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83.
Thierry Conroy Bernard Paillot Eric Fran?ois Roland Bugat Jacques-Henri Jacob Ulrich Stein Salvador Nasca Jean-Philippe Metges Olivier Rixe Pierre Michel Emmanuelle Magherini Aliette Hua Gael Deplanque 《Journal of clinical oncology》2005,23(6):1228-1236
PURPOSE: To evaluate response rate and toxicity of irinotecan and oxaliplatin plus fluorouracil (FU) and leucovorin (Folfirinox) in advanced pancreatic adenocarcinoma (APA). PATIENTS AND METHODS: Chemotherapy-naive patients with histologically proven APA and bidimensionally measurable disease were treated with Folfirinox therapy every 2 weeks, which comprised oxaliplatin 85 mg/m(2) and irinotecan 180 mg/m(2) plus leucovorin 400 mg/m(2) followed by bolus FU 400 mg/m(2) on day 1, then FU 2,400 mg/m(2) as a 46-hour continuous infusion. Quality of life (QOL) was assessed using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). RESULTS: Forty-seven patients were entered, and 46 received treatment. Thirty-five patients (76%) had metastatic disease. A total of 356 cycles were delivered, with a median of eight cycles per patient (range, one to 24 cycles). All patients were assessable for safety. No toxic death occurred. Grade 3 to 4 neutropenia occurred in 52% of patients, including two patients with febrile neutropenia. Other relevant toxicities included grade 3 to 4 nausea (20%), vomiting (17%), and diarrhea (17%) and grade 3 neuropathy (15%; Levi's scale). The confirmed response rate was 26% (95% CI, 13% to 39%), including 4% complete responses. Median time to progression was 8.2 months (95% CI, 5.3 to 11.6 months), and median overall survival was 10.2 months (95% CI, 8.1 to 14.4 months). Between baseline and end of treatment, patients had improvement in all functional scales of the EORTC QLQ-C30, except cognitive functioning. Responders had major improvement in global QOL. CONCLUSION: With a good safety profile, a promising response rate, and an improvement in QOL, Folfirinox will be further assessed in a phase III trial. 相似文献
84.
Pascal Sève Sylvie Isaac Olivier Trédan Pierre-Jean Souquet Yves Pachéco Maurice Pérol Laurence Lafanéchère Aurélie Penet Eva-Laure Peiller Charles Dumontet 《Clinical cancer research》2005,11(15):5481-5486
PURPOSE: To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins. RESULTS: The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III beta-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High Delta2 alpha-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II beta-tubulin, class III beta-tubulin, and Delta2 alpha-tubulin levels, confirmed that class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012). CONCLUSIONS: These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy. 相似文献
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Localisation of drug permeability along the rat small intestine, using markers of the paracellular, transcellular and some transporter routes 总被引:1,自引:0,他引:1
Olivier Lacombe John Woodley Claude Solleux Jean-Marie Delbos Claire Boursier-Neyret Georges Houin 《European journal of pharmaceutical sciences》2004,23(4-5):385-391
The small intestine is the major site of drug absorption. Some reports in the literature have evoked the concept of “absorption windows” in the small intestine: are there specific regions where drug absorption is significantly higher than others? To investigate this question, we used an everted gut sac method to study the permeability of drugs and markers every 3–4 cm down the entire small intestine in rat. These markers were chosen to be representative of the mechanisms by which drugs cross the small intestinal mucosa: paracellular and transcellular passive diffusion, via influx transporters, and a drug (digoxin) that is effluxed from cells by P-glycoprotein (P-gp). The passive diffusion and influx transporter markers gave similar profiles with a plateau of permeability along the jejunum, and with the exception of L-Dopa, lower permeability in the ileum. Digoxin showed a linear decrease in the profile from the proximal jejunum to the ileum. Permeability in the duodenum was two to three times lower than the jejunum for all compounds. There were no narrow specific regions of high permeability and so the concept of discrete “absorption windows” along the small intestine as suggested from some pharmacokinetic studies may be related to other effects such as pH and/or solubility. 相似文献
87.
Christiane Devaux Besma Jouirou Mohamed Naceur Krifi Olivier Clot-Faybesse Mohamed El Ayeb Hervé Rochat 《Toxicon》2004,43(6):661-669
Scorpion stings represent a medical problem in numerous countries. The scorpion Androctonus australis hector produces three alpha toxins (Aah I to III), which are responsible for most of the lethality in mammals. These toxins act on sodium channel and do not cross-react immunologically. We used RIA and ELISA to measure the concentrations of these three toxins in plasma, urine and different organs after i.v. and s.c. injections of water extracts of venoms in rabbits or mice. In both animals, the toxins rapidly appeared in plasma after s.c. injection as it was previously described for the whole venom. However, the toxins disappeared from the blood more quickly than did other main components of the venom. Thus, serotherapy must be initiated immediately to prevent the toxin from reaching its target. We also detected the toxins in urine, kidneys, heart and lungs, but not in the brain. However, the concentration of Aah II was always lower than that of Aah I. Analysis of five samples of venom collected in different areas of southern Tunisia showed that a large polymorphism exists for the three toxins. This is yet another difficulty for serotherapy as there is no cross-antigenicity between them. 相似文献
88.
OBJECT: Changes in cortical representation in patients with cerebral lesions may alter the correlation between cortical anatomy and function. This is of potential clinical significance when the extent of cortical resection is based on surface anatomical landmarks. METHODS: Fifty-one patients with supratentorial lesions were studied. Nineteen harbored noncentral lesions (no involvement of pre- or postcentral gyrus), whereas 32 had central lesions. Control studies consisted of stimulation of the hand contralateral to the unaffected hemisphere. Positron emission tomography activation studies were performed using the [15O]H2O tracer. Somatosensory stimulation of the hand or foot was performed using a mechanical vibrator. Motor activation consisted of hand clenching or foot tapping. The t-statistic volumes were generated from images showing the mean change in regional cerebral blood flow, and coregistered with a T1-weighted magnetic resonance image. At the threshold selected, exclusive contralateral primary sensorimotor cortex activation was elicited in 100% of the control studies. A different pattern of cortical activation was associated with central lesions in 35 (78%) of 45 patients, which occurred significantly more often than with noncentral lesions (eight [31%] of 26 patients). The most common difference in the pattern of activation with central lesions was activation of cortical regions outside the central area (including the supplementary sensorimotor area and the secondary somatosensory cortex). No sensorimotor activation was observed in gyri adjacent to the pre- or postcentral gyrus. CONCLUSIONS: Central lesions are more frequently associated with altered patterns in activation than lesions in noncentral locations. Characteristic patterns include activation of secondary sensorimotor areas. The absence of activation in gyri adjacent to the sensorimotor strip has clinical significance for the planning of resections in the central area. 相似文献
89.
MarcOlivier Pilon Grgoire Leclair Essaïd Oussaïd Isabelle StJean Martin Jutras MarieJose Gaulin Ian Mongrain David Busseuil Jean Lucien Rouleau JeanClaude Tardif MariePierre Dub Simon de Denus 《CTS Clinical and Translational Science》2022,15(8):2024
ABCG2 is a gene that codes for the human breast cancer resistance protein (BCRP). It is established that rs2231142 G>T, a single nucleotide polymorphism of the ABCG2 gene, is associated with gout and poor response to allopurinol, a uric acid‐lowering agent used to treat this condition. It has also been suggested that oxypurinol, the primary active metabolite of allopurinol, is a substrate of the BCRP. We thus hypothesized that carrying the rs2231142 variant would be associated with decreased oxypurinol concentrations, which would explain the lower reduction in uric acid. We performed a cross‐sectional study to investigate the association between the ABCG2 rs2231142 variant and oxypurinol, allopurinol, and allopurinol riboside concentrations in 459 participants from the Montreal Heart Institute Hospital Cohort. Age, sex, weight, use of diuretics, and estimated glomerular filtration rate were all significantly associated with oxypurinol plasma concentration. No association was found between rs2231142 and oxypurinol, allopurinol and allopurinol riboside plasma concentrations. Rs2231142 was not significantly associated with daily allopurinol dose in the overall population, but an association was observed in men, with T carriers receiving higher doses. Our results do not support a major role of ABCG2 in the pharmacokinetics of allopurinol or its metabolites. The underlying mechanism of the association between rs2231142 and allopurinol efficacy requires further investigation. Study Highlights
- WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
- WHAT QUESTION DID THIS STUDY ADDRESS?
- WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
- HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
90.
Sagan S Karoyan P Lequin O Chassaing G Lavielle S 《Current medicinal chemistry》2004,11(21):2799-2822
Numerous backbone constraints can be used to develop pseudopeptides or pseudomimetics of biologically active peptides. Among those, N- and Calpha-methyl amino acids that can be incorporated by solid-phase peptide synthesis in a bioactive sequence represent important tools to restrict phi and psi angles of peptide backbone. This review will focus on the chemical syntheses of N- and Calpha-methyl amino acids, their effects on peptide conformation and structure, and their role on the peptide stability towards enzymatic degradation and on the biological activities of the resulting analogues. 相似文献