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V Quemener

Publications and source records attributed to V Quemener.

At least 55 records · Page 3Linked to original sources

Diagnostic value of erythrocyte-free polyamines and histaminemia in malignant hepatic tumors and in liver cirrhosis.

The present study tries to evaluate the diagnosit value in malignant hepatic tumors of polyamines, of which the relationship with cellular kinetics is known, and histamine, of which catabolism follows a similar pathway. One hundred and fifty six patients were studied: 53 with malignant liver tumors (27 primary, 26 metastatic) and 103 with non-tumoral liver diseases of which 65 were cirrhotic and 38 non-cirrhotic. Erythrocyte polyamines (spermidine and spermine) and histamine levels were assayed. The results indicate the following. 1. Polyamine levels were significantly increased (a) in cirrhotic patients, not only when compared with controls (p less than 10(-8)), but also when compared with the non-cirrhotic patients (p less than 10(-7)); (b) in primary malignant hepatic tumors (p less than 10(-3)). 2. Histamine was significantly increased (a) in the non-tumoral liver diseases (p less than 10(-4)), but with no difference between cirrhotic and non-cirrhotic patients; (b) in the secondary malignant tumor patients, histamine levels were lower than in primary tumor patients (p less than 0.04). 3. There was no correlation, in all groups studied, between polyamine and histamine levels. These results suggest the following practical implications. 1. For non-tumor liver diseases, appreciably increased polyamine levels may represent a further argument favoring a cirrhotic condition. 2. In diagnosing hepatic scintigraphic defects, increased polyamine levels would suggest a primary malignant hepatic tumor; low histamine levels are more in favor of a secondary malignant hepatic process.

Adult↗

Red blood cell polyamines in mice bearing the Lewis lung carcinoma (3LL) and in patients with bronchopulmonary cancers.

Experimentally, during Lewis lung carcinoma (3LL) growth, the red blood cell (RBC) polyamine levels increase with tumor volume and are inversely correlated to tumoral concentrations of spermidine and spermine. The RBC level of spermidine is continually correlated to both the volume and the tumoral concentration of this polyamine. Clinically, high levels of RBC polyamine are observed in cases of squamous-cell carcinoma or anaplastic cancer, and not in cases of adenocarcinoma. RBC polyamine levels only permit the establishment of statistical differences between groups of patients. Therefore, clinical use of these molecules as tumor markers depends on an understanding of polyamine distribution within blood.

Adenocarcinoma↗

Polyamines in human brain tumors. A correlative study between tumor, cerebrospinal fluid and red blood cell free polyamine levels.

Polyamine levels have been studied in brain tumor patients. We focused our study on the relationship between tumor, cerebrospinal fluid (CSF) and red blood cell (RBC) polyamine levels. Our results are the following: Polyamine levels in CSF are consistently increased, whatever the histological type may be. The highest tumoral concentrations are found in medulloblastoma. In glioblastomas, the RBC spermidine levels are higher than in the other types of tumors and there is a highly significant correlation between the spermidine/spermine ratio in tumor and RBC. Therefore, RBC polyamine determination might be of clinical interest in the monitoring of patients with glioblastomas.

Astrocytoma↗

In vitro studies on the entry of polyamines into normal red blood cells.

Polyamines are mainly transported in the blood by erythrocytes: Putrescine, spermidine and spermine can be taken up in vitro by red blood cells (RBC); their entry is greater in the presence of serum than in the presence of plasma, and spermine entry is lower than that observed for the two other polyamines. In the presence of serum, the affinity of RBC for spermidine is 30 fold greater than that for putrescine. The majority of RBC polyamines are present in the hemolysate and are not complexed to high molecular weight material. At + 4 degrees C the polyamine uptake is considerably reduced and for putrescine and spermine practically non existent, but it seems that it is internalization rather than binding which constitutes the dependent step. Though intracellular spermidine and spermine levels reflect differences in uptake rather than in outward flux across the cell membrane, the values of putrescine appear to be the resultant of influx and efflux. The presence of specific receptor sites for polyamines visualized by SEM on the surface of RBC using latex-putrescine spheres, confirms the results obtained with labelled polyamines. Therefore, only the understanding of the polyamine repartition inside the blood compartments would permit the clinical use of those molecules as non statistical tumor markers.

Biological Transport↗

[Effect of aminoguanidine sulfate on the hepatic level of polyamines after partial hepatectomy in rats].

The injection of amino-guanidine sulfate, which is a diamine-oxydase inhibitor to Wistar rats partially hepatectomized modifies the putrescine, spermidine and spermine liver concentrations, estimated by thin layer chromatography after dansylation. The three polyamines reach a peak three hours after the beginning of the treatment, then decrease six hours later, especially for putrescine and spermine. Forty eight hours later, the spermidine rate increase again to reach a level superior to that of animals which were only hepatectomized, whereas putrescine and spermine levels remain until about the fourth day inferior to those of control animals. Contrary to shamoperated rats, those injected with amino-guanidine sulfate show higher polyamine concentrations. These observations probably show a reduction of the activity of the diamine oxidase under the influence of amino-guanidine sulfate. According to those results, the action of amino-guanidine sulfate previously observed on the hyperplasic component of liver regeneration, doesn't seem to have an effect upon diamine oxidase.

Amine Oxidase (Copper-Containing)↗

[Dynamics of the elevation of hepatic polyamines after partial hepatectomy in the rat].

Following McCormick's method we have studied the rates of spermine, spermidine and putrescine in regeneration Wistar-rat liver until 4 days posthepatectomy. The putrescine rate exhibits marked increase during the first 6 hours, then slowly drops and returns about to its original value within 90 hours. The concentrations in spermidine and spermine both increase until 10 h; whereas the first concentration keeps on rising, the second one declines to control level within 24 h, but rises again after 72 h. This evolution can be easily explained on the basis of previous studies and may be interpreted in relation to cell divisions which mark early liver regeneration.

Animals↗

[Use of polyamine levels in the study of the antitumor activity of natural substances; use of hepatic regeneration as a study model].

The effect of antitumor drugs has been considered according to in vivo variations of the polyamine levels. The experimental model of cellular proliferation is not a tumoral process but a hepatic regeneration in partially hepatectomized normal rats. This study consists of the treatment of regenerating animals with antiproliferative, therefore antitumor natural drugs, such as colchicine, vincaleucoblastine, and 9-methoxy-ellipticine. Tissular free polyamines (putrescine, spermidine, spermine) in the livers of the animals are estimated. Important rate fluctuations are observed and are related, first, to regeneration time, thus to cellular cycle, and, second, to the presumed effect of these natural drugs. Such a study would, first show the antiproliferative activity of an unknown drug and, second, indicate its mechanism.

Animals↗

[The effect of modification of the intracellular distribution of polyamines on the proliferation of hepatocytes treated with 2-methyl-9-hydroxyellipticine].

2-Methyl-9-hydroxyellipticine (MHE) added to tumoral hepatocyte cultures (400 ng MHE/ml medium) is responsible for a cytostatic effect. This decrease of cellular proliferation and of DNA synthesis is accompanied by an increase of intracellular free spermidine levels. We could not attribute this result to a deviation of this polyamine metabolism. These increased concentrations of free spermidine are connected to a decrease of the amount of nuclear bound polyamines, mainly joined with the RNA fraction. Thus, the cytostatic effect observed with this drug might be related to a decrease in the amount of spermidine connected to RNA; therefore, its intercalating effect is only indirectly responsible for the cellular proliferation decrease.

Alkaloids↗

Procedural memory and Parkinson's disease.

A detailed analysis of the mnestic deficits associated with Parkinson's disease (PD) contributes to explaining the cognitive disorders and their well documented consequences. This study was designed to show that, in PD declarative as well as procedural memory is severely impaired. Three tests designed to explore this aspect of mnestic functioning were proposed to a group of 16 parkinsonian patients whose motoricity was controlled: inverted reading, braille reading, sound form association. The results obtained, compared with those of young and aged controls, show that PD is associated with marked deficits in both declarative and procedural memory. Declarative memory impairment was similar to that observed in the control population (healthy elderly subjects, age-matched with the PD patients) but more marked in PD subjects. The procedural memory deficit was linked with age and pathology. Procedural memory involves a variety of processing modules dedicated to the type of information (visual, auditive, tactile codes). The deficits observed were more like a loss of automatism than procedural impairment stricto sensu ('knowing how'). It would be worth pursuing research by studying akinesia and motor disorders from the angle of automatic memory impairment.

Adult↗

Polyamine binding sites in the rat brain hippocampus plasma membranes: MK 801 does not influence the binding process.

The study was undertaken to characterize the polyamine binding sites in rat brain hippocampus plasma membranes. There were two types of binding sites for putrescine, Bmax 650 and 100 pmol/mg protein, with Kd1 = 39.2 and Kd2 = 6.7 microM, respectively, while those for spermidine (Spd) and spermine (Spm) represented only one type of population with Bmax 2.55 and 15 nmol/mg protein, respectively. The Kd values for Spd and Spm were 34 and 30.3 microM, respectively. The maximum binding of polyamines was found at pH 8.0. The binding capacity of these molecules was curtailed at 4 degrees C, indicating that the binding is an energy-dependent phenomenon. The specific binding was not appreciably influenced by the addition of MK 801, an antagonist of NMDA receptor, indicating that there are polyamine-specific binding sites that are different from those for MK 801. Glycine also did not significantly influence the binding of these biogenic amines. Interestingly, the addition of polyamino acids (polylysine, polyornithine, and polyglutamic acid) inhibited the polyamine binding to their receptor sites, supporting the notion that positive charge of polyamines could be important factor in the binding process.

Animals↗

Protein kinase C inhibitor (H-7) potentiates antiproliferative effects of a polyamine biosynthesis inhibitor.

In this study, a protein kinase C inhibitor, H-7, was found to potentiate the antiproliferative effects of difluoromethyl ornithine (DFMO), inhibitor of the polyamine biosynthesis, on NIH 3T3 and 3T3/SV40 cells in culture. Incubation of the cells with DFMO inhibited the cell growth, whereas the addition of polyamine spermidine to these cells restored the normal rate of cell proliferation with the fact that these cells took up the polyamine from the extracellular medium to compensate the intracellular needs. The addition of H-7 to both the 3T3 and 3T3/SV40 cells, inhibited the cell proliferation, though the level of inhibition was always lower than in those treated with the DFMO alone. The addition of H-7 to the DFMO containing cells potentiated the antiproliferative effects of the latter with the fact that the former inhibited the uptake of the spermidine, though there might be additional targets, like the protein kinase C, involved in the inhibition process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Polyamine deprivation enhances antitumoral efficacy of chemotherapy.

We reported previously that polyamine deprivation by feeding a polyamine deficient diet combined with gastrointestinal tract decontamination and polyamine oxidase inhibition considerably enhanced the antitumoral effect of DFMO, a selective inhibitor of ornithine decarboxylase. The combination of polyamine deprivation and administration of well established cytotoxic drugs was expected to improve further the antitumoral effect of polyamine deprivation in Lewis lung carcinoma grafted in mice. Simultaneous treatment, i.e. administration of the cytotoxic drugs during the polyamine deprivation regimen, reduced tumor growth, but enhanced toxic effects. By alternating treatment and polyamine deprivation (1st day methotrexate (1.7 mg/kg), 2nd day cyclophosphamide (90 mg/kg), 3rd day vindesine (0.25 mg/kg), followed by five days of polyamine deprivation), tumor growth was reduced by 90% and an increase of 64% in the survival time of the animals was observed, demonstrating that a significant enhancement of the efficacy of chemotherapy was achieved without concomitant enhancement of toxic effects.

Animals↗

Proton NMR spectroscopy of plasma lipoproteins in the experimental Lewis lung carcinoma.

Plasma and fractionated lipoproteins from 40 Lewis Lung Carcinoma grafted mice were tested from the first day up to the fatal issue by biochemical analyses and water suppressed 1H NMR spectroscopy. We have confirmed first, that the 1H NMR spectra of plasma lipoproteins are modified by the tumoral state and could provide a useful marker of the disease as long as they are used for individual follow-up with appropriate spectral parameters. Using fractionated lipoproteins we have demonstrated secondly, that the observed spectral modifications do not result from a specific cancer lipoprotein but from quantitatively modified ratio between Very Light Density Lipoproteins and High Density Lipoproteins.

Animals↗

Red blood cell polyamine evolution during normal growth in mouse.

Red blood cell (RBC) polyamine levels were studied at different ages in growing mice. Contrary to RBC from adult mice, high levels of the three polyamines Putrescine, Spermidine (Spd), Spermine (Spm) were detected in erythrocytes from newborn mice. These levels progressively decreased during growth. As previously reported in experimental and clinical studies related to tumor progression or normal tissue regeneration, a statistical correlation between Spd and Spm was noticed in this study concerning normal growth. As regards this correlation, two separate periods appeared during development. The slope values of the straight regression line were calculated for these periods and showed highly significant differences.

Aging↗

Accumulation of polyamine analogs in red blood cells: a potential index of tumor proliferation rate.

It has previously been demonstrated that during Lewis lung carcinoma (3LL) growth, red blood cell (RBC) spermidine (Spd) levels change concominantly with the tumor volume and [14C] Spd accumulates in proportion with the tumor volume, if [14C] putrescine (Put) is administered. In the present study we substituted a non-radioactive analogue for labelled Put with the aim to perform human studies, should the method prove suitable to quantify malignant cell proliferation intensity. 2-Methylputrescine (2MPut) is an excellent substrate of spermidine synthase and is transformed in vivo into methylspermidine (MSpd) and 6-methylspermine (6MSpm). After a single i.p. dose of 2MPut, MSpd accumulated in RBC of mice with 3LL xenografts. The concentration of MSpd correlated directly with tumor progression. No significant amounts of MSpd were found in RBC of normal mice. It appears that 2MPut has the potential to become a new tool in tumor diagnostics.

Animals↗

Inhibition of the growth of U-251 human glioblastoma in nude mice by polyamine deprivation.

An almost complete prevention of tumor growth was achieved in U-251 human glioblastoma xenografted nude mice, by partial decontamination of the gastrointestinal tract and feeding of a polyamine-free diet containing inhibitors of ornithine decarboxylase (DFMO) and of polyamine oxidase (MDL 72527). After one week of polyamine deprivation, spermidine concentrations were lowered, and spermine levels were increased in all tissues. In contrast, putrescine concentrations were only reduced in tumor and in brain. Erythrocyte polyamine determinations revealed differences similar to those observed in tissues: spermidine concentration was lowered by 50% and spermine level was 3-fold increased. If this or related treatments should become of therapeutic importance in the future, then the determination of erythrocyte polyamine levels might be of diagnostic value.

Animals↗

Effect of a pulsed magnetic field on healthy mice: a study of the weight of the thymus.

The hypothesis that magnetic fields act only on deficient functions has been tested through the weight of the thymus in mice. The involution of the thymus in mice is known to begin early in life. It is marked by a decrease in weight. Female Swiss mice of different ages were exposed to a pulsed magnetic field 0.6 or 6 mT in intensity, 12 or 460 Hz in frequency. It was shown that the weight of the thymus in 8-week-old mice was not modified by the exposure, while the weight of the thymus in 15-week-old mice was increased. The maximum increase, about 16% relative to the controls, was obtained 24 hours after a 30 minutes' exposure. Hydrocortisone or cyclophosphamide prevented the effect. The increase in weight has been considered to be due to an increase of the number of the cells in the thymus.

Animals↗