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991.
Giovanni Biggio Laura Dazzi Francesca Biggio Luisa Mancuso Giuseppe Talani Fabio Busonero Maria Cristina Mostallino Enrico Sanna Paolo Follesa 《European neuropsychopharmacology》2003,13(6):411
Here, we summarize recent data pertaining to the effects of GABAA receptor modulators on the receptor gene expression in order to elucidate the molecular mechanisms behind tolerance and dependence induced by these drugs. Drug selectivity and intrinsic activity seems to be important to evidence at the molecular level the GABAA receptor tolerance. On the contrary, we suggested that all drug tested are equally potentially prone to induce dependence. Our results demonstrate that long-lasting exposure of GABAA receptors to endogenous steroids, benzodiazepines and ethanol, as well as their withdrawal, induce marked effects on receptor structure and function. These results suggest the possible synergic action between endogenous steroids and these drugs in modulating the functional activity of specific neuronal populations. We report here that endogenous steroids may play a crucial role in the action of ethanol on dopaminergic neurons. 相似文献
992.
Peter Ericsson Per Norln Maria Bernsand Per Alm Peter Hglund Rolf Hkanson 《Basic & clinical pharmacology & toxicology》2003,93(2):57-65
Abstract: The ECL cells are endocrine/paracrine cells in the acid‐producing part of the stomach. They secrete histamine in response to circulating gastrin. Gastric submucosal microdialysis has been used to study ECL‐cell histamine mobilization in awake rats. In the present study we assess the usefulness and limitations of the technique. Microdialysis probes were implanted in the gastric submucosa. Histological analysis of the stomach wall around the probe revealed a moderate, local inflammatory reaction 1–2 days after implantation; the inflammation persisted for at least 10 days. Experiments were conducted 3 days after the implantation. The “true” submucosal histamine concentration was determined by perfusing at different rates (the zero flow method) or with different concentrations of histamine at a constant rate (the no‐net‐flux method): in fasted rats it was calculated to be 87±5 (means±S.E.M.) nmol/l and 76±9 nmol/l, respectively. The corresponding histamine concentrations in fed rats were 93±5 and 102±8 nmol/l, respectively. With a perfusion rate of 74 μl/hr the recovery of submucosal histamine was 49%, at 34 μl/hr the recovery increased to 83%. At a perfusion rate below 20 μl/hr the microdialysate histamine concentration was close to the actual concentration in the submucosa. The ECL‐cell histamine mobilization was independent of the concentrations of Ca2+ in the perfusion medium (0–3.4 mmol/l Ca2+). In one experiment, histamine mobilization in response to gastrin (10 nmol/kg/hr subcutaneously) was monitored in rats pretreated with prednisolone (60 mg/kg) or indomethacin (15 mg/kg). The two antiinflammatory agents failed to affect the concentration of histamine in the microdialysate either before or during the gastrin challenge, which was in accord with the observation that the inflammatory reaction was modest and that inflammatory cells were relatively few around the probe and in the wall of the probe. In another experiment, rats were given aminoguanidine (10 mg/kg) or metoprine (10 mg/kg) 4 hr before the start of gastrin infusion (5 nmol/kg/hr intravenously). Metoprine (inhibitor of histamine N‐methyl transferase) did not affect the microdialysate histamine concentration, while aminoguanidine (inhibitor of diamine oxidase) raised both basal and gastrin‐stimulated histamine concentrations. We conclude that microdialysis can be used to monitor changes in the concentration of histamine in the submucosa of the stomach, and that the inflammatory reaction to the probe is moderate and does not affect the submucosal histamine mobilization. 相似文献
993.
Raphael P Viscidi Mark Schiffman Allan Hildesheim Rolando Herrero Philip E Castle Maria C Bratti Ana Cecilia Rodriguez Mark E Sherman Sophia Wang Barbara Clayman Robert D Burk 《Cancer epidemiology, biomarkers & prevention》2004,13(2):324-327
Whether antibodies to human papillomavirus (HPV) capsids, elicited by natural infection, are protective is unknown. This question was addressed in a population-based cohort of 7046 women in Costa Rica by examining the association between baseline seroreactivity to HPV-16, HPV-18, or HPV-31 virus-like particles and the risk of subsequent HPV infection at a follow-up visit 5-7 years after enrollment. Seropositivity to HPV-16, HPV-18, or HPV-31 was not associated with a statistically significant decreased risk of infection with the homologous HPV type [relative risk (RR) and [95% confidence interval (CI)], 0.74 (0.45-1.2), 1.5 (0.83-2.7), and 0.94 (0.48-1.8), respectively]. Seropositivity to HPV-16 or HPV-31 was not associated with a decreased risk of infection with HPV-16 or its genetically related types [RR (95% CI), 0.82 (0.61-1.1) and 0.93 (0.68-1.2), respectively]. Seropositivity to HPV-18 was not associated with a decreased risk of infection with HPV-18 or its genetically related types (RR 1.3; 95% CI 1.0-1.8). Thus, we did not observe immunity, although a protective effect from natural infection cannot be excluded because of the limits of available assays and study designs. 相似文献
994.
Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma. 总被引:1,自引:0,他引:1
Nam H Dang Fredrick B Hagemeister Barbara Pro Peter McLaughlin Jorge E Romaguera Dan Jones Barry Samuels Felipe Samaniego Anas Younes Michael Wang Andre Goy Maria A Rodriguez Pamela L Walker Yolanda Arredondo Ann T Tong Luis Fayad 《Journal of clinical oncology》2004,22(20):4095-4102
PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted. 相似文献
995.
996.
HMGA1 protein overexpression in human breast carcinomas: correlation with ErbB2 expression. 总被引:6,自引:0,他引:6
Gennaro Chiappetta Gerardo Botti Mario Monaco Rosa Pasquinelli Francesca Pentimalli Maurizio Di Bonito Giuseppe D'Aiuto Monica Fedele Rodolfo Iuliano Emiliano A Palmieri Giovanna Maria Pierantoni Vincenzo Giancotti Alfredo Fusco 《Clinical cancer research》2004,10(22):7637-7644
We measured, by immunohistochemistry, HMGA1 protein expression in 212 breast tissue specimens: 6 normal samples, 28 hyperplastic lesions (13 with cellular atypia), 11 fibroadenomas, 10 in situ ductal carcinomas, 144 ductal carcinomas, and 13 lobular carcinomas. HMGA1 was not expressed in normal breast tissue; HMGA1 staining was intense in 40% of hyperplastic lesions with cellular atypia and in 60% of ductal carcinomas and weak in fibroadenomas and in hyperplastic lesions without cellular atypia. Because HMGA1 expression was similar among ductal breast carcinomas with different histologic grading, we evaluated the association between HMGA1 expression and that of other markers of breast carcinoma invasion (estrogen and progesterone receptors, Ki-67 antigen, and ErbB2) in 21 cases of grade 3 breast ductal carcinomas and 7 cases of breast lobular carcinomas. We found that HMGA1 expression tended to be associated only with c-erbB-2 expression (Spearman rho: 0.36; P=0.065). Taken together, these results suggest that HMGA1 expression might be a novel indicator for the diagnosis and prognosis of human breast cancer. 相似文献
997.
Eduardo Bruera J Lynn Palmer Snezana Bosnjak Maria Antonieta Rico Jairo Moyano Catherine Sweeney Florian Strasser Jie Willey Mariela Bertolino Clarissa Mathias Odette Spruyt Michael J Fisch 《Journal of clinical oncology》2004,22(1):185-192
PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain. 相似文献
998.
Prognostic value of CD40 in adult soft tissue sarcomas. 总被引:4,自引:0,他引:4
Alessandro Ottaiano Anna De Chiara Francesco Perrone Gerardo Botti Flavio Fazioli Vincenzo De Rosa Nicola Mozzillo Vincenzo Ravo Brunello Morrica Ciro Gallo Carmela Pisano Maria Napolitano Paolo Antonio Ascierto Rosario Vincenzo Iaffaioli Gaetano Apice 《Clinical cancer research》2004,10(8):2824-2831
PURPOSE: The purpose is to evaluate the expression of CD40, a membrane protein predominantly expressed on B cells, dendritic cells, and macrophages, in a series of adult soft tissue sarcomas and to test its possible prognostic value. EXPERIMENTAL DESIGN: CD40 expression was studied by immunohistochemistry. Correlations with other baseline characteristics of patients and tumors were analyzed with chi(2) test. The prognostic value was studied with univariable and multivariable analysis adjusted by age, sex, tumor size, grade, location, and distant metastases. RESULTS: Eighty-two patients, between January 1994 and May 2001, were analyzed. Membrane or cytoplasmic staining for CD40 protein was absent in 30% of the tumors but present in <10% of cells in 22 (27%), in 10% to 50% in 23 (28%), and in >50% of cells in 12 (15%) tumors. There was no correlation between CD40 expression and age, sex, size, grade, and location of the primary tumor and distant metastases. With 61 patients (74.4%) progressed and 31 (37.8%) dead, CD40 expression was a significant prognostic factor for disease-free and overall survival at univariable and multivariable analysis. Patients with tumors expressing CD40 in >50% of cells had a dramatically unfavorable prognosis with median disease-free and overall survival of 7 and 17 months, respectively, and hazard ratios of relapse and death as compared with patients with CD40-negative tumors of 2.89 (95% confidence interval: 1.26-6.60) and 6.92 (95% confidence interval: 2.18-22.0), respectively. CONCLUSIONS: These data suggest that expression of CD40 protein in >50% of cells might indicate an unfavorable prognosis in adult soft tissue sarcomas. 相似文献
999.
Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years' follow-Up. 总被引:2,自引:0,他引:2
Carlos Fernández-Martos Jorge Aparicio Carles Bosch Marilo Torregrosa Juan Manuel Campos Salvador Garcera Jose Maria Vicent Inmaculada Maestu Miguel Angel Climent Jose Luis Mengual Alejandro Tormo Ana Hernandez Rafael Estevan Jose Maria Richart Vicente Viciano Natalia Uribe Jorge Campos Ramon Puchades Francisco Arlandis Daniel Almenar 《Journal of clinical oncology》2004,22(15):3016-3022
PURPOSE: To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy (RT) followed by surgery and postoperative flurouracil (FU)/leucovorin (LV) in patients with rectal cancer. PATIENTS AND METHODS: Patients (n = 94) with potentially resectable tumors, ultrasound at stages T2N+ (n = 4), T3 (n = 77), T4 (n = 13) were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV. Primary end points included downstaging, pathologic responses, and sphincter-preserving surgery. Secondary end points were recurrence-free survival and overall survival. RESULTS: All patients received the full RT dose. Fifteen patients (16%) needed UFT dose reduction. Preoperative G3+ toxicities included diarrhea (14%), leukopenia (1%), thrombocytopenia (1%), and nausea (4%). The downstaging rate was 54%, pathologic complete response (pCR) was 9% and, in an additional 23%, there were only residual microscopic foci. When cellular viability criteria were taken into account, the pCR was 15%. From 43 patients with abdominoperineal resection indication, 11 (25%) had sphincter-preserving surgery performed. Postoperative scheduled chemotherapy dose was not administered to 24% of patients because of G3+ toxicity (diarrhea, 8%; mucositis, 9%; and leukopenia, 7%). Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without. At 3 years, actuarial patterns of failure were pelvic, 5% and distant, 11%. OS was 75%. CONCLUSION: UFT combined with RT is safe and effective. In resectable rectal cancer, if preoperative treatment is considered, this approach can be an option. 相似文献
1000.
Donato Gemmati Alessia Ongaro Gian L Scapoli Matteo Della Porta Silvia Tognazzo Maria L Serino Eros Di Bona Francesco Rodeghiero Giuseppe Gilli Roberto Reverberi Angelo Caruso Michela Pasello Agnese Pellati Monica De Mattei 《Cancer epidemiology, biomarkers & prevention》2004,13(5):787-794
Folate and methionine metabolism is involved in DNA synthesis and methylation processes. Polymorphisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In a case-control study, we evaluated whether four common polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G), and methionine synthase reductase (MTRR A66G) genes may have a role in altering susceptibility to adult acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). We analyzed DNA of 120 adult ALL, 200 NHL, and 257 healthy control subjects. Individual carrying the MTHFR 677TT genotype showed a 3.6-fold decreased ALL risk [odds ratio (OR) 0.28, 95% confidence interval (95% CI) 0.12-0.72] than wild-types. Similarly, MS 2756GG individuals showed a 5.0-fold decreased ALL risk (OR 0.20, 95% CI 0.02-1.45) than wild-types. In combined results, subjects with the MTHFR 677CT/TT and MS 2756AG/GG genotypes revealed a 3.6-fold ALL risk reduction (OR 0.28, 95% CI 0.14-0.58) and those with the MTHFR 677TT and MTRR 66AG genotypes revealed a 4.2-fold ALL risk reduction (OR 0.24, 95% CI 0.06-0.81). Finally, those with the MS 2756AG/GG and MTRR 66AG/GG genotypes revealed a 2.2-fold ALL risk reduction (OR 0.45, 95% CI 0.10-0.85). Single analysis for NHL did not show any significant difference for all the polymorphisms investigated, but in the low-grade NHL subgroup, we found a 2.0-fold risk reduction for the MTRR 66GG homozygous genotype (OR 0.50, 95% CI 0.25-0.99), which was higher (OR 0.37, 95% CI 0.14-0.85) when analyzed in combination with MS 2756AA genotype. These data are in accordance with the hypothesis that polymorphisms in the genes for folate and methionine metabolism might play a greater role in the occurrence of ALL than NHL by influencing DNA synthesis and/or DNA methylation. 相似文献