Interaction of the heterozygous nude gene with the asplenia trait in mammary tumorigenesis.

The BALB/c mouse strain has been shown to contain endogenous mouse mammary tumor virus (MMTV) proviral sequences. However, no exogenous MMTV particles have been detected in their tissues. Female BALB/c mice from our colonies exhibit a very low incidence of spontaneous mammary tumors (SMT); less than 1% at up to 20 mo of age.

Proliferation and differentiation of human myeloid leukemic cells in immunodeficient mice: electron microscopy and cytochemistry.

To study the influence of a biologic environment on cultured human leukemia cells, KG-1, KG-1a, and HL-60 cells were inoculated subcutaneously into newborn nude mice. The cells developed myelosarcomas at the site of inoculation and in lungs and kidneys. KG-1 and HL-60 myelosarcomas were successfully passaged through adult nude mice, whereas KG-1a tumors proliferated only after transplantation into newborn hosts.

K562 human leukemia cell passages differ in embryonic globin gene expression.

K562 is a human leukemia cell line inducible by a variety of agents for the synthesis of embryonic and fetal hemoglobins. We compared early and late passages to determine whether a change has occurred in globin synthetic pattern. Clone LA4, derived from passage 199 which had been frozen by Lozzio in 1973, was compared with clone RA6, derived from a line received from Rutherford in 1979.

Proliferation of human malignant hematopoietic cells in immunodeficient mice: suppression by antibody to pluripotent K-562 leukemia cells involves direct cytolysis and effector cells.

Six human hematopoetic cell lines were successfully heterotransplanted into athymic (nude) and asplenic-athymic (lasat) neonatal mice. The tumors arising from leukemia and lymphoma cells could then be serially transplanted into adult nude mice. Seven days after the fourth serial mouse passage, each mouse was treated with goat immune gamma globulin against K-562 cells.

Immunotherapy of human leukemia with antibody to pluripotential K-562 stem cells.

Gamma (gamma) globulin was fractionated from the serum of a goat immunized with the pluripotential leukemia cell line K-562. The lyophilized gamma-globulin preparation, termed leukoglobulin, contained about 50% immune IgG and suppressed the proliferation of heterotransplanted leukemia and lymphoma cells of human origin. The main aims of this study were to evaluate the potential therapeutic value of leukoglobulin and to determine its toxicity in humans with terminal leukemia and patients whose disease was unresponsive to current therapy.

Relationship between the Fc receptor for IgG and the specific associated antigen of the pluripotential leukaemia cell line, K-562.

The cells in the K-562 line have been shown to express Fc receptors as demonstrated by rosette formation with sheep erythrocytes (E) sensitized with haemagglutinin (EA). Rosette formation is inhibited by prior incubation of the cells with goat or monkey anti-K-562 serum, gammaglobulin fraction, or Fab fragments. Alkaline aggregated human IgG also inhibits rosette formation.

Absence of morphological, chromosomal and antigenic changes in the K-562 cell line growing as localized or disseminated tumours in nude mice.

Transplantation of K-562 cells into adult and newborn nude mice led to the development of localized s.c. and disseminated myelosarcomas, respectively.

Antibody lysis of human hematopoietic cells in the absence of complement and effector cells.

The incubation of K-562 leukemia cells with specific goat immunoglobulin resulted in gradual cytolysis in the absence of complement and effector cells. Optimal lysis (100%), reached in 3-4 days, occurred when the concentration of the antibody in the culture medium was about 20 micrograms/ml containing an initial inoculum of 15,000 cells. A lower concentration (10 micrograms/15,000 cells/ml) led to partial cytolysis; the surviving cells, cultured in fresh medium, were still vulnerable to antibody lysis (30 micrograms/ml), thus indicating the lack of an apparent resistant cell population.

Identification and quantitation of embryonic and three types of fetal hemoglobin produced on induction of the human pluripotent leukemia cell line K-562 with hemin.

The hemoglobins synthesized by the pluripotent K-562 leukemia cell line of human origin after induction with hemin have been isolated by DEAE-cellulose chromatography and characterized by electrophoresis, high pressure liquid chromatography, and a radioimmunological assay. Six hemoglobin zones have been observed with the following likely compositions. Zone 1: alpha 2 epsilon 2, or HB Gower-2; zone 2: zeta 2 epsilon 2, or HB Gower-1; zone 3: zeta 2 gamma 2, or HB Portland-I; zone 4: Hb F, or alpha 2 gamma 2; zone 5: a mixture of acetylated HB Portland-I and Hb F; zone 6: Hb Bart's, or gamma 4.

Arrest and extravasation of neoplastic cells. An electron microscopy study of serial sections at sequential stages.

The morphological aspects of the arrest and extravasation of malignant cells of human origin (K-562 cell line) in the lungs of athymic (nude) and asplenic-athymic (lasat) mice were studied by electron microscopy examination of serial sections. The specimens were obtained at sequential stages after the sc inoculation into newborn mice of 10(7) malignant cells. K-562 cells (10(5)) were also injected iv into control groups of nude and lasat mice to assess the influence of the route of inoculation on the in vivo behavior of K-562 cells.

Antibody-dependent cytolysis of the human leukemia cell line K-562 in the absence of effector cells or complement.

K-562 human leukemia cells grown in the presence of specific goat anti-K-562 gamma globulin, F(ab)'2, Fab', or Fab showed a decrease in DNA and protein syntheses and a loss of cell viability within several hours. Eventually all cells died and lysed within 2-5 days. These events occurred in the absence of added effector cells or complement.

Relevance of lipids to heterotransplantation of human malignancies.

Although the transplantation of human neoplasms in immunodeficient mice is now a well-established procedure, the majority of primary malignancies cannot be successfully maintained for long periods of time in adult athymic (nude) and asplenic-athymic (lasat) mice. Various lipids such as cholesterol, cholesterol oleate, stearic and palmitic acid esters markedly depress the RES phagocytic activity and immunocompetence of mammals. In view of the immunosuppressive properties of certain lipids and in order to graft and grow as many tumors as possible, further studies into the effects of lipids on the growth of heterotransplanted human tumors is warranted.

Correlation if circulating immune complexes and disease status in patients with leukaemia.

The occurrence of soluble immune complexes (IC) was investigated in 177 serum samples from 92 patients with various leukaemias using the Raji cell immunoassay. In general, patients with myeloproliferative diseases had a higher incidence and higher quantities of IC than did patients with lymphoproliferative disorders. Elevated levels of IC were found in the sera of patients as follows: 17% with chronic lymphocytic leukaemia (mean value of 13.

Induction of hemoglobin synthesis in original K 562 cell line.

Cells of the original human myelogenous leukemia cell line, K 562 were induced to synthesize hemoglobin by incubation with 0.05 mM hemin. Analysis by isoelectric focusing indicated major bands in the region of hemoglobin F, Bart's hemoglobin, and embryonics.

Recurrent melanotic neuroectodermal tumor of infancy: report of case and tumor heterotransplantation studies.

A fifth case of rapidly recurring melanotic neuroectodermal tumor of infancy is reported. The possibility of recurrence and subsequent encroachment on vital facial structures is emphasized. Vigorous bony curettage at initial excision of this benign lesion may aid in the preventing recurrence.

Evaluation of drug-antibody conjugates in the treatment of human myelosarcomas transplanted in nude mice.

Methotrexate, daunomycin, and chlorambucil were independently conjugated to immune goat gamma-globulins specifically raised to the Ph1 + chronic myelogenous leukemia cell line K-562. The drug-antibody conjugates were then tested against myelosarcomas made up of K-562 cells growing in nude mice and their efficacy was compared with that of the drug alone, gamma-globulins, a mixture of the two, or conjugates of drugs with normal goat gamma-globulin. Conjugation methods for methotrexate and daunomycin abrogate the antibody activity as indicated by the absence of complement-mediated cytotoxicity of the conjugates in vitro and the lack of effect on myelosarcomas in vivo.

Thymocyte reconstitution of athymic and athymic-asplenic mice: graft rejection and antibody synthesis.

Hereditarily athymic and athymic-asplenic mice were reconstituted with syngeneic thymocytes at various times prior to and after tumor challenge. These mice were able to reject heterotransplanted human tumors in as little as 19 days after thymocyte transfer but were unable to do so when the thymocytes were given 7 days after tumor implantation. The humoral immunity of athymic nude mice was fully restored as determined by the primary immune response to sheep erythrocytes (SRBC), a thymocyte-dependent antigen.

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.

High incidence of mammary tumors in mice with inherited asplenia carriers for the nude gene.

A colony of mice suffering from dominant hemimelia associated with agenesis of the spleen has been developed and characterized during the past 7 years. The hereditarily asplenic (Dh/+) mice have a very low incidence (9%) of spontaneous mammary tumors (SMT). Asplenic (Dh/+) females were mated with mice homozygous (nu/nu) for hereditary athymia (nude) having a BALB/c background.

Hematopoiesis of hereditarily asplenic-athymic (lasat) mice.

The hematopoiesis of athymic-asplenic (lasat) mice was compared with that of normal, asplenic, and athymic littermates with the same strain background. Erythrocyte blood volume, number and survival time were normal when related to the body weight of the animals. Peripheral blood showed leukopenia with absolute and relative lymphopenia, resembling the athymic rather than the asplenic pattern.