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Biomedical subjects

C B Lozzio

Publications and source records attributed to C B Lozzio.

At least 55 records · Page 3Linked to original sources
PubMed1979

Reproducible metastatic growth of K-562 human myelogenous leukemia cells in nude mice.

A reproducible metastatic growth of K-562 human myelogenous leukemia cells occurred in immunodeficient athymic (nude) mice. Although previous studies have shown that K-562 cells grow as local subcutaneous myelosarcomas which continuously release leukemia cells into the systemic circulation in adult mice, metastases were not observed. However, the subcutaneous "priming" of newborn nude mice resulted in the metastatic proliferation of leukemia cells in the lungs, kidneys, brain, and lymph nodes. Three sc injections of 5 X 10(6) K-562 cells on days 1, 7, and 14 of life produced metastases in 51% of the mice. When the initial series of injections was followed by iv injections on days 35 and 42, the incidence of metastases increased to 67%. Karyotypes demonstrated that the tumor cells retained the same human chromosome markers as those in the human patient and tissue culture. These procedures may provide a model for study of the mechanisms of metastases and for chemotherapeutic and immunotherapeutic trials against metastases of neoplasms of human origin.

Animals↗
PubMed1978

Cytotoxicity of a factor from normal and abnormal human spleens for allogenic leukemia cells.

A search for an endogenous cytotoxic factor (ECF) was made by analyzing 103 spleens from normal humans and patients suffering from hematopoietic malignancies, solid tumors, inflammatory diseases, and congestive and hyperplastic splenomegalies. A highly purified ECG was obtained by a combination of gel filtration and ion-exchange column chromatography. The factor is a low-molecular-weight (less than 2,000) substance and is probably a peptide or peptide-nucleotide complex. The biologic activity of EC was assayed on myelogenous and lymphatic leukemia cells of human origin. The spleens from normal individuals produced and/or stored the largest quantity of the ECF. The amount of ECF extractable from the pathologic spleen was drastically diminished regardless of the disease or therapeutic regimen. The ECF was significantly more cytotoxic for lymphatic than for myelogenous leukemia cells.

Anemia↗
PubMed1977

Characterization of an antigen from the myelogenous leukemia cell line K-562.

A protein was solubilized from the myelogenous leukemia cell line K-562 WITh 3 M KCl that specifically inhibited the antibody-dependent, complement-mediated cytolysis of 51Cr-labeled K-562 cells by a monkey antiserum to K-562. When the crude 3 M KCl extract uas fractionated with ammonium sulfate, an eightfold increase in specific activity (U inhibition/mg protein) resulted. This purified fraction migrated as a single protein band after polyacrylamide gel electrophoresis (PGE) with no detectable carbohydrate or lipid. The molecular weight of the denatured protein determined by sodium dodecyl sulfate-PGE was 77,000, similar to that of the native protein (80,000) determined by Sephadex exclusion chromatography. The protein was stable at pH 6-8, with an apparent isoelectric point between pH 5 and 6. In addition to being irreversibly denatured at pH 5 or less, it was unstable at osmolarities below 0.25 M (NaCl). It was denatured at temperatures of 56 degrees C or above. Normal human peripheral blood leukocytes were extracted similarly with 3 M KCl and fractionated with ammonium sulfate. Neither the crude preparation nor any fraction purified as described for the specific antigen inhibited the cytolytic assay, which indicated at least a quantitative lack of the protein on the surfaces of normal leukocytes.

Ammonium Sulfate↗
PubMed1977

Suppression of human myelosarcoma growth in athymic mice by a primate antiserum.

A primate (Macaca speciosa) antiserum prepared against the human chronic myelogenous leukemia cell line K-562 suppressed the growth of the human myelosarcomas in nude mice. The ip administration of 0.5 ml of immune serum plus 0.5 ml of guinea pig complement, starting 7 days after sc tumor transplantation, resulted in a fourfold to fivefold decrease in tumor weight at 15 days when compared to nude mice given pre-immune serum plus complement or complement alone. Whereas the other two groups experienced an exponential increase in tumor volume at 7-9 days after tumor transplantation, the immune serum-treated mice remained in a "lag" phase of tumor growth during which the tumor volume neither increased nor decreased substantially. Histopathologic studies revealed various degrees of tumor alterations ranging form focal hydropic cellular degeneration to massive coagulation necrosis. The incorporation of tritiated thymidine into the tumors was also markedly diminished in the mice given immune serum.

Animals↗
PubMed1976

Hereditary asplenic-athymic mice: transplantation of human myelogenous leukemic cells.

A new animal model characterized by hereditary athymia and asplenia was used as a recipient of chronic myelogenous leukemic (CML) cells with the Philadelphia (Ph1+) chromosome. Transplanted CML cells form solid vascularized tumors containing cells similar to those seen in the patient in a long-term culture. Cells taken from the tumors were nearly triploid, retained all human chromosome markers, and had the same antigenic determinants(s) as cells in culture.

Abnormalities, Multiple↗
PubMed1976

Cytotoxicity of antisera to a myelogenous leukemia cell line with the Philadelphia chromosome.

Rabbit antisera to myelogenous leukemia (ML) cells were raised; ML cells from line K-562 that has the Philadelphia (Ph) chromosome were used as antigen. Antibodydependent, complement-mediated cytotoxicity was demonstrated by the trypan blue test and Cr release assay for cultured ML cells, whereas no cytotoxicity was demonstrated for cells from B (SB) and T (MOLT 4) lymphoblastoid cell lines. The antisera showed no cross-reactivity for normal human peripheral leukocytes or purified granulocytes. A low level (less than 8%) of cytotoxicity was directed against cell membrane associated fetal bovine serum proteins. Absorption of the immune serum with normal human bone marrow cells of first trimester human whole embryo cells reduced the cytotoxic titer to a similar extent; this suggested the possibility of crossreactivity between ML cells and fetal antigen(s). However, the ML antigen(s) was unrelated to carcinoembryonic antigen (CEA), since absorption with CEA had no effect on the serum cytotoxic titer. The anti-ML sera were cytotoxic for cells taken from 10 patients with chronic myelogenous leukemia and from 3 with acute myelogenous leukemia. In contrast, the leukocytes of 1 of 4 patients with acute lymphocytic leukemia, and 3 of 7 with chronic lymphocytic leukemia shared similar antigenic determinants as demonstrated by cytotoxicity tests. The significance of the cross-reactivity of some lymphatic and ML cells may be the result of the use of rabbit sera that did not distinguish antigens common to both granulocytic and lymphocytic cells, or it may reflect an "immature" or "blastic" antigen present on many leukemia cells.

Adult↗
PubMed1976

Absence of thymus-derived lymphocyte markers in myelogenous leukemia (Ph1+) cell line K-562.

The myelogenous leukemia cell line K-562 with a Ph1+chromosome, derived from a patient with chronic myelogenous leukemia in terminal blastic crisis, is not a bone marrow-derived lymphoblastic cell line, because the cells neither produce immunoglobulins nor possess complement receptors. Since it has been suspected that blasts found in some patients with chronic myelogenous leukemia in blastic crisis might be thymus-derived cells, we have studied several parameters to demonstrate that K-562 cells are not thymus-derived lymphoblasts. The results of this study show: (a) no cross-reactivity of antisera to K-562 cells with normal human thymocytes; (b) lack of cytotoxicity of a specific horse anti-human thymocyte globulin for K-562 cells; (c) failure of the treatment of K-562 cells with bovine thymosin to induce antigenic determinant and erythrocyte rosette receptors on K-562 cells; (d) presence of receptors for the Fc portion of immunoglobulin G; (e) absence of terminal deoxynucleotidyl transferase; and (f) cytotoxicity of monkey antiserum to K-562 cells for malignant thymus-derived cells (Molt-4). However, absorption with Molt-4 cells abolished the cross-reactivity with Molt-4 cells, whereas 60% of the antibody to K-562 cells remained in the immune serum. Studies of DNA polymerase activities revealed that K-562 cells have levels of polymerase alpha and beta, like other proliferating cells, and an RNA-dependent DNA polymerase activity, presumably representing polymerase gamma.

Antigens, Neoplasm↗
PubMed1975

Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome.

A cell-line derived from a patient with chronic myelogenous leukemia (CML) is described. The new cell-line, which has over 175 serial passanges in a 3 1/2-yr period, has the following characteristics: (1) CML cells started to proliferate actively since they were first incubated in culture media. A threefold increase in the total number of cells was observed during the first seven passages; the cell population increased by a factor of 10 to 20 every 7 days from passage 8 through 85; from 20 to 40 times from passage 86 through 150, and more than 40 times after 150 passages. (2) The majority of the nononucleated cells are undifferentiated blasts. (3) The karyotype of all the cells examined show the Philadelphia (Ph1) chromosome and a long acrocentric marker plus aneuploidy. The Giemsa-banding studies identified the Ph1 chromosome as a terminal deletion of the long arm of chromosome 22:del(22)(q12) and the long acrocentric marker as an unbalanced reciprocal translocation of one chromosome 17 and the long arm of one chromosome 15. (4) The CML cells do not produce immunoglobulins, are free of mycoplasma, Epstein-Barr virus, and herpes-like virus particles. (5) CML cells have no alkaline phosphatase and myeloperoxidase activities and did not engulf inert particles. (6) Cultured CML cells provide a constant source of a specific antigen. This CML cell-line represents a unique source of CML cells with meaningful indicators of malignancy for clinical and experimental studies.

Alkaline Phosphatase↗