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Biomedical subjects

R Dummer

Publications and source records attributed to R Dummer.

At least 19 recordsLinked to original sources
PubMed2000

Intralesional therapy with anti-CD20 monoclonal antibody rituximab in primary cutaneous B-cell lymphoma.

BACKGROUND: We report the use of a new treatment modality in 2 patients with primary cutaneous B-cell lymphoma. In a 58-year-old woman with progressive nodular lesions on the scalp and face, several treatment attempts either failed or could not be used because of severe adverse effects and underlying epilepsy. The patient declined radiotherapy. A 30-year-old man presented with recurrence of tumor nodules occipitally, thoracically, on the arm, and on the right thigh after several excisions. OBSERVATIONS: Intralesional injection of rituximab, a chimeric antibody directed against the CD20 transmembrane antigen present in malignant and normal B cells, resulted in partial regression of tumor nodules. No adverse effects occurred except pain during or shortly after injection and, in one patient, a slight rise in body temperature. Due to the treatment a prolonged complete disappearance of B cells from peripheral blood samples was observed. CONCLUSION: Intralesional rituximab therapy is a nontoxic and effective treatment for cutaneous B-cell lymphoma that deserves further investigation in larger clinical trials.

Adult↗
PubMed2000

Pathogenesis of cutaneous lymphomas.

Cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders derived from T cells, B cells and, in rare cases, natural killer cells. The precise mechanisms of the lymphomagenesis are still obscure. However, there are various factors involved. These factors include environmental, especially infectious factors, translocations, mutations and genetic instability. The special microenvironment in the skin is responsible for the peculiar behavior of these neoplasms by providing various key factors, such as adhesion molecules and cytokines. Newly identified molecular disturbances in cutaneous lymphomas might be targeted by specific molecular or immunologic interventions in the future.

Cell Transformation, Neoplastic↗
PubMed2000

Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors.

p53 mutations are common genetic alterations in human cancer. Gene transfer of a wild-type (wt) p53 gene reverses the loss of normal p53 function in vitro and in vivo. A phase I dose escalation study of single intratumoral (i.t.) injection of a replication-defective adenoviral expression vector containing wt p53 was carried out in patients with metastatic melanoma or breast cancer with increased p53 protein immunoreactivity in pretreatment tumor biopsies. The biological activity of the injected wt p53 was assayed by reverse transcriptase-polymerase chain reaction in tumor tissue. A total of six (five melanoma and one breast adenocarcinoma) patients were treated at dose levels dependent upon tumor size/dose escalation sequence. Five of six patients became positive for the transfer of wt p53 into tumor tissue 2 days after injection of the vector. Of the four patients assayed, all developed anti-adenoviral antibodies. Adverse reactions associated with i.t. injection were mild, with no obvious correlation between the incidence, severity, or relationship of the events and drug dose. p53 gene therapy by i.t. injection of a replication-defective adenoviral expression vector is safe, feasible, and biologically effective (with respect to transduction frequency) in patients with either metastatic melanoma or breast cancer.

Adenocarcinoma↗
PubMed2000

CD4 + /CD7- T cell frequency and polymerase chain reaction-based clonality assay correlate with stage in cutaneous T cell lymphomas.

In cutaneous T cell lymphomas, tumor cells can be found in skin and in other compartments. A precise definition of extracutaneous spread including blood involvement is necessary for staging and treatment design. We investigated peripheral blood in 51 patients with various types of cutaneous T cell lymphomas by the analysis of blood smears for Sézary cells, the CD4 + /CD7- T helper cell frequency in the peripheral blood by fluorescence activated cell sorter analysis and by polymerase chain reaction for the T cell receptor gamma-chain followed by denaturing gradient gel electrophoresis. Eleven polymerase chain reaction products were sequenced. Thirty-five per cent of patients with stage Ia-IIb cutaneous T cell lymphomas presented a peripheral blood T cell clone. In patients with stage III-IVb cutaneous T cell lymphomas 75% were positive for clonality in the peripheral blood by polymerase chain reaction. Interestingly, three of 13 Sézary patients showed a TCR-gamma joining region pseudogene (JgammaP1/JgammaP2) usage. CD4 + /CD7- cell counts were significantly higher in patients with advanced cutaneous T cell lymphomas than in patients with early cutaneous T cell lymphomas. There was a correlation between increased percentage of circulating CD4 + /CD7- cells and detection of clonality by polymerase chain reaction (p = 0.001). There was no significant correlation between the polymerase chain reaction data and the percentage of Sézary cells on blood smears. A significant correlation between CD4 + /CD7- cells and Sézary cells was found, however. Stepwise logistic regression analysis showed that the CD4 + /CD7- cell count and clonal T cell detection in peripheral blood are independently correlated with stage. The combination of both parameters gives more information than each one separately. In conclusion, our data indicate that fluorescence activated cell sorter analysis of peripheral blood and polymerase chain reaction-based clonality assays can improve the accuracy of staging investigations in cutaneous T cell lymphomas patients.

Antigens, CD7↗
PubMed1999

Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia.

BACKGROUND: The cause of persistent eosinophilia and the hypereosinophilic syndrome is unknown. Recent work suggests that in some patients with the hypereosinophilic syndrome, a clone of abnormal T cells produces large amounts of interleukin-5, a cytokine required for the growth and differentiation of eosinophils. We examined T-cell surface markers, rearranged T-cell-receptor genes, and in vitro production of cytokines by T cells from patients with idiopathic eosinophilia. METHODS: The expression of surface molecules on T cells was measured by flow cytometry. Cytokine expression was measured by enzyme-linked immunosorbent assay, flow cytometry, and immunohistochemical analysis. To identify dominant (clonal) rearrangements of the T-cell receptor within the lymphocyte population, Southern blot analysis (beta chain) and the polymerase chain reaction (gamma chain) were performed according to standard protocols. RESULTS: Among 60 patients with idiopathic eosinophilia, 16 had circulating T cells with an aberrant immunophenotype. In each of these patients, the abnormal immunophenotype was unique. Evidence of clonal rearrangements of the T-cell receptor was obtained in 8 of the 16 patients. In most instances, the abnormal T cells expressed large amounts of surface proteins associated with T-cell activation (the alpha chain of the interleukin-2 receptor and the HLA-DR antigen). Moreover, the aberrant T cells produced large amounts of interleukin-5 in vitro. CONCLUSIONS: Clonal populations of abnormal T cells producing interleukin-5 occur in some patients with idiopathic eosinophilia.

Adult↗
PubMed1999

Inverse regulation of neuronal cellular adhesion molecule (NCAM) by IFN-gamma in melanoma cell cultures established from CNS lesions.

In advanced stages of malignant melanoma (MM), metastases to the CNS are frequently observed. Few results are available on trophic factors and immunological features involved in the process of invasion and adhesion of circulating metastatic cells into the CNS. A direct comparison of remote metastases found in different locations of the same patient might help to identify such properties. For this purpose, we screened a panel of MM cell cultures, which had been established from patients with surgically removed MM lesions of the CNS, for expression and regulation of immunorelevant molecules. The results were compared with standard controls and cultures established from non-CNS metastatic lesions of the same patients. No significant differences were observed for expression of HLA-I, HLA-II, ICAM-1 and the melanoma-associated antigens Mage-3, MelanA and tyrosinase. Constitutive expression of the neuronal cell adhesion molecule (NCAM) was found in all CNS-derived samples and in fewer than 50% of non-CNS derived cultures. IFN-gamma was found to have a weak up-regulating effect in all non-CNS-derived cultures, except normal melanocytes. However, in 6/7 CNS-derived cultures, pre-treatment with IFN-gamma reduced expression of NCAM to 28% to 77% of the level in untreated cultures. The presence and regulation of NCAM differs between MM cells derived from CNS metastases and non-CNS-derived melanocytic cells. Thus, NCAM might be a candidate immunoregulating molecule involved in the formation of CNS metastases of MM.

Antibodies, Monoclonal↗
PubMed1999

[Delay of the diagnosis of an amelanotic malignant melanoma due to CO2-laser treatment--case report and discussion].

The incidence of malignant melanoma is steadily increasing. The best prognostic indicator of melanoma is the vertical tumor thickness. Early recognition of melanoma by the naked eye is often difficult, because many lesions simulate its clinical presentation. We report on a 47-year-old man with a red papular skin lesion treated by CO2 laser. The histological diagnosis of an amelanotic malignant melanoma was thus delayed for one year. Clinically ambiguous skin tumors should never be treated by laser prior to a diagnostic biopsy.

Carbon Dioxide↗
PubMed1999

[UV exposure in Switzerland: time- and topography-associated factors important for the skin].

The intensity of UV-A and UV-B-radiation in Switzerland shows big differences that result from the various altitudes, the season and the time of the day. Additionally the intensity of UV-radiation is influenced by other factors like aerosols, cloudiness and ozone. In higher altitudes there is an additional enhancement by reflection of snow. The most important consequences of the UV-radiation for the population are, however, relevant in spring and summer time during the bathing season and during the late winter season for ski tourists. On a day with a clear sky in summer the UV-radiation can reach maximum values for UV-A of 45 W/m2 and for UV-B of 0.175 W/m2. The ratio of UV-A/UV-B shows an annual course with a maximum in winter of about 500 and a minimum of about 220 in summer. The possible effects on health by extensive UV-exposition are photoageing, skin cancer, inflammation processes and cataract. In Switzerland about 5000 new melanoma cases in men and about 4000 in women occur per year. In contrast to other environmental factors like pollen UV-radiation has the big advantage that the personal exposition can be controlled. Therefore, it is very essential that the general rules of a judicious behaviour such as avoiding the sun at noon, always wearing a hat, shirt and trousers as well as sunglasses with UV-filter are often reiterated.

Female↗
PubMed1999

Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma.

BACKGROUND: Hodgkin's disease and non-Hodgkin's B-cell lymphoma occasionally occur in the same patient. The identification of a common precursor of the two types of lymphoma would show definitively that Reed-Sternberg cells originate from B cells. METHODS: We studied lymphomas from two patients, one with a composite lymphoma (classic Hodgkin's disease and a follicular lymphoma in the same lymph node) and the other with a T-cell-rich B-cell lymphoma that was followed by classic Hodgkin's disease. Single Reed-Sternberg cells and non-Hodgkin's lymphoma cells from frozen sections were micromanipulated. The rearranged immunoglobulin variable-region genes (V genes) of the heavy and light chains were amplified by the polymerase chain reaction from genomic DNA and sequenced. RESULTS: In both patients, the Reed-Sternberg cells were related clonally to the non-Hodgkin's lymphoma B cells. The V genes carried somatic mutations (a hallmark of germinal-center B cells and their descendants). In both patients, some somatic mutations were shared by the Reed-Sternberg and non-Hodgkin's lymphoma cells, whereas other somatic mutations were found exclusively in one or the other cell type. CONCLUSIONS: In two patients with classic Hodgkin's disease and non-Hodgkin's B-cell lymphoma, we identified a common B-cell precursor, probably a germinal-center B-cell, for both lymphomas. This finding suggests that the two types of lymphoma underwent both shared and distinct transforming events and provides proof of the B-cell derivation of Reed-Sternberg cells in classic Hodgkin's disease.

Aged↗
PubMed1999

Constitutive and interleukin-7/interleukin-15 stimulated DNA binding of Myc, Jun, and novel Myc-like proteins in cutaneous T-cell lymphoma cells.

Members of the Myc and Jun/Fos gene families have been found to be expressed in late stages of cutaneous T-cell lymphoma (CTCL) and may be responsible for the transition from low-grade to high-grade tumors. The composition of these complexes is an important parameter, as the different homo- and heterodimeric jun and myc complexes can have gene transcription activating or suppressing activities. We determined the composition of the jun and myc DNA-binding complexes in three CTCL cell lines and malignant cells of seven Sézary patients by electrophoretic mobility shift assays (EMSAs) and "supershift" assays in which specific antibodies against the different members of the tested gene families were included in the binding reactions. Complexes containing JunD were found in three cell lines and two patients. The three cell lines and one patient contained also c-Myc/Max heterodimers. Because c-Myc/Max heterodimers are strong gene transcription activators and are necessary for cell-cycle progression, they may play a role in the progression of CTCL. JunD may also promote cell-cycle progression and influence the expression of cell death survival genes. Interleukin-7 (IL-7) and IL-15, which have been identified as growth factors for CTCL cells, stimulated the DNA binding of JunD and two novel c-Myc recognition site (E-box) binding proteins, but not the DNA binding of c-Myc/Max heterodimers.

Adult↗
PubMed1999

Tumor burden index as a prognostic tool for cutaneous T-cell lymphoma: a new concept.

OBJECTIVES: To introduce a prognostic tool for cutaneous T-cell lymphoma that takes into account the tumor burden and to compare the prognostic value of this tumor burden index (TBI) with that of other prognostic factors. DESIGN: Retrospective clinical and statistical study. PATIENTS: One hundred sixteen patients with cutaneous T-cell lymphoma. METHODS: A TBI was designed that takes into account the types, numbers, and severity of skin lesions with the use of the Cox proportional hazard model. RESULTS: Models of the TBI were developed to test the relative contributions of patches, plaques, and tumors to the total tumor burden and, hence, survival time. Weighting factors reflecting the severity of each skin lesion were tested and incorporated. The best prognostic correlation was a dichotomized index with the following formula: TBI = 1 + (patches x 2) + (plaques x 2) + (tumor x 1.3), where the patches factor equals 0 if 30% or less of the skin area is involved and 1 if greater than 30% of the skin area is involved and where the plaque or tumor factor equals 1 if plaques or tumors are present. Both the TBI and TNM provided predictive information. Discrimination of survival curves and significance of differences was better for TBI (P < .001) than for TNM (P = .009). Sex was also statistically related to survival (males had a better prognosis; P < .04), whereas neither age at first symptoms (P = .35) nor age at time of diagnosis (P = .36) was of prognostic value. CONCLUSIONS: The TBI offers a simple prognostic index for the evaluation of cutaneous T-cell lymphoma. It may become a valuable tool for designing therapeutic strategies for patients according to their specific survival expectancies. However, this model is preliminary and has to be validated on a larger number of patients.

Adolescent↗
PubMed1999

IL-12 directly up-regulates the expression of HLA class I, HLA class II and ICAM-1 on human melanoma cells: a mechanism for its antitumor activity?

IL-12 enhances cytolytic activity and proliferation of NK and T cells, and induces cytokines such as IFN-gamma. No direct effects on non-hematopoietic cells have been shown. This study investigates the effects of IL-12 on melanoma cells in vitro. We analyzed 15 melanoma cell cultures and 1 melanoma cell line. Out of 16 samples 13 expressed the beta chain of the IL-12 receptor (IL-12Rbeta). Preincubation with IL-12 increased the surface levels of human leukocyte antigen (HLA) class I, HLA class II and intercellular adhesion molecule (ICAM)-1 of those cultures with IL-12Rbeta expression. The effects of IL-12 on HLA class I could be blocked by an IL-12-neutralizing monoclonal antibody (mAb), but not by an mAb against IFN-gamma. Melanoma cells transduced with IL-12 expressed enhanced levels of HLA class I, HLA class II and ICAM-1 compared to controls. Co-incubation of the melanoma cells with allogeneic peripheral blood mononuclear cells (PBMC) resulted in enhanced proliferation and increased production of IL-2 and IFN-gamma after pretreatment with IL-12. IL-12 pretreatment increased the susceptibility of melanoma cells to lysis by prestimulated autologous PBMC. Since IL-12 induced immunocritical surface molecules on melanoma cells, it might be beneficial during immune interventions in melanoma patients.

Antibodies, Monoclonal↗
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↗