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U Rodeck

Publications and source records attributed to U Rodeck.

87 records · Page 5Linked to original sources
PubMed1987

Interactions between growth factor receptors and corresponding monoclonal antibodies in human tumors.

Monoclonal antibodies (MAbs) to the human epidermal growth factor (EGF) receptor, the type I insulin-like growth factor (IGF) receptor, and the nerve growth factor (NGF) receptor were used to study the growth regulation of malignant cells. Anti-EGF receptor MAb 425 inhibited the growth of A 431 squamous carcinoma cells which express high numbers of EGF receptors on their surfaces. Growth inhibition induced by MAb 425 was accompanied by alterations of the cell-cycle distribution of these cells, indicating the ability of a monoclonal antibody to act as a biologically active ligand. Growth stimulation of melanoma cells by EGF was unrelated to EGF receptor expression on the cell surface. Insulin- and IGF-I-induced growth stimulation of melanoma cells was inhibited by MAb alpha IR-3 which reacts with the type I IGF receptor. This result indicates that the type I IGF receptor mediated growth stimulation not only by IGF-I but also by insulin. Normal melanocytes and cells of all stages of tumor progression expressed in tissue culture the receptor for NGF, but no effect on the growth of these cells has been observed.

Antibodies, Monoclonal↗
PubMed1987

A mucin containing the X, Y, and H type 2 carbohydrate determinants is shed by carcinoma cells.

Monoclonal antibody BR 15-6A directed to the Y carbohydrate determinant (Fuc alpha 1----2Gal beta 1----4GlcNAc(3----1Fuc) beta 1----3Gal beta 1----4Glc beta 1----1Cer) reacted with the cell surface and conditioned media of colorectal and breast carcinoma cell lines. Double determinant immunoassays using BR 15-6A as detector antibody showed that the Y determinant is part of a high molecular weight mucin that coexpressed other carbohydrate antigens based on a type 2 chain (X, H type 2). Type 1 chain carbohydrates such as sialylated Lewisa, Lewisa and Lewisb blood group antigens were predominantly expressed on a separate mucin molecule as determined by double-determinant immunoassays with other anticarbohydrate monoclonal antibodies. The X, Y, and H type 2-bearing mucin was present in conditioned media of the majority of colorectal carcinoma cell lines and in all three breast cancer cell lines tested. Thus, monoclonal antibodies against X, Y, and H type 2 determinants are potentially useful in the serodiagnosis of gastrointestinal and breast cancer.

Antibodies, Monoclonal↗
PubMed1987

Biology of tumor progression in human melanocytes.

Tumor progression in the human melanocyte system can be delineated into 6 sequential stages. The first three steps represent nonmalignant melanocyte lesions from focal proliferations of structurally normal melanocytes to lesions with architectural and cytologic atypia. Primary melanoma may be divided into radial growth phase without competence for metastasis and vertical growth phase with metastatic competence. Melanocytes isolated from normal skin, nonmalignant pigmented lesions, and melanomas and maintained in culture have properties that are characteristic for each stage of tumor progression. Cytogenetic studies revealed nonrandom chromosomal abnormalities of advanced melanomas involving chromosomes 1, 6, and 7. Recent progress in tissue culture techniques has allowed studies of growth regulation of normal and malignant cells. Six growth factor receptor-growth factor systems seem to be of biologic significance in the melanocyte system: EGF, NGF, FGF, PDGF, insulin, and beta-TGF. Monoclonal antibodies have characterized a large number of antigens on melanocytes of the various stages of tumor progression, making melanoma one of the most widely studied human tumor systems.

Antigens, Neoplasm↗
PubMed1986

Chromatin binding of epidermal growth factor, nerve growth factor, and platelet-derived growth factor in cells bearing the appropriate surface receptors.

We analyzed the uptake and intracellular distribution of 125I-labeled epidermal growth factor, nerve growth factor, and platelet-derived growth factor in different cell lines that express or do not express the respective surface receptors for these factors. After 1 hr of incubation, all three growth factors were detected in the cytoplasmic fraction and in the nucleus, tightly bound to chromatin. The amount of chromatin-bound growth factors continued to increase during the incubation, and analysis at 48 hr revealed each chromatin-bound labeled growth factor in a nondegraded form. After limited digestion of chromatin with DNase II (10-20% digested sequences), specific release of all three growth factors was detected only after 1 hr of incubation but not after 24 and 48 hr, suggesting that the DNA regions involved in growth factor binding became nuclease-resistant. Binding of labeled epidermal growth factor and nerve growth factor to isolated chromatin was inhibited by monoclonal antibodies specific for the respective growth factor receptor. The data suggest that chromatin binding may represent an important step in the pathway of growth factor action.

Biological Transport↗
PubMed1986

Human melanoma cell lines of primary and metastatic origin express the genes encoding the chains of platelet-derived growth factor (PDGF) and produce a PDGF-like growth factor.

Normal human melanocytes and five human melanoma cell lines were analyzed for production of platelet-derived growth factor (PDGF)-like activity. Three of the melanoma cell lines released an activity that inhibited binding of 125I-labeled PDGF to human foreskin fibroblasts and stimulated [3H]thymidine incorporation in such cells. These activities were inhibited by the addition of anti-PDGF antibodies. All three factor-producing cell lines were derived from the same patient--one originated from the primary tumor (WM 115), and two were from individual lymph-node metastases (WM 239A and WM 266-4). The factor produced by WM 266-4 cells was characterized biochemically in detail. Immunoprecipitated, the metabolically labeled factor migrated in NaDod-SO4/gel electrophoresis as a homogeneous Mr 31,000 species, which under reducing conditions was resolved into two species of Mr 16,500 and Mr 17,000, implying a dimeric structure of the molecule. The factor was purified to homogeneity. Analysis by reverse-phase high-pressure liquid chromatography of reduced and alkylated factor revealed an elution pattern identical to that of PDGF A chains. Thus, the native molecule appears to be a homodimer of PDGF A chains. Blot-hybridization analysis of poly(A)+ RNA from the cell lines with 32P-labeled PDGF A chain and B chain (SIS product) cDNA probes revealed a relative abundance of B chain transcripts in the cell line originating from the primary tumor tissue only but expression of A chain in all three cell lines. We conclude that the two structural genes encoding each of the subunit chains of PDGF can be expressed in human melanoma cells and that the two genes can be independently expressed in such cells.

Cell Line↗
PubMed1986

[Follow-up of immunological parameters and therapy of systemic lupus erythematosus].

In a longitudinal study of a female patient with systemic lupus erythematosus, we determined numbers of T-lymphocytes and subpopulations (OKT4+- and OKT8+-lymphocytes), B-lymphocytes, production of anti-double-stranded DNA antibody (anti-ds-DNA-Ab), and we investigated the effects of corticosteroids and cyclophosphamide on these parameters and clinical disease activity. The results demonstrate that an increase of OKT4+-T-lymphocytes/OKT8+-T-lymphocytes ratio apparently augments B-lymphocyte numbers resulting in anti-ds-DNA-Ab production. Whereas steroids exerted limited, possibly dose-dependent effects on this sequence, cyclophosphamide seemed to cause normalization of OKT4+/OKT8+ ratio, precipitous drop of anti-ds-DNA-Ab titers, and dramatic clinical improvement.

Adrenal Cortex Hormones↗
PubMed1985

T lymphocyte populations in multiple sclerosis.

In 36 patients representing different clinical stages of multiple sclerosis (MS) (9 patients with acute exacerbations; 21 patients in remission; 5 patients with chronic progressive MS) determinations of T lymphocyte populations using monoclonal antibodies against surface antigens (OKT3 (pan T cells), OKT4 (helper T cells), OKT8 (cytotoxic/suppressor T cells] were performed. Compared to the control group (40 healthy individuals) a clear elevation of the T4/T8 ratio was found in acute exacerbations and to a lesser degree in patients with inactive phases of MS. Patients with chronic progressive disease did not show increased T4/T8 ratios. Serial determination of lymphocyte populations after corticosteroid therapy in 10 selected patients revealed no significant changes which could be attributed to this therapeutic modality. Pathogenetic and clinical implications of the shifts in surface antigen expression of T lymphocyte populations mirroring the clinical course of MS are discussed.

Adult↗
PubMed1984

[Regulatory T-lymphocytes in the immune deficiency syndrome].

A 25-year-old patient presented with hypogammaglobulinemia diagnosed at the age of 7, causing recurrent infections of the gastrointestinal and bronchial tracts. He was treated with gammaglobulins and infusions of fresh human plasma. At admission he had an exacerbation of his chronic enteric symptoms. X-ray investigation and coloscopy showed mucosal changes as in enteritis regionalis . A biopsy of rectal mucosa showed accumulations of amyloid. Routine examination of humoral and cellular immune parameters revealed a pattern characteristic for common variable immunodeficiencies. Analysis of T-cell subsets with monoclonal antibodies of the OKT series showed unusually high relative numbers of OKT8+ cells (suppressor-T-lymphocytes) and a comparatively low number of OKT4+ cells (helper-T-lymphocytes). Suppressor-T-cells exert inhibitory effects on B-lymphocyte function (i.e. antibody production). The numerical excess of T-lymphocytes with suppressive properties could be a pathogenetically important factor with immunotherapeutic implications in a number of non-classifiable immunodeficiency syndromes.

Adult↗
PubMed1983

[Age- and sex-dependent changes in human T-lymphocyte subpopulations].

Changes in the expression of T-lymphocyte membrane antigens are seen in many diseases, particularly in autoimmune diseases. The reliability of these parameters, as well as their changes associated with age and sex, were examined in 232 healthy subjects using monoclonal antibodies of the OKT series. The precision of the indirect immunofluorescence method for determining the T3, T4 and T8 antigens (corresponding antibodies OKT 3, OKT 4, OKT 8) is within a range expected for biological testing methods (median variation coefficients 7-20%). In both sexes a statistically significant reduction of the T3+ cells (P = 0.0001; T-lymphocytes) and of the T8+ cells (P = 0.0004; T-suppressor lymphocytes) was seen with increasing age. In women (n = 115) the rate of T3+ and T4+ cells was 2-5% higher on the average (the T4+ cell population contains T-helper lymphocytes). According to these findings there is a statistically significant increase of the T4+ to T8+ cell ratio (P = 0.0001); due to the greater number of helper cells, the average T4/T8 quotients are greater in women than in men (P = 0.0076). The changes in the ratio of T-helper to T-suppressor cells are discussed as predisposing factors in the genesis of autoimmune diseases.

Adolescent↗
PubMed1983

[Trehalose-load test in gastroenterology].

In 35 infants trehalose-load-tests were carried out, biopsies of the intestinal mucosa of each patient were taken, and examined histologically. Furthermore, the enzyme activities of trehalase and lactase in each biopsy were determined. It was possible to demonstrate that morphology and function of the intestinal mucosa correlate differently depending on the severity of the mucosal damage. If there is only moderate mucosal damage, a rather weak correlation is seen either for the trehalose-load-test or for the disaccharidase activities with morphological changes. If damage was absent or severe, correlation improved. Both methods in comparison show a better correlation between trehalase activity and morphology than between trehalose-load-test and morphology. Furthermore, trehalase activity corroborated the histological findings better than lactase activity.

Adolescent↗
PubMedDate not supplied

The EGF receptor - an essential regulator of multiple epidermal functions.

Epidermal keratinocytes express both the epidermal growth factor receptor (EGFR) and several of its ligands, establishing the constitutive elements of an autocrine loop in this cell type. Activation of the EGFR provides signals essential to several aspects of normal keratinocyte biology including cell cycle progression, differentiation, cell movement and cellular survival. It may be argued that enhanced keratinocyte survival via EGFR activation is the most important function as it limits the manifestation of other phenotypes. The frequent deregulation of EGFR expression and activation in benign and malignant hyperproliferative skin diseases motivates the investigation of EGFR-dependent intracellular pathways which contribute to the varied EGFR-dependent phenotypes.

Cell Division↗
PubMedDate not supplied

Transforming growth factor-alpha secretion by epidermal growth factor-dependent human tumor cell lines.

Pairs of cell lines from spontaneous human tumors (cervical adenocarcinoma, melanoma, and synovial sarcoma) were established using serum-free culture conditions with and without exogenous epidermal growth factor (EGF). EGF-adapted cultures of melanoma and cervical adenocarcinoma origin secreted higher levels of bioactive transforming growth factor alpha (TGF-alpha) when compared to cultures maintained in the absence of EGF. Depletion of EGF for these EGF-adapted cultures resulted in growth arrest. In contrast, the sarcoma cell lines did not secrete TGF-alpha regardless of the culture conditions but EGF significantly stimulated proliferation of these cells in short-term assays. We show that exogenous EGF induces TGF-alpha production and supports proliferation of tumor cells of various tissue origin but is not essential for in vitro growth factor-deprived conditions.

Carcinoma↗
PubMedDate not supplied

Tumor progression in the human melanocytic system.

The isolation and routine tissue culture of melanocytic cells from normal skin, precursor nevi, primary and metastatic melanomas has allowed the experimental study of different stages of tumor progression. Characteristic differences between cultured normal melanocytes and highly malignant metastatic melanoma cells were: 1) limited life span for normal melanocytes and non-malignant nevus cells versus infinite growth for malignant melanoma cells; 2) inability to grow anchorage-independently versus high colony forming-efficiency in soft agar; 3) non-tumorigenicity versus tumorigenicity in athymic nude mice; 4) dependence on exogenous growth factors and other mitogens versus autonomous growth in protein-free medium; 5) expression of melanocyte-associated antigens versus expression of melanoma-associated antigens; and 6) diploid karyotype versus non-random chromosomal abnormalities. The only major distinction found between advanced primary and metastatic melanomas was that only metastatic melanoma cells proliferated continuously in the absence of growth factors or other proteins. However, advanced primary melanoma cells could be clearly distinguished from dysplastic nevus cells by their growth behavior and growth factor requirements. Only limited information is available on the biologic, genetic, immunologic and molecular properties of dysplastic nevus cells and early (radial growth phase) primary melanoma cells but these cells appear to differ markedly from advanced primary and metastatic cells. The availability of cells from sequential steps of tumor progression in the human melanocytic system offers a unique experimental model for the study of malignant transformation.

Animals↗