Cell cycle dysregulation is prerequisite for cancer formation. However, it is unknown whether the mode of dysregulation affects disease characteristics. Here, we conduct comprehensive analyses of cell cycle checkpoint dysregulation using patient data and experimental investigations.
View Article and Find Full Text PDFObjective: To evaluate the accuracy of the AutoPap System (TriPath Imaging, Inc., Burlington, North Carolina, U.S.
View Article and Find Full Text PDFDifferentiation therapy is an attractive option for malignant melanoma, as traditional forms of chemotherapy seem to have little effect on this type of tumour. Among the several pathways for the experimental induction of differentiation of melanoma, we have focused on signal transduction mediated by protein kinases. We have examined the effects of calphostin C (a protein kinase C inhibitor), genistein and methyl 2,5-dihydroxycinnamate (tyrosine kinase inhibitors), and exogenous phosphotyrosine (an activator of protein tyrosine phosphatases) on the growth, morphology and differentiation of malignant melanomas in vitro.
View Article and Find Full Text PDFThe expression by melanomas of multiple antigens that are recognized by specific MHC class I-restricted CTLs has been clearly demonstrated. The goal of many immunotherapy protocols being developed is, therefore, the induction and/or augmentation of CTLs specific for such antigens. One approach has been to immunize using irradiated autologous melanoma cells.
View Article and Find Full Text PDFThe MAGE-1 gene codes for tumor-associated peptides recognized by cytolytic T lymphocytes in association with MHC-class-1 molecules such as HLA-A1 and HLA-Cw16. In the course of a study aiming at the immunohistochemical detection of the MAGE-1 gene product in tumor samples, 2 mouse monoclonal antibodies (MAbs) directed against a full-length recombinant MAGE-1 fusion protein were found to react strongly not only with the 46-kDa MAGE-1 protein, but also with a 72-kDa product in immunoblots of lysates obtained from several MAGE-1-mRNA-positive melanoma cell lines. Pre-incubation of the antibodies with the recombinant MAGE-1 fusion protein abolished their reactivity both with MAGE-1 protein and with the 72-kDa product, thus confirming the occurrence of antigenic determinant(s) shared by the 2 proteins.
View Article and Find Full Text PDFHuman genes MAGE-1 and MAGE-3 code for antigens that are recognized on melanoma cells by autologous cytolytic T lymphocytes. These antigens may constitute useful targets for specific anti-tumor immunization of cancer patients, since genes MAGE-1 and MAGE-3 are expressed in a number of tumors of different histological types, but are not expressed in normal adult tissues other than testis. This also applies to genes MAGE-2 and MAGE-4, which are closely related to MAGE-1 and MAGE-3.
View Article and Find Full Text PDFLocal administration of high-dose r-TNF alpha with IFN gamma in the limbs of melanoma patients has proved to be a very promising treatment. To understand the role played by the effect of TNF on melanoma cells in tumor destruction, we have investigated the expression of TNF-receptors in melanoma cells using monoclonal antibodies specific for the type-A (75-kDa) and the type-B (55-kDa) TNF receptors. Flow cytometric analysis of cultured melanoma cells indicated the presence of both types of receptor.
View Article and Find Full Text PDFBalb/c mice were immunized with cells from the mouse mastocytoma line P815 transfected with an HLA-A1 gene. The splenocytes of the immunized mice were fused with cells from the murine myeloma NS-1. In an initial screening, supernatants of growing cultures were tested for their binding capacity to the immunizing P815/A1+ cells as well as to P815/A2+ cells.
View Article and Find Full Text PDFThe reactivity spectrum of an anti-CALLA/CD10 monoclonal antibody for cutaneous melanoma was analysed by immunohistochemistry in a series of lesions of different Breslow thickness. Similar proportions of small primary tumours, advanced primary tumours and metastatic lesions were found to express CALLA/CD10 (31-47%). However the proportion of stained cells within a given lesion increased with tumour progression.
View Article and Find Full Text PDFBackground: A number of experimental studies have substantiated changes in angiogenesis and in laminin/laminin-receptor interactions during tumorigenesis and tumor progression. However, these observations have never been verified objectively in tissues from a well-defined model of tumor progression.
Methods: Tissues from 97 proliferative lesions of the melanocyte lineage defining distinct steps in tumor progression were investigated immunohistochemically for changes in angiogenesis and expression of the laminin receptor (67-kilodalton molecule).
In order to investigate the effects of in vivo treatment with interferon-alpha (IFN-alpha) on melanoma antigens, a clinical EORTC trial (No. 18852) was accompanied by an immunohistological study. Twenty patients with melanoma metastases of skin and soft tissues, eventually also of the lung, who were treated with systemic IFN-alpha, were evaluated for a comparison of metastases before (40) and during (42) treatment.
View Article and Find Full Text PDFMelanoma cells can secrete several cytokines and express various cell surface molecules, such as the intercellular adhesion molecule ICAM-1, class II histocompatibility antigens, and the CALLA antigen, typically found in cells of the immune system. We have investigated the possible expression of interleukin-2 (IL-2) receptors in melanoma using monoclonal antibodies specific for the p55/alpha chain (TAC antigen) and the p75/beta subunit. Flow cytometric analysis of cultured melanoma cells showed the presence of low levels of the TAC antigen and of the beta chain on the surface of several cell lines.
View Article and Find Full Text PDFThe pyrogenic (erythrogenic) exotoxins A and C (SPEA and SPEC) of Streptococcus pyogenes belong to the family of mitogenic toxins of which the staphylococcal enterotoxins are the prototypes. The erythrogenic toxin B (SPEB) is a proteinase precursor. All SPE have been reported to be superantigens.
View Article and Find Full Text PDFCurr Opin Oncol
March 1993
T lymphocytes specifically recognizing autologous tumor cells in vitro can be generated from melanoma patients. Recognition of tumor cells by both CD4 and CD8 lymphocytes is mediated through the T-cell receptor and is restricted by HLA antigens. Although HLA-A2 has been identified as a restricting allele for many melanoma-specific cytotoxic T lymphocytes, T cells directed against antigens unique to each patient's tumor as well as antigens common to melanomas from unrelated individuals can be restricted by several different HLA alleles.
View Article and Find Full Text PDFCell Mol Biol (Noisy-le-grand)
February 1993
A five min. incubation of peripheral blood mononuclear cells (PBMN) with either phytohaemagglutinin (PHA) or concanavalin A (ConA) resulted in distinct subcellular redistribution patterns of phosphatidylinositol 4,5-bisphosphate phospholipase C [PtdIns(4,5)P2-PLC] and myo-inositol 1,4,5-trisphosphate monophosphatase [Ins(1,4,5)P3-monophosphatase] activities. When compared to control cells, PHA-treated PBMN cells displayed a significant increase of PtdIns(4,5)P2-PLC and Ins(1,4,5)P3-monophosphatase relative specific activities in the nuclear fraction along with an increment (D) in enzyme amount of 6.
View Article and Find Full Text PDFThe serum protein lipopolysaccharide (LPS)-binding protein (LBP) seems to play an important role in regulating host responses to LPS. Complexes of LPS and LBP form in serum and stimulate monocytes, macrophages, or polymorphonuclear leukocytes after binding to CD14. Previous reports have described the structure and properties of LBP from human and rabbit sera.
View Article and Find Full Text PDFActa Neurochir (Wien)
July 1993
The present study demonstrates interleukin-1 (IL-1) production by human glioblastoma cells both in vitro and in vivo. The presence of IL-1 alpha and IL-1 beta transcripts was analyzed in 4 cell lines. IL-1 alpha mRNA was expressed constitutively in one cell line whereas constitutive IL-1 beta mRNA could not be detected in any of the cell lines.
View Article and Find Full Text PDFJ Lipid Mediat
September 1992
A monoclonal antibody, B66.6, previously classified in the cluster of differentiation 4 (CD4), has been studied and compared with another CD4 monoclonal antibody, IOT4. It was found that B66.
View Article and Find Full Text PDFThe reactivity of four monoclonal antibodies (MAbs) directed against IFN-gamma inducible antigens with melanocytic cells was investigated in the course of local and systemic tumor progression of human malignant melanoma. Frozen sections of histologically defined melanocytic tissues at different stages of progression were stained with these MAbs using an indirect immunoperoxidase technique. The reactivity of MAbs Me15/B3 and Me15/F9, directed against two different epitopes of a 90-kDa molecule, was found to correlate with melanoma progression.
View Article and Find Full Text PDFSeveral studies have shown that melanoma-associated gangliosides are immunogenic in melanoma patients and that antibodies against them have a favorable prognostic effect. Our study aims at characterizing the humoral immune response in disease-free, advanced melanoma patients vaccinated with a total ganglioside fraction extracted from pooled metastases of human melanoma, containing as major gangliosides GM3 and GD3, and as minor ones GM2 and GD2. Prior to vaccination, all patients were made disease-free by surgical removal of skin, lymph-node or other distant metastases.
View Article and Find Full Text PDFDuring the development and testing of a radioreceptor assay (RRA) for human IL-1, we have detected and identified the presence of auto-antibodies to IL-1 in normal human plasma (NHP). The RRA is based on the competition between human 125I-labeled rIL-1 alpha and standard or unknown quantities of IL-1 alpha or IL-1 beta for binding to a limited amounts of IL-1 receptor (IL-1R) isolated from the EL4 mouse thymoma cell line. NHP from 20 out of 100 unselected blood donors were found to completely inhibit the binding of 125I-labeled IL-1 alpha to its receptor, suggesting the presence in these NHP samples of either abnormal amounts of IL-1 or of a factor binding to the 125I-labeled IL-1 alpha.
View Article and Find Full Text PDFThe human melanoma-associated antigen identified by the monoclonal antibody (mAb) Me14-D12 is a cell surface protein whose expression is induced by interferon-gamma (IFN-gamma). We have recently reported the molecular cloning of a genomic probe specific for the gene and mRNA of this protein. By screening with the genomic probe, we have now isolated a full length 3.
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