共查询到20条相似文献，搜索用时 31 毫秒
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Garcia-Barros M Paris F Cordon-Cardo C Lyden D Rafii S Haimovitz-Friedman A Fuks Z Kolesnick R 《Science (New York, N.Y.)》2003,300(5622):1155-1159
About 50% of cancer patients receive radiation therapy. Here we investigated the hypothesis that tumor response to radiation is determined not only by tumor cell phenotype but also by microvascular sensitivity. MCA/129 fibrosarcomas and B16F1 melanomas grown in apoptosis-resistant acid sphingomyelinase (asmase)-deficient or Bax-deficient mice displayed markedly reduced baseline microvascular endothelial apoptosis and grew 200 to 400% faster than tumors on wild-type microvasculature. Thus, endothelial apoptosis is a homeostatic factor regulating angiogenesis-dependent tumor growth. Moreover, these tumors exhibited reduced endothelial apoptosis upon irradiation and, unlike tumors in wild-type mice, they were resistant to single-dose radiation up to 20 grays (Gy). These studies indicate that microvascular damage regulates tumor cell response to radiation at the clinically relevant dose range. 相似文献
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In higher metazoans, phagocytosis is essential in host defense against microbial pathogens and in clearance of apoptotic cells. Both microbial and apoptotic cells are delivered on a common route from phagosomes to lysosomes for degradation. Here, we found that activation of the Toll-like receptor (TLR) signaling pathway by bacteria, but not apoptotic cells, regulated phagocytosis at multiple steps including internalization and phagosome maturation. Phagocytosis of bacteria was impaired in the absence of TLR signaling. Two modes of phagosome maturation were observed, constitutive and inducible; their differential engagement depended on the ability of the cargo to trigger TLR signaling. 相似文献
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Peng G Guo Z Kiniwa Y Voo KS Peng W Fu T Wang DY Li Y Wang HY Wang RF 《Science (New York, N.Y.)》2005,309(5739):1380-1384
CD4+ regulatory T (Treg) cells have a profound ability to suppress host immune responses, yet little is understood about how these cells are regulated. We describe a mechanism linking Toll-like receptor (TLR) 8 signaling to the control of Treg cell function, in which synthetic and natural ligands for human TLR8 can reverse Treg cell function. This effect was independent of dendritic cells but required functional TLR8-MyD88-IRAK4 signaling in Treg cells. Adoptive transfer of TLR8 ligand-stimulated Treg cells into tumor-bearing mice enhanced anti-tumor immunity. These results suggest that TLR8 signaling could play a critical role in controlling immune responses to cancer and other diseases. 相似文献
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为寻找医治艾氏腹水癌的新型制剂,并评价药效,对小鼠腹腔注射肿瘤细胞,建立荷艾氏腹水癌细胞(EAC)的小鼠模型;并于接种后第7天开始用抗癌药,观察荷瘤小鼠(接种EAC后产生血性腹水的小鼠)的生存周期,通过对动物体内抗氧化水平指标(SOD、GSH、MDA)的检测,判定硒化合物的保护作用;用流式细胞术及对细胞进行DNA梯检测,评估药物对肿瘤细胞调亡的影响。结果表明含硒化合物,尤其是有机硒化合物,甲基硒代半胱氨酸(SeMC)与抗癌药长春新碱联合应用可使荷瘤小鼠的生存期延长、机体的抗氧化水平升高及肿瘤细胞凋亡率增多,较对照组有显著差异(P<0.01)。研究认为,含硒化合物与医用长春新碱联用对荷瘤小鼠的保护性,主要是出于硒的抗氧化能力,以及使长春新碱促进肿瘤细胞的凋亡来实现的。 相似文献
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Lin JH Li H Yasumura D Cohen HR Zhang C Panning B Shokat KM Lavail MM Walter P 《Science (New York, N.Y.)》2007,318(5852):944-949
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Decapentaplegic (Dpp) is a signaling molecule that controls growth and patterning of the developing Drosophila wing. Mutant cells lacking Dpp signal transduction have been shown to activate c-Jun amino-terminal kinase (JNK)-dependent apoptosis and to be lost from the wing disc epithelium. These observations have led to the hypothesis that Dpp promotes cell survival by preventing apoptosis. Here, we show that in the absence of JNK-dependent apoptosis, mutant cells lacking Dpp signal transduction can survive; however, they are still lost from the wing disc epithelium. This loss correlates with extensive cytoskeletal changes followed by basal epithelial extrusion. We propose that Dpp promotes cell survival within disc epithelia by affecting cytoskeletal organization. 相似文献
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Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA 总被引：1，自引：0，他引：1
Diebold SS Kaisho T Hemmi H Akira S Reis e Sousa C 《Science (New York, N.Y.)》2004,303(5663):1529-1531
Interferons (IFNs) are critical for protection from viral infection, but the pathways linking virus recognition to IFN induction remain poorly understood. Plasmacytoid dendritic cells produce vast amounts of IFN-alpha in response to the wild-type influenza virus. Here, we show that this requires endosomal recognition of influenza genomic RNA and signaling by means of Toll-like receptor 7 (TLR7) and MyD88. Single-stranded RNA (ssRNA) molecules of nonviral origin also induce TLR7-dependent production of inflammatory cytokines. These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses. 相似文献
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Janes KA Albeck JG Gaudet S Sorger PK Lauffenburger DA Yaffe MB 《Science (New York, N.Y.)》2005,310(5754):1646-1653
Signal transduction pathways control cellular responses to stimuli, but it is unclear how molecular information is processed as a network. We constructed a systems model of 7980 intracellular signaling events that directly links measurements to 1440 response outputs associated with apoptosis. The model accurately predicted multiple time-dependent apoptotic responses induced by a combination of the death-inducing cytokine tumor necrosis factor with the prosurvival factors epidermal growth factor and insulin. By capturing the role of unsuspected autocrine circuits activated by transforming growth factor-alpha and interleukin-1alpha, the model revealed new molecular mechanisms connecting signaling to apoptosis. The model derived two groupings of intracellular signals that constitute fundamental dimensions (molecular "basis axes") within the apoptotic signaling network. Projection along these axes captures the entire measured apoptotic network, suggesting that cell survival is determined by signaling through this canonical basis set. 相似文献
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Oda E Ohki R Murasawa H Nemoto J Shibue T Yamashita T Tokino T Taniguchi T Tanaka N 《Science (New York, N.Y.)》2000,288(5468):1053-1058
A critical function of tumor suppressor p53 is the induction of apoptosis in cells exposed to noxious stresses. We report a previously unidentified pro-apoptotic gene, Noxa. Expression of Noxa induction in primary mouse cells exposed to x-ray irradiation was dependent on p53. Noxa encodes a Bcl-2 homology 3 (BH3)-only member of the Bcl-2 family of proteins; this member contains the BH3 region but not other BH domains. When ectopically expressed, Noxa underwent BH3 motif-dependent localization to mitochondria and interacted with anti-apoptotic Bcl-2 family members, resulting in the activation of caspase-9. We also demonstrate that blocking the endogenous Noxa induction results in the suppression of apoptosis. Noxa may thus represent a mediator of p53-dependent apoptosis. 相似文献
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Yarovinsky F Zhang D Andersen JF Bannenberg GL Serhan CN Hayden MS Hieny S Sutterwala FS Flavell RA Ghosh S Sher A 《Science (New York, N.Y.)》2005,308(5728):1626-1629
Mammalian Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs). Although TLRs are clearly involved in the detection of bacteria and viruses, relatively little is known about their function in the innate response to eukaryotic microorganisms. Here we identify a profilin-like molecule from the protozoan parasite Toxoplasma gondii that generates a potent interleukin-12 (IL-12) response in murine DCs that is dependent on myeloid differentiation factor 88. T. gondii profilin activates DCs through TLR11 and is the first chemically defined ligand for this TLR. Moreover, TLR11 is required in vivo for parasite-induced IL-12 production and optimal resistance to infection, thereby establishing a role for the receptor in host recognition of protozoan pathogens. 相似文献
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The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota 总被引：4，自引：0，他引：4
Round JL Lee SM Li J Tran G Jabri B Chatila TA Mazmanian SK 《Science (New York, N.Y.)》2011,332(6032):974-977
Mucosal surfaces constantly encounter microbes. Toll-like receptors (TLRs) mediate recognition of microbial patterns to eliminate pathogens. By contrast, we demonstrate that the prominent gut commensal Bacteroides fragilis activates the TLR pathway to establish host-microbial symbiosis. TLR2 on CD4(+) T cells is required for B. fragilis colonization of a unique mucosal niche in mice during homeostasis. A symbiosis factor (PSA, polysaccharide A) of B. fragilis signals through TLR2 directly on Foxp3(+) regulatory T cells to promote immunologic tolerance. B. fragilis lacking PSA is unable to restrain T helper 17 cell responses and is defective in niche-specific mucosal colonization. Therefore, commensal bacteria exploit the TLR pathway to actively suppress immunity. We propose that the immune system can discriminate between pathogens and the microbiota through recognition of symbiotic bacterial molecules in a process that engenders commensal colonization. 相似文献
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Lipid phosphates can act as signaling molecules to influence cell division, apoptosis, and migration. wunen and wunen2 encode Drosophila lipid phosphate phosphohydrolases, integral membrane enzymes that dephosphorylate extracellular lipid phosphates. wun and wun2 act redundantly in somatic tissues to repel migrating germ cells, although the mechanism by which germ cells respond is unclear. Here, we report that wun2 also functions in germ cells, enabling them to perceive the wun/wun2-related signal from the soma. Upon Wun2 expression, cultured insect cells dephosphorylate and internalize exogenously supplied lipid phosphate. We propose that Drosophila germ cell migration and survival are controlled by competition for hydrolysis of a lipid phosphate between germ cells and soma. 相似文献
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Tournier C Hess P Yang DD Xu J Turner TK Nimnual A Bar-Sagi D Jones SN Flavell RA Davis RJ 《Science (New York, N.Y.)》2000,288(5467):870-874
The c-Jun NH2-terminal kinase (JNK) is activated when cells are exposed to ultraviolet (UV) radiation. However, the functional consequence of JNK activation in UV-irradiated cells has not been established. It is shown here that JNK is required for UV-induced apoptosis in primary murine embryonic fibroblasts. Fibroblasts with simultaneous targeted disruptions of all the functional Jnk genes were protected against UV-stimulated apoptosis. The absence of JNK caused a defect in the mitochondrial death signaling pathway, including the failure to release cytochrome c. These data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway. 相似文献
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细胞凋亡进程中的信号传导途径 总被引：1，自引：0，他引：1
本文对当前生物学的热点研究领域——细胞凋亡过程中所涉及的一些与凋亡相关的信号传导途径做了详尽概述。本文主要介绍了MAPK超家族信号传导途径,Caspases信号传导途径,抑癌基因P53信号传导途径及TNF信号传导途径,这对于阐明肿瘤的发生机制及如何通过特定的信号传导途径调控肿瘤细胞凋亡的进程具有十分重要的理论意义。 相似文献
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Chipuk JE Bouchier-Hayes L Kuwana T Newmeyer DD Green DR 《Science (New York, N.Y.)》2005,309(5741):1732-1735
The Trp53 tumor suppressor gene product (p53) functions in the nucleus to regulate proapoptotic genes, whereas cytoplasmic p53 directly activates proapoptotic Bcl-2 proteins to permeabilize mitochondria and initiate apoptosis. Here, we demonstrate that a tripartite nexus between Bcl-xL, cytoplasmic p53, and PUMA coordinates these distinct p53 functions. After genotoxic stress, Bcl-xL sequestered cytoplasmic p53. Nuclear p53 caused expression of PUMA, which then displaced p53 from Bcl-xL, allowing p53 to induce mitochondrial permeabilization. Mutant Bcl-xL that bound p53, but not PUMA, rendered cells resistant to p53-induced apoptosis irrespective of PUMA expression. Thus, PUMA couples the nuclear and cytoplasmic proapoptotic functions of p53. 相似文献
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大蒜素可以降低某些肿瘤的患病率。试验证明,大蒜素不仅能抑制致癌物的致癌作用,而且对肿瘤细胞的增殖也有抑制作用。目前的研究结果显示,大蒜素的抑癌机制为:抗氧化,抑制致癌物的形成,影响肿瘤细胞的细胞周期并诱导肿瘤细胞凋亡,增强机体免疫功能,对抗肿瘤药物有增敏作用等。 相似文献