排序方式: 共有57条查询结果,搜索用时 15 毫秒
41.
Braig M Lee S Loddenkemper C Rudolph C Peters AH Schlegelberger B Stein H Dörken B Jenuwein T Schmitt CA 《Nature》2005,436(7051):660-665
Acute induction of oncogenic Ras provokes cellular senescence involving the retinoblastoma (Rb) pathway, but the tumour suppressive potential of senescence in vivo remains elusive. Recently, Rb-mediated silencing of growth-promoting genes by heterochromatin formation associated with methylation of histone H3 lysine 9 (H3K9me) was identified as a critical feature of cellular senescence, which may depend on the histone methyltransferase Suv39h1. Here we show that Emicro-N-Ras transgenic mice harbouring targeted heterozygous lesions at the Suv39h1, or the p53 locus for comparison, succumb to invasive T-cell lymphomas that lack expression of Suv39h1 or p53, respectively. By contrast, most N-Ras-transgenic wild-type ('control') animals develop a non-lymphoid neoplasia significantly later. Proliferation of primary lymphocytes is directly stalled by a Suv39h1-dependent, H3K9me-related senescent growth arrest in response to oncogenic Ras, thereby cancelling lymphomagenesis at an initial step. Suv39h1-deficient lymphoma cells grow rapidly but, unlike p53-deficient cells, remain highly susceptible to adriamycin-induced apoptosis. In contrast, only control, but not Suv39h1-deficient or p53-deficient, lymphomas senesce after drug therapy when apoptosis is blocked. These results identify H3K9me-mediated senescence as a novel Suv39h1-dependent tumour suppressor mechanism whose inactivation permits the formation of aggressive but apoptosis-competent lymphomas in response to oncogenic Ras. 相似文献
42.
肿瘤放疗并发症概率预测模型参数拟合方法 总被引:1,自引:0,他引:1
为了建立具有群体特异性的肿瘤放疗NTCP预测模型,提出了一种模型参数拟合方法.首先,基于NTCP模型的特点构建最大似然函数;然后,分别采用确定性优化方法和随机性优化方法对最大似然函数进行优化,分析优化过程的时间成本及优化结果,探讨用于拟合NTCP模型参数的最优方法.实验结果表明,用于拟合NTCP模型参数的最大似然函数是非凸的,存在局部最优解;遗传算法是一种最稳定的最大似然函数优化方法,其运行时间比模拟退火算法短,而且可以在每次优化结束后给出全局最优解,以作为NTCP模型参数.所提方法可以帮助肿瘤放疗工作者在临床随访数据的基础上建立具有群体特异性的放疗并发症预测模型. 相似文献
43.
Karnoub AE Dash AB Vo AP Sullivan A Brooks MW Bell GW Richardson AL Polyak K Tubo R Weinberg RA 《Nature》2007,449(7162):557-563
Mesenchymal stem cells have been recently described to localize to breast carcinomas, where they integrate into the tumour-associated stroma. However, the involvement of mesenchymal stem cells (or their derivatives) in tumour pathophysiology has not been addressed. Here, we demonstrate that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft. The breast cancer cells stimulate de novo secretion of the chemokine CCL5 (also called RANTES) from mesenchymal stem cells, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. This enhanced metastatic ability is reversible and is dependent on CCL5 signalling through the chemokine receptor CCR5. Collectively, these data demonstrate that the tumour microenvironment facilitates metastatic spread by eliciting reversible changes in the phenotype of cancer cells. 相似文献
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45.
The neural underpinnings of sleep involve interactions between sleep-promoting areas such as the anterior hypothalamus, and arousal systems located in the posterior hypothalamus, the basal forebrain and the brainstem. Hypocretin (Hcrt, also known as orexin)-producing neurons in the lateral hypothalamus are important for arousal stability, and loss of Hcrt function has been linked to narcolepsy. However, it is unknown whether electrical activity arising from Hcrt neurons is sufficient to drive awakening from sleep states or is simply correlated with it. Here we directly probed the impact of Hcrt neuron activity on sleep state transitions with in vivo neural photostimulation, genetically targeting channelrhodopsin-2 to Hcrt cells and using an optical fibre to deliver light deep in the brain, directly into the lateral hypothalamus, of freely moving mice. We found that direct, selective, optogenetic photostimulation of Hcrt neurons increased the probability of transition to wakefulness from either slow wave sleep or rapid eye movement sleep. Notably, photostimulation using 5-30 Hz light pulse trains reduced latency to wakefulness, whereas 1 Hz trains did not. This study establishes a causal relationship between frequency-dependent activity of a genetically defined neural cell type and a specific mammalian behaviour central to clinical conditions and neurobehavioural physiology. 相似文献
46.
O T Njajou N Vaessen M Joosse B Berghuis J W van Dongen M H Breuning P J Snijders W P Rutten L A Sandkuijl B A Oostra C M van Duijn P Heutink 《Nature genetics》2001,28(3):213-214
Hereditary hemochromatosis (HH) is a very common disorder characterized by iron overload and multi-organ damage. Several genes involved in iron metabolism have been implicated in the pathology of HH (refs. 1-4). We report that a mutation in the gene encoding Solute Carrier family 11, member A3 (SLC11A3), also known as ferroportin, is associated with autosomal dominant hemochromatosis. 相似文献
47.
Sansone SA Rocca-Serra P Field D Maguire E Taylor C Hofmann O Fang H Neumann S Tong W Amaral-Zettler L Begley K Booth T Bougueleret L Burns G Chapman B Clark T Coleman LA Copeland J Das S de Daruvar A de Matos P Dix I Edmunds S Evelo CT Forster MJ Gaudet P Gilbert J Goble C Griffin JL Jacob D Kleinjans J Harland L Haug K Hermjakob H Ho Sui SJ Laederach A Liang S Marshall S McGrath A Merrill E Reilly D Roux M Shamu CE Shang CA Steinbeck C Trefethen A Williams-Jones B Wolstencroft K Xenarios I 《Nature genetics》2012,44(2):121-126
To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' framework to support that vision. 相似文献
48.
Deschaseaux F Delgado D Pistoia V Giuliani M Morandi F Durrbach A 《Cellular and molecular life sciences : CMLS》2011,68(3):397-404
HLA-G plays a particular role during pregnancy in which its expression at the feto–maternal barrier participates into the
tolerance of the allogenic foetus. HLA-G has also been demonstrated to be expressed in some transplanted patients, suggesting
that it regulates the allogenic response. In vitro data indicate that HLA-G modulates NK cells, T cells, and DC maturation
through its interactions with various inhibitory receptors. In this paper, we will review the data reporting the HLA-G involvement
of HLA-G in human organ transplantation, then factors that can modulate HLA-G, and finally the use of HLA-G as a therapeutic
tool in organ transplantation. 相似文献
49.
Thomas G Jacobs KB Yeager M Kraft P Wacholder S Orr N Yu K Chatterjee N Welch R Hutchinson A Crenshaw A Cancel-Tassin G Staats BJ Wang Z Gonzalez-Bosquet J Fang J Deng X Berndt SI Calle EE Feigelson HS Thun MJ Rodriguez C Albanes D Virtamo J Weinstein S Schumacher FR Giovannucci E Willett WC Cussenot O Valeri A Andriole GL Crawford ED Tucker M Gerhard DS Fraumeni JF Hoover R Hayes RB Hunter DJ Chanock SJ 《Nature genetics》2008,40(3):310-315
50.
Assembly of microarrays for genome-wide measurement of DNA copy number. 总被引:20,自引:0,他引:20
A M Snijders N Nowak R Segraves S Blackwood N Brown J Conroy G Hamilton A K Hindle B Huey K Kimura S Law K Myambo J Palmer B Ylstra J P Yue J W Gray A N Jain D Pinkel D G Albertson 《Nature genetics》2001,29(3):263-264
We have assembled arrays of approximately 2,400 BAC clones for measurement of DNA copy number across the human genome. The arrays provide precise measurement (s.d. of log2 ratios=0.05-0.10) in cell lines and clinical material, so that we can reliably detect and quantify high-level amplifications and single-copy alterations in diploid, polyploid and heterogeneous backgrounds. 相似文献