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81.
82.
Mycosis fungoides shows concurrent deregulation of multiple genes involved in the TNF signaling pathway: an expression profile study 总被引:2,自引:2,他引:0
Tracey L Villuendas R Dotor AM Spiteri I Ortiz P Garcia JF Peralto JL Lawler M Piris MA 《Blood》2003,102(3):1042-1050
Mycosis fungoides (MF) is the most frequent type of cutaneous T-cell lymphoma, whose diagnosis and study is hampered by its morphologic similarity to inflammatory dermatoses (ID) and the low proportion of tumoral cells, which often account for only 5% to 10% of the total tissue cells. cDNA microarray studies using the CNIO OncoChip of 29 MF and 11 ID cases revealed a signature of 27 genes implicated in the tumorigenesis of MF, including tumor necrosis factor receptor (TNFR)-dependent apoptosis regulators, STAT4, CD40L, and other oncogenes and apoptosis inhibitors. Subsequently a 6-gene prediction model was constructed that is capable of distinguishing MF and ID cases with unprecedented accuracy. This model correctly predicted the class of 97% of cases in a blind test validation using 24 MF patients with low clinical stages. Unsupervised hierarchic clustering has revealed 2 major subclasses of MF, one of which tends to include more aggressive-type MF cases including tumoral MF forms. Furthermore, signatures associated with abnormal immunophenotype (11 genes) and tumor stage disease (5 genes) were identified. 相似文献
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85.
Aparicio J de las Peñas R Vicent JM Garcerá S Llorca C Maestu I Yuste AL Farrés J 《Oncology》2002,63(1):42-47
Irinotecan and raltitrexed are active against advanced colorectal cancer, act through different mechanisms, and have non-overlapping toxicity profiles. In vitro studies have shown a schedule-dependent synergism between both drugs. The aim of this multicenter study was to determine the maximum tolerated dose (MTD) of this combination. Patients with 5-fluorouracil-refractory, advanced colorectal cancer were eligible. Dose escalation consisted of irinotecan (250-350 mg/m(2) as a 60-min infusion) in combination with a fixed dose of raltitrexed (3 mg/m(2) as a 15-min infusion, 1 h after irinotecan). Courses were repeated every 21 days. Three to 6 patients were to be included at each dose level. Dose limiting (NCI-CTC grade 3-4) toxicities (DLT) were assessed during the first 2 cycles. Thirteen patients were recruited (4, 3 and 6 in levels I, II and III, respectively). Main toxicity was diarrhea and asthenia, whereas myelotoxicity was mild. At level III, 2/6 patients experienced DLT (grade 4 diarrhea and neutropenia). The MTD was not reached, but further dose escalation was not attempted. Among 12 patients with measurable disease, 2 partial responses were observed for an overall response rate of 17%. The combination of single-agent full doses of irinotecan (350 mg/m(2)) and raltitrexed (3 mg/m(2)) in a 3-weekly schedule is feasible, with mild toxicity and a promising clinical activity. Diarrhea is the DLT, but it is not more common or severe than that described with irinotecan alone. 相似文献
86.
Inmaculada Fuertes Antonia Miranda Mónica Millán Isidoro Caraballo 《European journal of pharmaceutics and biopharmaceutics》2006,64(3):336-342
The principles of percolation theory were applied to design controlled release matrix tablets containing acyclovir. This statistical theory studies disordered or chaotic systems where the components are randomly distributed in a lattice. The application of this theory to study the release and hydration rate of hydrophilic matrices allows to explain the changes in release and hydration kinetics of swellable matrix type controlled delivery systems. The objective of the present paper is to estimate the percolation threshold of HPMC K4M in matrices of acyclovir and to apply the obtained result to the design of hydrophilic matrices for the controlled delivery of this drug. Matrix tablets have been prepared using acyclovir as drug and HPMC K4M as matrix forming material, employing five different excipient/drug percentages. Dissolution studies were carried out using the paddle method. Water uptake measurements were performed using a modified Enslin apparatus. In order to estimate the percolation threshold, the behaviour of the kinetic parameters with respect to the excipient volumetric fraction at time zero plus initial porosity was studied. According to percolation theory, the critical points observed in dissolution and water uptake studies can be attributed to the excipient percolation threshold. This threshold was situated between between 20.76% and 26.41% v/v of excipient plus initial porosity. The knowledge of the percolation threshold of the components of the matrix formulations contributes to improve their design. First, reducing the time to market and second, increasing their robustness when they are prepared at Industrial scale, avoiding the formulation in the nearby of the percolation threshold. 相似文献
87.
Matilde López-Grancha Carmen Sánchez-Amate Montserrat Navarro Francisca Carvajal Fernando Sánchez-Santed Inmaculada Cubero 《Toxicological sciences》2006,91(1):210-217
Preliminary clinical evidence obtained in Gulf War veterans and patients suffering multiple chemical sensitivity points to the existence of a potential link between environmental exposure to organosphosphates (OPs) and the emergence of unspecific sickness syndromes in which associative Pavlovian conditioning might be partly involved. A laboratory animal model might be a useful tool for analyzing the involvement of conditioning in sickness syndromes potentially linked to OP poisoning. The first objective in the present study was to determine if paraoxon (PX), the neuroactive metabolite of the OP parathion, elicits a conditioned avoidance response to a novel stimulus (a taste-odor compound) in a conditioned flavor aversion procedure. Data obtained in Experiment 1 show conditioned flavor avoidance, demonstrative of the associative nature of the sickness properties of PX. The second objective was to characterize the nature of the specific physiological cue serving as the unconditioned stimulus in PX-induced conditioned avoidance. Despite PX administration did induce cholinergic hyperactivity, as measured by body hypothermia and increased jaw movements, lesions of the lateral parabrachial area (lPB) disrupted PX-elicited flavor avoidance responses, indicating that cholinergic signs were not sufficient as unconditioned stimuli supporting avoidance responses. Given that lPB neural integrity is necessary to process aversive interoceptive information, disruption of conditioned flavor avoidance as a result of lPB lesions is consistent with a central interruption of interoceptive processing in PX-poisoned animals. Data are discussed under the light of the hypothesis claiming the importance of associative processes and noncholinesterase targets in sickness syndromes potentially induced by OP exposure. 相似文献
88.
M Arslan O Pata T U K Dilek A Aktas M Aban S Dilek 《International journal of gynaecology and obstetrics》2005,89(2):163-166
OBJECTIVE: Pregnancy in previous cesarean scar is the rarest form of ectopic pregnancy. All reported cases in the literature that were treated with uterine curettage either become unsuccessful or complicated. We aimed to present a case of cesarean scar ectopic pregnancy that was successfully treated with suction curettage without any additional therapy. CASE: A 32-year-old asymptomatic woman, gravida 2, para 1 was referred to our hospital with the possible diagnosis of cervical ectopic pregnancy. Transvaginal and transabdominal sonographic examination revealed the diagnosis of viable ectopic pregnancy in a previous cesarean scar. Suction curettage with carman canulles was performed under transabdominal ultrasonographic guidance. beta-hCG decreased progressively postoperatively. CONCLUSION: Suction curettage under ultrasonography guidance can be used in termination of selected cases (early diagnosed, without symptoms that necessitates emergency intervention) of cesarean scar pregnancy. 相似文献
89.
Tormo JR DePedro N Royo I Barrachina I Zafra-Polo MC Cuadrillero C Hernández P Cortes D Peláez F 《Oncology research》2005,15(3):129-138
90.
Quintana JM Cabriada J Aróstegui I Oribe V Perdigo L Varona M Bilbao A 《Annals of surgery》2005,241(1):110-118
OBJECTIVE: To evaluate the relationship among appropriateness of the use of cholecystectomy and outcomes. SUMMARY BACKGROUND DATA: The use of cholecystectomy varies widely across regions and countries. Explicit appropriateness criteria may help identify suitable candidates for this commonly performed procedure. This study evaluates the relationship among appropriateness of the use of cholecystectomy and outcomes. METHODS: Prospective observational study in 6 public hospitals in Spain of all consecutive patients on waiting lists to undergo cholecystectomy for nonmalignant disease. Explicit appropriateness criteria for the use of cholecystectomy were developed by a panel of experts using the RAND appropriateness methodology and applied to recruited patients. Patients were asked to complete 2 questionnaires that measure health-related quality of life-the Short Form 36 (SF-36) and the Gastrointestinal Quality of Life Index (GIQLI)-before the intervention and 3 months after it. RESULTS: Patients judged as being appropriate candidates for cholecystectomy, using the panel's explicit appropriateness criteria, had greater improvements in the bodily pain, vitality, and social function domains of the SF-36 than those judged to be inappropriate candidates. They also demonstrated improvements in the GIQLI's physical impairment domain. Interventions judged as inappropriate were performed primarily among patients without symptoms of cholelithiasis. Those asymptomatic had a lower improvement in the bodily pain, social functioning, and physical summary scale of the SF-36 and in the symptomatology, physical impairment, and total score domains of the GIQLI. CONCLUSIONS: These results suggest a direct relationship between the application of explicit appropriateness criteria and better outcomes, as measured by health-related quality of life. They also indicate that patients without symptoms are not good candidates for cholecystectomy. 相似文献