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B Chevalier

Publications and source records attributed to B Chevalier.

At least 37 records · Page 2Linked to original sources
PubMed2001

Phase I and pharmacokinetic study of weekly oral therapy with vinorelbine in patients with advanced breast cancer (ABC).

BACKGROUND: A phase I dose-escalation study of a new formulation of oral vinorelbine was conducted to determine the maximum tolerated dose (MTD) of a once weekly regimen and preliminary pharmacokinetic profile in patients with advanced breast cancer (ABC). Twenty-six patients were treated at dose levels ranging from 60 to 100 mg/m2/week. Pharmacokinetics was assessed during the first administration. PATIENTS AND METHODS: All patients had histologically confirmed locally advanced or metastatic breast cancer and had received no more than two prior chemotherapy regimens for ABC. RESULTS: The MTD was 100 mg/m2/week due to the occurrence of dose-limiting neutropenia, nausea/vomiting and constipation in five of six patients. Toxicities at 80 mg/m2/week were manageable, neutropenia being the main toxicity (grade 3-4 seen in 10 of 13 patients). Nausea, vomiting and diarrhoea were common but rarely severe. Vinorelbine was rapidly absorbed with maximum blood concentration (Cmax) of 103.8 +/- 41.6 ng x ml(-1) observed 1.2 +/- 0.8 hours (Tmax) after administration of 80 mg/m2. Pharmacokinetic exposure increased linearly with dose. Area under the concentration-time curve (AUC) and concentration measured 24 hours after drug intake (C24h) were significantly correlated with depletion of neutrophils. Objective tumour responses were reported in 6 of the 14 evaluable patients treated at doses > or = 80 mg/m2/week. CONCLUSION: The safety profile of oral vinorelbine appears comparable to that of intravenous dosing. The recommended phase II dose is 80 mg/m2/week and requires regular monitoring of neutrophil counts.

Administration, Oral↗
PubMed2001

Ras1 interacts with multiple new signaling and cytoskeletal loci in Drosophila eggshell patterning and morphogenesis.

Little is known about the genes that interact with Ras signaling pathways to regulate morphogenesis. The synthesis of dorsal eggshell structures in Drosophila melanogaster requires multiple rounds of Ras signaling followed by dramatic epithelial sheet movements. We took advantage of this process to identify genes that link patterning and morphogenesis; we screened lethal mutations on the second chromosome for those that could enhance a weak Ras1 eggshell phenotype. Of 1618 lethal P-element mutations tested, 13 showed significant enhancement, resulting in forked and fused dorsal appendages. Our genetic and molecular analyses together with information from the Berkeley Drosophila Genome Project reveal that 11 of these lines carry mutations in previously characterized genes. Three mutations disrupt the known Ras1 cell signaling components Star, Egfr, and Blistered, while one mutation disrupts Sec61beta, implicated in ligand secretion. Seven lines represent cell signaling and cytoskeletal components that are new to the Ras1 pathway; these are Chickadee (Profilin), Tec29, Dreadlocks, POSH, Peanut, Smt3, and MESK2, a suppressor of dominant-negative Ksr. A twelfth insertion disrupts two genes, Nrk, a "neurospecific" receptor tyrosine kinase, and Tpp, which encodes a neuropeptidase. These results suggest that Ras1 signaling during oogenesis involves novel components that may be intimately associated with additional signaling processes and with the reorganization of the cytoskeleton. To determine whether these Ras1 Enhancers function upstream or downstream of the Egf receptor, four mutations were tested for their ability to suppress an activated Egfr construct (lambdatop) expressed in oogenesis exclusively in the follicle cells. Mutations in Star and l(2)43Bb had no significant effect upon the lambdatop eggshell defect whereas smt3 and dock alleles significantly suppressed the lambdatop phenotype.

Animals↗
PubMed2001

Insulin-like growth factors and body growth in chickens divergently selected for high or low growth rate.

Insulin-like growth factors (IGFs) stimulate growth rate in a number of animal species and are likely to contribute to genetic variations of growth potential. The present study was designed to link levels of IGF-I and IGF-II mRNA and peptides with growth rate in divergently selected genotypes of chickens with high (HG) or low (LG) growth rates. Circulating IGF-I and -II and hepatic mRNA levels were measured under ad libitum feeding conditions from 1 to 12 weeks of age, and at 6 weeks of age under three different nutritional conditions (fed, fasted for 16 or 48 h, re-fed for 4 or 24 h after a 48-h fast). IGF binding proteins (IGFBPs) were also measured. Circulating IGFs increased with age and were higher in HG chickens from 1 to 6 weeks. They decreased with fasting and only IGF-II was fully restored after 24 h of re-feeding, while IGF-I remained low. A significant decrease in steady state IGF-I mRNA levels was also observed with fasting. Across the nutritional study, hepatic IGF-I mRNAs were significantly higher in HG chickens. Variations of IGF-II mRNA levels with nutritional state or genotype exhibited a similar trend. IGFBP (28, 34 and 40 kDa) levels increased with age, while only faint differences were observed between genotypes. IGFBP-28 transiently increased with fasting and was inversely related to blood glucose and insulin levels, suggesting that it is equivalent to mammalian IGFBP-1. In HG chickens, IGFBP-28 and IGFBP-34 levels decreased markedly following re-feeding. Therefore, high and low growth rates were respectively associated with high and low IGF-I and -II levels, supporting the hypothesis of a stimulatory role for both IGFs during post-hatching growth of chickens.

Aging↗
PubMed2000

Phase II trial of vinorelbine in patients with advanced and/or recurrent cervical carcinoma: an EORTC Gynaecological Cancer Cooperative Group Study.

The objective of this phase II study was to assess the efficacy and toxicity of vinorelbine administered as a single agent in the treatment of chemonaïve cervical cancer patients. 46 patients (41 eligible) with cervical cancer (epidermoid or adenocarcinoma) and measurable metastatic and/or recurrent disease localised outside irradiated areas were treated with weekly intravenous (i.v.) vinorelbine 30 mg/m2 infused over 20 min. No prior chemotherapy was allowed. Median age was 53 years (range: 33-73), and performance status 1 (0-2). 31 patients (76%) had prior radiation therapy. There were 7 partial responders (17, 95% confidence interval (CI) 7-32) and 8 stable diseases (20%). Median duration of response was 5 months (4-11). Granulocytopenia was the major toxicity, with 47% of patients exhibiting grade 3 or 4 toxicity. Dose reduction and/or treatment delay was necessary in 28 patients (78%). Peripheral neuropathy reported in 10 patients was mild (grade 1 in 9 patients and grade 2 in 1 patient). In conclusion, single agent vinorelbine has moderate activity in recurrent or metastatic cervical cancer, but its reduced neurotoxicity warrants further study in combination with cisplatin.

Adult↗
PubMed2000

Plasma glucose-insulin relationship in chicken lines selected for high or low fasting glycaemia.

1. Selected Fat or Lean chickens differ in their plasma glucose insulin relationship: in the fed or fasted state, Fat chickens have a lower glycaemia associated with normal or higher insulinaemia, depending upon the difference in glycaemia. 2. Conversely, chickens selected for low fasting glycaemia (LG) are fattier than their counterparts selected for high fasting glycaemia (HG), although the divergence in fat content is lower than in the Fat-Lean model. 3. The plasma glucose insulin relationship has been investigated in males of the HG and LG lines in the F4 and F5 generations. 4. A difference in glycaemia is suggested during embryonic development and was present at hatching and later on in the fasted or the fed state; insulinaemia did not differ. 5. During refeeding after an overnight fast, glycaemia differed between lines (except at intermediate times); cumulative food intake and insulinaemia were similar. 6. During a glucose tolerance test, glucose disposal rate and insulinaemia were rather similar. 7. Exogenous insulin exerted a very similar hypoglycaemic effect in both lines. 8. Other variables (body temperature, plasma concentrations of potassium and alpha NH2-non protein nitrogen) did not differ between HG and LG chickens. 9. In conclusion, HG and LG chickens do not exhibit any differences in glucose disposal rate, insulinaemia (in various nutritional conditions) or sensitivity to exogenous insulin, which contrasts with Fat or Lean chickens and may explain why HG and LG chickens have diverged to a lesser extent in fat content.

Animals↗
PubMed2000

Converting enzyme inhibition normalizes QT interval in spontaneously hypertensive rats.

We quantified the repolarization time (so-called QT interval) in a rat, an animal species that does not show a well-characterized T wave on surface ECG. We used spontaneously hypertensive rats (SHR) and converting enzyme inhibition to demonstrate a reversible increase in QT interval in pressure-overloaded hearts in the absence of ischemia. An implanted telemetry system recording ECG data in freely moving rats was used to automatically calculate the RR interval. The QT duration was manually determined by use of a calibrated gauge, and a time-frequency domain analysis was used to evaluate heart rate variability. Left ventricular mass was sequentially assessed by echocardiography. Before treatment, 12-month-old SHR had higher left ventricular mass, QT and RR intervals, and unchanged heart rate variability compared with age-matched Wistar rats. A 2-month converting enzyme inhibition treatment with trandolapril reduces systolic blood pressure, left ventricular mass, and QT interval. The RR interval and heart rate variability remains unchanged. There is a positive correlation between the QT interval and left ventricular mass. The SHR is suitable for longitudinal studies on the QT interval. Thus, the detection of the QT interval reflects the phenotypic changes that occur during mechanical overload and, on the basis of these criteria, allows an in vivo determination of the adaptational process.

Age Factors↗
PubMed1999

A novel endonuclease mechanism directly visualized for I-PpoI.

A novel mechanism of DNA endonucleolytic cleavage has been visualized for the homing endonuclease I-PpoI by trapping the uncleaved enzyme-substrate complex and comparing it to the previously visualized product complex. This enzyme employs a unique single metal mechanism. A magnesium ion is coordinated by an asparagine residue and two DNA oxygen atoms and stabilizes the phosphoanion transition state and the 3'oxygen leaving group. A hydrolytic water molecule is activated by a histidine residue for an in-line attack on the scissile phosphate. A strained enzyme-substrate-metal complex is formed before cleavage, then relaxed during the reaction.

Amino Acid Substitution↗
PubMed1999

Circulating insulin-like growth factors (IGF-I and -II) and IGF binding proteins in divergently selected fat or lean chickens: effect of prolonged fasting.

Possible differences in insulin-like growth factors (IGF-I and -II) and their binding proteins (IGFBPs) were investigated in genetically fat or lean chickens. Comparisons were performed at 9 weeks of age in the fed or the fasted (48 h) state. Plasma concentrations of both IGFs were altered by nutrition and genotype. IGF-I, and to a lower extent IGF-II, decreased following fasting. IGF-I and -II were higher in fat compared to lean chickens, in both the fasted and the fed states. Of four circulating IGFBPs with molecular weights of 28, 34, 40 and 60 kDa, IGFBP-28, and to a lesser extent IGFBP-34 and -60, increased in the fasted state. No consistent differences were observed between genotypes for IGFBPs. Therefore in chickens, as in mammals, IGFs are downregulated, and IGFBP-28 upregulated by fasting. An increase in IGFs levels in Fat chickens may contribute to enhance fat deposition in this genotype.

Adipose Tissue↗
PubMed1999

[Pre-hospitalization treatment with Abciximab in the preparation of patients for primary angioplasty in the acute phase of myocardial infarct. Immediate and long-term (one month) results].

Percutaneous transluminal coronary angioplasty (PTCA) is an alternative to fibrinolysis in the treatment of acute myocardial infarction (AMI). However, after balloon PTCA, the rate of early re-occlusion, of re-infarctus and of restenosis remains high. Stent implantation with antiplatelet drug regimen (aspirin, ticlid) limits these risks. Abciximab (new GPIIb/IIIa receptors inhibitor) reduces PTCA complications rate in the acute coronary syndromes. Intravenous administration of abciximab can restore a normal flow in the infarcted related coronary artery (IRA) after few minutes. A monocentric, non randomized, prospective pilot study was iniated to assess the feasibility of pre-hospital treatment with abciximab in preparation to primary PTCA stenting in AMI (primary endpoint) and to appreciate potential benefits in initial IRA patency as well as prevention of PTCA thrombotic complications (secondary endpoint). Between April 1997 and January 1998, 38 AMI were treated with abciximab in pre-hospital phase (group A). Mobil Intensive Care Unit (MICU) team implemented the treatment and guaranteed immediate transport to the cathlab (abciximab bolus-coronary angiography time = 37 +/- 17 min). Immediate results were compared to those of 198 paired patients who were treated for AMI during the same period (Group T). Initial IRA flow TIMI grade 3 was significantly higher in group A, 24%, than in group T, 9% (p < 0.017). The rates of per-procedural complications (no flow, distal embolism), of local complications, of transfusions were not significantly different. During 1 month follow-up, there was no significant difference between group A and group T concerning death, re-MI, stent thrombosis and new revascularization. To conclude, the pre-hospital treatment with abciximab in AMI is feasible by MICU medical team without any delay of the cathlab admission. It is associated with no increased hemorrhagic complications rate. The abciximab pre-hospital treatment improves the initial IRA patency. These encouraging preliminary results expect to be confirmed by larger, multicentric, randomized and prospective studies.

Abciximab↗
PubMed1998

Placement of coronary stents in bifurcation lesions by the "culotte" technique.

Coronary angioplasty of bifurcation lesions remains a technical challenge. Balloon angioplasty induces recoil and the "snow-plow" effect with a risk of side branch occlusion. The late result is associated with a high rate of reintervention. Randomized studies in nonbifurcated lesions have demonstrated better short- and midterm results after stent placement. We propose the "culotte" technique as a new technique to place intracoronary stents in bifurcation lesions: implantation of 2 similar stents in 2 steps in the main branch and in the side branch with overlapping of the 2 stents in the main branch before bifurcation. We performed this technique in 50 patients (in the left anterior diagonal branch in 33, in the left circumflex obtuse marginal branch in 12, in the right coronary artery in 4, and in the left main coronary artery in 1). The clinical success rate was 94% with 3 non-Q-wave myocardial infarctions. Late results indicated a 24% target lesion revascularization rate, which improved when a true kissing balloon inflation was used to achieve final deployment of both stents. This culotte technique is highly feasible and provides excellent short-term results. Assessment of its midterm benefit requires further study.

Angioplasty, Balloon, Coronary↗