myelin-basic-protein and Lung-Neoplasms

Human brain myelin basic protein (MBP) distributes in nervous system and other tissues extensively, and can be detected in many kinds of tumor cells, such as lung cancer, breast cancer, and neuroglioma. However, it has not been reported whether MBP is relevant to the activity of neural invasion of tumors and whether MBP plays a role in biological behaviors of human lung cancer cells. This study was to investigate the inhibitory effect of MBP on hydrogen peroxide (H2O2)-induced apoptosis of human lung cancer cell line YTLMC-90.. YTLMC-90 cells were transfected with plasmid pSVCEPMBPCAT containing MBP cDNA minigene (test group), or empty vector pSVCEPCAT, or received no transfection (control group), and exposed to H2O2. The expression of MBP in YTLMC-90 cells was detected by Western blot. Cell proliferation was measured by MTT assay. The morphologic and ultra-structural changes of apoptotic cells were observed by microscopy with fluorescent staining of acridine orange (AO) and electron microscopy. The DNA fragmentation was examined by agarose gel electrophoresis.. After exposed to 200 micromol/L H2O2 for 24 h, the inhibitory rate of cell growth was significantly lower in test group than in empty vector group and control group (36.67% vs. 78.67% and 84.00%, P<0.001). The morphologic and biochemical changes of apoptotic cells, such as shrinkage of cytoplasm and nucleus, fragmentation of chromatin, and ladder pattern of DNA, were commonly observed in cells in control group, but these apoptotic features were not discovered in test group.. MBP markedly inhibits H2O2 cytotoxicity to YTLMC-90 cells through promoting cell proliferation and antagonizing H2O2-induced apoptosis.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; DNA Fragmentation; DNA, Complementary; Humans; Hydrogen Peroxide; Lung Neoplasms; Myelin Basic Protein

The significance of neurospecific proteins in the diagnosis of neurotoxicity in patients with breast, lung, testicular, and ovarian cancer treated by taxane and cisplatin drugs was evaluated. The most pronounced increase in the content of these proteins and titers of autoantibodies to these proteins was observed in patients with clinical manifestations of neurotoxicity induced by cytostatics. A strong correlation was found between the concentration of myelin basic protein and cumulative dose of the drug (R=0.922; p<0.0001). These data suggest that myelin basic protein and gliofibrillar acid protein can be used as markers in the diagnosis and monitoring of antitumor drug neurotoxicity.

Topics: Antineoplastic Agents; Autoantibodies; Breast Neoplasms; Cisplatin; Dose-Response Relationship, Drug; Female; Glial Fibrillary Acidic Protein; Humans; Lung Neoplasms; Male; Myelin Basic Protein; Neurons; Ovarian Neoplasms; Testicular Neoplasms; Time Factors

Several non-small cell lung carcinomas (squamous cell carcinomas and adenocarcinomas) were analyzed for protein kinase activity. Soluble protein extracts derived from these tumors and from the lung parenchyma adjacent to the tumors were resolved by Mono Q anion exchange chromatography, and the fractions were assayed for phosphotransferase activity towards in vitro substrates. Myelin basic protein, casein, and a ribosomal S6-1 COOH-terminus peptide were efficient substrates for protein kinases that exhibited elevated phosphotransferase activity in the tumor extracts when compared to extracts derived from the adjacent nonneoplastic lung or from the lung parenchyma from patients with nonneoplastic lung disorders. Casein phosphotransferase activity was resolved into two peaks that eluted at 0.44 M NaCl and 0.56 M NaCl. The second peak was identified as casein kinase 2, based upon immunoreactivity to casein kinase 2-specific antipeptide antibodies and its sensitivity to inhibition by heparin sulfate. Myelin basic protein phosphotransferase activity eluted at 0.44 M NaCl, but Western blot analysis revealed that this could not be ascribed to mitogen-activated protein (MAP) kinases. This tumor associated protein kinase, designated p40TAK, exhibited a molecular mass of approximately 40 kDa upon gel filtration. In addition to myelin basic protein, it phosphorylated S6 peptide analogues and histone H1 on seryl residues. Like casein kinase 2, p40TAK exhibited elevated basal phosphotransferase activity in squamous cell carcinomas and adenocarcinomas of the lung when compared to the nonneoplastic lung parenchyma adjacent to the tumor.

Topics: Adenocarcinoma; Amino Acid Sequence; Antibodies; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Casein Kinases; Caseins; Chromatography, Ion Exchange; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Humans; Kinetics; Lung; Lung Neoplasms; Molecular Sequence Data; Myelin Basic Protein; Peptides; Phosphoserine; Phosphothreonine; Phosphotyrosine; Protein Kinases; Protein Serine-Threonine Kinases; Ribosomal Protein S6; Ribosomal Proteins; Substrate Specificity; Tyrosine

Monoclonal antibody was prepared against myelin basic protein a so-called pancarcinoma antigen. After labelling with 131I the monoclonal antibody was injected into Lewis-lung cancer mice and rats with Walker breast cancer. Two, 24, 48, 72 and 96 hours after the labelled monoclonal antibody injection, radioimmunoimaging studies were carried out. After each gamma-camera study, organ distribution of the labelled monoclonal antibody was determined with radiobioassay technique which showed significantly higher activity in the tumour tissue than in healthy ones. Significant sample radioactivity could be recovered in the tumour masses 48 hours after injection, which persisted even after 96 hours. The later finding might enable diagnosing types of malignancy with isotope-labelled monoclonal antibody against myelin basic protein.

Topics: Animals; Antibodies, Monoclonal; Carcinoma; Iodine Radioisotopes; Lung Neoplasms; Mice; Mice, Inbred C57BL; Myelin Basic Protein; Neoplasm Transplantation; Radionuclide Imaging; Rats; Rats, Inbred Strains; Time Factors

Topics: Carcinoma, Small Cell; Creatine Kinase; Humans; Isoenzymes; Lung Neoplasms; Myelin Basic Protein; Nervous System Neoplasms

Tumors from two patients with carcinomatous neuropathy were studied with an immunohistochemical method using anti-myelin basic protein (anti-MBP) sera. In both cases, immunoreactive MBP was clearly demonstrated in some of the tumor cells, which were widely distributed either singly or, more often, in clusters. The staining intensity varied from cell to cell. An autoimmune mechanism to nervous elements has been suggested in the pathogenesis of carcinomatous neuropathy. MBP is known to be a highly specific and potent antigen that can induce allergic neuritis in animals. In one patient the progressively worsening neurologic condition rapidly improved after gastrectomy removed the carcinoma. It is possible that immunoreactive MBP in tumor cells may function as an "antigen" in the development of carcinomatous neuropathy.

Topics: ACTH Syndrome, Ectopic; Adenocarcinoma; Aged; Autoimmune Diseases; Humans; Lung Neoplasms; Male; Myelin Basic Protein; Neoplasm Proteins; Peripheral Nervous System Diseases; Stomach Neoplasms

Leucocytes from 4 cancer patients showed cellular reactivity in the leucocyte adherence inhibition (LAI) assay in the presence of the synthetic encephalitogenic peptide of human myelin basic protein. All patients exhibited reactivity at a peptide concentration of 500 ng/ml. Leucocytes from 4 non-cancer patients failed to react. Suppression of LAI was detected in all 4 cancer patients by adding their serum to reactive mixtures containing peptide and autologous leucocytes. Each serum was subjected to column chromatography on Sephacryl S-200 to determine the molecular weight distribution of suppressive (blocking) factors. The greatest suppression was found in all cases within the range 90-155 kdalton.

Topics: Aged; Antigens, Neoplasm; Female; Humans; Immunity, Cellular; Immunologic Techniques; Intestinal Neoplasms; Leukocyte Adherence Inhibition Test; Lung Neoplasms; Lymphocytes; Middle Aged; Myelin Basic Protein; Neoplasms; Ovarian Neoplasms; Urinary Bladder Neoplasms

Leukocyte migration tests under agarose (Clausen technique) were performed in 28 patients tentatively diagnosed as having any malignancy with the use of a 3 M KCl-extract panel prepared from bronchogenic, gastric, colonic, renal, and mammary carcinoma, corresponding normal tissues, carcinoembryonic antigen (CEA), and human encephalitogenic protein (HEP). 17 out of 22 proven carcinoma patients showed sensitization by reaction with optimal concentrated KCl-extract of cancer from the same organ type as their own tumor. In some cases positive reactions could be observed also with normal tissue antigen (NTA) of tumor organ type (7/22) or with an additional carcinoma extract of organ type differing from patients own primary tumor (8/22). Gastrointestinal carcinomas, especially, showed sensitization to CEA (7/12) contrary to nongastrointestinal carcinomas (1/10). With HEP no positive reactivity could be found (0/10). With the use of tumor antigen panel (5 antigens) only few positive reactions (MI less than 0.80 or greater than 1.20) could be observed in 6 patients with nonmalignant diseases (1/30 tests) and 8 healthy blood donors (1/40 tests). A widespread individual screening program using tissue antigens for patients suspected of malignancies could give a pattern of reactivities and improve the recognition of cell-mediated sensitization against tumor tissues.

Topics: Aged; Antigens, Neoplasm; Breast Neoplasms; Carcinoembryonic Antigen; Cell Migration Inhibition; Colonic Neoplasms; Epitopes; Female; Humans; Immunity, Cellular; Kidney Neoplasms; Leukocytes; Lung Neoplasms; Male; Middle Aged; Myelin Basic Protein; Neoplasms; Sepharose; Stomach Neoplasms

The specific lymphocyte sensitization of patients with malignant diseases against a basic protein, isolated from human brain, was studied by the lymphocyte migration inhibition technique. A sensitization of lymphocytes of cancer patients against this encephalitogenic factor (EF) was first reported by FIELD and CASPARY in 1970. Their test system was the Macrophage-Electrophoretic-Mobility-Test (MEMT). In 17 out of 18 patients with malignant disease we found a specific inhibition or enhancement of the migration area of lymphocytes more than 15%.

Topics: Carcinoma, Bronchogenic; Cell Migration Inhibition; Humans; Intestinal Neoplasms; Lung Neoplasms; Lymphocyte Activation; Lymphoma; Macrophages; Male; Melanoma; Myelin Basic Protein; Neoplasms; Stomach Neoplasms

Topics: Amyotrophic Lateral Sclerosis; Antigens, Viral; Brain; Brain Neoplasms; Cell Migration Inhibition; Female; Gastrointestinal Neoplasms; Glioma; Humans; Immunity, Cellular; Infarction; Leukocytes; Lung Neoplasms; Meningioma; Methods; Multiple Sclerosis; Myelin Basic Protein; Peptides; Polysaccharides