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Biomedical subjects

G Rovera

Publications and source records attributed to G Rovera.

At least 127 records · Page 7Linked to original sources
PubMed1980

Differentiation of human leukemias in response to 12-0-tetradecanoylphorbol-13-acetate in vitro.

Leukemic cells from patients with acute myeloid leukemia underwent morphological, functional, and histochemical changes within 24-48 hr after treatment with 1.6 x 10-18 M 12-0-tetradecanoylphorbol-13-acetate (TPA). The changes included adhesion to the plastic substrate, a 4-6-fold increase in the number of phagocytic cells, and an increase in the number of alpha-naphthyl-acetate esterase (alpha-NAE) positive cells. In contrast, TPA treatment of cells from patients with acute lymphoblastic leukemia caused some aggregation of cells in suspension, but no changes in adhesion, phagocytosis, or alpha-NAE. Of the four cases of undifferentiated or unclassified leukemias studied, two failed to respond to TPA, one responded with a myeloid (adhesion) pattern, and one with a lymphoid (aggregation) pattern. These data suggest that leukemic myeloblasts retain the ability to express a variety of differentiated functions, and in some cases, it may be possible to use TPA as a tool to test the differentiative potential of undifferentiated human leukemias.

Cell Adhesion↗
PubMed1979

Induction of differentiation in human promyelocytic leukemia cells by tumor promoters.

Phorbol diester tumor promoters and the promoter mezerein convert human promyelocytic leukemia cells in culture into adherent, nonproliferating cells with many of the characteristics of macrophages. Other types of promoters such as anthralin, phenobarbital, and saccharin do not have this effect. Various compounds that can inhibit some of the biological and biochemical effects of tumor promoters do not interfere with the induction of cell adherence and differentiation by the effective promoters.

Cell Adhesion↗
PubMed1979

Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester.

When suspension cultures of human promyelocytic leukemia cells (line HL60) were treated with 12-O-tetradecanoylphorbol 13-acetate (TPA; 1.6-160 nM), more than 80% of the cells adhered to the plastic substrate within 24 hr. Within the same time period the immature azurophilic granulations typical of HL60 promyelocytic cells disappeared and the nuclear chromatin became more condensed, but the nucleolus was retained. The attached cells stopped dividing and synthesizing DNA. The phenomenon was irreversible and independent of the continuous presence of TPA. Approximately 60% of the untreated cells and of TPA-treated cells bore surface Fc receptors for IgG. Under the experimental conditions used, about 10% of the TPA-treated cells were also able to phagocytize IgG-coated erythrocytes and more than 80% were able to phagocytize latex beads, but untreated controls were unable to do so. Cellular levels of NADase, acid phosphatase, and non-specific esterase were markedly increased after treatment with TPA, whereas little or no increase was seen after treatment with dimethyl sulfoxide (Me2SO), a drug that induces myeloid differentiation of HL60 cells. Peroxidase activity was lower in TPA-treated and Me2SO-treated cells than in HL60 cells. More lysozyme was found in the medium of TPA-treated cells than in the medium of untreated or Me2SO-treated cells. These data indicate that, after treatment with TPA, human promyelocytic leukemia cells can differentiate into cells that have several characteristics of macrophages.

Cell Adhesion↗
PubMed1979

Regulation of acid phosphatase activity in human promyelocytic leukemic cells induced to differentiate in culture.

Induction of differentiation of a human promyelocytic leukemic cell line (HL60) in culture is accompanied by changes in acid phosphatase (Acpase) activity. The increase in activity is less than twofold when the leukemic cells are stimulated by dimethylsulfoxide (DMSO) to differentiate into metamyelocytes and granulocytes but is eightfold when the cells are stimulated by the tumor-promoting agent 12-0-tetradecanoylphorbol 13-acetate (TPA) to differentiate into macrophage-like cells. Five different isozymes of Acpase were separated by acrylamide gel electrophoresis. Isozyme 1, the most anodal isozyme, was found to be present in undifferentiated, DMSO-treated and TPA-treated cells; isozyme 2 was a very faint band observed both in DMSO- and TPA-treated cells, the isoenzymes 3a and 3b were present only in TPA-induced cells; and isozyme 4, the most cathodal isozyme, was present both in TPA- and DMSO-induced cells. A time sequence study on the appearance of the various forms after TPA treatment indicated that the expression of the isozymes is regulated in an uncoordinated fashion. Acpase activity has been shown by ultrastructural cytochemistry to be localized in the entire rough endoplasmic reticulum (RER) and in areas of the smooth endoplasmic reticulum (SER) located near the Golgi complex in differentiating cells but to be extremely weak, if at all detectable, in undifferentiated promyelocytes.

Acid Phosphatase↗
PubMed1978

Hemin controls the expression of the beta minor globin gene in Friend erythroleukemic cells at the pretranslational level.

When clone 745 Friend erythroleukemia cells are induced to differentiate by treatment with 1 X 10(-4) M hemin, the beta minor globin gene is preferentially expressed over the beta major gene. An analysis of the beta-mRNA molecules in in vitro translation systems indicates that essentially only the beta minor message is available for translation. This indicates that in Friend erythroleukemia cells hemin selectively controls the expression of the beta minor globin gene at the pretranslational level.

Cell Line↗
PubMed1978

Membrane fusion as a mechanism of simian virus 40 entry into different cellular compartments.

Permissive and nonpermissive simian virus 40 (SV40)-infected cells were ultrastructurally analyzed. Viral particles were found in the cytoplasm, rough endoplasmic reticulum, nuclear envelope, lysosomes, and mitochondria. Upon entering the cell the virion obtains a tight membrane envelope. It seems to be either released from the envelope upon fusion with other membranes of the cell or aggregated into tubular membrane specializations upon fusion with other membrane-enveloped particles. Reconstructed morphological sequences and the finding of SV40 in different spaces of the cell suggest that entry of SV40 into the different compartments and eventually into the site of replication is facilitated by its capacity for being enveloped by a variety of membranes (notably the cell membrane and the nuclear membrane) and the sequential fusion and fission of these membranes.

Cell Line↗
PubMed1977

Tumor promoters inhibit spontaneous differentiation of Friend erythroleukemia cells in culture.

Clones of Friend erythroleukemia cells, characterized by the presence of 40-70% benzidine-positive cells synthesizing hemoglobin in the absence of inducing drugs, were treated with several phorbol diesters with a known range of tumor-promoting activity on mouse skin. Good correlation was found between the reported tumor-promoting activity of a particular phorbol diester and its ability to inhibit spontaneous erythroid differentiation in culture. The inhibition of differentiation by 12-O-tetradecanoyl-phorbol-13-acetate, the most active tumor promoter, was maximum after 4 days of treatment; this inhibition was reversed by removal of the phorbol diester no matter how long the period of treatment. Unlike control cells, which gradually revert to a population with a low percentage of benzidine-positive cells, cells treated with 12-O-tetradecanoyl-phorbol-13-acetate retained a high potential for spontaneous differentiation.

Animals↗
PubMed1977

Temperature-sensitive variants for saturation density and anchorage dependencey of a simian virus 40-transformed human X mouse hybrid cell line.

Several variant clones temperature sensitive for some parameters of transformation from a hybrid cell line containing a stable diploid mouse genome and two human chromosomes 7 carrying an integrated defective simian virus 40 have been isolated. Like the wild-type (wt) cells, at the permissive temperature the temperature-sensitive (ts) clones grew to high saturation densities and readily formed colonies in methyl cellulose. In contrast to the wt cells, at the nonpermissive temperature they had variable but always lower saturation densities and were unable to form colonies in methyl cellulose. The fraction of cells that synthesized DNA decreased at both temperatures when the cells reached saturation density, but it represented always at least 20% of the total population. All of the ts clones so far tested had a near triploid chromosome number, contained from one to three human chromosomes 7, and were T-antigen-positive both at the permissive and nonpermissive temperatures. The ts clones maintained low saturation density at the nonpermissive temperature because of a decrease in the number of cells that were actively proliferating and because of the shedding of cells into the medium. Temperature downshifts and refeeding allowed for expression of the permissive phenotype. In most of the isolated clones anchorage independency was not correlated with unrestricted cell proliferation. These variant clones may provide useful systems for a better understanding of the number of interdependent pathways involved in the expression of the phenotype of a transformed cell and elucidate the molecular mechanism required for the maintenance of a normal state in a cell population.

Antigens, Viral↗
PubMed1976

The phenotypes of variant clones of Friend mouse erythroleukemic cells resistant to dimethyl sulfoxide.

The cloning efficiency of Friend erythroleukemic mouse cells is reduced by approximately 50% at every generation when the cells are continuously grown in the presence of 2% dimethyl sulfoxide (DMSO). Clones of murine erythroleukemic cells, resistant to the effect of the drug, have been selected from a nonmutagenized, hemoglobin (Hb)-inducible clone 745. The variant cells are present in the population with a frequency of 3 X 10(-5) cells. Twelve clones, characterized by different growth rates, have been examined in more detail. All the clones can grow in the continuous presence of 2% DMSO, are noninducible or poorly inducible by the drug, and consist of a homogeneous proerythroblastic cell population and a low number of Hb-synthesizing cells, except for clone R22S in which about 30% of the cells synthesize Hb. All but one (R2102) of the noninducible clones can be induced to synthesize Hb to various degrees by treatment with 1 mM butyric acid for 4 days. One clone (R1Z) forms colonies at a much higher efficiency in 2% DMSO than in nonselective plates, suggesting that it is conditional for DMSO. These and other resistant clones could be useful for the study of the mechanisms of induction of terminal differentiation.

Animals↗