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排序方式: 共有8218条查询结果,搜索用时 11 毫秒
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Foà R Vitale A Vignetti M Meloni G Guarini A De Propris MS Elia L Paoloni F Fazi P Cimino G Nobile F Ferrara F Castagnola C Sica S Leoni P Zuffa E Fozza C Luppi M Candoni A Iacobucci I Soverini S Mandelli F Martinelli G Baccarani M;GIMEMA Acute Leukemia Working Party 《Blood》2011,118(25):6521-6528
Dasatinib is a potent BCR-ABL inhibitor effective in chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia (ALL) resistant/intolerant to imatinib. In the GIMEMA LAL1205 protocol, patients with newly diagnosed Ph(+) ALL older than 18 years (with no upper age limit) received dasatinib induction therapy for 84 days combined with steroids for the first 32 days and intrathecal chemotherapy. Postremission therapy was free. Fifty-three patients were evaluable (median age, 53.6 years). All patients achieved a complete hematologic remission (CHR), 49 (92.5%) at day 22. At this time point, 10 patients achieved a BCR-ABL reduction to < 10(-3). At 20 months, the overall survival was 69.2% and disease-free survival was 51.1%. A significant difference in DFS was observed between patients who showed at day 22 a decrease in BCR-ABL levels to < 10(-3) compared with patients who never reached these levels during induction. In multivariate analysis, BCR-ABL levels of < 10(-3) at day 85 correlated with disease-free survival. No deaths or relapses occurred during induction. Twenty-three patients relapsed after completing induction. A T315I mutation was detected in 12 of 17 relapsed cases. Treatment was well tolerated; only 4 patients discontinued therapy during the last phase of the induction when already in CHR. In adult Ph(+) ALL, induction treatment with dasatinib plus steroids is associated with a CHR in virtually all patients, irrespective of age, good compliance, no deaths, and a very rapid debulking of the neoplastic clone. 相似文献
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Moore PA Zhang W Rainey GJ Burke S Li H Huang L Gorlatov S Veri MC Aggarwal S Yang Y Shah K Jin L Zhang S He L Zhang T Ciccarone V Koenig S Bonvini E Johnson S 《Blood》2011,117(17):4542-4551
We describe the application of a novel, bispecific antibody platform termed dual affinity retargeting (DART) to eradicate B-cell lymphoma through coengagement of the B cell-specific antigen CD19 and the TCR/CD3 complex on effector T cells. Comparison with a single-chain, bispecific antibody bearing identical CD19 and CD3 antibody Fv sequences revealed DART molecules to be more potent in directing B-cell lysis. The enhanced activity with the CD19xCD3 DART molecules was observed on all CD19-expressing target B cells evaluated using resting and prestimulated human PBMCs or purified effector T-cell populations. Characterization of a CD19xTCR bispecific DART molecule revealed equivalent potency with the CD19xCD3 DART molecule, demonstrating flexibility of the DART structure to support T-cell/B-cell associations for redirected T cell-killing applications. The enhanced level of killing mediated by DART molecules was not accompanied by any increase in nonspecific T-cell activation or lysis of CD19(-) cells. Cell-association studies indicated that the DART architecture is well suited for maintaining cell-to-cell contact, apparently contributing to the high level of target cell killing. Finally, the ability of the CD19xTCR DART to inhibit B-cell lymphoma in NOD/SCID mice when coadministered with human PBMCs supports further evaluation of DART molecules for the treatment of B-cell malignancies. 相似文献
996.
Ghisi M Corradin A Basso K Frasson C Serafin V Mukherjee S Mussolin L Ruggero K Bonanno L Guffanti A De Bellis G Gerosa G Stellin G D'Agostino DM Basso G Bronte V Indraccolo S Amadori A Zanovello P 《Blood》2011,117(26):7053-7062
Ontogenesis of T cells in the thymus is a complex process whose molecular control is poorly understood. The present study investigated microRNAs involved in human thymocyte differentiation by comparing the microRNA expression profiles of thymocytes at the double-positive, single-positive CD4(+) and single-positive CD8(+) maturation stages. Microarray analysis showed that each thymocyte population displays a distinct microRNA expression profile that reflects their developmental relationships. Moreover, analysis of small-RNA libraries generated from human unsorted and double-positive thymocytes and from mature peripheral CD4(+) and CD8(+) T lymphocytes, together with the microarray data, indicated a trend toward up-regulation of microRNA expression during T-cell maturation after the double-positive stage and revealed a group of microRNAs regulated during normal T-cell development, including miR-150, which is strongly up-regulated as maturation progresses. We showed that miR-150 targets NOTCH3, a member of the Notch receptor family that plays important roles both in T-cell differentiation and leukemogenesis. Forced expression of miR-150 reduces NOTCH3 levels in T-cell lines and has adverse effects on their proliferation and survival. Overall, these findings suggest that control of the Notch pathway through miR-150 may have an important impact on T-cell development and physiology. 相似文献
997.
Iovino F Meraviglia S Spina M Orlando V Saladino V Dieli F Stassi G Todaro M 《Immunotherapy》2011,3(1):97-106
In the last 10 years, cancer stem cells have interested the scientific community because this small tumorigenic population is also associated with tumor progression in human patients and specific targeting of cancer stem cells could be a strategy to eradicate cancers currently resistant to conventional therapy. Clinical studies have recently demonstrated that adding immune therapy to chemotherapy has survival benefits in comparison with chemotherapy alone that can sensitize tumors to immune cell-mediated killing (e.g., increasing sensitivity of tumor cells to subsequent cytotoxicity by T cells via upregulation of death receptors DR5 and Fas). However, loss of MHC molecules is often observed in cancer cells, rendering tumor cells resistant to CD8 T-cell-mediated cytotoxicity. For this reason, we review the role of other T-cell subsets, such as γδ T and NK cells that are able to efficiently recognize and kill tumor cells and that could be used in passive or active immunotherapy in cancer stem cell eradication. 相似文献
998.
Elisevich K Shukla N Moran JE Smith B Schultz L Mason K Barkley GL Tepley N Gumenyuk V Bowyer SM 《Epilepsia》2011,52(6):1110-1119
Purpose: This study examines whether magnetoencephalographic (MEG) coherence imaging is more sensitive than the standard single equivalent dipole (ECD) model in lateralizing the site of epileptogenicity in patients with drug‐resistant temporal lobe epilepsy (TLE). Methods: An archival review of ECD MEG analyses of 30 presurgical patients with TLE was undertaken with data extracted subsequently for coherence analysis by a blinded reviewer for comparison of accuracy of lateralization. Postoperative outcome was assessed by Engel classification. MEG coherence images were generated from 10 min of spontaneous brain activity and compared to surgically resected brain areas outlined on each subject’s magnetic resonance image (MRI). Coherence values were averaged independently for each hemisphere to ascertain the laterality of the epileptic network. Reliability between runs was established by calculating the correlation between epochs. Match rates compared the results of each of the two MEG analyses with optimal postoperative outcome. Key Findings: The ECD method provided an overall match rate of 50% (13/16 cases) for Engel class I outcomes, with 37% (11/30 cases) found to be indeterminate (i.e., no spikes identified on MEG). Coherence analysis provided an overall match rate of 77% (20/26 cases). Of 19 cases without evidence of mesial temporal sclerosis, coherence analysis correctly lateralized the side of TLE in 11 cases (58%). Sensitivity of the ECD method was 41% (indeterminate cases included) and that of the coherence method 73%, with a positive predictive value of 70% for an Engel class Ia outcome. Intrasubject coherence imaging reliability was consistent from run‐to‐run (correlation >0.90) using three 10‐min epochs. Significance: MEG coherence analysis has greater sensitivity than the ECD method for lateralizing TLE and demonstrates reliable stability from run‐to‐run. It, therefore, improves upon the capability of MEG in providing further information of use in clinical decision‐making where the laterality of TLE is questioned. 相似文献
999.
Daelli V 《Neuropsychologia》2011,49(7):1923-1927
Recent perceptual experience can strongly influence the way in which ambiguous stimuli are interpreted and categorized. A well known example is the phenomenon of adaptation aftereffects that occurs when prolonged exposure to a clear, prototypical image induce a repulsive bias in the perception of a subsequently presented ambiguous stimulus. When an ambiguous image is used as adapter, however, a facilitatory, attractive effect can be observed (priming effect). In this study, the role of a pre-existing representation in the induction of the perceptual effect was investigated, with the use of novel, unfamiliar objects (Greebles). The results of two experiments indicate that a pre-existing representation is necessary for aftereffects to be observed, but only when the contribution of low-level adaptation is controlled for. Increased familiarity with the stimuli is able to restore the repulsive effect, as indicated by a third experiment. The priming effect found for ambiguous adapters, on the other hand, seems not to be influenced by a previously stored memory representation. 相似文献
1000.