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Biomedical subjects

R Dummer

Publications and source records attributed to R Dummer.

At least 109 records · Page 6Linked to original sources
PubMed1999

Genotypic, phenotypic and functional analysis of CD4+CD7+ and CD4+CD7- T lymphocyte subsets in Sézary syndrome.

The expansion of CD4+CD7- T cells in the peripheral blood of Sézary syndrome (SS) is well known. It remains unclear whether this population contains the dominant T cell clone. Peripheral blood mononuclear cells (PBMC) of five SS patients were sorted by fluorescence-activated cell sorting into CD4+CD7- and CD4+CD7+ populations. These populations were analysed separately for clonality of the T cell receptor gamma chain (TCR-gamma) by PCR-DGGE. The cytokine profile of both populations was investigated by RT-PCR ELISA for IFN-gamma, IL-2, IL-4, IL-5, IL-10, IL-13 and IL-15. In three other patients with known Vbeta-usage, the dominant T cell clones were phenotypically characterized by double staining. PCR-DGGE of TCR-gamma demonstrated that all patients had a clonal population in their blood and that this population was present in CD4+CD7- and CD4+CD7+ populations. Concerning mRNA cytokine transcription, the two populations did not show any consistent differences. In three patients with identified clones (Vbeta 3.1, 5.3 and 6.7), double staining revealed positivity for CD2, CD3, CD4, CD5, CD45RO and CD7 in a significant proportion (at least 35%). We conclude that the CD4+CD7- population does not represent the dominant T cell clone in patients with SS. An increase in this population of PBMC in SS might account for deviations in the T cell functions of the patients.

Antigens, CD7↗
PubMed1999

[Systemic therapy of metastatic melanoma].

Therapy of metastatic melanoma still remains difficult. All therapeutic strategies have to consider the individual patient's condition and number and localisation of the metastases. Solitary metastases in lung, CNS, soft tissues and lymph nodes have to be removed by surgery. Multiple metastases are treated with a systemic chemoimmunotherpy. Promising approaches use interleukin-2, interferons, DTIC, temozolamide, vindesine and cisplatin. Radiotherapy is the treatment of first choice for bone and CNS metastases. These therapeutic strategies have improved the prognosis of metastatic melanoma. Additional multi-center trials and experimental approaches will help to reach the goal of a curative systemic therapy for metastatic melanoma.

Adjuvants, Immunologic↗
PubMed1999

[Vaccination therapy of malignant melanoma].

There is no cure for advanced melanoma. Chemo- or chemo-immunotherapy may lead to tumor regression in a minority of patients. New perspectives for treatment derive from recent efforts to develop vaccination strategies for melanoma. Insights into the immunobiology of this disease combined with the characterization of tumor specific peptide epitopes as well as appreciation of the crucial role of dendritic cells for the induction of anti-tumor immunity are beginning to be translated into the every day clinical practice.

Antibody Formation↗
PubMed1999

Combination treatment with extracorporeal photopheresis, interferon alfa and interleukin-2 in a patient with the Sézary syndrome.

Extracorporeal photopheresis is generally accepted as standard therapy for the leukaemic and erythrodermic variant of cutaneous T-cell lymphoma, the Sézary syndrome (SS). Because of the limited efficacy in some patients with SS, combination therapy is often necessary. We report a new combination therapy for an intensively treated 62-year-old woman with advanced SS (T4N1BM1, stage IVb). Previous treatment with PUVA, retinoids alone and in combination with photopheresis, chlorambucil, and chemotherapy using cyclophosphamide, doxorubicin, vincristine and prednisone failed and were associated with significant side-effects. Six cycles of combination therapy with extracorporeal photopheresis, low-dose interferon alfa and interleukin-2 resulted in fading of the erythroderma and in a decrease of Sézary cells in the white blood cell count. The CD4/CD8 ratio decreased from 66 to 6 and the proportion of CD4 + CD7 - cells from 47% to 11%. Only mild side-effects such as influenza-like symptoms, fever and nausea were observed. Two months after this therapy, the patient developed enlarged lymph nodes without erythroderma, and died 1 year later from the lymphoma. Combination therapy with extracorporeal photopheresis, interferon alfa and interleukin-2 might be useful in selected patients with SS.

Combined Modality Therapy↗
PubMed1999

Non-invasive assessment of tumour cell proliferation with positron emission tomography and [76Br]bromodeoxyuridine.

In oncology, a number of new potential therapeutic modalities, including gene targeting, are currently under investigation. To evaluate their response at a preclinical level, a non-invasive method providing information about cell proliferation would be highly valuable. The growth fraction can be assessed by the incorporation of thymidine into the DNA of S-phase cells. We report the use of the thymidine analogue bromodeoxyuridine (BrUdR) labelled with bromide-76 (76Br) in positron emission tomography (PET). PET scans using [76Br]BrUdR were performed in seven patients with metastatic melanoma. The in vitro cell proliferation in these metastases (n = 7) was compared with immunohistochemically evaluated cell proliferation using anti-bromo-deoxyuridine and MIB-1 antibodies after excision. Blood samples were taken to analyse the kinetics of the radiopharmaceutical. The accumulation of [76Br]BrUdR in PET correlated significantly with the immunohistochemically assessment of S-phase and cycling cells. In one patient a clinically unexpected metastases was found on [76Br]BrUdR-PET which became evident 4 weeks later. Analysis of blood samples showed a fast disappearance of [76Br]BrUdR; 30 min after injection free bromide was the main form of radioactivity, resulting in a high background activity. Assessment of cell proliferation using [76Br]BrUdR is hampered because of fast debromation and high background activity. The results are thus rather the effect of the increased circulation in more rapidly proliferating metastases than Incorporation of [76Br]BrUdR into proliferating cells.

Adult↗
PubMed1999

Mycosis fungoides with mucinosis follicularis in childhood.

Mycosis fungoides is a cutaneous T-cell lymphoma (CTCL) usually observed in mid to late adulthood. It occurs only rarely during childhood. Follicular mucinosis is a chronic dermatosis involving the sebaceous glands and outer root sheaths. It is normally differentiated into a juvenile benign form and an adult form possibly associated with mycosis fungoides. We report a 12-year-old boy who presented with an 8-month history of erythematous mucinous plaques on the scalp. Three months later, he developed erythematous patches and plaques on his whole body, accompanied by cervical lymphadenopathy. A biopsy showed follicular mucinosis and epidermotropism of the lymphocytic infiltrate. Immunophenotyping and a PCR clonality test were consistent with CTCL. The patient received PUVA treatment and local steroids, resulting in partial remission. Mycosis fungoides should be considered in the differential diagnosis of chronic, scaling dermatoses in childhood. Moreover, follicular mucinosis in childhood can be associated with mycosis fungoides.

Child↗
PubMed1999

Immune escape mechanisms in malignant melanoma.

Malignant melanoma is an antigenic tumor recognized by specific lymphocytes. Several melanoma-associated antigens have been shown to cause tumor rejection in vitro. Escape from immunosurveillance by melanoma cells is the result of several mechanisms such as total loss or decreased expression of HLA antigens, alterations in the expression of tumor-associated antigens or deficiencies in the antigen-processing machinery. Additional important features include the influence of endogenous and exogenous cytokines such as interferons or interleukins and expression of adhesion molecules or co-stimulatory molecules. All these factor have to be considered for the development of new immunoregulatory treatment modalities against advanced melanoma.

Antigens, CD↗
PubMed1999

Immunomodulators in the treatment of cutaneous lymphoma.

BACKGROUND: Cutaneous lymphoma involves clonal proliferation of immunocompetent cells. Immunointerventional strategies are a rational approach to the treatment of cutaneous lymphoma given the pathophysiological aspects of the disease. OBJECTIVE: Immunomodulatory therapies in cutaneous lymphoma are reviewed, including interferons, interleukin-2, cyclosporin A, monoclonal antibodies, autologous bone marrow transplantation, fusion toxins, thymopentin and extracorporeal photopheresis as well as recently reported methods such as vaccination therapy, mycophenolate, and new retinoids. RESULTS/CONCLUSION: Cutaneous lymphoma is sensitive to immunointerventions. This approach should be used in early stages of the disease when it is more susceptible and benefits better from immunomodulatory treatment modalities.

Antibodies, Monoclonal↗
PubMed1999

Approach to lymphoproliferative infiltrates of the skin. The difficult lesions.

Primary cutaneous lymphomas (CLs) are the second most common group of extranodal non-Hodgkin's lymphomas. Cutaneous T-cell lymphomas (CTCLs) account for 60% to 65% of all primary CLs, whereas 20% to 25% of CLs are of B-cell origin. Besides the most common and well-known forms of CL, such as mycosis fungoides and follicular B-cell lymphomas, there are some rare and unusual variants of CL that represent about 10% of lymphoproliferative skin infiltrates. Discussed in detail are T- and B-cell pseudolymphomas as simulators of CL, the group of parapsoriasis and early mycosis fungoides, circumscribed CTCL, such as pagetoid reticulosis and syringolymphoid hyperplasia, granulomatous variants of CTCL, the group of primary CD30+ CTCL and the controversies in the classification and some rare, but distinct cutaneous B-cell lymphomas. The final diagnosis in CL is based on a constellation of clinical, histopathologic, and molecular-biologic criteria.

Humans↗
PubMed1998

The presence of human coxsackievirus and adenovirus receptor is associated with efficient adenovirus-mediated transgene expression in human melanoma cell cultures.

Adenovirus (AdV)-mediated gene expression of immune stimulators represents a valuable in vivo approach for gene therapy of human cancer. The expression level of the therapeutic gene is of crucial importance for the efficacy of this type of treatment. Entry of AdV is dependent on the primary adenovirus receptor CAR and the secondary AdV receptor identified earlier to be a member of the integrin family of surface molecules. We have analyzed 14 different human melanoma cell cultures from different stages together with one melanoma cell line for their AdV-mediated transduction and expression efficiency. Recombinant viruses at various concentrations were used for expression of the B7-1 costimulatory molecule under the control of different promoters and the expression levels of B7-1 were analyzed by flow cytometry. AdV-mediated IL-12 expression was measured using a commercial ELISA. Levels of transgene expression were compared with the expression levels of HCAR, the alpha(v)beta3 and alpha(v)beta5 integrins, and HLA class I. In 4 of 14 cell cultures tested, the presence of the primary virus receptor CAR was associated with the high transduction efficiency phenotype when using the B7-1- and IL-12-expressing viruses at a relatively low multiplicity of infection (MOI) of 50. Immunohistochemistry on cryosections from the original biopsies yielded a strong signal specific for CAR. In contrast, cell cultures expressing low or undetectable levels of CAR needed a 20- to 40-fold higher viral input to show comparable expression level of B7-1 or IL-12. Expression levels of the transgenes hardly varied when using different promoters and no association was observed with the presence or absence of HLA class I molecules or with the expression levels of integrins.

Adenoviridae↗
PubMed1998

Interleukin-15 is an autocrine/paracrine viability factor for cutaneous T-cell lymphoma cells.

In this study we investigated the role of interleukin-15 (IL-15) in the immunobiology of cutaneous T-cell lymphoma (CTCL) cells. Using cell culture techniques, reverse transcriptase-polymerase chain reaction (RT-PCR), and immunhistochemistry we found that IL-15, like IL-7, is a growth factor for the Sézary cell line SeAx and that both cytokines prolonged the survival of malignant T cells directly isolated from Sézary syndrome (SS) patients. Both IL-15 and IL-7 were more potent than IL-2. IL-4 and IL-9, whose receptors share the same gamma chain with the receptors of IL-2, IL-7, and IL-15, did not sustain the growth of CTCL cells, indicating that signaling through the common gamma chain (gammac) is not sufficient for continuous growth. IL-13 and tumor necrosis factor-alpha (TNF-alpha) had no effect. IL-7 and IL-15 also supported the growth of SeAx cells in the presence of the apoptosis inducing agents dexamethasone and retinoic acid. The analysis of patient Sézary cells and three CTCL cell lines by RT-PCR showed that all these cells expressed IL-15 mRNA, but only a few (25%) produced IL-7 mRNA. Immunohistological analyses of skin biopsy samples of SS and Mycosis fungoides patients showed immunoreactivity for IL-15 in basal cell layer keratinocytes and in the infiltrating lymphocytes. We conclude that IL-15 is a growth or viability factor for CTCL-derived cell lines or shortly cultivated Sézary cells. The findings that IL-15 mRNA can be detected in Sézary syndrome peripheral blood mononuclear cells and that the IL-15 protein is detected in skin sections from CTCL patients suggest that IL-15 plays an important role in the biology of CTCL.

Autocrine Communication↗