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91.
92.
Important increase of invasive lobular breast cancer incidence in Geneva,Switzerland 总被引:6,自引:0,他引:6
Verkooijen HM Fioretta G Vlastos G Morabia A Schubert H Sappino AP Pelte MF Schäfer P Kurtz J Bouchardy C 《International journal of cancer. Journal international du cancer》2003,104(6):778-781
A recent paper from the United States reported a sharp and unexplained increase in invasive lobular breast cancer incidence since 1977 (Li et al., Cancer 2000;88:2561-9). We investigated if this trend was also present in Geneva, Switzerland, where breast cancer incidence is one of the highest in Europe. We analyzed trends in breast cancer incidence according to histologic subtype, age and stage, to clarify the pattern. Our population-based study includes all histologically confirmed invasive breast carcinomas (n = 6,247) recorded between 1976 and 1999 at the Geneva Cancer Registry. Breast histology was classified as ductal carcinoma, lobular carcinoma and other. Incidence trends were studied by log-linear regression analyses. Models including effects of age, period and birth cohorts were used to describe rising incidence trends. The incidence of ductal carcinoma increased 1.2% per year (p(trend) < 0.001) from 85.2 to 110.1/100,000. This increase concerned women aged 50-69 years and early-stage tumors. Lobular cancer incidence increased disproportionately (14.4% per year, p(trend) < 0.01) and rose from 2.9 to 20.5/100,000. This increase affected all age categories and both localized and advanced stages. In addition, a strong age-cohort effect was present (p < 0.05), and women aged 50-59 years born after 1944 experienced the most marked increase. Our study shows a disproportionate increase of lobular breast cancer incidence compared to ductal cancer incidence. Contrary to ductal cancer, trends for lobular cancer are unlikely to be explained by increased use of screening mammography. Other explanations must be researched, in particular the role played by hormone replacement therapy. 相似文献
93.
Rousseau-Merck MF Fiette L Klochendler-Yeivin A Delattre O Aurias A 《Cancer Genetics and Cytogenetics》2005,157(2):127-133
The human rhabdoid tumorigenesis orchestrated by INI1 inactivation is associated with specific rearrangements of chromosome 22 that correlate with preferential anatomic tumor locations. A literature review revealed significant correlations between an apparently normal karyotype and kidney tumors, monosomy 22 and cerebral tumors, and chromosome 22 translocations and tumors at other anatomic sites. In the mouse rhabdoid tumor model, specifically in the four tumors that we tested for loss of heterozygosity, neither partial deletion nor monosomy of chromosome 10 could be detected. In contrast to the human data, the only chromosome mechanism involved in the 18 mouse tumors studied appears to be a mitotic recombination or a nondisjunction-duplication. Additionally, and despite mouse tumor incidence across a variety of sites, no rhabdoid tumor could be observed in the mouse kidney. These data suggest that the chromosome mechanisms for INI1 inactivation and the selective cell survival pressure differ in human and mouse. 相似文献
94.
Neonatal tolerance to a Th2-mediated autoimmune disease generates CD8+ Tc1 regulatory cells 总被引:2,自引:0,他引:2
Immunological tolerance can be achieved in animals by exposure of newborn to a foreign antigen. Depending on the dose and timing of the antigenic challenge, tolerance has been reported to result in clonal deletion, anergy or active suppression. In this latter case, regulatory T cells prevent autoimmunity by suppressing the reactivity of pathogenic self-reactive T cells. We have previously reported the generation of a neonatal, mercury-specific, and dominant tolerance to autoimmunity induced by mercury salts in rats. Chronic exposure to mercury salts can lead to SLE-like autoimmune responses, mediated by autoreactive CD4+ Th2 cells, that regulate and are followed by a resistant state mediated by protective CD8+ T cells. The aim of the study was to compare the resistance to the neonatal tolerance to mercury disease, and to further characterize the CD8+ T cells endowed with regulatory capacity in the neonatal tolerance model. We report here that resistance to mercury disease is long lasting and not mercury-specific, suggesting that different CD8+ T cells are involved in resistance and neonatal tolerance, and that regulatory CD8+ Tc1 cells generated in tolerance are required to control the CD8- cell population from developing Th2-mediated autoimmunity. Upon mercury recall, CD8+ CD45RC(high) T cells, that represent the Tc1 subset in the rat, expanded and were polarized towards IFNgamma production. Interestingly, identical results were obtained with the CD8+ CD25+T cell population. Substantial amounts of FasL gene expression were detected in CD8+ T lymphocytes upon recall with the tolerogen. AICD may be one of the regulatory mechanisms used by these regulatory CD8+ Tc1 cells that control neonatal tolerance to a Th2-mediated autoimmune disorder. 相似文献
95.
Zipper-like internalization of Dr-positive Escherichia coli by epithelial cells is preceded by an adhesin-induced mobilization of raft-associated molecules in the initial step of adhesion 下载免费PDF全文
Kansau I Berger C Hospital M Amsellem R Nicolas V Servin AL Bernet-Camard MF 《Infection and immunity》2004,72(7):3733-3742
We undertook a study of the mechanism by which Dr-positive bacteria invade epithelial cells. Our findings show that Dr-positive bacteria enter via a zipper-like mechanism that is independent of the Dr-induced mobilization of F-actin and of the signaling molecules that control Dr-induced F-actin rearrangements. We also observed that Dr-positive IH11128 bacteria entered cells that were positive for the caveola marker VIP21/caveolin (HeLa and Caco-2/Cav-1 cells) to the same extent as those that were not (parental Caco-2 cells). Using fluorescence labeling and confocal laser scanning microscopy, we provide evidence that during the adhesion step, the alpha5beta1 integrin, which plays a pivotal role in Afa/Dr diffusely adhering Escherichia coli bacterial entry, is mobilized around adhering Dr-positive bacteria. We show that the receptor for Afa/Dr adhesins, glycosylphosphatidylinositol-anchored CD55; the raft marker, ganglioside GM1; and VIP21/caveolin are all recruited around adhering Dr-positive bacteria. We also observed that extracting membrane cholesterol with methyl-beta-cyclodextrin (MBCD) did not affect the recruitment of CD55, GM1, or beta1 integrin to adhering Dr-positive bacteria. In contrast, extracting or changing membrane-bound cholesterol by means of drugs that modify lipid rafts (MBCD, filipin III, or mevalonate plus lovastatin plus MBCD) inhibited the entry of Dr-positive IH11128 both into cells that expressed VIP21/caveolin (HeLa and Caco-2/Cav-1 cells) and into those that did not (parental Caco-2 cells). Finally, restoring cholesterol within the cell membrane of MBCD-treated cells restored Dr-positive IH11128 internalization. 相似文献
96.
Geneviève Durand Marie-Fran?oise Hubert Hiroshi Kuno William O Cook Christine Boussiquet-Leroux Roger Owen Yukio Fujimaki Masayuki Kemi Michel Virat Matthew J van Zwieten 《Toxicological sciences》2002,66(1):166-172
Investigations on compound A, an M2-sparing M3 muscarinic receptor antagonist, showed that focal polar anterior subcapsular lenticular opacities, characterized by focal epithelial proliferation, developed in Sprague-Dawley rats. The incidence and bilateral localization of this change increased generally with dose and time, though plateauing after 8 months of treatment; however the severity progressed very slightly. Over a 1-year period, no anterior cortical lens fiber changes or other histological ocular changes developed. A decreased severity of the change and apoptosis suggested some regression after a 26-week recovery period. Two nonselective muscarinic receptor antagonists, atropine and tolterodine, induced similar lenticular changes in rats. A hypothesis in relation to an indirect effect of the drug, such as increased illumination of the lens due to mydriasis observed with all these compounds, was investigated and disproven. Because these opacities are induced by structurally unrelated muscarinic receptor antagonists (atropine and tolterodine), it is likely that these lenticular changes are the result of muscarinic receptor inhibition. However, hypotheses regarding a direct effect of the drug on muscarinic receptors in the lens epithelium, possibly mediated by drug and/or metabolite(s) in the aqueous humor and/or lens epithelium, remain to be investigated. This lenticular opacity is similar to that observed spontaneously in Sprague-Dawley rats, although the latter occur at a lower incidence. No such lenticular opacities have been reported in other animal species, including man, after treatment with muscarinic receptor antagonists. 相似文献
97.
98.
Prevention of blood coagulation is very often a prerequisite for successful medical devices. For that purpose, passivation of the key coagulation enzyme thrombin through the derivatization of the material's surface with an amidine-based molecule has been found to be promising. To further enhance the efficiency of this approach, thin layers of maleic anhydride copolymers offering different physico-chemical characteristics were tethered with carboxyl terminated polyethylene glycol to covalently immobilize a benzamidine-type derivative. The free carboxyl surface groups produced by the attachment of polyethylene glycol (PEG) were quantified by Ag(+) labeling and subsequent XPS detection. The film thickness as well as the carboxyl group content were found to be clearly dependent on the copolymer hydrophobicity and the nature of the PEG molecule. For the assessment of the anchorage of the thrombin to the benzamidine-derivative functionalized surfaces, the substrates were immersed in a buffered thrombin solution and the enzyme adsorption was studied using immunostaining/confocal laser scanning microscopy. Higher degrees of thrombin binding were observed for substrates configured with the hydrophilic compared to the more hydrophobic copolymer. Moreover, surface-bound spacers based on alpha,omega-heterobifunctional PEG amino acids (alphaAm,omegaAc-PEG) also enhanced the benzamidine surface density in comparison to homofunctional PEG diacids (alphaAc,omegaAc-PEG) because of a lower degree of carboxyl inactivation due to PEG 'bridging'. Altogether, the choice of copolymer coatings and the type of PEG spacers were demonstrated to enhance the efficiency of the thrombin scavenging by the covalently immobilized coagulation inhibitor. 相似文献
99.
Comparison of low and high initial tacrolimus dosing in primary heart transplant recipients: a prospective European multicenter study 总被引:1,自引:0,他引:1
Podesser BK Rinaldi M Yona NA Pulpón LA Villemot JP Haverich A Duveau D Brandrup-Wognsen G Gronda E Costard-Jäckle A Crespo-Leiro MG Khazen CS Viganó M Segovia J Mattei MF Harringer W Treilhaud M Karason K Mangiavacchi M Laufer G 《Transplantation》2005,79(1):65-71
BACKGROUND: The purpose of this prospective, randomized, open-label, phase II, multicenter study was to optimize the initial oral dose of tacrolimus. METHODS: A total of 113 patients were randomly assigned to initial low-dose (0.075 mg/kg/day, n=55) or high-dose (0.15 mg/kg/day, n=58) oral tacrolimus and followed for 3 months. Target whole-blood trough levels were 10 to 20 ng/mL. Prophylactic use of corticosteroids and azathioprine was identical in both groups, and antibody induction was mandatory. The primary endpoint was the time to and incidence of the initial oral tacrolimus dose adjustment because of toxicity or rejection, or withdrawal before initial dose change. Efficacy was assessed by the occurrence of biopsy-proven rejection (International Society for Heart and Lung Transplantation grade > or =1B). RESULTS: In the primary endpoint, no significant difference was observed between the low- and high-dose groups. After 3 months, there was no difference in freedom from initial oral tacrolimus dose change because of rejection, toxicity, or withdrawal (89.0% vs. 87.6%; not significant [NS]). In both groups, dose adjustments were mainly required to achieve and maintain target blood levels (80.0% vs. 82.8%; NS). Patient survival was 92.7% and 98.3% (NS). There was no significant difference between groups regarding freedom from biopsy-proven acute rejection (57.1% vs. 66.3%; NS). The overall safety profiles indicated a tendency toward better tolerability in the low-dose group. CONCLUSIONS: Although low-dose and high-dose tacrolimus had similar efficacy, low-dose tacrolimus was associated with a more favorable safety profile. Therefore we recommend starting tacrolimus therapy after antibody induction at 0.075 mg/kg and adjust dose according to whole-blood trough levels. 相似文献
100.
Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1 总被引:7,自引:0,他引:7
OBJECTIVES: Delta(9)-Tetrahydrocannabinol, the active agent of Cannabis sativa, exhibits well-documented antitumor properties, but little is known about the possible effects mediated by endogenous cannabinoids on human tumors. In the present study, we analyzed the effect of arachidonyl ethanolamide (AEA) on cervical carcinoma (CxCa) cell lines. METHODS: To assess the sensitivity of CxCa cells to AEA, we selected three cell lines that were exposed to increasing doses of AEA with or without antagonists to receptors to AEA. DNA fragmentation and caspase-7 activity were used as apoptosis markers. The expression of receptors to AEA were analyzed in CxCa cell lines as well as CxCa biopsies. RESULTS: The major finding was that AEA induced apoptosis of CxCa cell lines via aberrantly expressed vanilloid receptor-1, whereas AEA binding to the classical CB1 and CB2 cannabinoid receptors mediated a protective effect. Furthermore, unexpectedly, a strong expression of the three forms of AEA receptors was observed in ex vivo CxCa biopsies. CONCLUSIONS: Overall, these data suggest that the specific targeting of VR1 by endogenous cannabinoids or synthetic molecules offers attractive opportunities for the development of novel potent anticancer drugs. 相似文献