Biomedical subjects

L Giroldi

Publications and source records attributed to L Giroldi.

5 recordsLinked to original sources

PubMed1992

Role of activator protein-1 and methylation function in 12-O-tetradecanoylphorbol-13-acetate--mediated inhibition of differentiation of Friend erythroleukemia cells.

Friend erythroleukemia cells (FELCs) differentiate after hexamethylene-bis-acetamide treatment. This differentiation is characterized by an increase in beta-globin gene expression that is followed by appearance of the hemoglobin. Phorbol-ester tumor promoters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), inhibit differentiation of TPA-sensitive cells but not TPA-resistant cells. We have shown that the increase in beta-globin expression is inhibited by TPA in a TPA-sensitive clone but not in a TPA-resistant clone. To study the molecular mechanisms of regulation of gene expression by TPA, we examined the possible involvement of gene methylation and the TPA-responsive element (TRE). Both clones showed similar patterns of methylation around the beta-globin gene. Moreover, TPA-induced TRE binding and TRE enhancer activity were similar in both variants. These results suggest that the TPA inhibition of induced differentiation may not be explained by regulation of the methylation state. The activator protein-1 also does not play a crucial role in the sensitivity of FELCs to TPA.

Animals↗

PubMed1990

Pharmacokinetics of tiaprofenic acid after oral administration in fasting patients during and between migraine attacks.

This study examined the pharmacokinetics of 300 mg of tiaprofenic acid, a NSAID belonging to the 2-arylpropionic class, as a single oral dose, in 10 migraine patients during and out of migraine attacks. Plasma concentration of tiaprofenic acid was determined by HPLC analysis. Drug absorption appeared to be the same during and out of migraine attacks (absorption half life: during attack, 0.249 +/- 0.122 hr; out of attack, 0.249 +/- 0.105 hr; maximum plasma concentration: during attack, 37.8 +/- 9.8 ug/ml; out of attack, 40.1 +/- 13.2 ug/ml). The other pharmacokinetic parameters evaluated were not affected by headache attacks as well. We conclude that tiaprofenic acid absorption and metabolism are not affected by migraine attacks. Also, our data suggest that tiaprofenic acid might be useful in the treatment of migraine.

Administration, Oral↗

PubMed1988

Cellular-oncogene expression in Friend erythroleukemia cells: relationship to differentiation, commitment and TPA effects.

Induced differentiation of Friend erythroleukemia cells can be continuously and reversibly inhibited by phorbol ester tumor promoters, e.g. 12-O-tetradecanoylphorbol-13-acetate (TPA), for many years, allowing us to study the mechanisms of differentiation and its inhibition by TPA. We previously identified two steps in the differentiation process, which can be inhibited by TPA, before and after commitment to differentiation. Using permanently committed cells and TPA-resistant variants we examined the role of cellular oncogenes in Friend cell differentiation control, and their possible modulation by tumor-promoting phorbol esters. We report here characteristic changes in myc, myb and fos mRNA levels upon induction of differentiation by hexamethylene bisacetamide treatment, and present evidence that c-myb mRNA decline is one feature of Friend cell commitment to differentiation. In addition, using our TPA-sensitive and resistant cell lines, we observed that the hexamethylene bis-acetamide induced pattern of oncogene expression is unperturbed by TPA, regardless of whether the cells are differentiating or not.

Cell Differentiation↗

PubMed1986

1-Oleoyl 2-acetyl glycerol inhibits differentiation of TPA-sensitive but not of TPA-resistant Friend cells.

Recent studies have shown that diacylglycerols mimic several effects of 12-O-tetradecanoylphorbol 13-acetate (TPA) on cultured cells and suggest that diacylglycerols are the endogenous functional analogues of phorbol esters. However, all such studies have been of short duration, and although a single application of diacylglycerol induces these effects, tumour promotion usually requires long and repeated application of tumour-promoting agents. Here we investigated the effect of 1-oleoyl 2-acetyl glycerol (OAG) on differentiation of Friend erythroleukaemia cells (FELC), since TPA must be present continuously to inhibit differentiation in this system throughout the experiment. We also studied the effects of OAG in both TPA-sensitive and TPA-resistant clones, to investigate whether OAG and TPA have a similar mode of action. We found a dose-dependent inhibition of differentiation by OAG in the TPA-sensitive clone, but not in the TPA-resistant clone. Repeated treatment was necessary to achieve these results; almost complete inhibition could be obtained when OAG was applied 7 times/day for 3.5 days at 3 micrograms/ml per application, whereas a single application of OAG at a higher dose had no effect. Protein kinase C, which is believed to be the common target of OAG and TPA, was present in both TPA-sensitive and TPA-resistant FELC clones. These results suggest that OAG mimics the long-term effect of TPA and that the mechanism by which FELC clones resist TPA and OAG is not a lack or functional deficiency of protein kinase C.

Acetamides↗

PubMedDate not supplied

Okadaic acid and phorbol esters: comparative effects of these tumor promoters on cell transformation, intercellular communication and differentiation in vitro.

Okadaic acid is a non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoter in the mouse skin carcinogenesis system. Here we report on the in vitro activity of okadaic acid in 3 assay systems: BALB/c 3T3 cell transformation, gap junctional intercellular communication (GJIC) in various cell types, and inhibition of induction of differentiation of Friend virus-transformed murine erythroleukemia (MEL) cells. The activity of okadaic acid was compared to that of the phorbol ester tumor promoters TPA and phorbol-12,13-didecanoate (PDD). In a test system involving a 2-week exposure of BALB/c 3T3 cells following 3-methylcholanthrene initiation, okadaic acid at a concentration of 10 ng/ml was equipotent to PDD as a promoter of cell transformation (4.9 and 3.7 foci/dish, respectively). Longer exposures to okadaic acid resulted in cytotoxicity. Okadaic acid-generated as well as PDD-generated transformed foci displayed a selective lack of GJIC between focus cells and surrounding normal cells, i.e., transformed cells communicate among themselves but not with surrounding cells. However, in contrast to TPA, there was no inhibition by okadaic acid, except at toxic doses, of homologous GJIC in BALB/c 3T3 cells or human and mouse keratinocytes. Furthermore, okadaic acid, unlike TPA, did not inhibit MEL cell differentiation. Together, these results indicate that okadaic acid acts as a promoter of cell transformation but that its mechanism of action is different from that of the phorbol ester tumor promoters.

Animals↗