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Biomedical subjects

D J Ruiter

Publications and source records attributed to D J Ruiter.

At least 19 recordsLinked to original sources
PubMed1992

Expression of calcyclin in human melanoma cell lines correlates with metastatic behavior in nude mice.

Since our aim was to isolate and identify new progression markers of human cutaneous melanoma, we applied the differential hybridization technique, in which we compared the gene expression in two subsequent stages of this progression. Tumors in nude mice arising after transplantation and serial passage in vivo of either the horizontally and early vertically growing part or the advanced vertically growing part of a primary melanoma of the same patient were used for this assay. This resulted in the isolation of a number of complementary DNA clones that were differentially expressed. Based on the marked difference in expression, one of them, designated pMW1, was chosen for further characterization and appeared to be coding for calcyclin, a cell cycle-regulated protein, belonging to a family of small calcium-binding proteins. Calcyclin expression was elevated in high-metastatic human melanoma cell lines in nude mice compared to low-metastatic ones. Immunoprecipitation of calcyclin showed that the differential expression at the RNA level is also reflected at the protein level. These findings show that expression of calcyclin is related to metastasis of human melanoma cell lines in nude mice and emphasize the role of this family of calcium-binding proteins in neoplastic progression as was reported for the mouse homologue of calcyclin and other members of the same family.

Aged↗
PubMed1992

[3 children with a melanoma of the skin].

Melanoma rarely occurs in children not over 14 years of age. We report on the clinical and pathological features of three patients (two girls and one boy aged 6, 12 and 11 years respectively) from the St Laurentius hospital (Roermond, Netherlands) with melanoma of the skin, in whom the lesions histologically resembled the more frequently occurring spindle and epithelioid cell naevus (SE naevus). In all three cases, metastases were found in the regional lymph nodes. Further metastases were found in the last patient only, after follow-up periods of 29, 8 and 3 years respectively. The problems in distinguishing between melanoma and SE naevus are discussed, on the basis of a literature study and a retrospective analysis of 40 cases retrieved from PALGA (the nationwide computerized pathological archive in the Netherlands) up to and including 1990. As the diagnosis in such cases has important therapeutic consequences, we advise to submit the slides to experienced pathologists in the field, such as the Pathology Panel of the Dutch Melanoma Committee (Nederlandse Melanoom Werkgroep).

Child↗
PubMed1992

Macrophages in melanocytic naevi.

Whereas the inflammatory infiltrates of malignant melanoma have been widely investigated, little is known about the infiltrates accompanying benign melanocytic naevi. Using monoclonal antibodies directed against HLA-DR antigens, the CD1 antigen, the transferrin receptor and functionally divergent macrophage subpopulations, frozen fresh material of 87 melanocytic naevi (MN), ten primary cutaneous melanomas (PCM) and ten samples of normal skin were studied. Compared with normal skin, abundant HLA-DR+ cells were found in the stroma of MN equivalent to the quantity present in PCM. In MN we found higher numbers of dermal CD1+ dendritic cells compared with PCM and normal skin. There were more macrophages that expressed the transferrin receptor or the antigens 27E10, RM3/1 and 25F9 in MN than in normal skin but fewer than in PCM. No significant differences were found between congenital MN (n = 40), common acquired MN (n = 27) and dysplastic MN (n = 20) macrophage subpopulations. Also, no correlations were evident between macrophage infiltrates and naevus location or patients' age. Our data show that potential melanoma precursors among melanocytic naevi cannot be identified by the pattern of macrophage infiltrates.

Antigens, CD↗
PubMed1992

Clinical and pathologic diagnosis, staging and prognostic factors of melanoma and management of primary disease.

To increase detection of melanoma, medical practitioners and the general public should know the signs of early invasive melanoma. The Scottish Melanoma Group recently presented a revised checklist of the major and minor signs. The validity of the reported clinical and histopathologic criteria for the dysplastic nevus, a precursor to cutaneous melanoma, is not fully established. However, expert pathologists agreed on the use of major and minor criteria. The differential diagnosis between spindle-epitheloid cell nevi and melanoma remains problematic, because the former lesions often show cellular atypia. Other lesions that can cause considerable diagnostic difficulties are melanoma in situ and minimal-deviation melanoma. Immunohistochemical studies of human melanocytic lesions have contributed to the diagnosis of poorly differentiated tumors but, so far, have not helped in the discrimination among benign, premalignant, and malignant lesions. They have provided additional prognostic information in cases of primary melanoma and locoregional melanoma metastasis. Quality control of antibody reagents continues to be a problem. Microstaging of primary melanoma using Breslow depth and Clark's level of invasion may be subject to considerable intra- and interobserver variation. To improve the accuracy of the measurements, using a vernier scale is recommended. The type of melanoma is relevant in considering clinicopathologic prognostic factors. Acral melanoma (for example, that arise from glabrous skin) has been reported to carry a grave prognosis. Polypoid melanoma may have a less unfavorable outlook than previously thought. DNA cytophotometry provides prognostic information in case of primary melanoma but loses significance when stratified for tumor thickness. In patients with lymph node-positive melanoma, however, DNA ploidy analysis appears to yield additional prognostic information. In the management of primary disease, the width of the surgical excision and whether to approach the regional lymph nodes remain the main issues. A multicenter study conducted by the World Health Organization Melanoma Programme has found that a "narrow" excision is a safe procedure for primary melanomas not thicker than 1 mm. Several investigators underline the need for continued annual follow-up for all melanoma patients; recurrence may occur late. Currently, elective lymph node dissection is not recommended in the management of "thick" primary melanoma. Because data from randomized trials conducted in patients with a tumor of intermediate thickness are not yet available, only guidelines on management offered by experienced surgeons can be given. Patients with the dysplastic nevus syndrome should be closely followed so that melanomas can be diagnosed as early as possible.

Humans↗
PubMed1992

Human leukocyte antigen expression in renal cell carcinoma lesions does not predict the response to interferon therapy.

Human leukocyte antigen (HLA) classes I and II molecules are essential for antigen presentation to cytotoxic T cells and helper T cells, respectively. Consequently, they may play a role in anticancer immunotherapy as well. We studied whether the pretreatment HLA phenotype of the tumor is predictive for response to interferon immunotherapy in vivo. Therefore, renal cell carcinoma (RCC) primary tumor lesions from 31 patients treated with interferon-alpha and interferon-gamma (13 responders and 18 nonresponders) were analyzed retrospectively for HLA antigen expression with immunohistochemical methods. Furthermore, from eight patients, pretreatment metastatic lesions were examined. In the primary tumors HLA class I expression was high: in 26 of 30 lesions more than 50% cells were stained. HLA class II expression was mostly low: in 14 of 31 primary tumors less than 5% cells were stained. A significant correlation was found between HLA phenotype of primary tumors and corresponding metastases. There was no association between tumor HLA classes I and II antigen expression and clinical response to interferon therapy. In conclusion, pretreatment HLA phenotype of RCC has no predictive value for outcome of interferon immunotherapy. A role for treatment-induced changes in HLA expression in vivo, however, can not be excluded. These findings do not provide indications for the working mechanism of interferon immunotherapy in vivo.

Adult↗
PubMed1992

In situ detection of supernumerary aberrations of chromosome-specific repetitive DNA targets in interphase nuclei in human melanoma cell lines and tissue sections.

The use of non-radioactive in situ hybridization (ISH) with chromosome-specific repetitive DNA probes to study genomic changes, aneuploidy, and heterogeneity during melanocytic tumor progression, relies on its applicability to non-mitotic interphase nuclei, present in cell suspensions and tissue sections. Therefore, we studied the feasibility of detecting numerical aberrations with respect to the (peri-) centromere regions of chromosomes 1 and 7 in intact nuclei of two human melanoma cell lines with different metastatic behavior in nude mice. In addition, we used paraffin sections from xenograft lesions, obtained by inoculation of these cell lines in nude mice (subcutaneous tumors and spontaneous lung metastases). Paraffin sections from the original primary cutaneous melanoma (with a subepidermal and a dermal part) and two loco-regional metastases were also studied, one of which was the source for the cell lines. These cells and tissues represent examples of materials used in different approaches to the study of melanocytic tumor progression. Regarding the targeted sequences, ISH analysis showed that both cell lines were heterogeneous and aneuploid. The results correlated well with those obtained by ISH on metaphase spreads. Differences between the lines, which could not be detected by flow-cytometric or conventional karyotyping analysis, included data suggestive of a polyploid subpopulation and an extra copy of chromosome 7 in the metastasizing cell line. The polyploid population could be detected also in the paraffin sections of the corresponding subcutaneous xenografts and lung metastases in the mice. Both areas in the patients' primary melanoma could be evaluated separately and showed similar supernumerary aberrations of the chromosome-specific targets. These abnormalities matched those found in both metastases. Our results demonstrate that ISH can be used to visualize genomic abnormalities at the single-cell level in melanocytic nuclei in their natural context, which makes it a promising tool in the histopathology of melanocytic lesions and in the study of melanocytic tumor progression.

Aged↗
PubMed1992

Increasing epidermal growth factor receptor expression in human melanocytic tumor progression.

Different results have been reported on the expression of epidermal growth factor receptor (EGFR) in human melanocytic lesions, which may be due to different methodologic approaches. Therefore, we compared EGFR expression in six human melanoma cell lines by utilizing the monoclonal antibodies 2E9, 425, and 225, applying four immunocytochemical staining procedures. The results were compared with those obtained by a multiple point ligand binding assay. In addition, Northern blot analysis was performed. A three-step immunoperoxidase method using the monoclonal antibody 2E9 proved most sensitive. Staining intensities, estimated semiquantitatively, correlated well with the quantitative data obtained by the ligand-binding assay. Expression on the mRNA level was also in agreement with these results. Immunohistochemical staining of a large series of human cutaneous melanocytic lesions using the method selected showed differential EGFR expression in various stages of melanocytic tumor progression: 19% of common nevocellular nevi; 61% of dysplastic nevi, 89% of primary cutaneous melanomas, and 91% of melanoma metastases showed staining of the melanocytic cells. Intralesional heterogeneity of EGFR expression was present. Although the mean percentage of positive melanocytic cells in positive lesions did not increase with progression, mean staining intensity was stronger in malignant lesions compared to benign lesions. Ligand binding assays showed that EGFR expression in the highly metastasizing cell lines MV3 and BLM was at least 40 times higher than in the cell lines IF6, 530, M14, and Mel57, which do not or only sporadically metastasize after subcutaneous inoculation in nude mice. Although the differences between the various stages of progression are not absolute, we provide further evidence that EGFR expression increases in human melanocytic tumor progression.

Blotting, Northern↗
PubMed1992

Accessory function of endothelial cells in anti-CD3-induced T-cell proliferation: synergism with monocytes.

Monoclonal antibodies to CD3 can induce proliferation of resting T cells. In vitro this effect is dependent on the presence of monocytes. They serve as accessory cells providing a co-stimulatory signal after cross-linking of the antibody-coated TcR/CD3 complex by the Fc receptor on the monocytes. We have studied whether endothelial cells can replace monocytes with regard to this function. Highly purified T-cell preparations were cultured in the presence of anti-CD3 antibody, purified monocytes, and human umbilical vein endothelial cells. Anti-CD3 and endothelial cells alone were unable to support T-cell proliferation, due to lack of FcR expression. Addition, however, of as few as 1000 FcR+ monocytes (0.8% of the number of T cells present) to a coculture of T cells and endothelial cells (EC) in the presence of soluble anti-CD3 resulted in a strong proliferation of T cells. When anti-CD3 was presented in an immobilized form (coated to the culture well or to Sepharose beads), or when phytohaemagglutinin was added to the culture as a cross-linking agent, EC could support T-cell proliferation in the absence of any monocytes. We conclude that EC by themselves cannot support the proliferation of pure T cells induced by soluble anti-CD3, but are potent generators of the co-stimulatory signal(s). They provide a suitable starting material to further define this co-stimulatory activity.

Antigen-Presenting Cells↗
PubMed1991

The EORTC Melanoma Group exchange program: evaluation of a multicenter monoclonal antibody study.

In the framework of the European Organisation for Research and Treatment of Cancer (EORTC), the Immunology and Pathology Subgroups of the Malignant Melanoma Cooperative Group undertook a large multicenter monoclonal antibody (MAb) study. Fourteen laboratories from 7 European countries tested a panel of 23 MAbs for immunohistological staining reactivity for malignant and non-malignant lesions involving the melanocytic lineage. A standardized immunoperoxidase procedure was used and the results were evaluated using a standard protocol and data evaluation form developed in collaboration with the EORTC Data Center. According to this analysis, the antibodies in the panel could be classified into 3 main groups. The first group of MAbs includes those antibodies which stained the majority (greater than 80%) of all primary tumors, irrespective of their Breslow thickness and the majority of metastatic lesions. In addition, these MAbs stained a high percentage of cells within a given lesion. Several antibodies of Group I were likewise reactive with the majority of naevoblasts and with normal melanocytes. The second group of MAbs included antibodies reacting only with a limited number of primary melanomas and metastatic lesions. Antibodies of Group II reacted only weakly, if at all, with normal melanocytes or naevocytes. The percentage of cells within a malignant lesion stained by these MAbs was always rather low. The MAb group III detected surface structures whose expression appeared to be related to tumor progression; they did not react or reacted only weakly with naevi, and they all reacted with a small number of early primary melanomas (less than 0.75 mm). The number of lesions stained increased with increasing Breslow thickness. Our study suggests that the application of a panel of well defined MAbs might be of diagnostic and prognostic value in evaluating malignant melanoma.

Antibodies, Monoclonal↗
PubMed1991

Establishment and characterization of a human melanoma cell line (MV3) which is highly metastatic in nude mice.

To select human melanoma cells that are highly tumorigenic and metastatic in nude mice we have implanted fragments of a fresh human melanoma metastasis subcutaneously (s.c.) into a nude mouse. After 3 passages in nude mice, part of the xenograft was cultured and a new melanoma cell line, MV3, was established. After intravenous (i.v.) inoculation of 2 x 10(6) MV3 cells, 95% of the nude mice (n = 20) developed lung colonies within 6 weeks. S.c. inoculation of 2 x 10(6) MV3 cells resulted in 95% tumor take, while 90% of the mice (n = 20) showed spontaneous metastases in the lungs within 7 weeks. Histological and immunohistological features of the original tumor of the patient were largely retained in the tumors of the mice and in the cell line in vitro. As shown by Alcian blue staining, MV3 cells contain large quantities of glycosaminoglycans (GAGs) and/or proteoglycanes (PGs), both in vivo and in vitro. The cells showed a marked expression of transferrin receptor, ICAM-1, EGF-receptor, and VLA-2 integrin. As only few human melanoma cell lines are available that frequently show metastasis in nude mice, the highly metastatic MV3 cell line represents a useful tool for studying the expression and regulation of molecules on human melanoma cells involved in the process of metastasis.

Aged↗
PubMed1991

HLA antigen expression in routinely processed head and neck squamous cell carcinoma primary lesions of different sites.

HLA class I and II antigen expression in routinely processed head and neck squamous cell carcinoma (HNSCC) primary lesions was evaluated. Paraffin embedded samples from 66 squamous cell carcinomas and 7 verrucous carcinomas were studied immunohistochemically using recently developed anti-HLA class I monoclonal antibodies (MAbs) HC10 and HCA2, and anti-HLA-DR rabbit serum. Percent stained tumor cells were scored in 1 of 5 categories. The scores of 40 tumors were compared to the staining results obtained on frozen sections of the corresponding lesions, including those of the anti-class I MAb W6/32. High percentage-matched scores for paraffin and frozen sections were obtained, with HC10 vs. HC10, HC10 vs. W6/32, and anti-HLA-DR vs. anti-HLA-DR showing the best correlations. In the squamous cell carcinomas HLA class I expression was high (i.e., in 49/66 lesions more than 50% cells were stained), and correlated with the degree of differentiation, and inversely with the modified Jakobsson score. HLA class II expression (more than 5% cells stained) was found in 21/66 tumors and correlated inversely with the degree of differentiation. All verrucous carcinomas exhibited very high HLA class I expression, whereas class II was locally expressed in 5/7 lesions. Comparison of 4 subsites of HNSCC showed that carcinomas of the oral cavity had the highest HLA class I expression. This suggests susceptibility to CD8+ T cells, and together with the well developed submucosal lymphoid tissue, makes the oral cavity carcinomas probably well suited for local immunotherapeutic approaches in HNSCC.

Antibodies↗
PubMed1991

Immunohistochemical detection of proliferation and differentiation in discoid lupus erythematosus.

Discoid lupus erythematosus lesions show hyperkeratosis and atrophy, which may reflect abnormal epidermal proliferation, differentiation, or both. In this investigation, markers for epidermal proliferation, differentiation and inflammation were studied in cutaneous lesions of discoid lupus erythematosus. Frozen sections of biopsy specimens from 20 patients were examined immunohistochemically regarding Ki-67 staining and keratin 16 expression (parameters for proliferation), and the expression of keratin 10, involucrin, and filaggrin (parameters for differentiation). The inflammatory infiltrate was characterized with the use of antibodies against T lymphocytes, monocytes/macrophages, and Langerhans cells. With these markers, epidermal proliferation was found to be increased in discoid lupus erythematosus. Keratin 10 expression, a marker for early differentiation, showed the pattern of normal skin. Involucrin and filaggrin, markers for terminal differentiation, were expressed already in the lower part of the stratum spinosum, whereas in normal skin these markers were restricted to the stratum granulosum and the upper layers of the stratum spinosum, and the stratum granulosum and stratum corneum, respectively. Infiltrate analysis revealed the well-established picture. We conclude that in cutaneous lesions of discoid lupus erythematosus, hyperproliferation is combined with normal early differentiation and premature terminal differentiation of keratinocytes.

Adult↗
PubMed1991

Metastatic behavior of human melanoma cell lines in nude mice correlates with urokinase-type plasminogen activator, its type-1 inhibitor, and urokinase-mediated matrix degradation.

Five out of six human melanoma cell lines tested were able to degrade in vitro a smooth muscle cell extracellular matrix in a plasmin-dependent way. In three of these five cell lines, this process was mediated by tissue-type plasminogen activator (t-PA) and in the other two cell lines by urokinase-type plasminogen activator (u-PA). All melanoma cell lines produced t-PA mRNA and protein, whereas only the two cell lines showing u-PA-mediated matrix degradation produced u-PA mRNA and protein. These latter cell lines also produced plasminogen activator inhibitor type-1 (PAI-1) and type-2 (PAI-2) mRNA and protein. u-PA receptor (u-PA-R) mRNA and binding of radiolabeled u-PA was found in all melanoma cell lines. The metastatic capacity of these cell lines was studied in nude mice. All cell lines were able to develop primary tumors at the subcutaneous inoculation site. The production of plasminogen activators, their inhibitors and urokinase receptor by subcutaneous tumors corresponded with the production by the parental cell lines in vitro. The two u-PA and PAI-1 producing cell lines showed the highest frequency to form spontaneous lung metastases after subcutaneous inoculation, whereas five of the six cell lines formed lung colonies after intravenous inoculation. In conclusion, u-PA mediated matrix degradation in vitro and production of u-PA and PAI-1 by human melanoma cell lines correlated with their ability to form spontaneous lung metastasis in nude mice. No correlation was found with the ability to form lung colonies after intravenous injection. These findings suggest a role for u-PA and PAI-1 in a relatively early stage of melanoma metastasis.

Animals↗
PubMed1991

Clinical and immunopathological results of a phase II study of perilymphatically injected recombinant interleukin-2 in locally far advanced, nonpretreated head and neck squamous cell carcinoma.

Fifteen patients with locally far advanced, nonpretreated head and neck squamous cell carcinoma were treated with low-dose recombinant interleukin-2, using 10 daily perilymphatic injections. The therapy was well tolerated. No tumor regression was observed. Tumor biopsies were taken before and after treatment. Histopathological studies including evaluation of the mononuclear cell infiltrate and immunohistochemical detection of human leukocyte antigen (HLA) expression on tumor cells were performed. HLA class I was not detectable in 1 of 10 samples, and HLA class II expression was seen in 2 of 10 samples. As compared to pretreatment biopsies, no changes were found after treatment. This is in agreement with the lack of a clinical response.

Adult↗
PubMed1991

Antiperinuclear factor, a marker autoantibody for rheumatoid arthritis: colocalisation of the perinuclear factor and profilaggrin.

The antiperinuclear factor, an autoantibody specific for rheumatoid arthritis, was found in 51/63 (81%) patients with rheumatoid arthritis by indirect immunofluorescence on human buccal mucosa cells. The sensitivity of the antiperinuclear factor test was increased by pretreating the buccal mucosa cells with 0.5% Triton-X100. The specificity of the test for rheumatoid arthritis as compared with control serum samples was maintained. The localisation of the perinuclear factor in the keratohyalin granules of the buccal mucosa cells was verified by immunoelectron microscopy. The perinuclear factor was found to be an insoluble protein whose antigenicity was sensitive to various fixation procedures. In serum samples from patients with rheumatoid arthritis there was a positive correlation between the presence of antiperinuclear factor and the presence of the so called antikeratin antibodies as detected by immunofluorescence on unfixed rat oesophagus cryostat sections. No relation was found between the presence of the perinuclear factor and either the rheumatoid factor, Epstein-Barr virus components, or any cytokeratin. By double immunofluorescence an exact colocalisation of the perinuclear factor and profilaggrin was found. Although the precise biochemical identity of the perinuclear factor remains unclear, our results suggest that it is a protein only present in the fully differentiated squamous epithelial cell layer.

Antibodies, Antinuclear↗
PubMed1991

Differential expression of markers for endothelial cells, pericytes, and basal lamina in the microvasculature of tumors and granulation tissue.

The structure and function of the tumor microvasculature is of great interest for cancer biology, diagnosis, and therapy. The distribution of endothelial cells, pericytes, and basal lamina in tumors is not well documented. In this study, the authors investigated the distribution of markers for these different components in a series of malignant human tumors and in human granulation tissue, both situations with extensive angiogenesis. Their results show a striking heterogeneity in the expression of markers for pericytes and endothelial cells between different tumors, but also within a single tumor lesion. To be able to distinguish between these two adjacent cell types decisively, all marker studies were carried out both on the light and the electron microscopical level and compared with staining results in granulation tissue of cutaneous wounds in healthy volunteers and of decubitus lesions. In granulation tissue of decubitus lesions, well-defined zones with increasing levels of maturation can be delineated. It was found that antibodies recognizing von Willebrand factor often failed to stain the tumor capillaries. Of the pericyte markers, alpha-smooth muscle actin was only locally expressed by pericytes in the tumor vasculature, whereas the high-molecular-weight melanoma-associated antigen, a chondroitin sulfate proteoglycan, stained the microvasculature broadly. Staining of the basal lamina components collagen type IV and laminin was, within the tumor, not restricted to the microvasculature. From their findings the authors conclude that 1) for the visualization of the tumor vasculature, antibodies recognizing endothelial markers, especially monoclonal antibodies PAL-E and BMA 120, are preferable to those recognizing pericytes or basal lamina; 2) within the microvasculature of tumors and granulation tissue, a heterogeneity of expression of endothelial and pericyte markers is observed; 3) during the formation of granulation tissue, all three microvascular components can be demonstrated already in the histologically earliest stage, suggesting not only an involvement of endothelial cells but also of pericytes and basal lamina in the initial steps of angiogenesis in wound healing.

Adult↗
PubMed1991

Cytokeratin expression patterns in metastatic transitional cell carcinoma of the urinary tract. An immunohistochemical study comparing local tumor and autologous metastases.

The cytokeratin (CK) expression patterns of local, ie, primary or recurrent, high-grade-malignant transitional cell carcinomas (TCCs) of the human urinary tract and autologous lymphogenic and hematogenic metastases (n = 33) were compared. Special attention was paid to CK expression in the tumor invasion front and other areas where tumor-stroma interaction occurred to visualize cell populations with a metastatic phenotype. For this purpose, polypeptide-specific monoclonal antibodies to CKs 4, 7, 8, 10, 13, 14, 16, 17, 18, and 19 were used, employing the immunoperoxidase method. Results show that: 1) An increased expression of CK8 and CK18 is seen in the TCC tumor cells at the interface with peritumoral stroma in the tumor invasion front and with intratumoral stroma ('interface phenomenon'). Other than reflecting a quantitative change, this phenomenon might be explained by unmasking of CK8 and CK18 epitopes occurring in these regions. 2) Although in general the expression of CK13 in local TCC is decreased with increase of histopathologic parameters for progression, ie, grade and stage, an extensive proportion of CK13-positive tumor cells still can be found in some TCCs, even in metastases. 3) Morphologically recognizable types of aberrant differentiation in TCC, i.e., pseudosarcomatous or squamous differentiation and marked loss of differentiation, show altered expression of many of the CKs studied.

Carcinoma, Transitional Cell↗