RESUMO
From the first two non-brain cancer cell types examined, mammary cancer cells (MCF-7) and lymphoma cells (P3G), two new acidic polypeptides of approximately 10,000 M.W. each have been produced, called recognin M and recognin L, respectively. These are very closely related in amino acid composition and in immunological reactions to the first two cancer recognins, astrocytin from human gliomas in vivo and malignin from malignant glial cells grown in vivo. Together with earlier findings, these observations suggest that the cancer polypeptide recognins may be produced from members of a closely related family of substances characteristic of malignant cells.
Assuntos
Neoplasias da Mama/metabolismo , Linfoma não Hodgkin/metabolismo , Proteínas de Neoplasias/biossíntese , Antígenos de Neoplasias/biossíntese , Antígenos de Neoplasias/isolamento & purificação , Neoplasias Encefálicas/metabolismo , Linhagem Celular , Glioma/metabolismo , Humanos , Proteínas de Neoplasias/isolamento & purificação , Proteínas do Tecido NervosoRESUMO
By reference to a "checklist" of requirements for substances or processes to qualify as surrogate endpoint biomarkers, both malignin and antimalignin antibody are found to be suitable for use in breast cancer chemoprevention trials. Antimalignin has been shown to be highly specific and sensitive, modulatable and reversible, detectable early in appearance of malignancy and upon recovery therefrom, and differentially expressed in high-risk individuals as compared with the general population.
Assuntos
Anticarcinógenos/uso terapêutico , Autoanticorpos/sangue , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Proteínas de Neoplasias/análise , Antígenos de Neoplasias/análise , Antígenos Glicosídicos Associados a Tumores/sangue , Neoplasias da Mama/sangue , Antígeno Carcinoembrionário/sangue , Método Duplo-Cego , Seguimentos , Humanos , Proteínas de Neoplasias/imunologia , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Valores de ReferênciaRESUMO
Human antimalignin antibody (AMA) appears to have clinical significance because in actuarial studies its concentration relates quantitatively to survival (Bogoch et al. Protides Biol Fluids 1984; 31:739-747). Therefore isolation, characterization, and production in vitro of AMA were undertaken. Serum AMA concentrations are elevated in cancer, regardless of cell type, as demonstrated by earlier blind studies of 1,026 (Bogoch et al. J. Med 1982; 13:49-69) and 501 (Bogoch and Bogoch. Protides Biol Fluids 1983; 30:337-352) and independently confirmed by others on 354 (Bogoch et al. Protides Biol Fluids 1984; 31: 739-747) cancer patients and controls. Mouse monoclonal AMA was produced earlier (Bogoch et al. Lancet 1981; 2:141-142). To validate the identity of the natural substrate AMA in the serum determination (AMAS test) and to prepare for human imaging and therapeutic trials, human AMA has now been produced in vitro from human lymphocytes and has been shown to be increased when primed with its specific 10,000-dalton peptide antigen malignin. This synthesized human AMA adsorbs specifically to its immobilized antigen in vitro and resembles in cancer cell staining and in other properties human AMA isolated from sera of cancer patients and mouse monoclonal AMA. All are predominantly IgM, as shown by reduction to heavy and light chains followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
Assuntos
Anticorpos/análise , Proteínas de Neoplasias/imunologia , Neoplasias/imunologia , Células Cultivadas , Eletroforese em Gel de Poliacrilamida , Humanos , Imunoglobulina M/análise , Linfócitos/análiseRESUMO
The serum anti-malignin antibody (AMA) test determines the antibody to malignin, a 10,000-Da peptide present in patients with a wide variety of cancers. A total of 3315 double-blind tests demonstrated that AMA is a general transformation antibody, elevated in active nonterminal cancer, regardless of the site or tissue type, with sensitivity and specificity of 95% on the first determination and > 99% on repeat determinations. Data have not however been published yet that indicate whether, in daily clinical practice, the AMA test provides accurate prospective and predictive information. Forty-two physicians from 11 states, who ordered the AMA test, performed blind, report here on their results on 208 determinations in the first consecutive 181 patients and controls. Used in monitoring treatment in 56 patients, the test predicted or agreed 94.1% overall with the clinical status. Used in early detection in 125 patients and controls, of which 118 now have confirmed diagnoses, AMA was elevated in 21, all of whom were proven to have cancer; AMA was normal in 97, none of whom had cancer. Transient elevated AMA occurred in 3%, followed by normal values. Seven patients with still uncertain diagnosis who have had elevated AMA on repeated tests for 1 year or longer include six who are symptomatic, and three whose families have a high frequency of cancer. The conditions of these 7 may include undetected cancer because of the 118 with now certain diagnosis the AMA test predicted all correctly. From our experience, the AMA test should be used together with other routine procedures whenever signs and symptoms suggest cancer to facilitate early detection.