Search PubMed⌕ Search

Biomedical subjects

D Schadendorf

Publications and source records attributed to D Schadendorf.

At least 127 records · Page 7Linked to original sources
PubMed1993

Tumour progression and metastatic behaviour in vivo correlates with integrin expression on melanocytic tumours.

In order to evaluate the significance of adhesion molecules expressed on melanocytic tumours for progression and prognosis in vivo, we studied integrin expression (VLA-1 to VLA-6, CD18, CD51, CD61) on 10 naevi, 40 primary malignant melanomas, and 11 metastases by immunohistology using the APAAP technique. Evaluation was done by grouping the percentage of positive tumour cells in six categories. Statistical analysis (Wilcoxon rank test, Scheffe test) revealed significant differences in the expression of VLA-1 (P < 0.0001), VLA-2 (P = 0.0001), VLA-5 (P = 0.0093), VLA-6 (P = 0.0232), and CD61 (P = 0.0002) between naevi and primary melanomas. Comparing primary melanomas with metastases, a statistically significant decrease in the expression of VLA-1, VLA-2, and VLA-6 was detectable, as well as a significant increase in VLA-4 and VLA-5. There was no correlation between integrin expression and tumour type (superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma), regression and ulceration. Changes of VLA-1, VLA-4, and VLA-6 expression correlated with the tumour thickness of the primary melanoma, but only VLA-4 and VLA-6 expression on primary melanomas correlated significantly with the development of metastases (P = 0.024 and P = 0.001). These changes of integrin expression during tumour progression particularly, the data showing an increase of VLA-4, and a decrease of VLA-6 expression support the concept that integrins are a new additional set of prognostic markers which indicate predisposition to the development of metastases.

Antigens, CD↗
PubMed1993

Determination of granulocyte/macrophage-colony-stimulating factor secretion by human melanoma cells and its effects on human melanoma cell proliferation.

Recently, granulocyte/macrophage-colony-stimulating factor (GM-CSF) became available for overcoming chemotherapy-induced granulocytopenia. GM-CSF not only has a prominent role in the regulation of proliferation and differentiation of haematopoietic cells but it is also secreted by a variety of solid tumours and is capable of exerting growth-stimulatory effects. To evaluate the safety of GM-CSF administration in the treatment of malignant melanoma, we investigated GM-CSF secretion, GM-CSF receptor expression and the effect of GM-CSF on the proliferation of human melanoma cells in vitro. A panel of eight human melanoma cell lines and two fresh tumour specimen was studied. GM-CSF protein was not detectable in culture supernatants by ELISA without stimulation. Interleukin-1 and tumour necrosis factor alpha induced GM-CSF secretion in all four melanoma cell lines tested. When biotinylated GM-CSF was used, the corresponding receptor was not detectable by immunohistochemical or FACScan analysis. The proliferation of eight human melanoma cell lines and two fresh melanoma specimens was determined by the MTT test after 4-6 days of growth in the presence of different concentrations of GM-CSF (0.1-1000 U/ml). Neither proliferation nor growth inhibition was observed. Therefore the effect of GM-CSF on residual tumour cells in vivo may not present a problem during clinical use to stimulate marrow regeneration after or during chemotherapy of metastatic malignant melanoma.

Cell Division↗
PubMed1993

Brain metastases of metastatic malignant melanoma: response to DTIC and interferon-gamma.

The prognosis of patients with malignant melanoma and brain metastases is poor. Therapy of brain metastases is difficult and mostly unsuccessful, with brain metastases being the predominant factor which determines overall survival. We report here on a patient whose brain metastases responded to DTIC + INF-gamma. We present a short summary on the different effects on INF-alpha and INF-gamma and reach the conclusion that clinical trials which combine DTIC and INF-gamma should be performed. Based on this observation, combinations including INF-alpha are not necessarily comparable to modalities which include INF-gamma.

Aged↗
PubMed1993

Acute monoblastic leukemia with skin nodules in an adult.

An 18-year-old man had a 3-week history of malaise, a 1-week history of a papular eruption, and increasingly severe multisystem neurologic symptoms. A diagnosis of acute monoblastic leukemia was made. Immunophenotypic characterization of peripheral blood, bone marrow, and cutaneous infiltrates revealed a predominant myelomonocytic phenotype with the coexpression of intercellular adhesion molecule type 1, IgE receptor, terminal deoxynucleotidyl transferase, and some T-cell markers. These findings may have important clinical and pathogenetic implications regarding the biologic and pathologic behavior of the myelomonocytic leukemic cells. They also explain in part the impressive presentation of the disease in the skin.

Adolescent↗
PubMed1993

The polymerase chain reaction. Method and applications in dermatopathology.

Since it was first reported in 1985, the polymerase chain reaction (PCR) has revolutionized the way molecular studies are performed, and has developed into one of the most powerful tools in molecular pathology. By use of a cyclic change of temperature, a specific and exponential in vitro amplification of a target DNA sequence can be achieved within hours. As a template for PCR reactions, total genomic DNA is used; this can be readily extracted from clinical specimens. Very low quantities of DNA, as well as DNA degraded by fixation, can also be used as a template for PCR reactions, allowing formalin-fixed, paraffin-embedded tissue to become amenable to detailed molecular analysis. Sequences specific for certain viruses and other microorganisms, as well as molecular marker sequences associated with various types of human cancer, can be readily detected in paraffin-embedded tissue sections. The methodology of PCR, along with various applications in dermatopathology, are reviewed.

DNA↗
PubMed1993

Responsiveness to interferon treatment of human melanoma cells correlates to immunophenotype.

Clinical trials with interferon (INF) treatment in patients with advanced metastatic melanoma have met with limited success, suggesting that only a small subgroup of patients with melanoma is sensitive to INF therapy. For therapeutic strategies, it would be of great value to discriminate and define markers related to the anti-proliferative effects of INF. In the present study, we report on the in vitro growth inhibitory effects of INF in six human melanoma cell lines; this is associated with a modulation of cell surface markers. The responsiveness of human melanoma cell lines in vitro to INF-alpha shows a good correlation with a specific immunophenotype (TA99-/EGF-R+ or HLA-DR+). No marker correlated with sensitivity or resistance to INF-beta or INF-gamma. This is the first report identifying cell surface markers of human melanoma cells which might have a predictive value for the clinical response to INF-alpha.

Antibodies, Monoclonal↗
PubMed1993

Amelanotic malignant melanoma presenting as malignant schwannoma.

A 78-year-old woman presented with a 14-month history of a nodule on the sole of her left foot. It had been increasing in size, and had become ulcerated. Histological, immunochemical and ultrastructural studies of the primary tumour revealed melanocytic and Schwannian characteristics, and posed diagnostic difficulties. The final diagnosis of a malignant melanoma with Schwannian differentiation was established on the basis of the clinical course, with the development of metastases in the subcutis, lymph nodes, liver and brain, as well as a shift in differentiation of the metastases towards cells containing giant melanosomes, typical of melanoma.

Aged↗
PubMed1993

Verrucous cysts: histopathologic characterization and molecular detection of human papillomavirus-specific DNA.

Verrucous cyst is an uncommon newly described benign epithelial cyst which may be associated with human papillomavirus infection. The purpose of this project was to study the clinicopathological features of verrucous cysts and to demonstrate human papillomavirus (HPV) by polymerase chain reaction (PCR) in these lesions. We have analyzed 5 examples of verrucous cysts: the age range of the patients was between 37-82 years and the most common locations were face and extremities. Clinically the lesions were interpreted as cyst (2), dermatofibroma (2) and basal-cell carcinoma (1). Histopathologic examination of the biopsy specimens showed in all cases an intradermal infundibular cyst lined by a papillated and/or digitated epithelium with focal prominent hypergranulosis and irregular keratohyalin granules. Furthermore, numerous whorls of keratinocytes (so-called squamous eddies) were present within the squamous areas of the hyperplastic epithelium of the cyst, morphologically reminiscent of inverted follicular keratosis. Architectural and cytological features of malignancy were not present. Sections of paraffin-embedded tissue of the 5 verrucous cysts and of 5 "conventional" follicular cysts, infundibular type, were investigated for the presence of HPV DNA sequences by PCR using consensus primers. In all 5 cases of verrucous cysts, HPV-specific DNA sequences were detected, whereas all follicular cysts, infundibular type, were negative. These results support the concept that verrucous cysts can be added to the large spectrum of HPV-induced cutaneous neoplasms. Further studies are needed to identify the specified HPV-type in these distinctive benign cystic proliferations.

Adult↗
PubMed1993

Expression of growth factor receptors on human melanoma cells: comparison of modulating effects of interferons and retinoids.

Autocrine and paracrine growth factors are important mediators in malignant transformation. Interferons (IFN) and retinoids (RX) are well-known differentiative and immunomodulating agents with effects on subsets of different human tumors including malignant melanoma. In this study, we examined the modulating effects of three IFN and seven different RX on human melanoma cell lines regarding growth factor receptor expression. Growth factor receptor expression, including PDGF-R, NGF-R, EGF-R, IR, IGF-I-R, TFR and c-kit, was studied by immunohistochemistry and FACSscan analysis. Both groups of substances modulated the expression of some growth factor receptors. Upregulation of PDGF-R was seen after treatment with IFN as well as with RX. In contrast, EGF-R was found to be downregulated in two EGF-R-positive cell lines by IFN and, on the other hand, induced by RX in two EGF-R-negative cell lines. The expression of NGF-R was modulated ambiguously by these substances but demonstrated a cell line specificity in the different melanoma cell lines tested. Additionally, some of the tested growth factor receptors were not markedly changed regarding their expression by treatment with IFN and RX (IR, IGF-I-R, c-kit, TFR).

Adjuvants, Immunologic↗
PubMed1993

Primary leiomyosarcoma of the skin. A histological and immunohistochemical analysis.

We report a rare case of a cutaneous leiomyosarcoma on the extensor surface of the proximal part of the left arm of an 84-year-old man. The tumour exhibited a number of histological and immunohistochemical features which are characteristic of a leiomyosarcoma. Leiomyosarcomas are frequently misdiagnosed on clinical grounds. Therefore, clinical features, differential diagnosis, histological and immunohistochemical criteria, therapy and prognosis of this rare malignant tumour are summarized on the basis of the present case and previously published reports.

Aged↗
PubMed1991

Detection of human papillomaviruses in paraffin-embedded condylomata acuminata--comparison of immunohistochemistry, in situ hybridization, and polymerase chain reaction.

The polymerase chain reaction (PCR) is used for detection of human papillomavirus (HPV) DNA in paraffin-embedded tissue sections of condylomata acuminata. Incorporation of biotinylated nucleotides during the amplification process allows a highly sensitive, fast, and non-isotopic detection of viral DNA in a subsequent Southern dot blot. In 100% (13 of 13) of histologically confirmed condylomata, HPV-6 or -11 could be detected by polymerase chain reaction. By in situ hybridization 77% (10 of 13) and by immunohistochemistry (IHC) 69% (nine of 13) positive results were obtained. Because HPV genital infection is linked to penile and cervical dysplasia, polymerase chain reaction provides a powerful and highly sensitive tool for epidemiologic studies on sexual transmission of HPV.

Adult↗
PubMed1991

Gene amplification by polymerase chain reaction in dermatology.

The polymerase chain reaction (PCR) is another new powerful technique in molecular biology that has begun to open new perspectives in modern science and also in dermatology. This brief report will therefore elucidate the general principles of the polymerase chain reaction, as well as its limitations and possible pitfalls. Furthermore an overview will be provided on the impact of PCR on molecular biologic approaches in oncology, immunology, and human genetics. The use of the method as a tool to detect microorganisms particularly viruses and bacteria, in cutaneous tissue and it potential other future applications are described as well. Because PCR is automated and is being more and more established in routine laboratories, physicians and scientists should be familiar with the basic principles and potential uses of this methodology.

Gene Amplification↗
PubMed1989

A novel heteromorphic human cell surface alloantigen, gp60, defined by a human monoclonal antibody.

A human mAb (DSM1) generated from a patient immunized with irradiated allogeneic melanoma cells detects a new cell surface alloantigen of restricted cell type distribution. The Ag is a 60,000-Da glycoprotein (gp60) that displays considerable heteromorphism in its cytosolic and cytoskeletal (52 to 62 kDa) and membrane forms (60 to 64 kDa). The gp60 Ag has been purified using lectin affinity, ion exchange, and Mono P fast performance liquid chromatography. Rabbit antiserum against purified gp60 recognizes a homologous gp60 molecule on DSM1-nonreactive cells. Molecular properties of gp60 and a partial amino acid sequence of a tryptic gp60-derived peptide distinguish it from other known human alloantigens. This is the first report of a human alloantigenic system whose definition required a cell type other than those of bone marrow derivation.

Amino Acid Sequence↗
PubMedDate not supplied

Phase 2 trial of vaccination with tyrosinase peptides and granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma.

This phase II study was performed to determine the induction of a specific T-cell response, the clinical response rate, and toxicity of vaccination with different HLA class I-binding peptide epitopes derived from the melanocyte differentiation antigen tyrosinase in patients with stage IV melanoma. The study population consisted of 16 patients with metastatic disease and two patients who were macroscopically free of disease at study entry after resection of recurrent skin lesions. Patients received intradermal injections of 200 microgram [corrected] peptide corresponding to their HLA type on day 3, and 75 or 150 microg granulocyte-macrophage colony-stimulating factor on days 1 to 4. Vaccinations were repeated at weeks 2, 4, 6, 10, and 14. Monitoring of peptide-specific T-cell frequencies in the peripheral blood was performed using an interferon gamma ELISPOT assay. Eleven of the 16 patients with metastatic disease went off the protocol within the first 10 weeks because of tumor progression. Of the five patients with metastatic disease who received all six vaccinations, one patient showed a mixed response with regression of some lung metastases; two patients with progressive disease before vaccination had stable disease for 6 and 18+ months; and two patients had progression of their disease. The two patients who had all their metastases resected before vaccination did not have relapses for 6 and 12+ months after vaccination. Induction of tyrosinase-reactive T cells was found in these two patients and in two others with metastatic disease, including the one who achieved a mixed response and one with stable disease. This study shows limited clinical and immunologic activity of HLA class 1-peptide vaccination in combination with granulocyte-macrophage colony-stimulating factor in stage IV melanoma patients.

Bone Neoplasms↗
PubMedDate not supplied

Comparison of S100 protein and MIA protein as serum marker for malignant melanoma.

BACKGROUND: Detection of S100 beta in serum has been shown to be a significant prognostic marker for malignant melanoma in earlier studies. Melanoma inhibiting activity (MIA) has recently been detected as a new serum marker for malignant melanoma. MATERIALS AND METHODS: In the present study, serum levels of S100 beta protein and MIA were measured over a time period of up to 18 months in 271 serum samples from 65 melanoma patients at different stages of disease, during chemotherapy and/or immunotherapy. In addition, 46 sera of control patients were analysed. The aim of this study was to compare both potential markers. S100 beta was measured using the immunoluminometric assay LIA-mat Sangtec (Byk Sangtec Diagnostica) with a cut-off level of 0.12 microgram/l. MIA was determined by the MIA ELISA kit (Roche) using a cut-off level of 6.5 ng/ml. RESULTS: In 53 patients a direct correlation of S-100 values and clinical course could be observed (81.5%), whereas in 48 patients MIA-values and clinical course (73.8%) showed an association. S100 beta levels were incorrectly elevated in 5 out of 25 sera, "false positive" (20%)) and were in 8 out of 40 sera not elevated despite the detection of metastases "false negative" (20%)). Assessing the MIA levels, 2 out of 25 probes were false positive (8%) and 13 out of 40 probes false negative(32.5%). CONCLUSION: Our data strongly suggest that S100 and MIA represent serum tumor markers that are valuable both in therapy-monitoring and in detection of tumour progression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Increase of cytotoxic sensitivity of primary human melanoma cells transfected with the interleukin-7 gene to autologous and allogeneic immunologic effector cells.

Patients with metastatic melanoma have a very poor prognosis. In many cases, the tumor recurs after surgical excision. Therefore, it might be beneficial for cancer patients to induce an immune attack against the tumor by inserting a cytokine gene into the tumor cells. Here, 14 primary cell cultures could be established from 45 patients with malignant melanoma. Primary cell cultures were transfected via electroporation with the gene encoding for human interleukin-7 (IL-7). Transfection resulted in the production of biologically active IL-7 with an average of 850 pg/mL per 10(6) cells per 24 hours. Irradiation with 10,000 cGy, which inhibited tumor cell growth in vitro, increased the amount of released IL-7 to an average amount of 1050 pg/mL per 10(6) cells per 24 hours. No significant differences in the phenotype were observed in the IL-7-transfected cells compared with nontransfected cells. The expression of HLA class I and II, ICAM-1, and of a melanoma-associated antigen remained unaltered. Transfection with IL-7 had no significant effect on the proliferation of melanoma cells as measured in a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. There was no significant change in the cytokine profile after transfection or irradiation of the cells, but one cell culture expressed a high amount of IL-6 (about 2 ng/mL). IL-6 was expressed in nontransfected cells and was not altered by transfection. Interestingly, transfected cells from primary melanoma cultures possessed a higher sensitivity to immunologic effector cells compared with nontransfected cells. This was true for allogeneic as well as autologous melanoma cells. Our results show the feasibility of a gene transfer into primary human melanoma cells, different from retroviral transduction. IL-7-transfected cells might be of value in vaccination protocols for melanoma patients.

Cytotoxicity, Immunologic↗