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Biomedical subjects

R Dummer

Publications and source records attributed to R Dummer.

At least 55 records · Page 3Linked to original sources
PubMed1998

Melan A/MART-1 immunoreactivity in formalin-fixed paraffin-embedded primary and metastatic melanoma: frequency and distribution.

Monoclonal antibody (MAb) A103 specifically detects Melan A/MART-1 protein expression. Melan A/MART-1-derived peptides are recognized by CD8+ T-cells and are used in immunotherapy. We examined formalin-fixed paraffin-embedded tissue from 57 melanomas (34 primary, 23 metastatic) and 39 control cases (junctional, dermal, compound, Spitz, Reed and balloon-cell naevi) using the alkaline phosphatase and anti-alkaline phosphatase immunochemical method after antigen retrieval. Immunoreactivity was rated as low, medium or high, and staining pattern as homogeneous or heterogeneous. Staining with MAb A103 showed a sensitivity of 88% for melanoma, with a very high specificity for melanocytic cells. Immunopositivity decreased along with clinical stage, with stage I showing 100%, stage II 88%, stage III 90% and stage IV 75% immunoreactivity. Staining changed from an exclusively homogeneous pattern in the early clinical stages to a more heterogeneous pattern in the later stages. Melanocytic control tissues consisting of naevi of different subtypes all showed weak to moderate homogeneous immunoreactivity, with polarity towards the epidermis. Analysis of short-term melanoma cell cultures using reverse transcription-polymerase chain reaction (RT-PCR) enzyme-linked immunosorbent assay (ELISA) demonstrated mRNA expression in only one third of the originally immunopositive tumours, suggesting rapid mRNA expression loss in culture. MAb A103 allows the detection of melanoma-associated Melan A/MART-1 protein expression in routine archival tissue and thus enables the profiling of melanomas suited for immunotherapy approaches involving Melan A/MART-1 derived epitopes.

Antibodies, Monoclonal↗
PubMed1998

Tyrosinase immunoreactivity in formalin-fixed, paraffin-embedded primary and metastatic melanoma: frequency and distribution.

Monoclonal antibody T311 specifically detects tyrosinase protein expression. Tyrosinase-derived peptides are recognized by CD8+ T-cells and applied in immunotherapy. We examined formalin-fixed paraffin-embedded tissue of 50 melanoma (primary n=31, metastatic n=19) and 41 control cases (junctional, dermal, compound, Spitz, Reed, balloon-cell nevi) by immunochemistry using the alkaline phosphatase-anti-alkaline phosphatase method after antigen retrieval. Staining with mAb T311 showed a sensitivity of 94% for melanoma with a very high specificity for melanocytic cells. Immunopositivity (94% of melanomas overall) correlated inversely with clinical stage: clinical stage I and stage II showed 100%, stage III and stage IV 86% immunoreactivity each. Staining changed from an exclusively homogeneous pattern in early stages to a more heterogeneous pattern in later stages. Melanocytic control tissue like nevi of different subtypes all showed weak to moderate, homogeneous immunoreactivity with polarity towards the epidermis. RT-PCR ELISA analysis of short-term melanoma cell cultures displayed mRNA expression in only half of the originally immunopositive tumors only, suggesting rapid mRNA expression loss in culture. mAb T311 allows detection of melanoma-associated tyrosinase protein expression and thus profiling of melanomas using routine archival tissue suited for immunotherapy approaches involving tyrosinase derived epitopes.

Antibodies, Monoclonal↗
PubMed1998

Comparative analysis of histological and immunohistological features in mycosis fungoides and Sézary syndrome.

Mycosis fungoides (MF) and Sézary syndrome (SS) are closely related cutaneous T-cell lymphomas, which differ in several clinical aspects. We compared histological and immunophenotypical features of these two entities, which could be implicated in the dermotropism and epidermotropism, characteristic for both of them. Thirteen biopsy specimens from patients with established plaque-stage MF and 13 from SS patients were examined retrospectively, and 21 histological criteria were assessed. Further, 9 cryosections from MF lesions and 9 from SS lesions were stained for LFA, ICAM1, CD40, CD40-ligand, CD28, CD80, CTLA-4, CD86, FAS, FAS-ligand, CLA and CD15s. The only histological criteria that showed persistent differences were acanthosis (in 12 of 13 SS and in 7 of 13 MF specimens) and Pautrier collections (detected in 6 SS and 11 MF biopsies). Patterns of staining with the antibodies mentioned above were found to be similar. Our results indicate that these interaction molecules seem to be involved in the pathogenesis of MF and SS, but their immunohistochemical distribution does not contribute to the differentiation between the two entities.

Abatacept↗
PubMed1998

Pseudo-melanoma after laser therapy.

A 44-year-old woman had several congenital melanocytic nevi that were treated with a CO2 laser. Six weeks after the laser treatment one lesion repigmented and was therefore excised. The initial histological diagnosis of malignant melanoma was revised to 'pseudo-melanoma' after re-evaluation of the history, the clinical presentation and the histology. We conclude that pseudo-melanoma is a complication of laser therapy that has to be recognised in order to avoid unnecessary surgical procedures.

Adult↗
PubMed1998

Comparison of 8-MOP aqueous bath and 8-MOP ethanolic lotion (Meladinine) in local PUVA therapy.

BACKGROUND AND OBJECTIVE: Local PUVA (psoralen plus UVA light) is an effective outpatient treatment for patients with palmoplantar eczema or psoriasis. In this study, the efficacy, applicability and patient acceptance of two local forms of 8-methoxypsoralen (8-MOP) PUVA therapy were compared. METHODS: The study design was a left-right comparison (n = 37): the left hand or foot was treated with (aqueous) 8-MOP bath PUVA whereas the right received (ethanolic) 8-MOP lotion PUVA. After 1 month, the more successful treatment was continued on both sides until lesions cleared. RESULTS: Both therapies were effective and both useful for particular clinical applications: patients with erosive lesions and rhagades appreciated the gentleness of bath PUVA. Those with pustules or hyperkeratotic lesions appreciated the greater effectiveness of 8-MOP lotion PUVA. The total UVA dose and number of sessions to clearance were smaller with 8-MOP lotion. There was no difference in the length of the relapse-free period. Therapy nonresponders usually became apparent within the first 12 sessions. CONCLUSIONS: The difference between bath PUVA and lotion PUVA can be described as 'gentle' versus 'strong' therapy. The better therapy depends on clinical indication.

Administration, Cutaneous↗
PubMed1998

Treatment of vascular lesions using the VersaPulse variable pulse width frequency doubled neodymium:YAG laser.

BACKGROUND: The flashlamp-pumped dye laser is considered the treatment of choice for vascular lesions including port-wine stains. However, this treatment is associated with an intensive postoperative purpura and considerable pain. OBJECTIVE: We tested a newly developed laser device with a 532-nm neodymium:YAG laser with variable pulse widths between 2 and 10 ms. METHODS: Forty-two consecutive patients from our laser clinics were treated with the new laser system delivering energy through a chilled tip by means of circulating water (cooling temperature was between 4 and 5.5 degreesC). Forty of them had been pre-treated with an argon laser and an argon-pumped dye laser. RESULTS: Out of the 42 patients, 1 patient had a complete clearing, 11 had an excellent result (more than 80% clearing), 21 patients had a good result (51-75% clearing), weak responses were seen in 9 patients. Significant success was already seen after 1 or 2 treatments. Side effects were rare. There was no purpura after treatment. Local anesthesia was only applied in 6 out of 42 patients. CONCLUSION: The variable pulse width frequency doubled neodymium:YAG laser seems to be an alternative to the flashlamp-pumped dye laser and deserves to be investigated in comparative trials.

Adolescent↗
PubMed1998

Results of interleukin-2-based treatment in advanced melanoma: a case record-based analysis of 631 patients.

PURPOSE: In patients with stage IV melanoma, durable responses have been reported with treatment regimens that involve high-dose interleukin-2 (IL-2). We analyze long-term results of 631 melanoma patients from 12 institutions who had received IL-2 alone, in combination with interferon alfa 2a or 2b (IFNalpha), or with cytotoxic drugs. METHODS: Case records that contained pretreatment parameters, response data, and updated survival information were collected. After univariate analysis, the multivariate evaluation of the impact of pretreatment parameters on response and survival was performed by logistic regression and Cox's regression, respectively. RESULTS: Patients were divided into four groups according to treatment: IL-2 alone (n=117), IL-2 and chemotherapy (n=49), IL-2 and IFNalpha (n=153), and IL-2, chemotherapy, and IFNalpha (n=312). The median survival of all patients was 10.5 months and the 2- and 5-year survival rates were 19.9% and 10.4%, respectively. Independent prognostic factors for response and survival were entirely different, treatment group being the only significant factor for response, and serum lactate dehydrogenase (LDH), metastatic site, and performance predicting survival. The addition of IFNalpha to IL-2 was associated with prolonged survival, but the effect of additional chemotherapy was less obvious. CONCLUSION: Serum LDH, metastatic site, and performance status are useful stratification factors for randomized trials in metastatic melanoma. The improved long-term survival rates observed in melanoma patients treated with IL-2/IFNalpha-containing regimens are notable in contrast to the reported 5-year survival rates of 2% to 6% achieved with chemotherapy, but because selection bias cannot be ruled out, the impact of IL-2, as well as all other components of the treatment regimens, on survival needs to be confirmed in prospective randomized trials.

Adult↗
PubMed1998

Sézary syndrome, T-helper 2 cytokines and accessory factor-1 (AF-1).

Mycosis fungoides and the Sézary Syndrome are characterized by clonal accumulation of well differentiated T-helper memory cells in the skin and, in the case of the Sézary Syndrome, also in the blood and lymph nodes. Well known immunological abnormalities in patients with MF and SS include reduced delayed type hypersensitivity, decreased proliferation upon stimulation with mitogens of the peripheral blood mononuclear cells, elevated IgE or IgA serum levels and eosinophilia. These abnormalities can be explained by the predominance of T-helper 2 cytokines. Clonal T-lymphocytes purified from the peripheral blood of SS patients transcribe mainly IL-10 and IL-5. They can be CD7 positive or negative. These clonal T cells express the accessory factor-1 (AF-1) or Interferon gamma receptor beta-chain that is essential for Interferon gamma signalling. These results imply perspectives for new therapeutical approaches, such as IL-12 or chimeric fusion proteins.

Humans↗
PubMed1998

[Therapy of cutaneous melanoma].

Therapy of melanoma considers the individual prognosis. Primary low-risk melanomas with tumor-thickness below 1 mm can be treated by surgery with a safety margin of 1 cm. If the tumor-thickness is more than 2 mm the safety margin should be 3 cm. Elective lymph node dissection for melanomas at the extremities is widely substituted by the sentinel lymph node procedure. This new technique shall be applied only in specialised centers in the context of clinical trials. After the resection of lymph node metastases adjuvant treatment using Interferon-alpha should be considered. Palliative therapy of metastases includes surgery, radiotherapy and chemo-immunotherapy depending on the number and location of the metastases. Recent progress in understanding the immunobiology of melanoma and the development of gene therapy has offered new perspectives for future therapeutical intervention including peptide vaccination alone or loaded on dendritic cells and gene therapy.

Antineoplastic Agents↗
PubMed1997

Prognostic value of serum 5-S-cysteinyldopa for monitoring human metastatic melanoma during immunochemotherapy.

The melanin metabolite 5-S-cysteinyldopa (5-S-CD) has been reported to be helpful in detecting occult melanoma metastases and as a prognostic marker in B16 melanoma-bearing mice. The goal of our study was to analyze the significance of the serum 5-S-CD level for the biochemical detection of metastases in human malignant melanoma (MM) and for monitoring the progression or the immunochemotherapeutically induced regression of MM. From 11 patients with metastatic MM observed between 1991 and 1995, serum samples were collected before and after each cycle of immunotherapy or immunochemotherapy. Samples were analyzed for 5-S-CD by automated high performance liquid chromatography with electrochemical detection. Cycles of immunochemotherapy consisted of human interleukin 2 and IFN-alpha (four patients) or of human interleukin 2, IFN-alpha, and dacarbazine (seven patients). Serum value of 5-S-CD in our normal controls was 1.9 +/- 0.6 ng/ml. All patients with metastatic MM showed 5-S-CD serum levels above the upper normal limit of 3.2 ng/ml (10 nM) and ranged from 2.3-fold (4.3 +/- 3.9 ng/ml) of the normal control values in early stages of metastases to more than 50-fold (94.3 +/- 220.3 ng/ml) of the normal control values in advanced stages of the disease. In 28 of 41 (68%) immunochemotherapeutical cycles, a decrease of 5-S-CD was seen during therapy, and in 13 cycles (31.7%), an increase was seen. Patients with more than 68% decreasing cycles (defined as responders; n = 5) showed significantly longer survival times (P = 0.008) than patients with less than 68% decreasing cycles (nonresponders; n = 6). High levels of 5-S-CD were also observed in metastasizing amelanotic melanoma. Serum 5-S-CD is a useful marker for monitoring the clinical course of MM patients, for discriminating between responders and nonresponders to immunochemotherapy, and as a prognostic factor concerning survival time and death risk.

Adult↗
PubMed1997

Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules.

IL-10 is a cytokine which shows various effects including inhibition of T-cell proliferation or HLA-dependent antigen presentation. In this study, we analysed the effects of exogenous or autocrine IL-10 on proliferation and expression of immunocritical surface molecules. Fourteen cultures of human melanoma cells were established from primary melanomas, locoregional lymph-node or distant metastases. In 5 melanoma cell cultures, proliferation in the presence of IL-10, anti-IL-10 antibodies (Ab) or control Ab was assessed with colorimetric and [3H]thymidine uptake assays. Flow cytometric analysis was used to quantify the expression of human leukocyte antigen (HLA) class-I, HLA class-II and intercellular adhesion molecule (ICAM)-1 and the IL-10 receptor (IL-10R). IL-10 production of melanoma cells was documented by RT-PCR and IL-10 protein was detected in the supernatants by means of ELISA. IL-10 enhanced proliferation and prolonged survival of melanoma cells in 5 out of 5 cultures. Anti-IL-10 Ab decreased proliferation. IL-10R expression was found in 12 out of 14 (86%) melanoma cell cultures. The expression of HLA-I, HLA-II and ICAM-1 on all melanoma cells that were positive for IL-10R showed a reduction of 10-60% by IL-10, whereas the surface levels of HLA-I, HLA-II and ICAM-1 in 5 out of 5 cell cultures revealed an increase of 10-170% by anti-IL-10 Ab. These findings suggest that IL-10 is an autocrine growth factor with significant impact on immunocritical molecules in melanoma. IL-10 effects have to be considered when planning therapeutic immunointerventions in melanoma patients.

Antibodies, Monoclonal↗
PubMed1997

[Current therapy concepts in cutaneous T-cell lymphomas].

Cutaneous T-cell-lymphomas (CTCL) include a group of rare diseases that are characterized by an accumulation of clonal T-lymphocytes in skin. The various disease entities may be classified by an adapted Kiel classification. For staging purposes the TNM system is most commonly used. Treatment modalities depend on the extent and the aggressiveness of the disease (low- or high-grade lymphoma) and on the individual situation of the patient. Stage-adapted therapy is currently recommended. Early stages of low-grade CTCL are successfully treated with PUVA, retinoids or interferon-alpha. Extracorporeal photopheresis is the treatment of choice in stage III patients with Sézary syndrome. Alternative therapeutic modalities for CTCL, such as radiotherapy, chemotherapy or various experimental protocols, are discussed.

Combined Modality Therapy↗
PubMed1997

[Unusual Koebner phenomenon in psoriasis caused by varicella and UVB].

An isomorphic response is defined as a nonspecific skin stimulus eliciting a disease-specific skin reaction. We report on the development of the Koebner phenomenon in a 32 year old patient with psoriasis after skin testing with UVB at a dose above 0.055 J/cm2. In addition we describe a 28 years old patient who developed new psoriatic plaques in the areas affected by the virus after a varicella infection.

Adult↗
PubMed1997

[Kaposi sarcoma in cyclosporin A therapy of actinic reticuloid].

A 76 year old patient with actinic reticuloid was treated with Cyclosporin A. 11 months after beginning the immunosuppressive therapy, he developed lymphoedema and livid nodular skin lesions of the right leg, which histologically showed Kaposi's sarcoma. After stopping the Cyclosporin A and intralesional therapy with Interferon alpha, no regression of the Kaposi sarcoma could be seen. The characteristics of Kaposi sarcoma arising during immunosuppressive therapy and the differences in incidence, risk groups and distribution pattern compared to the classic sporadic and the AIDS-related Kaposi sarcoma will be described. The development of Kaposi sarcoma during immunosuppressive therapy for actinic reticuloid has not been previously described.

Aged↗
PubMed1997

[Elastosis perforans serpiginosa in Down syndrome].

Elastosis perforans serpiginosa can arise as a rare complication in patients with Down syndrome. It is one of the primary perforating disorders characterized by transepithelial elimination of abnormal elastic fibers. This may reflect an immunological reaction aquist elastic fibers. We describe a 40-year-old woman with Down's syndrome whose skin lesions were histologically mistaken for lupus vulgaris for a long time.

Adult↗
PubMed1997

Adjuvant immunotherapy in malignant melanoma: impact of antibody formation against interferon-alpha on immunoparameters in vivo.

In an adjuvant clinical trial for high-risk patients with malignant melanoma by using recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha 2b (rIFN-alpha 2b), we monitored the development of antibodies against rIFN-alpha and various immunoparameters as biologic markers for IFN activity in vivo. Thirty-one patients (22 men, nine women) with high-risk malignant melanoma received eight 6-week cycles of rIL-2 and rIFN-alpha. Serum samples of all patients were screened for the presence of antibodies against IFN-alpha by a solid enzyme immunoassay (EIA). Specimens testing positive in the EIA were assessed for their ability to neutralize the antiviral effects of IFN-alpha in vitro in an antibody-neutralizing bioassay (ANB). Furthermore, serum levels of neopterin, beta 2-microglobulin, soluble IL-2 receptor (sIL-2R), anticardiolipin and antithyroglobulin were evaluated. Of 31 patients, 11 (36%) developed binding antibodies; three (27%) of them had antibodies with neutralizing capacities (range, 350-28,000 INU/ml). Of male patients, 8 (36%) of 22 versus 1 (11%) of nine female patients developed antibodies. Statistical analysis (unpaired t test) revealed that all patients with antibody titers showed significant (p < 0.04) lower serum levels of beta 2-microglobulin and reproducible decreases in sIL-2R levels, whereby those with neutralizing antibodies showed significantly (p < 0.0001) lower values than did those with binding antibodies. Elevations of anticardiolipin (17 of 31) and antithyroglobulin (one of 31) were not correlated to the presence of IFN antibodies. Our results show the in vivo significance of antibodies against rIFN-alpha, especially of those with neutralizing capacities. Monitoring of antibody formation as well as immunoparameters like beta 2-microglobulin in clinical trials can contribute to identifying patients who, if necessary, might benefit from alternative IFN treatment, for instance, by using natural IFNs.

Adjuvants, Immunologic↗
PubMed1997

D1 dopamine receptors are not expressed in human melanoma.

D1 dopamine receptor mRNA has been demonstrated in mouse melanoma cells, and the expression of these G-protein-coupled receptors in human melanoma was therefore presumed when dopamine receptor binding radiopharmaceuticals were found to be useful for the detection of metastases in whole-body scintigraphy. The aim of this study was thus to investigate if D1 dopamine receptor mRNA or protein could be directly demonstrated in melanoma cells. The presence of D1 dopamine receptor mRNA was investigated in six human melanoma cell lines from metastases using reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, in vitro binding assays with the D1 dopamine receptor agonist 125I-Sch 23982 were performed in 19 melanoma metastases. No D1 dopamine receptor mRNA could be detected by RT-PCR. All melanotic metastases were found to accumulate 125I-Sch 23982, with the presence of binding sites and intensity of 125I-Sch 23982 labelling correlating to the amount of melanin present in the metastases. Two amelanotic melanomas did not accumulate 125I-Sch 23982. D1 dopamine receptors could not be detected by means of RT-PCR or in vitro binding assays in human melanomas. Detection of antagonists is best explained by non-specific binding to melanin.

Animals↗