myelin-basic-protein and Adenocarcinoma

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

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

After incubation with an encephalitogenic factor from human (HEF) or rat (REF) brain, lymphocytes of Fischer 344 rats bearing a spontaneous mammary adenocarcinoma produced a soluble substance which reduced the mobility of tanned sheep red blood cells in the electrophoretic mobility test (EMT). For studying the kinetics of this lymphocyte response, 6 X 10(5) tumor cells were injected into the hind footpad. In correlation with time and tumor size, one was able to influence the appearance of metastases by amputation of the leg. As early as 16 hours after inoculation of tumor cells, sensitivity of lymphocytes against HEF and a KCl-extract of the tumor could be shown in the EMT. It decreased on days 2 and 5, but was still seen until the day of amputation. Rats without metastases showed sensitivity up to four weeks after amputation and then returned to normal levels. Rats with metastases showed sensitivity until death at about seven weeks later. With the use of Amicon membranes, Sephadex G-50, and ion-exchange chromatography, a protein could be isolated from human basic myelin extract with a molecular weight of about 16,000-20,000 daltons. It had no direct influence on the EIC by itself, but after incubation with lymphocytes from tumor-bearing rats it evoked the production of a slowing substance. Using Sephadex G-100, the slowing substance appeared in the region in front of BSA indicating a molecular weight of greater than 80,000 daltons. It was heat-stable for 30 min at 56 degrees C and was sensitive to trypsin.

Topics: Adenocarcinoma; Amputation, Surgical; Animals; Antigens; Chemical Fractionation; Dose-Response Relationship, Immunologic; Electrophoresis; Female; Humans; Kinetics; Lymphocytes; Macrophages; Mammary Neoplasms, Experimental; Myelin Basic Protein; Potassium Chloride; Puromycin; Rats; Rats, Inbred F344

Lymphocytes from 278 gynaecological patients (100 controls and 178 patients with a malignant condition) have been investigated for their response to encephalitogenic factor, cancer basic protein, and KCl extract of adenocarcinoma of the body of the uterus as "antigens", using tanned sheep erythrocytes ETS as indicator particles in the electrophoretic mobility test (EMT). Electrophoretic mobility was measured with a Zeiss cytopherometer. The study was split into three test series producing in the cancer group 66% correct positive test results (34% false negatives) and in the control group 83% correct negative results (17% false positives). Consequently, with the instrumentation used, EMT is, at least in our hands, not sufficiently reliable for the diagnosis of cancer.

Topics: Adenocarcinoma; Adult; Aged; Antigens, Neoplasm; Electrophoresis; Female; Genital Neoplasms, Female; Humans; Lymphocytes; Middle Aged; Myelin Basic Protein; Neoplasm Proteins; Uterine Neoplasms

Fifty-four patients with malignant and other diseases of the urinary bladder and the prostate were examined for lymphocyte sensitization by means of electrophoretic mobility test (EM test). In this antigens from brain tissue (EF) and from malignomas of kidney, urinary bladder and prostate were used. Positive HEP values were obtained in 40 patients out of 42 with malignant tumours and in 5 patients out of 12 with other kidney diseases. With the corresponding tumour-associated antigens (TAA) in the EM-test, the histological tumour diagnosis could be confirmed in every case. Positive findings after using EF as well as the corresponding TAA are with great probability an indication of a malignant disease.

Topics: Adenocarcinoma; Adult; Aged; Antigens, Neoplasm; Brain; Cell Migration Inhibition; Electrophoresis; Humans; Kidney Diseases; Lymphocyte Activation; Male; Middle Aged; Myelin Basic Protein; Prostatic Neoplasms; Urinary Bladder Neoplasms