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Biomedical subjects

M Presta

Publications and source records attributed to M Presta.

At least 127 records · Page 7Linked to original sources
PubMed1986

Both normal and tumor cells produce basic fibroblast growth factor.

We have previously purified from human placenta a basic fibroblast growth factor (FGF)-like molecule which stimulates the production of plasminogen activator (PA) and collagenase, induces DNA synthesis, produces an increase in motility in cultured bovine capillary endothelial (BCE) cells, and induces angiogenesis in vivo. The ability of basic FGF to stimulate PA production in BCE cells was used as an assay for the presence of basic FGF-like molecules in extracts of both normal and tumor-derived cultured cells. The identity of the PA-stimulatory activity with basic FGF was confirmed by its high affinity for heparin and by its cross-reactivity with antibodies to human placental basic FGF. Basic FGF-like molecules were identified in eight of ten cell lines tested, and the amount of FGF-like activity present in these cells bore no relation to their origin from normal or tumor tissue. The test cells, BCE cells, had one of the highest levels of FGF-like activity, suggesting that it may have an autocrine role in these cells.

Animals↗
PubMed1986

Purification of a factor from human placenta that stimulates capillary endothelial cell protease production, DNA synthesis, and migration.

A protein that stimulates the production of plasminogen activator and latent collagenase in cultured bovine capillary endothelial cells has been purified 10(6)-fold from term human placenta by using a combination of heparin affinity chromatography, ion-exchange chromatography, and gel chromatography. The purified molecule has a molecular weight of 18,700 as determined by NaDodSO4/PAGE under both reducing and nonreducing conditions. The purified molecule stimulates the production of plasminogen activator and latent collagenase in a dose-dependent manner between 0.1 and 10 ng of protein/ml. The purified protein also stimulates DNA synthesis and chemotaxis in capillary endothelial cells in the same concentration range. Thus, this molecule has all of the properties predicted for an angiogenic factor.

Angiogenesis Inducing Agents↗
PubMed1986

Purification from a human hepatoma cell line of a basic fibroblast growth factor-like molecule that stimulates capillary endothelial cell plasminogen activator production, DNA synthesis, and migration.

A 17,500-dalton protein which stimulates plasminogen activator production in cultured bovine capillary endothelial cells has been purified from a SK-Hep-1 human hepatoma cell lysate by using heparin affinity chromatography and fast protein-liquid ion exchange chromatography. The purified molecule stimulated plasminogen activator production in a dose-dependent manner between 0.01 and 1 ng/ml. It also stimulated collagenase synthesis, DNA synthesis, and motility in capillary endothelial cells in the same concentration range. This molecule was identified as a basic fibroblast growth factor-like molecule on the basis of its biological activity, its affinity for heparin-Sepharose, and its cross-reactivity with a polyclonal antibody raised against the human placental basic fibroblast growth factor.

Animals↗
PubMed1986

Further studies on the tumor-initiating activity of the beta-blocker DL-ZAMI 1305.

The purpose of this study was to evaluate the initiating activity of the hepatocarcinogen beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (DL-ZAMI 1305) by the initiation-promotion protocol of Pereira. Female Wistar rats were given a single dose 150 mg/kg of body weight of DL-ZAMI 1305 by gavage 24 hours before or 24 hours after partial hepatectomy. One week later rats were given phenobarbital (0.05%) in the diet for a period of 7 weeks. DL-ZAMI 1305-treatment resulted in the appearance of gamma-glutamyltranspeptidase foci and of other preneoplastic lesions in all animals. Preneoplastic lesions were also present in a fraction of DL-ZAMI 1305-treated animals not subjected to partial hepatectomy, whether given or not phenobarbital. Results obtained in a separate experiment demonstrated that DL-ZAMI 1305-treatment inhibits cell proliferation and induces DNA damage in the regenerating rat liver. The results of this study clearly demonstrated that the beta-blocker DL-ZAMI 1305 is an initiating carcinogen for the liver of female Wistar rats.

Adrenergic beta-Antagonists↗
PubMed1985

Inhibition of DNA and RNA synthesis in rat liver nuclei by oncogenic and non-oncogenic beta-blockers.

The beta-blocker DL-1-(2-nitro-3-methylphenoxy)-3-tert-butylaminopropan-2-ol (ZAMI 1305), hepatocarcinogenic to the female rat, and the non-oncogenic beta-blockers DL-1-(2-nitro-5-methylphenoxy)-3-tert-butylaminopropan-2-ol (ZAMI 1327), DL-propranolol, and DL-atenolol were studied for their capacity to interfere with hepatic DNA and RNA synthesis. These moieties inhibit DNA and RNA synthesis, in a dose-dependent fashion, when added in vitro to nuclei isolated from the liver of male or female rats. The inhibition is due to a decrease of the initial rate of synthesis and of the total amount of labeled precursor incorporated into the growing chains. When administered in vivo both the oncogenic ZAMI 1305 and its non-oncogenic isomer ZAMI 1327 inhibit hepatic DNA and RNA synthesis in female rats, as evaluated by the determination of nucleic acids synthesis in liver nuclei isolated from female rats 5 and 15 min after the injection of the drug. No influence on hepatic DNA and RNA synthesis is observed when the molecules are administered to male rats. The in vivo administration of DL-propranolol causes an increase of hepatic DNA and RNA synthesis in male rats, while it is uneffective in female rats.

Adrenergic beta-Antagonists↗
PubMed1984

Early liver alterations induced by the sex-dependent hepatocarcinogen beta-blocker ZAMI 1305.

Liver alterations occurring after 1, 6 or 10 days of treatment with the hepatocarcinogen beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butyl-amino-propan-2-ol (ZAMI 1305) were studied in male and female Wistar rats. In agreement with its sex-dependent oncogenicity, ZAMI 1305 administration causes DNA damage in the liver of the female but not of the male rat, with the only exception of 2 out of 4 males treated for 6 days. In female rat, the amount of DNA damage increases from 1 to 6 days of treatment, being unchanged at 10 days; a small portion of DNA is however damaged. ZAMI 1305 administration to female rat induces also: (i) an increase of the relative liver weight, of the DNA and RNA synthesizing activity; (ii) a decrease of the number of hepatocytes in mitosis; (iii) a minimal oval cell hyperplasia. When the same parameters were studied in ZAMI 1305-treated male rats, they were unaffected or changed to a less extent in respect to female rats.

Adrenergic beta-Antagonists↗
PubMed1984

Optical isomers of the hepatocarcinogenic beta-blocker ZAMI 1305: influence on nucleic acids synthesis and DNA integrity.

The influence on nucleic acids synthesis and DNA integrity of the D-isomer and of the DL-racemic form of the oncogenic beta-blocker 1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (ZAMI 1305) and of the non-oncogenic beta-blocker propranolol was tested in vitro and in vivo. Both D- and DL-ZAMI 1305, when added in vitro to nuclei isolated from rat liver, cause inhibition of DNA and RNA synthesis and DNA fragmentation, as evaluated by alkaline sucrose gradient analysis, in a similar dose-dependent fashion. D- and DL-ZAMI 1305 also inhibit to a similar extent the activity of DNA polymerase alpha and beta from regenerating rat liver. When administered in vivo to female rats both D and DL-ZAMI 1305 cause a dose-dependent fragmentation of liver DNA. The D-isomer and DL-racemic form of the non-oncogenic beta-blocker propranolol inhibit DNA and RNA synthesis and cause DNA fragmentation when added in vitro to isolated liver nuclei, being instead without effect when administered in vivo.

Adrenergic beta-Antagonists↗
PubMed1984

Age-dependent, seasonal and daily variations of the DNA damaging capacity of the hepatocarcinogen ZAMI 1305 in female rat liver.

A single injection of the sex-dependent hepatocarcinogen DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (ZAMI 1305) caused age-related DNA damage, as evaluated by alkaline sucrose gradient analysis, in the liver of female Wistar rats. DNA damage reached a maximum at 4-6 weeks of age, about the onset of sexual maturity, and decreased thereafter. In young rats (5-8 weeks of age), the amount of ZAMI 1305-induced DNA damage showed seasonal and daily differences, being higher when the molecule was administered in winter in respect to summer and in the evening in respect to the morning. In older rats (15-22 weeks of age), no seasonal and daily variations were observed.

Aging↗
PubMed1984

Tumor-initiating activity of the beta-blocker ZAMI 1305 in the liver of the female Wistar rat.

A 1-week treatment with the hepatocarcinogen beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (ZAMI 1305) induces the appearance of preneoplastic liver lesions--oval cell hyperplasia, basophilic and gamma-glutamyltranspeptidase positive (GGT+) foci--in female Wistar rats, as evidenced by the Solt and Farber short-term test of carcinogenesis. ZAMI 1305-treatment also induces liver DNA damage, as evaluated by alkaline sucrose gradient analysis. The data suggest that the oncogenic B-blocker ZAMI 1305 has initiating activity in the liver of the female Wistar rat.

2-Acetylaminofluorene↗
PubMed1984

Embryonic----Fetal Hb switch in humans: studies on erythroid bursts generated by embryonic progenitors from yolk sac and liver.

The synthesis of embryonic (zeta, epsilon), fetal (alpha, gamma), and adult (beta) globin was evaluated in human yolk sacs (YS) and livers at different ontogenic stages (i.e., from 6 through 10-12 wk of age) by means of analytical isoelectric focusing. Globin production was comparatively evaluated in vivo (i.e., in directly labeled erythroblasts from YS and liver) and in vitro [i.e., in erythroid bursts generated in culture by erythroid burst-forming units (BFU-E) from the same erythropoietic tissues]. Erythroid bursts generated in vitro by BFU-E from 6-wk livers and YS show essentially a "fetal" globin synthetic pattern: this is in sharp contrast to the "embryonic" pattern in corresponding liver and YS erythroblasts directly labeled in vivo. The invitro phenomenon suggests that (i) 6-wk BFU-E constitute a new generation of progenitors, which have already switched from an embryonic to a fetal program, and/or (ii) expression of their fetal program is induced by unknown in vitro factor(s), which may underlie the in vivo switch at later ontogenic stages. It is emphasized that 6- to 7-wk BFU-E are endowed with the potential for in vitro synthesis of not only epsilon- and gamma-chains but also some beta-globin. In general, we observed an inverse correlation between the levels of epsilon- and beta-chain synthesis. These results, together with previous studies on fetal, perinatal, and adult BFU-E, are compatible with models suggesting that in ontogeny the chromatin configuration is gradually modified at the level of the non-alpha gene cluster, thus leading to a 5'----3' activation of globin genes in a balanced fashion.

Embryo, Mammalian↗
PubMed1984

Thyroid and chemical hepatocarcinogenesis: further insights from the hepatocarcinogen ZAMI 1305.

The beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylaminopropan-2-ol (ZAMI 1305), oncogenic to the liver of the female but not of the male Wistar rat, was used to investigate some aspects of the relationship between liver and thyroid during chemical hepatocarcinogenesis. Thyroidectomy (TDX) strongly reduces the amount of hepatic DNA damage induced by a single administration of ZAMI 1305 in the female Wistar rat. One week of treatment with triiodothyronine (T3) completely restores the susceptibility of the liver of thyroidectomized animals to the genotoxic activity of the molecule. The amount of hepatic DNA damage in intact females varies with the age of the animal, being maximal in rats of 4-8 weeks of age, when T3 serum concentration are also maximal. An increase of relative thyroid weight, coupled with histological hyperplasia of the gland, is observed in female Wistar rats treated for 6 months with ZAMI 1305. Minimal changes of the thyroid are observed in ZAMI 1305-treated male rats. The increase of relative thyroid weight in female rats appears to be related to the severity of preneoplastic and neoplastic liver changes. These findings and several suggestions from the literature lead us to propose a model for the interaction between liver and thyroid during chemical hepatocarcinogenesis.

Animals↗
PubMed1983

Thyroid modifications in male and female rats treated with the hepatocarcinogen beta-blocker ZAMI 1305.

The morphology of the thyroid gland from Wistar rats treated for 6 months with the beta-blocker DL-1-(2-nitro-5-methyl-phenoxy)-3-tert-butyl-amino-propan-2-ol (ZAMI 1305), a potent sex-dependent hepatocarcinogen, was studied. A significant high incidence of cases with thyroid hyperplasia is found among female rats, the only sex susceptible to the carcinogenic effect of ZAMI 1305. Thyroid hyperplasia is instead much less evident in male rats. In female rats the increase in the relative thyroid weight is directly related to the gravity of the predominant liver lesion (clear cell foci, neoplastic nodules, hepatocellular carcinomas). The results suggest an influence of the preneoplastic and neoplastic liver on thyroid gland.

Adrenergic beta-Antagonists↗
PubMed1983

In vitro and in vivo DNA damage of male and female rat liver nuclei by oncogenic and nononcogenic beta blockers.

The beta blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (ZAMI 1305), hepatocarcinogenic to the female rat, and the nononcogenic beta blockers DL-1-(2-nitro-5-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (ZAMI 1327), DL-propranolol, and DL-atenolol were tested for their capacity to damage liver DNA in vitro and in vivo. As revealed by alkaline sucrose gradient analysis, all the beta blockers tested, with the exception of DL-atenolol, caused a dose-dependent DNA fragmentation when they were added in vitro to nuclei isolated from livers of both male and female Wistar rats. Analysis of the DNA sedimentation patterns in neutral sucrose gradients demonstrated the absence of DNA fragmentation, thus indicating that the drugs did not induce double-strand DNA breaks. When the beta blockers were administered in vivo, liver DNA damage was observed only in female Wistar rats treated with ZAMI 1305. A single injection of ZAMI 1305 caused the onset of two distinct episodes of DNA damage. The first episode occurred within 5 minutes, and the damage was repaired within 1 hour after the injection; the second, apparently spontaneous, episode occurred 14 hours after the injection, and the damage was more pronounced than that seen in the first episode and took a much longer time to subside. However, a second injection of ZAMI 1305 into female Wistar rats 8 hours after the first injection did not induce the immediate short-lived episode of DNA damage but, like the first injection, it caused late DNA damage that peaked about 16 hours after drug administration.

Adrenergic beta-Antagonists↗
PubMed1982

Inhibition in vitro of yeast DNA polymerase I activity by beta-blockers.

The activity of DNA polymerase I from Saccharomyces cerevisiae is inhibited, in a dose-dependent fashion, by the oncogenic beta-blocker 1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (ZAMI 1305) and by the non-oncogenic beta-blockers 1-(2-nitro-5-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (ZAMI 1327), atenolol, and propranolol, the latter having the highest inhibiting activity. The inhibition is due to an interaction of the beta-blockers with the free enzyme and with the enzyme-DNA complex. The degree of inhibition is directly related to the hydrophobicity of the aromatic moiety and to the length and hydrophilicity of the aliphatic chain of the inhibitor. No relation seems to exist between the in vitro inhibition of yeast DNA polymerase I by beta-blockers and their oncogenic activity.

Adrenergic beta-Antagonists↗
PubMed1982

Preferential induction of fetal versus embryonic globin chains in human leukemic cell lines.

By use of a newly developed technique combining affinity chromatography of hemoglobin on haptoglobin-Sepharose and IEF of globin chains, we analyzed the globin synthetic pattern of human K562 cells in both the basal state and after addition of several potential inducers. Hemin only was found effective: its addition at 50 microM results in a quantitative increase of globin chain synthesis (from 0.3 to 1% up to 5%) and a qualitative "switch" with a striking increase of alpha and a decrease of epsilon and zeta chains (relative to the prevailing gamma chains). This system, in which hemin induces changes that mimic to some extent the normal embryonic-fetal switch, might therefore provide a cellular model for investigating molecular mechanisms of globin gene regulation. In addition similar results were obtained with a different human myeloid leukemia cell line, the KG1, thus raising the possibility that the expression of embryonic globin genes in malignant cells might not be simply the consequence of abnormal gene expression but rather reflect a possibly physiological differentiation phenomenon.

Animals↗