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排序方式: 共有9805条查询结果,搜索用时 15 毫秒
911.
Peretto I Forlani R Fossati C Giardina GA Giardini A Guala M La Porta E Petrillo P Radaelli S Radice L Raveglia LF Santoro E Scudellaro R Scarpitta F Bigogno C Misiano P Dondio GM Rizzi A Armani E Amari G Civelli M Villetti G Patacchini R Bergamaschi M Delcanale M Salcedo C Fernández AG Imbimbo BP 《Journal of medicinal chemistry》2007,50(7):1571-1583
Pharmacophore-based structural identification, synthesis, and structure-activity relationships of a new class of muscarinic M3 receptor antagonists, the diaryl imidazolidin-2-one derivatives, are described. The versatility of the discovered scaffold allowed for several structural modifications that resulted in the discovery of two distinct classes of compounds, specifically a class of tertiary amine derivatives (potentially useful for the treatment of overactive bladder by oral administration) and a class of quaternary ammonium salt derivatives (potentially useful for the treatment of respiratory diseases by the inhalation route of administration). In this paper, we describe the synthesis and biological activity of tertiary amine derivatives. For these compounds, selectivity for the M3 receptor toward the M2 receptor was crucial, because the M2 receptor subtype is mainly responsible for adverse systemic side effects of currently marketed muscarinic antagonists. Compound 50 showed the highest selectivity versus M2 receptor, with binding affinity for M3 receptor Ki = 4.8 nM and for M2 receptor Ki = 1141 nM. Functional in vitro studies on selected compounds confirmed the antagonist activity toward the M3 receptor and functional selectivity toward the M2 receptor. 相似文献
912.
913.
Digiammarco G Liberi R Giancane M Canosa C Gallina S Di Francesco A Spira G Di Mauro M 《Interactive Cardiovascular and Thoracic Surgery》2007,6(3):340-344
This study was aimed at identifying predictive variables for recurrence of mitral regurgitation (MR) in patients with dilated cardiomyopathy (DCM) undergoing mitral valve (MV) repair. From January 1997 to December 2005, 142 patients with DCM, 105 (73.9%) ischemic and 37 (26.1%) non-ischemic, underwent MV repair. Mean age was 66+/-10 years and mean MR grade was 3.2+/-0.7 (scale 1+ to 4+). Ninety-seven (71% ischemic, 29% non-ischemic), out of 98 still alive at follow-up, were included in this retrospective analysis. In all cases MV posterior annuloplasty was performed; all patients were followed-up by echocardiography (mean time interval of 44+/-28 months) to evaluate MR recurrence (>or=2+/4+). Thirty-day mortality was 9.2% (13 patients). Mean MR grade at follow-up was 0.9+/-0.9. Four-year freedom from MR recurrence was 65.5%+/-8.3. Cox analysis showed left ventricular end-diastolic volume index (LVEDVi, OR=1.03, P=0.016, AUC=0.72), left ventricular end-systolic volume index (LVESVi, OR=1.03, P=0.033, AUC=0.71), left ventricular ejection fraction (LVEF, OR=0.82, P=0.001, AUC=0.72), mitral valve coaptation depth (MVCD, OR=1.6, P=0.017, AUC=0.72) to be predictive variables for MR recurrence. Preoperative left ventricular dilatation and function along with degree of papillary muscle displacement can be helpful in identifying patients with higher probability to undergo a durable MV repair. 相似文献
914.
Human osteoblast-like cell adhesion on titanium substrates covalently functionalized with synthetic peptides 总被引:5,自引:0,他引:5
Bagno A Piovan A Dettin M Chiarion A Brun P Gambaretto R Fontana G Di Bello C Palù G Castagliuolo I 《BONE》2007,40(3):693-699
Biomaterials to be used for the production of endosseous devices in dental, orthopedic and maxillo-facial applications, might be designed to support, guide and enhance osteoblast adhesion. Cell recruitment onto biomaterial surface is a fundamental step within the complex process responsible for implant osseointegration; this process involves several proteins from the extra cellular matrix (ECM), cytoskeleton and cell membrane. A new strategy to improve endosseous implant integration is based on preparing biomimetic surfaces able to present adhesive factors to cells. Osteoblast adhesion takes place by at least two different mechanisms: the most investigated one implies the interaction with RGD sequences via cell-membrane integrin receptors; a further mechanism concerns the interaction between cell-membrane heparan sulfate proteoglycans and heparin-binding sites of ECM proteins. In the present study two different biomimetic surfaces were obtained by covalently grafting two adhesive peptides on oxidized titanium substrates after silanization: an RGD-containing peptide and a peptide mapped on human vitronectin. The two sequences are known to act via different adhesive mechanisms. The amount of human osteoblasts adhered onto peptide-enriched or not enriched titanium oxidized surfaces and the strength of cell binding were estimated, thus comparing the capacity of the bioactive substrates in promoting cell adhesion. 相似文献
915.
Pupa SM Giuffré S Castiglioni F Bertola L Cantú M Bongarzone I Baldassari P Mortarini R Argraves WS Anichini A Menard S Tagliabue E 《Cancer research》2007,67(9):4271-4277
Doxorubicin treatment was found to augment the expression of the extracellular matrix (ECM) protein fibulin-1 in cultured human breast cancer cell lines and in MDA-MB-361 tumors grown in athymic mice. Doxorubicin was also found to augment tumor expression of the fibulin-1-binding proteins fibronectin and laminin-1. Growth of breast cancer cell lines on Matrigel, an ECM extract containing fibulin-1 and laminin-1, resulted in lower levels of doxorubicin-induced apoptosis as compared with controls. Moreover, tumors formed by injection of athymic mice with MDA-MB-361 cells mixed with Matrigel were significantly more doxorubicin resistant and displayed lower levels of apoptosis compared with those that formed in the absence of Matrigel. Monoclonal antibodies against fibulin-1 reversed Matrigel-dependent doxorubicin resistance. Furthermore, small interfering RNA-mediated suppression of fibulin-1 expression in breast cancer cells resulted in a 10-fold increase in doxorubicin sensitivity as compared with control cells. Together, these findings point to a role for fibulin-1 in breast cancer chemoresistance. 相似文献
916.
Deregulated CDC25A expression promotes mammary tumorigenesis with genomic instability 总被引:1,自引:0,他引:1
Ray D Terao Y Fuhrken PG Ma ZQ DeMayo FJ Christov K Heerema NA Franks R Tsai SY Papoutsakis ET Kiyokawa H 《Cancer research》2007,67(3):984-991
Checkpoint pathways help cells maintain genomic integrity, delaying cell cycle progression in response to various risks of fidelity, such as genotoxic stresses, compromised DNA replication, and impaired spindle control. Cancer cells frequently exhibit genomic instability, and recent studies showed that checkpoint pathways are likely to serve as a tumor-suppressive barrier in vivo. The cell cycle-promoting phosphatase CDC25A is an activator of cyclin-dependent kinases and one of the downstream targets for the CHK1-mediated checkpoint pathway. Whereas CDC25A overexpression is observed in various human cancer tissues, it has not been determined whether deregulated CDC25A expression triggers or promotes tumorigenesis in vivo. Here, we show that transgenic expression of CDC25A cooperates markedly with oncogenic ras or neu in murine mammary tumorigenesis. MMTV-CDC25A transgenic mice exhibit alveolar hyperplasia in the mammary tissue but do not develop spontaneous mammary tumors. The MMTV-CDC25A transgene markedly shortens latency of tumorigenesis in MMTV-ras mice. The MMTV-CDC25A transgene also accelerates tumor growth in MMTV-neu mice with apparent cell cycle miscoordination. CDC25A-overexpressing tumors, which invade more aggressively, exhibit various chromosomal aberrations on fragile regions, including the mouse counterpart of human 1p31-36, according to array-based comparative genomic hybridization and karyotyping. The chromosomal aberrations account for substantial changes in gene expression profile rendered by transgenic expression of CDC25A, including down-regulation of Trp73. These data indicate that deregulated control of cellular CDC25A levels leads to in vivo genomic instability, which cooperates with the neu-ras oncogenic pathway in mammary tumorigenesis. 相似文献
917.
Tumor-released microvesicles as vehicles of immunosuppression 总被引:10,自引:0,他引:10
Tumor-released microvesicles, or exosomes, which are abundant in the body fluids of patients with cancer, are likely to be involved in tumor progression. We recently showed that microvesicles released by human melanoma and colorectal carcinoma cells can promote the differentiation of monocytes to myeloid-derived suppressor cells which support tumoral growth and immune escape. These findings underscore an important role for these extracellular organelles in remodeling tumor-stromal interactions to promote malignancy. 相似文献
918.
Luini A Aguilar M Gatti G Fasani R Botteri E Brito JA Maisonneuve P Vento AR Viale G 《Breast cancer research and treatment》2007,101(3):349-353
The contribution of BRCA1 and BRCA2 to breast cancer incidence in Brazil has not yet been explored. In order to estimate the
proportion of breast cancers due to BRCA1 and BRCA2 mutations in Brazil, we conducted a study of unselected breast cancer
patients from Rio de Janeiro, Brazil. We enrolled 402 women with breast cancer from a large public hospital and two private
medical clinics in the city. A detailed family history was obtained from each patient and a blood sample was obtained for
DNA analysis. Mutations in BRCA1 and BRCA2 were sought using a combination of techniques, but all mutations were confirmed
by direct sequencing. Overall, nine mutations were identified (six in BRCA1 and three in BRCA2) representing 2.3% of the total.
The most common mutation, 5382insC in BRCA1, was seen five times and accounted for 56% of all identified mutations. A second
mutation, in BRCA2 (6633del5) was seen in two unrelated women. In summary, BRCA1 and BRCA2 mutations are not uncommon in Brazilian
women with breast cancer. It appears that a small number of founder mutations may be predominant. Moreover, a small number
of founder mutations may be prevalent in Brazil, raising the possibility that a rapid and inexpensive genetic test may be
developed to screen for inherited susceptibility to breast cancer in Brazil.
All studies listed in this paper are in accordance with the ethical standards of the regional hospitals in the listed study
area. 相似文献
919.
Multiplesignalingpathways,includingthec JunN terminalkinase (JNK)pathway ,areactivatedinmyocardialischemiaandreperfusion (MI/R)andcorrelatewithcelldeath .However,theroleoftheJNKpathwaywithrespecttoprotectionordestructioninMI/R inducedcelldeathispoorlyunderst… 相似文献