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排序方式: 共有191条查询结果,搜索用时 252 毫秒
11.
Zhang Z Lee JC Lin L Olivas V Au V LaFramboise T Abdel-Rahman M Wang X Levine AD Rho JK Choi YJ Choi CM Kim SW Jang SJ Park YS Kim WS Lee DH Lee JS Miller VA Arcila M Ladanyi M Moonsamy P Sawyers C Boggon TJ Ma PC Costa C Taron M Rosell R Halmos B Bivona TG 《Nature genetics》2012,44(8):852-860
Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer. 相似文献
12.
本文应用数量化理论,给出了如何建立煤层注水效果的预测数学模型,并结合实例,进行了预测.实例表明,根据本矿已知煤层注水工程的各种信息,采用数量化理论.建立的计算机预测煤层注水效果的方法,不仅可以确切地判定所给定的注水组合参数是否最优,同时还揭露了注水参数与水分增值的内在关系,为调控参数提供了科学手段 相似文献
13.
在常温下,以民用煤油作稀释剂,用磷酸三丁酯(TBP)萃取处理镀铬废水。经4—5级萃取,可使水相中Cr~(6+)由70mg/L降至国家排放标准以下。有机相用稀碱溶液经2—3级反萃取再生,Cr~(6+)完全回收利用,这对环境保护大有好处。 相似文献
14.
如何正视李约瑟博士的中国科技史研究 总被引:1,自引:0,他引:1
何丙郁 《西北大学学报(自然科学版)》1996,26(2):93-97
认为李约瑟博士对中国人民的伟大贡献在于他使中国科学技术史开始获得世界学术界的公认;他的里程碑式的巨著离不开中国政府与海内外华人精神上与金钱上长期的大力支持,同样也离不开众多华裔学者的合作与帮助。 相似文献
15.
HAb18G/CD147-mediated calcium mobilization and hepatoma metastasis require both C-terminal and N-terminal domains 总被引:4,自引:0,他引:4
Jiang JL Chan HC Zhou Q Yu MK Yao XY Lam SY Zhu H Ho LS Leung KM Chen ZN 《Cellular and molecular life sciences : CMLS》2004,61(16):2083-2091
HAb18G/CD147 is a heavily glycosylated protein containing two immunoglobulin superfamily domains. Our previous studies have indicated that overexpression of HAb18G/CD147 enhances metastatic potentials in human hepatoma cells by disrupting the regulation of store-operated Ca2+ entry by nitric oxide (NO)/cGMP. In the present study, we investigated the structure-function of HAb18G/CD147 by transfecting truncated HAb18G/CD147 fragments into human 7721 hepatoma cells. The inhibitory effect of HAb18G/CD147 on 8-bromo-cGMP-regulated thapsigargin-induced Ca2+ entry was reversed by the expression of either C or N terminus truncated HAb18G/CD147 in T7721C and T7721N cells, respectively. The potential effect of HAb18G/CD147 on metastatic potentials, both adhesion and invasion capacities, of hepatoma cells was abolished in T7721C cells, but not affected in T7721N cells. Release and activation of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were found to be enhanced by the expression of HAb18G/CD147, and this effect was abolished by both truncations. Thapsigargin significantly enhanced release and activation of MMPs (MMP-2 and MMP-9) in non-transfected 7721 cells, and this effect was negatively regulated by SNAP. However, no effects of thapsigargin or SNAP were observed in T7721 cells, and expression of HAb18G/CD147 enhanced secretion and activation of MMPs at a stable and high level. Taken together, these results suggest that both ectodomain and intracellular domains of HAb18G/CD147 are required to mediate the effect of HAb18G/CD147 on the secretion and activation of MMPs and metastasis-related processes in human hepatoma cells by disrupting the regulation of NO/cGMP-sensitive intracellular Ca2+ mobilization although each domain may play different roles.Received 1 April 2004; received after revision 15 June 2004; accepted 22 June 2004 相似文献
16.
The T-box genes Tbx4 and Tbx5 have been shown to have key functions in the specification of the identity of the vertebrate forelimb (Tbx5) and hindlimb (Tbx4). Here we show that in zebrafish, Tbx5 has an additional early function that precedes the formation of the limb bud itself. Functional knockdown of zebrafish tbx5 through the use of an antisense oligonucleotide resulted in a failure to initiate fin bud formation, leading to the complete loss of pectoral fins. The function of the tbx5 gene in the development of zebrafish forelimbs seems to involve the directed migration of individual lateral-plate mesodermal cells into the future limb-bud-producing region. The primary defect seen in the tbx5-knockdown phenotype is similar to the primary defects described in known T-box-gene mutants such as the spadetail mutant of zebrafish and the Brachyury mutant of the mouse, which both similarly exhibit an altered migration of mesodermal cells. A common function for many of the T-box genes might therefore be in mediating the proper migration and/or changes in adhesive properties of early embryonic cells. 相似文献
17.
ICOS is essential for effective T-helper-cell responses 总被引:60,自引:0,他引:60
Tafuri A Shahinian A Bladt F Yoshinaga SK Jordana M Wakeham A Boucher LM Bouchard D Chan VS Duncan G Odermatt B Ho A Itie A Horan T Whoriskey JS Pawson T Penninger JM Ohashi PS Mak TW 《Nature》2001,409(6816):105-109
The outcome of T-cell responses after T-cell encounter with specific antigens is modulated by co-stimulatory signals, which are required for both lymphocyte activation and development of adaptive immunity. ICOS, an inducible co-stimulator with homology to CD28, is expressed on activated, but not resting T cells, and shows T-cell co-stimulatory function in vitro. ICOS binds specifically to its counter-receptor B7RP-1 (refs 5,6,7), but not to B7-1 or B7-2. Here we provide in vivo genetic evidence that ICOS delivers a co-stimulatory signal that is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell-dependent antigens. To determine the physiological function of ICOS, we generated and characterized gene-targeted ICOS-deficient mice. In vivo, a lack of ICOS results in severely deficient T-cell-dependent B-cell responses. Germinal centre formation is impaired and immunoglobulin class switching, including production of allergy-mediating IgE, is defective. ICOS-deficient T cells primed in in vivo and restimulated in vitro with specific antigen produce only low levels of interleukin-4, but remain fully competent to produce interferon-gamma. 相似文献
18.
Quigg A Finkel ZV Irwin AJ Rosenthal Y Ho TY Reinfelder JR Schofield O Morel FM Falkowski PG 《Nature》2003,425(6955):291-294
Phytoplankton is a nineteenth century ecological construct for a biologically diverse group of pelagic photoautotrophs that share common metabolic functions but not evolutionary histories. In contrast to terrestrial plants, a major schism occurred in the evolution of the eukaryotic phytoplankton that gave rise to two major plastid superfamilies. The green superfamily appropriated chlorophyll b, whereas the red superfamily uses chlorophyll c as an accessory photosynthetic pigment. Fossil evidence suggests that the green superfamily dominated Palaeozoic oceans. However, after the end-Permian extinction, members of the red superfamily rose to ecological prominence. The processes responsible for this shift are obscure. Here we present an analysis of major nutrients and trace elements in 15 species of marine phytoplankton from the two superfamilies. Our results indicate that there are systematic phylogenetic differences in the two plastid types where macronutrient (carbon:nitrogen:phosphorus) stoichiometries primarily reflect ancestral pre-symbiotic host cell phenotypes, but trace element composition reflects differences in the acquired plastids. The compositional differences between the two plastid superfamilies suggest that changes in ocean redox state strongly influenced the evolution and selection of eukaryotic phytoplankton since the Proterozoic era. 相似文献
19.
Cellular turnover and extracellular matrix remodeling in female reproductive tissues: functions of metalloproteinases and their inhibitors 总被引:18,自引:0,他引:18
Fata JE Ho AT Leco KJ Moorehead RA Khokha R 《Cellular and molecular life sciences : CMLS》2000,57(1):77-95
Female reproductive tissues possess a unique ability to accommodate a remarkable amount of cell turnover and extracellular matrix (ECM) remodeling following puberty. Cellular structures within ovary, uterus, and mammary tissue not only change cyclically in response to ovarian hormones but also undergo differentiation during pregnancy, and eventually revert to that resembling the pre-pregnant stage. Cell proliferation, apoptosis, invasion, and differentiation are integral cellular processes that are precisely regulated in reproductive tissues, but become dysregulated in pathologies such as cancer. Explicit reorganization of ECM and basement membranes is also critical to preserve the form and function of these tissues. Here we review the evidence that coordinated spatiotemporal expression patterns of matrix metalloproteinase (MMP) genes and their tissue inhibitors (TIMPs) are important in cell and ECM turnover of the ovary, uterus, and mammary tissues. We discuss how perturbation in these gene families may impact the biology of these reproductive tissues and the factors implicated in the control of MMP and TIMP gene expression. The observed trends in MMP and TIMP expression involved in ovarian and mammary carcinomas are also presented. 相似文献
20.
Hep-2 cells infected with measles virus (MV) for as short as 6 h became refractory to superinfection with canine distemper virus (CDV) but not to vesicular stomatitis virus (VSV). The exact mechanism of such interference is unknown but probably occurs after virus attachment and penetration. These results verify the suggestion that virus interference may be a mechanism of heterotypic protection against canine distemper. 相似文献