Search PubMed⌕ Search

Biomedical subjects

T Kasukabe

Publications and source records attributed to T Kasukabe.

At least 73 records · Page 4Linked to original sources
PubMed1981

Induction of differentiation of cultured human and mouse myeloid leukemia cells by alkyl-lysophospholipids.

Alkyl-lysophospholipids are synthetic analogs of naturally occurring lysophospholipids. The effects of these compounds on cell proliferation and differentiation of cultured human (HL-60) and mouse (M1) myeloid leukemia cells were studied. Both cell lines were induced to differentiate into morphologically and functionally mature granulocytes and macrophages by incubation with a wide variety of these compounds. Some alkyl-lysophospholipids induced differentiation (judged morphologically and by the appearance of abilities to reduce nitro blue tetrazolium, to phagocytize latex particles, and to induce lysozyme activity) of both the cells lines at concentrations of 1 microgram/ml. However, these compounds did not affect colony formation of normal mouse bone marrow cells even at a higher concentration, 20 microgram/ml. These results suggest that alkyl-lysophospholipids induce cell differentiation of myeloid leukemia cells without affecting proliferation and differentiation of normal bone marrow cells. Thus, these compounds could be useful in therapy of myeloid leukemia.

Animals↗
PubMed1981

The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate inhibits or enhances induction of differentiation of mouse myeloid leukemia cells depending on the type of serum in the medium.

The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) inhibited the induction of both functional and morphological differentiation of mouse myeloid leukemia cells (Ml) cultured in medium containing 10% calf serum, but enhanced these inductions in medium containing 10% fetal calf serum and several inducers. These results suggest that some factor(s) in sera modifies the differentiation-inducing action of TPA on leukemia Ml cells.

Animals↗
PubMed1981

Selection and characterization of pulmonary colonizing cells from cultured mouse mammary carcinoma cells.

Pulmonary colonizing cells were selected by an in vivo-in vitro selection method from cultured mouse mammary carcinoma FM3A cells. When 10(6) parent cells (P-O) were injected iv into syngeneic C3H/He mice, no tumor nodules were reduced. However, when the selected variant cells (P-15) were injected iv, tumor nodules formed predominantly in the lungs within 2 weeks. Mice inoculated iv with 10(6) P-15 cells began to die on day 22, but mice inoculated with P-O cells survived for more than 6 months. When injected sc into C3H/He mice, P-O cells were as tumorigenic as P-15 cells to the syngeneic mice. There was no significant difference between P-O and P-15 cells in their proliferation in vitro or in the inducibility of alkaline phosphatase activity. During successive selection of colonizing variants, the proportion of adherent cells increased. Adherent P-15 cells had a higher colonizing potential than nonadherent P-15 cells. The correlation of the adhesive property of the cells and their colonizing potential is discussed.

Alkaline Phosphatase↗
PubMed1980

Regulation of prostaglandin synthesis during differentiation of cultured mouse myeloid leukemia cells.

Mouse myeloid leukemia cells (Ml) were induced to differentiate into mature macrophages and granulocytes by various inducers. The differentiated Ml cells synthesized and released prosetaglandins, whereas untreated Ml cells did not. When the cells wee prelabelled with [14C]arachidonate, the major prostaglandins released into the culture media were found to be prostaglandin E2, D2, and F2 alpha in an early stage of differentiation, but the mature cells produced predominantly prostaglandin E2. The synthesis and release of prostaglandins were completely inhibited by indomethacin. Dexamethasone, a potent inducer of differentiation of Ml cells, did not induce production of prostaglandins in resistant Ml cells that could not differentiate even with a high concentration of dexamethasone. These results suggest that production of prostaglandins in Ml cells is closely associated with differentiation of the cells. Homogenates of dexamethasone-treated Ml cells converted arachidonate to prostaglandins, but this conversion was scarcely observed with homogenates of untreated Ml cells. Dexamethasone and the other inducers stimulated the release of arachidonate from phospholipids. Therefore, induction of prostaglandin synthesis during differentiation of Ml cells may result from induction of prostaglandin synthetase activity and stimulation of the release of arachidonate from cellular lipids. Lysozyme activity, which is a typical biochemical marker of macrophages, was induced in Ml cells by prostaglandin E2 or D2 alone, as well as by inducers of differentiation of the cells, but it was not induced by arachidonate or prostaglandin F2 alpha. These results suggest that prostaglandin synthesis is important in differentiation of myeloid leukemia cells.

Animals↗
PubMed1980

Induction of differentiation of human promyelocytic leukemia cells (HL-60) by arginase.

Human promyelocytic leukemia cells (HL-60) were found to be induced by dimethylsulfoxide and several other compounds to phagocytize, reduce NBT dye, and change into forms that were morphologically similar to granulocytes and macrophages. Arginase also induced these differentiation-associated properties of the cells. The induction of differentiation by arginase was significantly inhibited by addition of excess arginine, but not by lysine or leucine; therefore, the effect of arginase may be due to arginase-mediated arginine depletion.

Arginase↗
PubMed1980

Survival of mice inoculated with non-differentiating myeloid leukemia cells is prolonged by the injection of an inducer of cell differentiation with a sensitizer.

The effect of injection of an inducer and sensitizer on the survival times of syngeneic SL mice inoculated with resistant mouse myeloid leukemia cells (Ml) was examined. In vitro, the resistant Ml cells could not be induced to differentiate into mature macrophages and granulocytes by inducer (certain proteins, bacterial lipopolysaccharides, or glucocorticoids) alone, but could be induced to differentiate by treatment with both the inducer and a sensitizer (actinomycin D). In vivo, lipopolysaccharide alone scarcely affected the survival of SL mice inoculated with the resistant cells, but lipopolysaccharide plus actinomycin D significantly prolonged their survival. Administration of both lipopolysaccharide and actinomycin D also prolonged the survival of athymic nude mice inoculated with resistant Ml cells. These results suggest that prolongation of the survival of SL mice inoculated with resistant Ml cells is associated with the induction of differentiation of the cells.

Animals↗
PubMed1979

Characterization of lysozyme synthesized by differentiated mouse myeloid leukemia cells.

Lysozyme was induced by dexamethasone during normal differentiation of cultured mouse myeloid leukemia cells (M1) to macrophages and granulocytes. A large amount of lysozyme was produced by macrophage-like line cells (Mm-1), established from spontaneously differentiated macrophage-like cells from a clonal line of M1 cells. Lysozyme purified from the culture medium of these Mm-1 cells (Mm-1 lysozyme) had a molecular weight of 15,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and showed maximal activity at pH 6.6 with an optimal NaCl concentration of 0.04 M. Its mobility on polyacrylamide gel electrophoresis at pH 4.5 was distinctly lower than those of lysozymes from hen egg white and human urine. Rabbit anti-Mm-1 lysozyme serum inhibited the activities of lysozyme preparations from peritoneal macrophages of normal mice and rats and dexamethasone-induced differentiated M1 cells, but not those of preparations from hen egg white and human urine. Lysozyme was also purified from normal mouse lung, which is rich in alveolar macrophages and was found to be similar to lysozyme purified from the culture medium of Mm-1 cells in size and electrophoretic mobility and in its pH optimum, trypsin peptide map, and antigenicity. Thus the molecular structure of the lysozyme induced in differentiated mouse myeloid leukemia cells is similar to that of lysozyme produced by normal cells.

Animals↗
PubMed1979

Inhibition of functional and morphological differentiation of cultured mouse myeloid leukemia cells by tumor promoters.

Addition of a potent tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), to mouse myeloid leukemia line cells (Ml) in suspension cultures inhibited both functional and morphological differentiation of the cells induced by dexamethasone or protein inducer. A positive correlation was found between the tumor-promoting activities of several plant diterpenes and their inhibition of cell differentiation. The inhibition of cell differentiation by TPA was reversible and was unrelated to its cytotoxic action.

Animals↗
PubMed1979

Prolongation of survival time of mice inoculated with myeloid leukemia cells by inducers of normal differentiation.

Studies were made on the effects of inducers on the leukemogenicity of sensitive mouse myeloid leukemia cells (M1) that could be induced to undergo cell differentiation into mature granulocytes and macrophages in vitro by incubation with inducers (certain proteins, bacterial lipopolysaccharides, or glucocorticoids) and of resistant M1 cells that could not be induced to differentiate into mature cells. Inducers of cell differentiation significantly enhanced the survival times of mice inoculated with sensitive cells but scarcely affected the survival times of mice inoculated with resistant cells. Some mice inoculated with the sensitive cells and treated with lipopolysaccharide did not develop leukemia. The sensitive and resistant clone cells contained similar common tumor-related surface antigens. Treatment with lipopolysaccharide was also effective in athymic nude mice inoculated with the sensitive M1 cells. Lipopolysaccharide or glucocorticoid significantly stimulated differentiation of the sensitive cells cultured in a diffusion chamber in vivo but had little effect on differentiation of resistant cells. These results suggest the possibility of treating, with partial success, leukemia in vivo with differentiation inducers.

Animals↗
PubMed1979

Inhibition of differentiation of cultured mouse myeloid leukemia cells by nonsteroidal antiinflammatory agents and counteraction of the inhibition by prostaglandin E1.

Mouse myeloid leukemia cells (M1) were induced to differentiate into mature macrophages and granulocytes by glucocorticoids or a protein inducer in ascitic fluid from tumor-bearing rats. Addition of nonsteroidal antiinflammatory agents to M1 cells in suspension cultures inhibited the induction of differentiation by glucocorticoid (dexamethasone) or the protein inducer. The inhibition was unrelated to cytotoxicity and was reversible. The nonsteroidal antiinflammatory agent indomethacin inhibited dexamethasone-induced differentiation only when added before the time of commitment of the cells to differentiation. The indomethacin-mediated inhibition was counteracted by prostaglandins E1 or E2 but not by prostaglandins F1alpha or F2alpha. Prostaglandin E stimulated phagocytosis induced by a suboptimal concentration of dexamethasone, but prostaglandin F did not. Moreover, lysozyme activity, which is a typical biochemical marker of macrophages, was induced in M1 cells by prostaglandin E alone, as well as by inducers of differentiation. These results suggest that prostaglandin E may be important in the induction of differentiation of myelod leukemia cells.

Animals↗
PubMed1978

Relationship between leukemogenicity and in vivo inducibility of normal differentiation in mouse myeloid leukemia cells.

Leukemogenicity was studied in sensitive mouse myeloid leukemia cells that could be induced to undergo cell differentiation in vitro into mature granulocytes and macrophages by incubation with the inducer (certain proteins or glucocorticoids) and in resistant myeloid leukemia cells that could not be induced to differentiate into mature cells. Three sensitive and five resistant clones were tested. The resistant cells were much more leukemogenic than the sensitive cells, and the survival time of syngeneic mice inoculated with the sensitive cells. In a diffusion chamber in a syngeneic, inbred SL mouse without any additional manipulation or injection of inducer, the resistant cells remained undifferentiated, but the sensitive cells were induced to differentiate into mature granulocytes and macrophages and their proliferation rate decreased. These results suggested that the greater leukemogenicity of resistant cells is associated with some defect in inducibility of cell differentiation.

Animals↗