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New tricks for old NODs
Eric M Pietras, Genhong Cheng
Genome Biology , 2008, DOI: 10.1186/gb-2008-9-4-217
Abstract: Upon infection with a pathogen, the host cell must recognize its presence, communicate this to neighboring cells and tissues and initiate a biological response to limit the spread of infection and clear the pathogen. Recognition of invading microbes proceeds via specialized intracellular and extracellular proteins termed pattern recognition receptors (PRRs), which recognize conserved molecular motifs found on pathogens, known as pathogen-associated molecular patterns (PAMPs). Recognition of PAMPs by PRRs leads to the activation of downstream transcription factors, resulting in induction of programs of host defense gene expression designed to effect immunity to the pathogen. In the innate immune response to viruses, the genes activated include those for the type I interferons - the primary cytokines mediating the innate response to viral infection. In mammals, these comprise IFNβ, 13 IFNαs and the more recently discovered IFNω. Type I interferons signal via the IFNα/β receptor to induce further sets of genes that regulate cellular metabolic processes, intracellular nutrient availability, apoptotic responses and direct elimination of the pathogen [1].The recognition of single-stranded RNA viruses in the intracellular space is based on the processing of their genomes by one of at least two cellular RNA helicases - RIG-I/DDX58 and MDA5/Helicard [2,3]. This processing generates a conformational change in the helicases, allowing their twin caspase-recruitment domains (CARDs) to interact directly with a single amino-terminal CARD in the adaptor protein MAVS (also known as IPS-1, VISA or Cardif), which is anchored to the outer mitochondrial membrane [4-7]. MAVS complexes with the adaptor protein TRAF3, recruiting the scaffold protein TANK and the IκB kinases (IKKs) TANK-binding kinase 1 (TBK1) and IKKε, which activate the transcription factor IRF3. IRF3 activation leads to the transcriptional activation of a number of antiviral genes, including that for IFNβ (Figure 1) [8-1
Breast Tumor Angiogenesis and Tumor-Associated Macrophages: Histopathologist's Perspective  [PDF]
Ewe Seng Ch'ng,Hasnan Jaafar,Sharifah Emilia Tuan Sharif
Pathology Research International , 2011, DOI: 10.4061/2011/572706
Abstract: Much progress has been made since the conceptualization of tumor angiogenesis—the induction of growth of new blood vessels by tumor—as a salient feature of clinically significant primary or metastatic cancers. From a practicing histopathologist's point of view, we appraise the application of this concept in breast cancer with particular reference to the evaluation of proangiogenic factors and the assessment of new microvessels in histopathological examination. Recently, much focus has also been centered on the active roles played by tumor-associated macrophages in relation to tumor angiogenesis. We review the literature; many data supporting this facet of tumor angiogenesis were derived from the breast cancer models. We scrutinize the large body of clinical evidence exploring the link between the tumor-associated macrophages and breast tumor angiogenesis and discuss particularly the methodology and limitations of incorporating such an assessment in histopathological examination. 1. Introduction Angiogenesis, the growth and remodeling of new blood vessels, is one of the hallmarks of cancer. Acquiring proangiogenic phenotype, tumor cells produce and release proangiogenic factors to initiate angiogenesis whereby the ensuing tumor growth, invasion, and metastasis take place. Subject to this angiogenic switch tenet for its progression, breast cancer has been shown to produce a number of proangiogenic factors. Studies have demonstrated that the evaluation of these proangiogenic factors carries predictive and prognostic values [1, 2]. Prognostic significance of tumor angiogenesis has also been highlighted in clinical studies where higher microvessel densities correlate with poorer survival outcome [3]. Via the control of angiogenesis, another dimension in therapeutic intervention is now unfolded. In relation to tumor angiogenesis, recent research also focuses on the role of tumor microenvironment. Tumor-associated macrophages, a major component in the leukocytic infiltration in tumor, have aroused much research interest since the propositions of their active involvement in tumor progression [4, 5]. Best summarized as M2 phenotype, tumor-associated macrophages show anti-inflammatory and tumor-promoting characteristics, especially in relation to tumor angiogenesis. Apart from the in vitro and in vivo animal studies based on the breast cancer models, there is accumulating evidence from the clinical studies that suggests tumor-promoting features of tumor-associated macrophages in breast cancer [6, 7]. In this paper, we outline the conceptual development of breast
Multiwalled Carbon Nanotubes Interact with Macrophages and Influence Tumor Progression and Metastasis  [cached]
Man Yang, Jie Meng, Xuelian Cheng, Jing Lei, Hua Guo, Weiqi Zhang, Hua Kong, Haiyan Xu
Theranostics , 2012,
Abstract: Macrophages are one of the most important types of immune effector cells and are closely associated with tumor progression and metastasis. In this work, we investigated the influences of oxidized multiwalled carbon nanotubes (o-MWCNT) on macrophages that are resting in the normal subcutis tissue or in the tumor microenvironment in vivo as well as on the macrophage cell line of RAW 264.7 treated with combination of IL4, IL10 and IL13 in vitro. The o-MWCNT were characterized with SEM, DLS, FTIR, TGA, and UV-vis-NIR spectroscopy, and their effects on the RWA 264.7 cell line and breast cancer tumor-bearing mice were analyzed using the MTS assay, flow cytometry analysis, and histological and immunohistochemical observations. Our experimental results showed that subcutaneously injected o-MWCNT not only induced phagocytosis of the local resident macrophages, but also competitively recruited macrophages from other tissues. These interactions resulted in macrophage reduction and decreased vessel density around the tumor mass, which together inhibited tumor progression and metastasis in the lung. In the cell line model, the o-MWCNT inhibited the ability of the interleukin treated RAW macrophages to promote tumor cell migration as well as decreased their proliferation rate.
Teaching an Old Elephant New Tricks  [PDF]
Nicolas Bruno
Computer Science , 2009,
Abstract: In recent years, column stores (or C-stores for short) have emerged as a novel approach to deal with read-mostly data warehousing applications. Experimental evidence suggests that, for certain types of queries, the new features of C-stores result in orders of magnitude improvement over traditional relational engines. At the same time, some C-store proponents argue that C-stores are fundamentally different from traditional engines, and therefore their benefits cannot be incorporated into a relational engine short of a complete rewrite. In this paper we challenge this claim and show that many of the benefits of C-stores can indeed be simulated in traditional engines with no changes whatsoever. We then identify some limitations of our ?pure-simulation? approach for the case of more complex queries. Finally, we predict that traditional relational engines will eventually leverage most of the benefits of C-stores natively, as is currently happening in other domains such as XML data.
The density of macrophages in the invasive front is inversely correlated to liver metastasis in colon cancer
Qiang Zhou, Rui-Qing Peng, Xiao-Jun Wu, Qing Xia, Jing-Hui Hou, Ya Ding, Qi-Ming Zhou, Xing Zhang, Zhi-Zhong Pang, De-Sen Wan, Yi-Xin Zeng, Xiao-Shi Zhang
Journal of Translational Medicine , 2010, DOI: 10.1186/1479-5876-8-13
Abstract: One hundred and sixty cases of pathologically-confirmed specimens were obtained from colon carcinoma patients with TNM stage IIIB and IV between January 1997 and July 2004 at the Cancer Center of Sun Yat-Sen University. The density of macrophages in the invasive front (CD68TFHotspot) was scored with an immunohistochemical assay. The relationship between the CD68TFHotspot and the clinicopathologic parameters, the potential of hepatic metastasis, and the 5-year survival rate were analyzed.TAMs were associated with the incidence of hepatic metastasis and the 5-year survival rate in patients with colon cancers. Both univariate and multivariate analyses revealed that the CD68TFHotspot was independently prognostic of survival. A higher 5-year survival rate among patients with stage IIIB after radical resection occurred in patients with a higher macrophage infiltration in the invasive front (81.0%) than in those with a lower macrophage infiltration (48.6%). Most importantly, the CD68TFHotspot was associated with both the potential of hepatic metastasis and the interval between colon resection and the occurrence of hepatic metastasis.This study showed evidence that TAMs infiltrated in the invasive front are associated with improvement in both hepatic metastasis and overall survival in colon cancer, implying that TAMs have protective potential in colon cancers and might serve as a novel therapeutic target.Colorectal cancer is the fourth leading cause of cancer deaths worldwide. Of patients with colorectal cancer, 35%-55% will develop hepatic metastases at some time during the course of their disease. Survival following hepatic resection of colorectal metastasis now approaches 35%-50%. However, approximately 65% of patients will have a recurrence at 5 years. Identifying the markers for hepatic metastasis would be helpful for the early treatment of patients at high-risk of hepatic metastasis [1-5].In addition to clonal selection and the predetermined metastatic potential of ca
M2型肿瘤相关巨噬细胞浸润与食管鳞癌发生、浸润及转移的关系*
Relationship of infiltration of M2 type tumor-associated macrophages with occurrence, invasion and metastasis of esophageal squamous cell carcinoma
 [PDF]

,,孙淼淼,,,贺璐璐,王正洋,张红新,陈奎生
- , 2017, DOI: 10.13705/j.issn.1671-6825.2017.05.003
Abstract: 目的:探讨M2型肿瘤相关巨噬细胞(M2型TAM)浸润与食管鳞癌发生、浸润、转移的关系及其可能机制。方法:采用免疫组化SP法分别检测50例食管鳞癌和50例正常食管黏膜组织中CD206(M2型TAM特异性标志物)、IL-8、MCP-1蛋白的表达; 应用原位杂交方法分别检测上述组织中IL-8、MCP-1 mRNA的表达。结果:食管鳞癌组织中M2型TAM的浸润数量多于正常食管黏膜(P=0.032); 食管鳞癌间质中IL-8、MCP-1蛋白及mRNA阳性表达率高于正常食管黏膜组织(P<0.05); M2型TAM浸润数量与食管鳞癌的浸润深度、淋巴结转移及患者的TNM分期有关(P<0.05),与患者的年龄、性别无关(P>0.05); 食管鳞癌间质中M2型TAM的浸润数量与IL-8、MCP-1蛋白和mRNA的表达呈正关联(蛋白:rP=0.432、0.315; mRNA:rP=0.373、0.332,P均<0.05)。结论:M2型TAM与食管鳞癌的发生、浸润、转移有关,其机制可能与TAM分泌的趋化因子IL-8和MCP-1有关。
Aim: To investigate the relationship between the infiltration of M2 type tumor associated macrophages(M2 type TAM)and the occurrence, invasion and metastasis of esophageal squamous cell carcinoma(ESCC)and its possible mechanism.Methods: The expressions of CD206, IL-8, MCP-1 proteins and IL-8, MCP-1 mRNA were detected using immunohistochemical method and in situ hybridization in 50 cases of the interstitial of ESCC and 50 cases of normal esophageal mucosa.Results: The number of M2 type TAM in the interstitial of ESCC was significantly higher than that in normal esophageal mucosa tissue(P=0.032); the positive expression rates of IL-8,MCP-1 protein and mRNA in the interstitial tissue of ESCC were significantly higher than those in the interstitial tissue of normal esophageal mucosa(P<0.05). The number of M2 type TAM was significantly associated with the depth of tumor invasion, lymph node metastasis and TNM stage(P<0.05), but not with the patients' age or gender(P>0.05). The number of M2 type TAM in ESCC was positively correlated with the expressions of IL-8,MCP-1 protein(rP=0.432,0.315)and mRNA(rP=0.373,0.332,P<0.05).Conclusion: M2 type TAM may be related with the occurrence, invasion and metastasis of ESCC, and the mechanism may be related with chemotactic factor IL-8 and MCP-1 secreted by M2 type TAM
Chemoattractant Signaling between Tumor Cells and Macrophages Regulates Cancer Cell Migration, Metastasis and Neovascularization  [PDF]
Chad E. Green, Tiffany Liu, Valerie Montel, Gene Hsiao, Robin D. Lester, Shankar Subramaniam, Steven L. Gonias, Richard L. Klemke
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006713
Abstract: Tumor-associated macrophages are known to influence cancer progression by modulation of immune function, angiogenesis, and cell metastasis, however, little is known about the chemokine signaling networks that regulate this process. Utilizing CT26 colon cancer cells and RAW 264.7 macrophages as a model cellular system, we demonstrate that treatment of CT26 cells with RAW 264.7 conditioned medium induces cell migration, invasion and metastasis. Inflammatory gene microarray analysis indicated CT26-stimulated RAW 264.7 macrophages upregulate SDF-1α and VEGF, and that these cytokines contribute to CT26 migration in vitro. RAW 264.7 macrophages also showed a robust chemotactic response towards CT26-derived chemokines. In particular, microarray analysis and functional testing revealed CSF-1 as the major chemoattractant for RAW 264.7 macrophages. Interestingly, in the chick CAM model of cancer progression, RAW 264.7 macrophages localized specifically to the tumor periphery where they were found to increase CT26 tumor growth, microvascular density, vascular disruption, and lung metastasis, suggesting these cells home to actively invading areas of the tumor, but not the hypoxic core of the tumor mass. In support of these findings, hypoxic conditions down regulated CSF-1 production in several tumor cell lines and decreased RAW 264.7 macrophage migration in vitro. Together our findings suggest a model where normoxic tumor cells release CSF-1 to recruit macrophages to the tumor periphery where they secrete motility and angiogenic factors that facilitate tumor cell invasion and metastasis.
Quantum Number Tricks  [PDF]
Takashi Mihara
Journal of Software Engineering and Applications (JSEA) , 2010, DOI: 10.4236/jsea.2010.33029
Abstract: Some results indicate that quantum information based on quantum physics is more powerful than classical one. In this paper, we propose new tricks based on quantum physics. Our tricks are methods inspired by the strategies of quantum game theory. In these tricks, magicians have the ability of quantum physics, but spectators have only classical one. We propose quantum tricks such that, by manipulating quantum coins and quantum cards, magicians guess spectators’ values.
Specificity of economical efficiency estimation of the management and marketing tricks
Yu.A. Daynovskyy
Marketing ì Mened?ment Innovacìj , 2012,
Abstract: Forms of economical efficiency tricks manifestation applied in spheres of management and marketing are studied. New tricks classification by the specificity of an effect obtained and demonstrated is proposed. The necessity of different approaches to the economical efficiency estimation for some groups of tricks is reasoned. Examples of the tricks with different economical efficiency manifestation are made.
M2-Polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma
Zhang, Bicheng;Yao, Guoqing;Zhang, Yafei;Gao, Juan;Yang, Bo;Rao, Zhiguo;Gao, Jianfei;
Clinics , 2011, DOI: 10.1590/S1807-59322011001100006
Abstract: objectives: tumor-associated macrophages have been implicated in promoting tumor growth, progression and metastasis. however, the activated phenotype (m1 or m2) of tumor-associated macrophages remains unknown in solid tumors. therefore, this study examined the density and prognostic significance of m2-polarized tumor-associated macrophages in lung adenocarcinoma. methods: tumor specimens from 65 lung adenocarcinoma patients were assessed by elisa for th1/th2 cytokine concentrations. the activated phenotype (m1 or m2) of tumor-associated macrophages was determined utilizing immunofluorescence staining. additionally, to evaluate lymphangiogenesis, peritumoral lymphatic microvessel density was measured using d2-40. the correlation between tumor-associated macrophage subtype and overall patient survival was analyzed using the kaplan-meier method and compared using the log-rank test. results: a shift toward th2 cytokine expression was detected within lung adenocarcinoma microenvironments. approximately 79.71±16.27% of tumor-associated macrophages were m2 polarized; the remaining 20.35±5.31% were m1 polarized. the infiltration of m2-polarized macrophages was significantly associated with p-tnm staging and lymph node metastasis. the peritumoral lymphatic microvessel density was significantly higher in the high m2-polarized tumor-associated macrophage group than in the low m2-polarized tumor-associated macrophage group. a significant difference in overall patient survival was detected not only between patients with tumors with high and low macrophage counts but also between patients with tumors with high and low counts of m2-polarized macrophages. conclusion: tumor-associated macrophages in lung adenocarcinoma have an m2-polarized subtype and are associated with poor prognoses, perhaps resulting from accelerated lymphangiogenesis and lymph node metastasis.
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