Regional chemotherapy with blood filtration for non resectable liver metastases.
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Antibiotics, Antineoplastic↗
Biomedical subjects
G Taton
Publications and source records attributed to G Taton.
Adjuvant treatment in gastric cancer. Possibilities to take or to leave it.
The primary mode of management of gastric carcinoma is surgical resection with 5-year survival rate following curative resection of about 30 to 40%. This article reviews the results of randomized clinical trials including adjuvant chemotherapy, radiation treatment and chemoimmunotherapy after curative surgical resection. Randomized trials done to date largely do not support the use of adjuvant chemotherapy in resected gastric cancer. Mitomycin C or FAM association have demonstrated the best efficiency with increase of median survival in treated patients. Mitomycin C demonstrated a significant advantage by reduction of the incidence of hematogenous metastases. Encouraging perspectives come from the association between chemotherapy and biochemical modulators.
Chemotherapy, Adjuvant↗
[Cholestatic hepatitis and amoxicillin-clavulanic acid combination. Personnel case report and literature review].
The association amoxicillin-clavulanic acid is a widely used medication. Only about 15 cases of cholestatic hepatitis were reported in Belgium between 1990 and 1993; about 100 cases have been reported to the pharmaceutical company. This effect is severe but reversible. The injury is probably idiosyncratic or immunologically based. Age, sex and treatment duration are as many agents of risk. The diagnosis is undertaken on basis of clinical examination, chronological study, biological evolution and histology.
Age Factors↗
Determination of leucovorin and 5-fluorouracil in plasma by high-performance liquid chromatography.
A method was developed for the determination of (6R)- and (6S)-leucovorin and 5-fluorouracil in plasma. As leucovorin diastereoisomers cannot be separated on a classical reversed-phase column, it was necessary to use a chiral stationary phase. The method presented is based on the same principle as the method described by Wainer and Stiffin [J. Chromatogr., 424 (1988) 158], i.e., coupling of a bovine serum albumin phase to an achiral stationary phase. Before the chromatography, the drug was isolated from the plasma matrix by solid-phase extraction. For 5-fluorouracil, chromatography was performed on a classical RP-18 column after extraction from the plasma by liquid-liquid extraction. Both methods were validated and applied to the analysis of patients' samples.
Buffers↗
Modulation by estrogen of the incidence of diethylnitrosamine-induced gamma-glutamyltranspeptidase-positive foci in rat liver.
We measured the number and size of foci of altered hepatocytes induced after 8 weeks by diethylnitrosamine (DENA) in the liver of rats pretreated with 17 beta-estradiol (E2), 1 or 24 h prior to the administration of the carcinogen. The average size of the lesions was the same in the E2 pretreated and unpretreated animals. The number of gamma-glutamyltranspeptidase (GGT)-positive foci per cm3 of liver increased from 364 +/- 57 in unpretreated animals to 1149 +/- 186 in animals receiving E2 24 h before DENA; it raised to 3779 +/- 280 when the hormone was injected 1 h before the carcinogen, i.e. about 25% of the number of foci scored in rats receiving the carcinogen 24 h after partial hepatectomy. The hypothesis is proposed that 1-h pretreatment with E2 increases hepatocyte susceptibility towards DENA action by enhancing the accessibility of the genome to the carcinogen.
Animals↗
Modulation by indomethacin of diethylnitrosamine-induced early changes in c-myc and c-ras expression and late incidence of preneoplastic lesions in rat liver.
We measured the levels of c-myc and c-ras expression before and after diethylnitrosamine (DENA) treatment in the liver of rats previously submitted to partial hepatectomy (PH), in the presence or absence of indomethacin (IMC), given at a dose that reduced by 75% the incidence of preneoplastic foci of altered hepatocytes scored 8 weeks after application of the carcinogen. The time-course evolution of c-myc response to PH was similar in IMC-treated and untreated rats (with a peak at 3-8 h at least as high in IMC-treated animals as in the hepatectomized reference group), whereas the overall c-ras response was significantly reduced by the IMC treatment, resulting in much lower c-ras expression at 18-24 h posthepatectomy. Treatment with DENA 24 h after PH did not significantly modify c-ras expression compared to partially hepatectomized controls. In contrast, DENA treatment resulted in a marked transient increase in c-myc expression that was at least as pronounced, if not the same, in the IMC-treated animals. These results leave open the possibility that increased c-myc expression under DENA influence might play a role in foci induction but exclude that this might be sufficient. They are consistent with a role for c-ras expression in determining the susceptibility of hepatocytes towards the carcinogenic action of DENA.
Animals↗
Modulation by indomethacin or prostaglandin E2 of the incidence of diethylnitrosamine-induced gamma-glutamyltranspeptidase-positive foci in rat liver.
We investigated the effect of a pretreatment with indomethacin (IMC, ip 3.6 mg/kg body weight (bw)) or dimethylprostaglandin E2 (PGE2, ip 10 micrograms/kg bw) on the incidence and development of gamma-glutamyltranspeptidase (GGT)-positive foci of altered hepatocytes, scored 8 or 14 weeks after ip injection of diethylnitrosamine (DENA, 50 mg/kg bw) to rats submitted to two-thirds hepatectomy (PH) or sham operation (Sh). IMC reduced by about 4 times the incidence of DENA-induced GGT-positive foci per cm3 of liver tissue in sham-operated as well as in two-thirds hepatectomized rats, compared to the respective unpretreated controls. In contrast, PGE2 pretreatment increased the incidence of DENA-induced foci in both groups, this effect, in terms of absolute numbers of foci, being additive to that of PH alone. IMC pretreatment resulted in foci with lower average size in the Sh but not in the PH animals, whereas with PGE2 pretreatment the mean volume of the foci was increased in the two groups of rats. At the dose used, IMC did not modify the proliferative response of hepatocytes to PH, and PGE2 did not stimulate proliferation in the sham-operated animals. Altogether, these results indicate that: 1, the incidence of DENA-induced foci can be negatively modulated by interfering with the prostaglandins pathway through a mechanism that does not involve an action either on proliferative activity or on any other process that would be specific to the post-hepatectomy regenerative state; 2, positive modulation of the incidence of DENA-induced foci does not necessarily require stimulation of proliferation.
Animals↗
Muscarinic cholinergic receptors in pancreatic acinar carcinoma of rat.
The active enantiomer of tritiated quinuclidinyl benzilate (3H(-)QNB) was used as a ligand to evaluate the muscarinic receptors. The 3H(-)QNB binding characteristics of muscarinic cholinergic receptors obtained from normal and neoplastic tissues were studied to determine changes in receptor properties during neoplastic transformation. Saturable and stereospecific binding sites for 3H(-)QNB are present in homogenates of rat pancreatic adenocarcinoma. The proportions of high- and low-affinity agonist binding sites are similar for neoplastic and normal tissues. The density of muscarinic receptors is higher in neoplastic (200 femtomoles/mg protein) than in normal pancreatic homogenates (80 femtomoles/mg protein). The muscarinic binding sites of the neoplastic and fetal pancreas show similar KD values which are higher than those observed for normal pancreas.
Adenocarcinoma↗
Modulation of rat pancreatic muscarinic cholinergic receptors by caerulein.
To evaluate the modulation of pancreatic muscarinic receptors in two states of pancreatic growth, hypertrophy and hyperplasia, caerulein, a cholecystokinin analog, (1 microgram/kg) was administered thrice daily for 2 and 4 days to adult rats. After 2 days of treatment, pancreatic hypertrophy was well established as evidenced by increases in pancreatic weight, cellular mass and protein content. Using an increase in DNA content as an index of hyperplasia, we demonstrated that pancreatic hyperplasia occurred only after 4 days of caerulein treatment. Caerulein increased the concentration of muscarinic receptors per DNA in pancreatic homogenate by 57% over control value after 2 days of treatment without modification of the receptor affinity for the ligand QNB. This increase involved mainly receptors in the low affinity state for carbamylcholine and their concentration returned to control levels after 4 days of treatment. The functional capacity of the acini was significantly increased after 2 days of caerulein as amylase release (U/mg DNA) was significantly increased but the sensitivity of these acini to carbamylcholine was significantly decreased. After 4 days of caerulein, the functional capacity has returned towards control values but the sensitivity to carbamylcholine remained decreased. The increase in muscarinic receptor concentration could be ascribed to a general increase in cellular proteins, as part of the hypertrophic effect of caerulein. This specific effect would also explain the increased functional secretory capacity of the caerulein-treated acini but the decreased sensitivity to carbamylcholine probably resulted in changes at a postreceptor loci since the affinities of the muscarinic receptors for carbamylcholine remained unaffected.
Amylases↗
A comparison between muscarinic receptor occupancy, adenylate cyclase inhibition, and inotropic response in human heart.
Binding to muscarinic receptors was compared with adenylate cyclase inhibition in membranes derived from human heart auricles, and with inhibition of the contraction of auricular muscle fibers. In the absence of GTP, agonists recognized two classes of receptors both of which bound antagonists with the same affinity. In the presence of GTP, both classes of receptors for agonists were converted into a single low affinity state. Carbachol and oxotremorine inhibited adenylate cyclase activity by 43%, pilocarpine being less efficient (-28%). The 3 agonists exerted similar inhibitory effects on the inotropic response, in 7 out of 9 preparations of electrically- and norepinephrine-stimulated fibers. Dose-effect curves suggested that spareness (or an amplification mechanism) was implicated in the occupancy of low affinity binding sites by carbachol and oxotremorine (but not by the partial agonist pilocarpine) and the resulting inhibition of both adenylate cyclase activity and contractile force.
Adenylyl Cyclase Inhibitors↗
Effects of full and partial beta-adrenergic agonists and antagonists on human lung adenylate cyclase.
The beta-adrenergic stimulation of adenylate cyclase in membranes from human lung was compared to that of adenylate cyclase in membranes with a majority of beta 2-adrenergic receptors (from rat lung) and in membranes with a homogeneous population of beta 2-adrenergic receptors (from rat erythrocytes and reticulocytes). In terms of adenylate cyclase stimulation, three full agonists (isoproterenol, epinephrine and norepinephrine), four partial agonists (procaterol, salbutamol, fenoterol and zinterol), and four antagonists (propranolol, metoprolol, atenolol and practolol) were tested. The potency (Kact or Ki) of the eleven beta-adrenergic agents, and the Hill coefficient (of 1) for the four antagonists tested indicated that the activation of human lung adenylate cyclase occurred through receptors of the beta 2-subtype only. Partial beta-adrenergic agonists were efficiently discriminated by the human lung preparation, as shown by distinct intrinsic activities. The mediocre efficacy and the relatively low potency of all beta-adrenergic agonists on adenylate cyclase suggested a relatively low density of beta 2-adrenergic receptors, as compared to the enzyme density.
Adenylyl Cyclase Inhibitors↗
The human heart beta-adrenergic receptors. I. Heterogeneity of the binding sites: presence of 50% beta 1- and 50% beta 2-adrenergic receptors.
Beta-adrenergic receptors were characterized in a particulate fraction of human auricles obtained from patients operated upon for coronary insufficiency or valvular disease. [125I] Hydroxybenzylpindolol binding was evaluated in terms of kinetics; KD and Bmax values; and inhibition of binding in the presence of 10 microM GTP and of increasing concentrations of four nonselective agonists giving a Hill coefficient of 1 (isoproterenol, salbutamol, fenoterol, and epinephrine), of two nonselective antagonists giving a Hill coefficient of 1 (pindolol and propranolol), and of a series of selective drugs giving a Hill coefficient of 0.60-0.72 that included three beta 1-selective antagonists (practolol, metoprolol, and atenolol) and two beta 2- selective agonists (procaterol and zinterol). KD values for all drugs were compatible with the coexistence in membranes from human auricles of beta 1- and beta 2-adrenergic receptors, the relative proportions of receptors of each subclass being approximately the same.
Adrenergic beta-Agonists↗
The human heart beta-adrenergic receptors. II. Coupling of beta 2-adrenergic receptors with the adenylate cyclase system.
The beta-adrenergic stimulation of adenylate cyclase in membranes from human auricles, ventricles, and fetal heart was compared with the binding properties of beta-adrenergic receptors in human auricles. In terms of adenylate cyclase activation, three full agonists (isoproterenol, epinephrine, and norepinephrine), four partial agonists (procaterol, salbutamol, fenoterol, and zinterol), and four antagonists (propranolol, metoprolol, atenolol, and practolol) were tested. The beta-adrenergic activation of adenylate cyclase in membranes from rat heart (with a majority of beta 1-adrenergic receptors), rat erythrocytes, and rat reticulocytes (with a homogeneous population of beta 2-adrenergic receptors) served as reference. The reactivity of human heart adenylate cyclase, estimated by the Kact or Ki values of 11 beta-adrenergic agents, indicated that the activation of this enzyme occurred through receptors of the beta 2-subtype only. Receptors of the beta 1-subtype (50% of the total population) were not coupled to the enzyme.
Adenylyl Cyclases↗
Effects of PHI on vasoactive intestinal peptide receptors and adenylate cyclase activity in lung membranes. A comparison in man, rat, mouse and guinea pig.
The presence of receptors, recognized by vasoactive intestinal peptide (VIP) as well as by PHI (a peptide with N-terminal histidine and C-terminal isoleucine amide), was documented in lung membranes from rat, mouse, guinea pig and man by the ability of these receptors, once occupied, to stimulate adenylate cyclase. In lung membranes from rat, mouse and guinea pig, the capacity of VIP, PHI and secretin to stimulate the enzyme and the potency of the same peptides to compete with 125I-VIP for binding to VIP receptors were similar, the affinity decreasing in the order: VIP greater than PHI greater than secretin. In addition, dose-effect curves were compatible with the coexistence of high-affinity and low-affinity VIP receptors, in the four animal species considered. If PHI was able to recognize all VIP receptors it could not, however, discriminate the subclasses of VIP receptors.
Adenylyl Cyclases↗
Characterization of the VIP- and secretin-stimulated adenylate cyclase system from human lung.
The response of a crude particulate adenylate cyclase preparation from surgically removed human lung to guanine nucleotides, sodium fluoride, beta-adrenergic agonists, prostaglandins, vasoactive intestinal peptide (VIP), secretin, and [Val5]secretin was investigated. The enzyme activity increased 5, 10, and 9-fold, respectively, with GTP, Gpp(NH)p, and sodium fluoride. This activity was stimulated (in the presence as well as in the absence of added GTP) by D,L-isoproterenol, L-epinephrine and L-norepinephrine, the relative potency of these agonists being compatible with the existence of beta-adrenoceptors of the beta2 subtype. Prostaglandins E1 and E2, but not PGF1alpha and PGF2alpha, stimulated the enzyme, PGE1 being at least 10 times more potent than PGE2. The biphasic pattern of stimulation of the same adenylate cyclase activity by VIP suggested the presence of high- and low-affinity VIP receptors coupled to the enzyme. This stimulation by VIP was not inhibited by secretin-(7-27). The stimulation of adenylate cyclase by secretin and [Val5]secretin was also biphasic, suggesting the coexistence of high- and low-affinity secretin receptors. Secretin-(7-27) was able to inhibit completely the secretin stimulation acting through high-affinity secretin receptors but exerted no effect on the stimulation operating through low-affinity secretin receptors, which might indicate that the latter receptors were in fact "VIP-preferring receptors". [Val5]secretin was also used to differentiate these peptide receptors, since its properties were more VIP-like than those of secretin.
Adenylyl Cyclases↗
Comparison of VIP-secretin receptors in rat and human lung.
The binding of 125I-VIP (Vasoactive Intestinal Peptide) to a crude particulate fraction from a rat lung was reversible and 125-I-VIP dissociation was accelerated by guanine triphosphate nucleotides. The relative potency of VIP and related peptides to compete with 125-VIP for binding was similar to their ability to stimulate adenylate cyclase in the same preparation. Dose-effect curves were compatible with the existence of two classes of VIP-receptors: a high-affinity type with equal affinity for VIP and [Val5] secretin, and a low-affinity type with affinity decreasing in the order VIP greater than [Val5] secretin greater than secretin. The response of a crude particulate adenylate cyclase preparation from human lung was also investigated. The biphasic pattern of adenylate cyclase stimulation by VIP suggested the presence of high- and low-affinity VIP receptors coupled to the enzyme. In addition, the stimulation of adenylate cyclase by secretin and [Val5] secretin was also biphasic, suggesting the coexistence of high- and low-affinity secretin receptors, Secretin (7-27) inhibited completely the secretin-stimulated activity operating through high-affinity secretion receptors, so that these receptors appear to be genuine secretin-preferring receptors.
Adenylyl Cyclases↗
Vasoactive intestinal peptide (VIP) and peptide having N-terminal histidine and C-terminal isoleucine amide (PHI) stimulate adenylate cyclase activity in human heart membranes.
The presence of receptors, recognized by Vasoactive Intestinal Peptide (VIP) and Peptide having N-terminal Histidine and C-terminal Isoleucine amide (PHI), was documented in membranes from human right auricle and left ventricular cardiac muscle by the ability of these peptides to stimulate adenylate cyclase. The capacity of VIP and PHI to activate the enzyme was comparable, in auricle as well as ventricle membranes, the affinity of the system being moderately higher for VIP than for PHI. In auricles, dose-effect curves appeared compatible with the coexistence of high-affinity and low-affinity VIP receptors. PHI could not, however, discriminate these subclasses of VIP receptors.
Adenylyl Cyclases↗
Colonoscopic snare polypectomy: analysis of 1485 resections comparing two types of current.
The complications related to 1485 colonic snare polypectomies were analyzed according to the type of current which was used for resection. From January 1982 to August 1986 (period 1), blended current was used in 758 snare polypectomies, while continuous coagulation current was applied in 727 polypectomies from September 1986 to October 1989 (period 2). The incidence of complications observed in the entire series was low, consisting of 0.26% perforations and 0.9% major hemorrhages. There were no deaths in this series. Twelve of 14 hemorrhages occurred after resection of polyps larger than 1 cm. Although the incidence of complications was not statistically different in the two groups, there was a significant difference in the timing of hemorrhages. All of the major hemorrhages were immediate (eight) when the blended current was used, but delayed (six; from 2 to 8 days after polyp resection), when pure coagulation current was applied.
Colonic Polyps↗