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Biomedical subjects

R Dummer

Publications and source records attributed to R Dummer.

213 records · Page 12Linked to original sources
PubMed1992

[Shedding of soluble intercellular adhesion molecule 1 (ICAM-1) from melanoma cells and the effect on cellular cytotoxicity].

ICAM-1-mediated cell-cell adhesion is essential for various immunologic functions, including non-MHC-restricted cytotoxicity. Shedding of ICAM-1 occurred after stimulation of melanoma cells with TNF alpha and IFN gamma. Soluble forms of ICAM-1 inhibited the conjugate formation of NK clones with K562 and of LAK cells with melanoma cells. Furthermore, the non-MHC-restricted cytotoxicity mediated by NK clones or LAK cells could be abrogated by soluble ICAM-1.

Cell Adhesion↗
PubMed1991

Shedding of ICAM-1 from human melanoma cell lines induced by IFN-gamma and tumor necrosis factor-alpha. Functional consequences on cell-mediated cytotoxicity.

ICAM-1-mediated cell-cell adhesion is essential for various immunologic functions, including non-MHC-restricted cytotoxicity. The present study was designed to establish whether shedding of ICAM-1 from melanoma cells occurred and to characterize the effects of soluble ICAM-1 on some cell adhesion-dependent functions. The shed soluble ICAM-1 molecule was detected and quantified by a specific ELISA. Shedding of ICAM-1 could be induced by IFN-gamma and TNF-alpha alone, or more effectively, by a combination of the two cytokines together. The use of purified soluble ICAM-1 enabled us to test for the functional significance of the ICAM-1 shedding from tumor cells. Conjugate formation between the cloned NK cell line CNK6 and the erythromyeloid cell line K562, as well as between lymphokine-activated killer cells and the melanoma cell line M26, could be inhibited by purified soluble ICAM-1 and cell-free supernatants from melanoma cell cultures containing shed ICAM-1. Furthermore, the non-MHC-restricted cytotoxicity mediated by NK and lymphokine-activated killer cells could be abrogated either by purified soluble ICAM-1 or by melanoma cell culture supernatants containing shed ICAM-1. Thus, shedding of ICAM-1 may be one of the mechanisms by which neoplastic cells escape immunosurveillance.

Cell Adhesion↗
PubMed1991

Prognostic significance of DNA cytometry in cutaneous malignant lymphomas.

The current classification of cutaneous malignant lymphomas (ML) into low-grade and high-grade lymphomas was found to be of limited reproducibility and permitted only a rough prediction about outcome. With this in mind, the relationship between nuclear DNA content and both prognosis and histologic grading according to the Kiel classification was evaluated on Feulgen-stained imprint specimens. In all, 49 cases of malignant non-Hodgkin's lymphoma, primary of the skin or with an involvement of the skin as one of the first symptoms, were studied using a computerized high-resolution image analysis system. The 2c deviation index (2cDI), which reflects the variation of the nuclear DNA values around the normal diploid peak, was found to be the best prognostically relevant criterion. Using the 2cDI, a significant discrimination (P less than 0.001 in the U test) between low-grade and high-grade ML was achieved. The prognostic benefit of the 2cDI was well documented by a significant inverse correlation between the 2cDI and the period of time until the patients progressed at least into one higher stage or died of lymphoma (r equals -0.63, P less than 0.05). In addition, the 2cDI enabled prognosis of the course of disease. In the group with low 2cDI values (2cDI, less than 0.5), no progression of the disease was observed after 1 year. In the groups presenting with a 2cDI between 0.5 and 1.0 and higher than 1.0, a progression was found in 57% and 64% of the cases studied, respectively. In conclusion, these measurements indicate that the determination of DNA distribution patterns in imprint specimens allows a precise and objective prognostic evaluation of cutaneous ML.

Adult↗
PubMed1991

Formation of neutralizing antibodies against natural interferon-beta, but not against recombinant interferon-gamma during adjuvant therapy for high-risk malignant melanoma patients.

In an adjuvant clinical trial, 34 high-risk malignant melanoma patients were treated with natural interferon (IFN)-beta and recombinant IFN-gamma. Patients with tumor location on head, neck, and trunk received 3 million IU IFN-beta intravenously (IV) three times weekly for 24 weeks. Patients with tumor location on the extremities received subcutaneous (SC) injection of 2 million IU of IFN-beta distal the locoregional lymph nodes instead. All patients were given 50 micrograms IFN-gamma SC on 3 consecutive days every 4 weeks. Antibody formation was detected by coincubation of IFN and patients' serum and assessment of the inhibition of the cytopathic effect by a virus suspension. Soluble interleukin-2 receptors (sIL-2R) were determined by enzyme-linked immunosorbent assay (ELISA) technique. No antibodies against IFN-gamma were observed. The overall incidence of antibody formation to IFN-beta was 55.8% (19/34). Ninety-two percent of the SC-treated patients (13/14) and 30% (six of 20) of the IV-treated patients developed antibodies. Soluble interleukin-2 receptors were found to be significantly lower in antibody-positive patients than in antibody-negative patients. The authors conclude that IFN-beta antibody formation is frequent and might influence IFN induced sIL-2R elevation in vivo.

Antibodies↗
PubMed1991

Imaging pattern of radiolabelled lymphokine-activated killer cells in patients with metastatic malignant melanoma.

In patients with metastatic malignant melanoma the distribution patterns of radiolabelled lymphokine-activated killer (LAK) cells were investigated. Peripheral mononuclear cells (PMC) were isolated from six patients. LAK cells were generated by culturing PMC in complete medium containing 1000 U interleukin (IL)-2/ml and labelled with indium 111 before retransfer. We obtained scans at 2.5, 24, 48 or 96 h after injection with a high resolution gamma-camera. Intravenously injected LAK cells distributed to the lungs, liver, spleen and bone marrow. External tumour detection of known lymph node and bone metastases was successful in four. It failed in one patient with a solitary lung metastasis and in another patient with subcutaneous metastases. Our results suggest that LAK cells show tumour homing, providing a direct interaction between tumour and cytotoxic cells. We conclude that PMC seem to retain their ability to migrate after IL-2 stimulation and 111In-labeling. This technique may be helpful for kinetics studies or external detection of metastases in patients with malignant melanoma.

Adult↗
PubMed1991

The skin: an immunoreactive target organ during interleukin-2 administration?

Six patients with metastatic malignant melanoma were treated systemically with dacarbazine and interleukin-2 (IL-2). During IL-2 administration all patients developed a macular erythematous rash followed by scaling which began 24-48 h after IL-2 infusion. The dermatological changes were associated with elevated interferon-gamma and tumor necrosis factor alpha serum levels (immunoradiometric assay). Histology revealed nonspecific spongiotic foci in the epidermis and a perivascular mononuclear infiltrate in the dermis. Immunohistochemistry characterized this infiltrate mainly as activated T helper lymphocytes and revealed the expression of intercellular adhesion molecule 1 by endothelial cells and keratinocytes that might have been induced by interferon-gamma. The skin reactions associated with systemic IL-2 administration, show that the skin actually participates as a target organ. They should be differentiated from drug eruptions.

Biopsy↗
PubMed1990

A modified cytotoxicity assay with high sensitivity.

Since adoptive immunotherapy using lymphokine activated killer (LAK) cells and interleukin-2 (IL-2) has been introduced into clinical medicine, there has been a growing interest in cytotoxicity assays. The standard 51chromium release assay has certain disadvantages, in particular limited sensitivity, because of a high, nonspecific background release. We examined the conditions under which tritiated thymidine, which has been used to assess slow macrophage mediated cytolysis, can be utilized to assess the rapid cytotoxic activity of unstimulated PBL and LAK cells. The optimal assay duration for the 3H-thymidine (3H-TdR) release assay is 24 h. Under standard conditions actively proliferating effector cells do incorporate some of the 3H-TdR released by the target cells during this time, leading to false low results. This problem can be abolished by the addition of excessive amounts of cold TdR to the assay medium. We found a good correlation of the results of the TdR release assay and the Cr release assay. Using the very sensitive TdR release assay, unexpected significant cytolysis of the so-called 'NK resistant' Daudi cells by unstimulated PBL is demonstrated. The modified 3H-TdR release assay is well-suited to monitor the immunological effects of immunotherapy, using IL-2 and LAK cells.

Chromium Radioisotopes↗
PubMed1990

[Interleukin 2: immunologic background and clinical use in tumor therapy].

The cytokine interleukin 2 (IL 2) has proved to be an effective agent in immunotherapy of human cancers. Natural killer cells and cytotoxic T-lymphocytes are activated via membrane receptors by IL 2. IL 2-activated natural killer cells and cytotoxic T-lymphocytes develop high cytolytic activity against a variety of tumor cells in vitro. After extensive animal experiments, IL 2 was used in humans either alone or in combination with lymphokine-activated killer cells or tumor-infiltrating lymphocytes. Its application in humans is still experimental, although initial results are very promising. Further studies are necessary to establish treatment protocols with high therapeutic efficacy and tolerable side effects.

Animals↗
PubMed1988

[A new approach in the treatment of metastatic melanoma: adoptive immunotherapy using lymphokine-activated killer cells and interleukin 2].

The treatment of metastatic malignant melanoma remains unsatisfactory. Recently, immunological approaches have been examined. In this respect, therapy with interleukin 2 (Il 2) and Lymphokine-activated killer cells (LAK-cells) is of special interest. In the present paper, the results from the literature are reviewed, and the first patient is reported, who was treated in our department with this therapeutic regimen in a phase-one study to examine the toxicity of a new Il 2 preparation.

Humans↗
PubMedDate not supplied

Clinical and immunological features of patients with interleukin-5-producing T cell clones and eosinophilia.

Recent work suggests that in some patients with the hypereosinophilic syndrome, a clone of abnormal T cells produces large amounts of interleukin-5. In this study, we examined 60 patients with idiopathic eosinophilia. Sixteen patients had circulating T cells with an aberrant immunophenotype that, in most cases, were associated with different forms of skin inflammation. The abnormal T cells produced large amounts of interleukin-5, which may have increased eosinophil differentiation in the bone marrow of these patients.

Clone Cells↗