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Biomedical subjects

A M Koros

Publications and source records attributed to A M Koros.

17 recordsLinked to original sources
PubMed2000

JLP5B9: new monoclonal antibody against polysialylated neural cell adhesion molecule is of value in phenotyping lung cancer.

Non-small-cell lung cancer (NSCLC) is currently one of the most prevalent malignant tumors. It displays a wide variety of phenotypes which includes neuroendocrine markers commonly found on small-cell lung cancers (SCLC) such as the neural cell adhesion molecule (NCAM) and in particular its highly polysialylated isoform, embryonic NCAM (eNCAM). NSCLC with neuroendocrine differentiation may represent a subset of tumors whose cells have a more aggressive biological behavior. A tumor marker that distinguishes this latter sub-type could be of clinical relevance. Accordingly, we have raised a monoclonal antibody of the IgM type (JLP5B9) directed against capsular polysaccharides of N. meningitidis B which bears polysialic acid groups. We have demonstrated that JLP5B9 recognizes eNCAM with high affinity and that it is specifically directed against the polysialic acid moieties of NCAM. JLP5B9 was also found to react with human SCLC, NSCLC and neuroblastoma cell lines. We then used JLP5B9 as a specific probe for the detection of tissue eNCAM and found that it was expressed on up to 20% of tumor cells obtained from 5 out of 13 patients with NSCLC. This mAb deserves further investigation to evaluate its potential as a tool for serodiagnosis of lung cancer.

Adult↗
PubMed1998

Chrysamine-G, a lipophilic analogue of Congo red, inhibits A beta-induced toxicity in PC12 cells.

Increasing evidence suggests that deposition of amyloid-beta (A beta) peptide leads to neurodegeneration in Alzheimer's disease. Congo red, a histologic dye that binds to amyloid has previously been shown to diminish the toxic effects of A beta in cell culture. Since Congo red is too highly charged to enter the brain in significant quantities, a lipophilic derivative, Chrysamine-G, was tested for the ability to attenuate A beta[25-35]-induced toxicity in PC12 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Chrysamine-G showed a concentration-dependent inhibition of A beta[25-35]-induced toxicity. This protective effect became significant at 0.2 microM, a concentration very close to the Ki for Chrysamine-G binding to synthetic A beta (0.37 microM). A decarboxy derivative of Chrysamine-G, which does not bind to A beta, also did not protect against A beta-induced toxicity. The protective effects of Chrysamine-G may relate to its ability to bind directly to A beta and may involve other post-binding effects as well.

Alzheimer Disease↗
PubMed1994

Phenotypic differences among morphologically similar small-cell carcinomas detected with a panel of monoclonal antibodies and indirect immunofluorescence and flow cytometry.

Indirect immunofluorescence and flow cytometry were used to determine reactivity of a panel of 75 monoclonal antibodies (MAbs) and controls (provided by the Third International IASLC Workshop on Lung Tumor and Differentiation Antigens) with 3 morphologically similar prototype continuous-culture small-cell-carcinoma cell lines (SCC) (NCI-H69, NCI-H146, and NCI-H510). All cell lines had some reactivity with some of the MAbs. There is, however, differential expression of antigens amongst the prototype cell lines, which may provide a useful method for phenotyping and sub-classifying SCC. The reactivity of the 3 cell lines was greatest with MAbs in Clusters I, 1c, 2, 4, 6, and 9, and least with MAbs in clusters W7, 8, 13, 14, and W15, with few exceptions. Although morphologically similar, each of the SCC cell lines has a unique pattern of reactivity with the workshop MAbs. For example, although a control MAb, CD56 (NKHI), which identifies an epitope on NCAM (neural cell adhesion molecule) common among many SCC lines, stained more than 90% of cells in each of the prototype cell lines, one MAb of the current panel, SEN7, which also identifies a CD56 epitope on 15 SCC lines did not react as strongly with H-146 and H-510 as with H-69. If appropriately reactive MAbs can be identified for individual patients' tumors, they can be coupled to suitable radioisotopes or toxins for individualized patient treatment.

Antibodies, Monoclonal↗
PubMed1991

Neural cell adhesion molecule expression and messenger RNA splicing patterns in lung cancer cell lines are correlated with neuroendocrine phenotype and growth morphology.

Diverse histological types of lung cancer express neuroendocrine (NE) markers. We studied the expression and alternative splicing forms of the neural cell adhesion molecule (NCAM) NKH-1, a member of the immunoglobulin superfamily, in 56 lung cancer cell lines representing all histological types. We found a strong correlation between expression of NCAM with both NE phenotype and lack of substrate adhesion in culture. Several cell lines expressed high levels of the leukocyte antigen Leu-7 (HNK-1) but were negative for NCAM antigen and mRNA, indicating that the Leu-7 antigen is distinct from NCAM. All of the NCAM-positive cell lines demonstrate a single 6.2-kilobase mRNA, and analysis of the known 3' alternative splices shows predominant expression of only the membrane form with the small intracytoplasmic domain. We conclude that (a) expression of NCAM is associated with NE phenotype regardless of the histological type of lung cancer; (b) these cell lines share a single form of NCAM; (c) with few exceptions, NCAM expression is associated with cell to cell adhesion and lack of substrate adhesion (growing as floating clusters); and (d) Leu-7 antigen is distinct from NCAM. This form of NCAM may play a functional role in NE differentiation or may be a part of the NE program expressed by these cells.

Antigens, Differentiation↗
PubMed1987

Antilung cancer activities of selenium.

Selenium is considered an essential trace element in most animal and plant species, although still reported in many texts as a highly toxic material. Epidemiological investigations have reported an inverse relationship between selenium and lung cancer. Explanations of reported observations have resulted in numerous mechanistic theories. Only recently have selenium metabolites involved in excretion been considered potential agents for antilung cancer activity. Anticancer properties have been shown in occupationally exposed copper smelter workers, dietary investigations and experimental studies. Supplementation with selenium of public water supplies, as is currently done with fluoride, is a potential method for increasing the blood concentration. This may permit development of a population prevention strategy against lung cancer and other diseases.

Humans↗
PubMed1985

Stability and utility of the unique human small cell carcinoma line SHP-77.

The human small cell (oat cell) carcinoma line, SHP-77, established by Fisher and Paulson in 1977 and originally described as a "large cell variant of oat cell cancer" has been evaluated by several different parameters and shown even after more than 200 passages to retain properties described for the original cell line. Karyotypic, histological, and biochemical features are retained, as well as tumorigenicity in nude mice. The original authors' suggestion that this is a propitious cell line for both in vitro and in vivo studies is supported by this report. Modulation of growth characteristics in vivo (in xenografts) emphasizes the plasticity of this unique line which serves as a valuable model for basic as well as therapeutic studies. SHP-77 can serve as an in vitro target in 51Cr and 111In release cytotoxicity assays as well as in in vivo nude mouse assays for evaluating immune reactivity of cells and serum from lung cancer patients. The potential histological variability of SHP-77, despite its biochemical stability, calls attention to the inadequacy of histological criteria for lung tumor classification.

Animals↗
PubMed1978

Fetal human hemolytic plaque-forming cells. Evidence of reactivity to maternal and other erythrocytes.

Lymphoid tissues from 24 human fetuses were assayed for hemolytic plaque-forming cells (PFC) against a variety of erythrocyte targets. PFC against maternal and other erythrocyte antigens were commonly detected in human fetal liver, lymph nodes, spleen, or thymus as early as 16 weeks gestation and were usually more abundant in liver than in spleen after 16 weeks gestation. These data corroborate studies from other laboratories which indicate that human fetuses develop some forms of immunocompetence very early during gestation.

Aging↗
PubMed1978

Anti-autologous erythrocyte plaque-forming cells in pregnancy. A parameter of immunoregulatory change.

Peripheral blood leukocytes (PBL) from 16 persons (6 Rh-sensitized pregnant women, 1 pregnant non-Rh-sensitized woman, 3 nonpregnant non-Rh-sensitized women, and 6 non-Rh-sensitized males) were assayed for plaque-forming cells (PFC) against several erythrocyte targets. 6 of 7 pregnant women had PFC, whereas only 1 of 6 males had PFC to autologous red cells. Antiautologous erythrocyte PFC in all of the pregnant Rh-sensitized women as well as the 1 nonpregnant multiparous woman may be the result of alloimmunization of mothers by their fetuses during gestation. Further studies in this area would be valuable in determining not only the immune status of a mother in relation to her fetus, but also would be of value in determining the consequences of that immune status on both mother and fetus. Such information would also provide a further clue to the etiology of autoimmune disease.

Adult↗
PubMed1968

Radioautographic studies of plaque-forming cells. I. Antigen-stimulated proliferation of plaque-forming cells.

A method has been described for obtaining radioautographs of plaque-forming cells. The method permits radioautographic analyses of small numbers of plaque-forming cells amidst large populations of non-plaque-forming cells. Spleen cells that were pulse-labeled with tritiated thymidine could be categorized readily as labeled or not labeled. Using this method it was found that (a) at least 55% of plaque-forming cells which appear 3 days after a maximal stimulus of 4 x 10(8) sheep red cells are still capable of DNA synthesis, and must have arisen by cell proliferation; (b) the rate of proliferation of plaque-forming cells is proportional to the log of the dose of antigen; (c) the S period of plaque-forming cells is at least 2 hr, appears to be constant, and is not influenced by antigen dose. The results suggest that antigen stimulates proliferation of plaque-forming cells by hastening their transit through the G(1) phase of the generative cycle.

Animals↗
PubMedDate not supplied

186Rhenium-HNK1 monoclonal antibody targets human small cell lung cancer cells in athymic nude mice: rapid screening model for therapy.

A model is described by which in vivo tumor-MOAB interactions may be investigated. The method is rapid and may aid in the selection of appropriate MOABS from a panel of MOABS for individualized patient treatment. Groups of athymic nude mice were injected intravenously with small cell lung cancer line SHP-77 cells which are trapped primarily in the lungs. Twenty-four hours post tumor cell inoculation, 186Rhenium tagged HNK1 MOAB (CD57) was injected intravenously. Controls which received no tumor cells were injected with unbound 186Re or radioactive MOAB. Biodistribution studies at 24 hours following MOAB injection showed significantly more radioactivity in lungs of mice inoculated with both SHP-77 cells and 186Re MOAB than did lungs of controls.

Animals↗