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81.
Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma 总被引:1,自引:0,他引:1
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Introduction
Little is known of the function and clinical significance of intratumoral dysregulation of xenobiotic-metabolizing enzyme expression in breast cancer. One molecular mechanism proposed to explain tamoxifen resistance is altered tamoxifen metabolism and bioavailability. 相似文献82.
In this study, we documented the effects of different peripheral benzodiazepine receptor (PBR) ligands: PK 11195, Ro5-4864 and the newly described SSR 180575 on the development of pulmonary inflammation in vivo. To this aim, we used MRL/lpr mice that develop pathological signs similar to the human lupus erythematosus (LE) signs. We found that a chronic treatment (at 3 mg/kg per i.p. for 30 days) with PBR ligands had a significant beneficial therapeutic action and decreased the inflammatory pulmonary responses and alveolitis onset. When analyzing PBR expression in inflamed tissues, we observed that in addition to the infiltrated leukocytes, PBR was expressed in the bronchial epithelium, and especially we evidenced for the first time that PBR in expressed in Clara cells. Interestingly, we observed that PBR expression in those cells was reduced when MRL/lpr mice developed the pathology and restored upon PBR ligand treatment. These original findings support a role of PBR in pulmonary inflammatory process and suggest new therapeutic applications in auto immune disorders for specific potent PBR ligands. 相似文献
83.
Frozen section examination of the endocervical margin of cervical conization specimens 总被引:5,自引:0,他引:5
Rouzier R Feyereisen E Constancis E Haddad B Dubois P Paniel BJ 《Gynecologic oncology》2003,90(2):305-309
OBJECTIVE: We conducted this retrospective study to determine accuracy of frozen section examination of endocervical margin during cold knife conization. METHODS: Between June 1993 and June 2001, 310 consecutive patients underwent cervical conization for squamous intraepithelial lesion or stage IA1 cervical cancer. Before 1997, the surgical specimens of 149 patients were processed following a standard pathological procedure (historical group). After 1997, a frozen section of the upper endocervical margin was processed during surgery for 161 patients. If the upper endocervical margin was involved with intraepithelial neoplasia, the surgeon performed a second resection if possible. Results of the frozen section examination were compared with the final diagnoses to determine sensitivity, specificity, and positive and negative predictive values. The usefulness of this procedure was evaluated by comparison of positive margin status rate with the one of the historical control group. RESULTS: For the diagnosis of intraepithelial neoplasia involving the endocervical margin, the sensitivity, specificity, and positive and negative predictive values of frozen section were 91%, 100%, 100%, and 98%, respectively. Eleven patients had definitive positive endocervical margin in the frozen section group (three false negatives, six patients without additional resection, and two patients with intraepithelial neoplasia involving the upper margin of the additional resection) and 17 patients in the historical group (P =.16). CONCLUSION: Frozen section examination of the endocervical margin of cervical specimen obtained during cold knife conization is highly accurate. Its clinical relevance has to be demonstrated in a multicenter study. 相似文献
84.
Humbey O Aubin F Cairey-Remonnay S Riethmuller D Pretet JL Fest T Seilles E Mougin C 《European journal of obstetrics, gynecology, and reproductive biology》2002,103(1):60-64
OBJECTIVE: To investigate the codon 72 TP53 polymorphism in women from eastern France with normal or abnormal cervical cytology.STUDY DESIGN: We analyzed the TP53 allele distribution by denaturant gradient gel electrophoresis assay and the human papillomaviruses (HPV) infection in 138 cervical smears: 50 normal, 20 atypical squamous cells of undetermined significance, 40 low grade squamous intraepithelial lesions, 28 high grade squamous intraepithelial lesions.RESULTS: The viral DNA prevalence increased with cytological abnormalities. The rates of arginine (Arg) and proline (Pro) homozygosity and Arg/Pro heterozygosity were 49, 0.72, and 51%, respectively. No association was found between HPV status and TP53 polymorphism. No differences were observed in the frequency of the TP53 genotypes according to cytology.CONCLUSION: The TP53 Arg/Arg genotype does not appear to represent a risk factor in the progression of HPV associated cervical lesions. We were not able to confirm that the TP53 genotype increases the susceptibility to be infected by HPV or to develop HGSIL, and a fortiori invasive carcinoma of the cervix. 相似文献
85.
Aizenfisz S Dauger S Durand E Vardon G Levacher B Simonneau M Pachnis V Gaultier C Gallego J 《Respiratory physiology & neurobiology》2002,131(3):213-222
The c-ret proto-oncogene encodes a tyrosine-kinase receptor involved in survival and differentiation of neural crest cell lineages. Previous studies have shown that homozygous c-ret-/- mice die soon after birth and have impaired ventilatory responses to hypercapnia. Heterozygous c-ret +/- mice develop normally, but their respiratory phenotype has not been described in detail. We used whole-body flow plethysmography to compare baseline breathing and ventilatory and arousal responses to chemical stimuli in unrestrained heterozygous c-ret +/- newborn mice and their wild-type c-ret +/+ littermates at 10-12 h of postnatal age. The hyperpnoeic and arousal responses to hypoxia and hypercapnia were not significantly different in these two groups. However, the number and total duration of apnoeas and periodic breathing episodes were significantly higher in c-ret +/- than in c-ret +/+ pups during hypoxia and post-hypoxic normoxia. These results are further evidence that respiratory control at birth is heavily dependent on genes involved in the neural determination of neural crest cells. 相似文献
86.
87.
Local anesthesia infiltration has been established as a preferred method of perioperative analgesia in many cosmetic operations. In an attempt to maximize the risk-benefit ratio of local anesthesia, a study was conducted to compare efficacy of two local anaesthetic agents. Bupivacaine was compared to ropivacaine in a bilaterally symmetrical breast surgery model. A local anaesthetic solution containing either bupivacaine or ropivacaine was infiltrated into each of the breasts of 15 patients undergoing either breast augmentation or breast reduction. Both surgeon and patient were blinded to the nature of local anaesthetic agent injected. Patients were requested to score their pain at 1, 2, 6, and 10 hours after surgery on a visual analog scale. The results were analyzed statistically using a cross-sectional time-series regression model employing the random effects option of the xtreg command from Strata Release 6 statistical software. We found that overall analgesia achieved with bupivacaine and ropivacaine infiltrations was not statistically different. The use of a higher dose of ropivacaine is likely to have removed the clinical advantage noted for the bupivacaine group. There was, however, a statistical and clinical difference in the efficacy of local anaesthetic infiltration of both agents in breast augmentation patients as compared to breast reduction patients, local anaesthetic being less effective in patients who had submuscular breast augmentation than in patients who had breast reduction. In view of these findings, it appears reasonable to recommend the use of ropivacaine in high-dose infiltration breast analgesia, as it is reported to be less cardiotoxic than bupivacaine. Serious attention needs also to be given to the adequacy of field infiltration of local anesthesia in submuscular breast augmentation. 相似文献
88.
Transgenic carrot plants were developed expressing a designer polyepitope combining tandem repeats of a protective loop-forming B cell epitope (H386-400) of the measles virus hemagglutinin protein with a human promiscuous, measles-unrelated T cell epitope (tt830-844). Despite the sensitivity of the loop conformation to its molecular environment, proper folding was confirmed by conformation-dependent monoclonal antibodies. The antibodies also reacted with the boiled antigen in Western blot. Immunisation of mice peritoneally with carrot plant extracts induced high titers of antibodies that crossreacted strongly with the virus. Furthermore, the sera neutralised field isolates of different geographic origins and genotypes in a modified plaque reduction neutralisation assay performed on CD150-transfected Vero cells. These results demonstrate that transgenic carrot plants can serve as an efficient expression system to produce highly immunogenic, randomly assembled polyepitope antigens. The combined features of the selected epitopes and the potential of the plant expression system may pave the way towards new vaccines against measles. 相似文献
89.
Behnke K Søgaard J Martin S Bäuml J Ravindran AV Agren H Vester-Blokland ED 《Journal of clinical psychopharmacology》2003,23(4):358-364
This multinational, randomized, double-blind study was specifically designed to prospectively compare the onset of antidepressant efficacy of mirtazapine orally disintegrating tablets and sertraline at dosages commonly used in clinical practice. A total of 345 patients with major depressive episode (DSM-IV) received mirtazapine (30-45 mg/d) or sertraline (50-150 mg/d) for 8 weeks. Mirtazapine was administered in the newly developed fast dissolving, orally disintegrating tablet formulation. Assessments were performed at baseline and on days 4, 7, 10, 14, 28, 42, and 56. The primary efficacy variable (mean absolute change from baseline in the Hamilton Depression Rating Scale [HAMD] total score [17 items]) showed that mirtazapine was significantly (P < 0.05) more effective than sertraline at all assessments during the first 2 weeks of the study. After this time, HAMD total scores were similar in both groups. These findings were supported by analysis of the HAMD response rate (ie, > or =50% reduction in HAMD total score from baseline), HAMD remission rate (HAMD total score of < or =7), and the Montgomery-Asberg Depression Rating Scale (MADRS). Both treatments were well tolerated. In addition, mirtazapine had a greater effect than sertraline on sexual functioning. In conclusion, this first prospective onset of action study using the orally disintegrating tablet indicates that mirtazapine has a faster onset of therapeutic effect than sertraline. The orally disintegrating tablet formulation of mirtazapine used in this study is known to enhance the convenience and compliance by the patient. 相似文献
90.
Reg IV,a new member of the regenerating gene family,is overexpressed in colorectal carcinomas 总被引:8,自引:0,他引:8
Violette S Festor E Pandrea-Vasile I Mitchell V Adida C Dussaulx E Lacorte JM Chambaz J Lacasa M Lesuffleur T 《International journal of cancer. Journal international du cancer》2003,103(2):185-193
A better understanding of the mechanisms by which colon tumor cells are able to survive exposure to drugs would be valuable for the development of new therapeutic strategies. We used differential display-PCR to compare gene expression in the drug-sensitive HT-29 colon cancer cell line and 3 drug-resistant subpopulations derived from this parental cell line. One of the genes identified is a new gene, Regenerating IV gene (Reg IV), and was strongly overexpressed in HT-29 drug-resistant cells. Other drug-resistant cell lines expressed Reg IV at a high level, whereas a low expression was noted in sensitive cell lines. Northern blot and real-time PCR analysis showed that Reg IV is more strongly expressed in 71% of colorectal tumors (in particular in mucinous carcinomas) than in normal colon tissues. The comparison of Reg IV expression with that of other REG genes, Regenerating Ialpha or (Reg Ialpha), Regenerating Ibeta (Reg Ibeta) and Pancreatitis-associated protein (PAP), highlights its predominant expression in colorectal tumors. Reg IV mRNA-positive tumor cells display different phenotypes: mucus-secreting, enterocyte-like or undifferentiated. Interestingly, whereas Reg IV expression is low in normal colon, its level in normal small intestine is similar to that in some colorectal tumors. In normal tissue, Reg IV mRNA-positive cells are mostly enteroendocrine cells and goblet cells. Our results point out the potential role of Reg IV in colorectal tumors and its subsequent interest as a pronostic indicator of tumor survival. 相似文献