradually to a maintenance dose of 10 mg/day for 6 to 12 months. CON disappeared completely in all patients. The thickening of affected eye muscles decreased in 5 patients, disappeared in 1 and remained unchanged in 2 patients. The shortest period for a measurable effect (either by echography or by CVFM, performed every week the first month and then every 3 months) was 1 week; the longest 1 month. The follow-up of the patients (range 6 months to 2.5 years) showed a relapse only in 1 patient. 2 patients were lost to follow-up 1 year after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Interleukin-6 production by peripheral blood monocytes in patients with chronic liver disease and acute viral hepatitis.

The in vitro production of the acute-phase mediator interleukin-6 by peripheral blood monocytes derived from patients with various liver diseases was studied. Compared with healthy controls (n = 45; 860 +/- 92 U/ml, mean +/- SEM), monocytes from patients with chronic hepatitis B produced significantly lower amounts of interleukin-6 (n = 14; 424 +/- 126 U/ml) after stimulation with lipopolysaccharide (p = 0.02), whereas monocytes from patients with chronic hepatitis non-A, non-B secreted normal amounts of interleukin-6 (n = 13; 672 +/- 151 U/ml; n.s.). In contrast, monocytes of patients suffering from alcoholic liver cirrhosis (n = 22; 1310 +/- 153 U/ml) or primary biliary cirrhosis (n = 6; 1450 +/- 186 U/ml) produced higher amounts of interleukin-6 than healthy control individuals (p = 0.03, respectively). Lipopolysaccharide-stimulated monocytes derived from patients with acute hepatitis A, B and non-A, non-B showed an interleukin-6 production not different from that seen in healthy control individuals and did not experience a discernible change during the course of the acute disease. These results suggest that the production of the acute-phase mediator interleukin-6 varies in chronic liver disease in accordance with various etiologies with a reduced lipopolysaccharide-inducible interleukin-6 response in chronic hepatitis B and an enhanced response in alcoholic liver cirrhosis and primary biliary cirrhosis.

Acute Disease↗
PubMed1992

Effect of elevated serum prolactin concentrations on cytokine production and natural killer cell activity.

In vitro and in vivo studies in rodents and human suggested an immunostimulatory effect of prolactin. The aim of the present study was to determine the impact of chronically elevated serum prolactin concentrations on the immune system in patients with prolactinomas. For this purpose parameters of the humoral and cellular immune system were studied in seven patients with prolactinomas on two occasions (1) when their serum prolactin concentration had been normalized through treatment with dopamine agonists and (2) when their serum prolactin concentration was high. Serum concentrations of immunoglobulines, interleukin 1, 3 and 6, TNF-alpha, interferon-gamma and the soluble interleukin 2 receptor, leukocyte subsets and the natural killer cell activity were found to be within the normal range on both occasions, i.e. at normal and at high serum prolactin concentrations. The assumption could be made that long-lasting elevation of serum prolactin concentration induces adaptive changes when the acute stimulatory effects of prolactin on several parameters of the immune system have subsided.

Adult↗