myelin-basic-protein and Neoplasm-Metastasis

Immunofluorescence and immunoperoxidase (peroxidase-antiperoxidase, PAP) techniques for the demonstration of neural and non-neural cell markers are contributing greatly to increase the diagnostic accuracy of difficult tumors of the central nervous system. Well characterized nervous system markers include glial fibrillary acidic (GFA) protein, the three protein subunits of neurofilaments, neuron-specific enolase (NSE), myelin basic protein, and S-100 protein. The most important and reliable of these is GFA protein, which is widely in use for the immunohistochemical diagnosis of tumors of the glioma group. Its many practical applications are reviewed and illustrated. Other neural markers, in particular the specificity of NSE and S-100 protein, need to be critically evaluated. Problems related to the immunohistochemical diagnosis of central neuroepithelial tumors of putative neuroblastic origin remain complex and still need to be resolved. Non-neural markers, such as vimentin, desmin, cytokeratins, Factor VIII, alpha-fetoprotein, human chorionic gonadotropin, and immunoglobulins have well defined, although more restricted, applications in surgical neuropathology.

Topics: alpha-Fetoproteins; Antibodies, Monoclonal; Antigens; Carcinoma; Central Nervous System Diseases; Chorionic Gonadotropin; Cytoskeleton; Desmin; Factor VIII; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Histocytochemistry; Humans; Immune Sera; Immunoenzyme Techniques; Immunoglobulins; Intermediate Filament Proteins; Keratins; Lymphoma; Medical Oncology; Meningeal Neoplasms; Myelin Basic Protein; Neoplasm Metastasis; Neoplasms; Neoplasms, Germ Cell and Embryonal; Neurology; Oligodendroglia; Phosphopyruvate Hydratase; S100 Proteins; Sarcoma; Vascular Diseases; Vimentin; von Willebrand Factor

Two characteristics of highly malignant cells are their increased motility and secretion of proteinases allowing these cells to penetrate surrounding basement membranes and metastasize. Activation of 21-kDa activated kinases (PAKs) is an important mechanism for increasing cell motility. Recently, we reported that binding of receptor-recognized forms of the proteinase inhibitor alpha2-macroglobulin (alpha2M*) to GRP78 on the cell surface of 1-LN human prostate cancer cells induces mitogenic signaling and cellular proliferation. In the current study, we have examined the ability of alpha2M* to activate PAK-1 and PAK-2. Exposure of 1-LN cells to alpha2M* caused a 2- to 3-fold increase in phosphorylated PAK-2 and a similar increase in its kinase activity toward myelin basic protein. By contrast, the phosphorylation of PAK-1 was only negligibly affected. Silencing the expression of the GRP78 gene, using either of two different mRNA sequences, greatly attenuated the appearance of phosphorylated PAK-2 in alpha2M*-stimulated cells. Treatment of 1-LN cells with alpha2M* caused translocation of PAK-2 in association with NCK to the cell surface as evidenced by the co-immunoprecipitation of PAK-2 and NCK in the GRP78 immunoprecipitate from plasma membranes. alpha2M*-induced activation of PAK-2 was inhibited by prior incubation of the cells with specific inhibitors of tyrosine kinases and phosphatidylinositol 3-kinase. PAK-2 activation was accompanied by significant increases in the levels of phosphorylated LIMK and phosphorylated cofilin. Silencing the expression of the PAK-2 gene greatly attenuated the phosphorylation of LIMK. In conclusion, we show for the first time the activation of PAK-2 in 1-LN prostate cancer cells by a proteinase inhibitor, alpha2-macroglobulin. These studies suggest a mechanism by which alpha2M* enhances the metastatic potential of these cells.

Topics: Actin Depolymerizing Factors; Actins; alpha-Macroglobulins; bcl-Associated Death Protein; Carrier Proteins; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cytoskeleton; Endoplasmic Reticulum Chaperone BiP; Enzyme Activation; Enzyme Inhibitors; Gene Expression Regulation, Neoplastic; Gene Silencing; Heat-Shock Proteins; Humans; Immunoprecipitation; Lim Kinases; Male; Microfilament Proteins; Models, Biological; Molecular Chaperones; Myelin Basic Protein; Neoplasm Metastasis; p21-Activated Kinases; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Binding; Protein Isoforms; Protein Kinases; Protein Serine-Threonine Kinases; Protein Transport; rac GTP-Binding Proteins; RNA, Double-Stranded; RNA, Messenger; Signal Transduction; Time Factors; Transfection

Theoretical aspects are considered on the requirements of immunological cancer tests. The criteria of clinical applicability are: Specificity, sensitivity, information with respect to tumour localisation. Immunodiagnostic tests cover the following areas: Early diagnosis on the basis of screening of the whole population or of risk groups, differential diagnosis, detection of relapse or metastases, prognosis. Experimental results are presented on a test for tumour detection. In a blind test study patients with clinically manifest tumours were recognized in about 80--90%, when using human fetal extract as antigen in the macrophage-electro-phoretic-mobility technique.

Topics: Antigens; Diagnosis, Differential; Fetus; Humans; Macrophages; Mass Screening; Myelin Basic Protein; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Prognosis; Serologic Tests; Tissue Extracts

The frequency of bronchial carcinoma has increased significantly during the last five years. The prognosis depends very much on early diagnosis. With non-invasive methods the diagnosis can often not be certified and the dignity of a tumor can often not be judged preoperatively. With the EMT a differentiation between malignant and non-malignant pulmonary diseases is possible. The EMT is an in vitro cancer test to detect specific sensitised lymphocytes. After incubation with the encephalitogenic factor (EF) lymphocytes of patients with malignant diseases release a factor that slows the mobility of tanned and sulphosalicylic-acid stabilised sheep erythrocytes (ETS) in an electrical field. 96 patients with pulmonary diseases were checked; all malignant pulmonary diseases but one showed an inhibition of the ETS mobility, while the controls showed an acceleration; in the groups with benign pulmonary diseases most patients showed an acceleration, only in sarcoidosis in four out of twelve patients a slight ETS inhibition was registered. The differences between both groups are significant (p less than 0.001). The EMT differentiates reliably in malignant and non-malignant diseases. False-negative results are obtained during radiation and chemotherapy. In connection with other diagnostic aids the EMT is a valuable diagnostic method, by which the early cancer detection can be improved and the prognosis of the patients bettered significantly.

Topics: Animals; Bronchial Neoplasms; Diagnosis, Differential; Electrophoresis; Erythrocytes; Humans; Lymphocytes; Lymphoma; Myelin Basic Protein; Neoplasm Metastasis; Sarcoidosis; Sheep

The macrophage electrophoretic mobility (MEM) test was performed on guinea-pig macrophages treated with the interaction products of encephalitogenic protein and peripheral lymphocytes from 44 patients with colorectal cancer and 33 "healthy" controls. In 54/60 tests involving patients, statistically significant reductions in electrophoretic mobilities were observed, compared with 12/33 in controls. Our overall results on the reductions in macrophage mobilities by lymphocyte products are in accord with the work of some other workers, but not all. In contrast to many other studies, the standard procedures used here to express the results should permit an exchange of data on an international basis and allow a more rapid, general appraisal of the MEM test.

Topics: Adult; Aged; Animals; Cell Movement; Colonic Neoplasms; Electrophoresis; Female; Guinea Pigs; Humans; Lymphocytes; Macrophages; Male; Middle Aged; Myelin Basic Protein; Neoplasm Metastasis; Rectal Neoplasms