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排序方式: 共有48条查询结果,搜索用时 31 毫秒
41.
Low surface expression of B7-1 (CD80) is an immunoescape mechanism of colon carcinoma 总被引:3,自引:0,他引:3
Tirapu I Huarte E Guiducci C Arina A Zaratiegui M Murillo O Gonzalez A Berasain C Berraondo P Fortes P Prieto J Colombo MP Chen L Melero I 《Cancer research》2006,66(4):2442-2450
Artificially enforced expression of CD80 (B7-1) and CD86 (B7-2) on tumor cells renders them more immunogenic by triggering the CD28 receptor on T cells. The enigma is that such B7s interact with much higher affinity with CTLA-4 (CD152), an inhibitory receptor expressed by activated T cells. We show that unmutated CD80 is spontaneously expressed at low levels by mouse colon carcinoma cell lines and other transplantable tumor cell lines of various tissue origins. Silencing of CD80 by interfering RNA led to loss of tumorigenicity of CT26 colon carcinoma in immunocompetent mice, but not in immunodeficient Rag-/- mice. CT26 tumor cells bind CTLA-4Ig, but much more faintly with a similar CD28Ig chimeric protein, thus providing an explanation for the dominant inhibitory effects on tumor immunity displayed by CD80 at that expression level. Interestingly, CD80-negative tumor cell lines such as MC38 colon carcinoma and B16 melanoma express CD80 at dim levels during in vivo growth in syngeneic mice. Therefore, low CD80 surface expression seems to give an advantage to cancer cells against the immune system. Our findings are similar with the inhibitory role described for the dim CD80 expression on immature dendritic cells, providing an explanation for the low levels of CD80 expression described in various human malignancies. 相似文献
42.
Castro R Erviti J Leyva R 《Cadernos de saúde pública / Ministério da Saúde, Funda??o Oswaldo Cruz, Escola Nacional de Saúde Pública》2007,23(Z1):S41-S50
This paper discusses the health status of indigenous populations in Mexico. The first section characterizes the concept of globalization and its links to the population's health. Based on available statistical data, the second section documents the current indigenous populations' health status in the country. The article then argues that the presupposition of equity, crucial to globalization theory, does not apply to this case. Using the Mexican National Health Survey (2000), the third section further analyzes the health status of indigenous populations and identifies important inconsistencies in the data. The discussion section contends that these inconsistencies derive from the fact that such health surveys fail to contemplate the cultural specificities of indigenous peoples, thus leading to erroneous interpretations of the data. The article concludes that statistics on indigenous peoples' health must be interpreted with extreme caution and always with the support of social science theories and research methods. 相似文献
43.
Oihana Murillo Juan Dubrot Asís Palazón Ainhoa Arina Arantza Azpilikueta Carlos Alfaro Sarai Solano María C. Ochoa Carmen Berasain Izaskun Gabari José. L. Pérez‐Gracia Pedro Berraondo Sandra Hervás‐Stubbs Ignacio Melero 《European journal of immunology》2009,39(9):2424-2436
Anti‐CD137 mAb are capable of inducing tumor rejection in several syngeneic murine tumor models and are undergoing clinical trials for cancer. The anti‐tumor effect involves co‐stimulation of tumor‐specific CD8+ T cells. Whether antigen cross‐presenting DC are required for the efficacy of anti‐CD137 mAb treatment has never been examined. Here we show that the administration of anti‐CD137 mAb eradicates EG7‐OVA tumors by a strictly CD8β+ T‐cell‐dependent mechanism that correlates with increased CTL activity. Ex vivo analyses to determine the identity of the draining lymph node cell type responsible for tumor antigen cross‐presentation revealed that CD11c+ cells, most likely DC, are the main players in this tumor model. A minute number of tumor cells, revealed by the presence of OVA cDNA, reach tumor‐draining lymph nodes. Direct antigen presentation by tumor cells themselves also participates in anti‐OVA CTL induction. Using CD11c diphtheria toxin receptor‐green fluorescent protein→C57BL/6 BM chimeric mice, which allow for sustained ablation of DC with diphtheria toxin, we confirmed the involvement of DC in tumor antigen cross‐presentation in CTL induction against OVA257–264 epitope and in the antitumor efficacy induced by anti‐CD137 mAb. 相似文献
44.
Judd NP Winkler AE Murillo-Sauca O Brotman JJ Law JH Lewis JS Dunn GP Bui JD Sunwoo JB Uppaluri R 《Cancer research》2012,72(1):365-374
Carcinogen-induced oral cavity squamous cell carcinoma (OSCC) incurs significant morbidity and mortality and constitutes a global health challenge. To gain further insight into this disease, we generated cell line models from 7,12-dimethylbenz(a)anthracene-induced murine primary OSCC capable of tumor formation upon transplantation into immunocompetent wild-type mice. Whereas several cell lines grew rapidly and were capable of metastasis, some grew slowly and did not metastasize. Aggressively growing cell lines displayed ERK1/2 activation, which stimulated expression of CD44, a marker associated with epithelial to mesenchymal transition and putative cancer stem cells. MEK (MAP/ERK kinase) inhibition upstream of ERK1/2 decreased CD44 expression and promoter activity and reduced cell migration and invasion. Conversely, MEK1 activation enhanced CD44 expression and promoter activity, whereas CD44 attenuation reduced in vitro migration and in vivo tumor formation. Extending these findings to freshly resected human OSCC, we confirmed a strict relationship between ERK1/2 phosphorylation and CD44 expression. In summary, our findings identify CD44 as a critical target of ERK1/2 in promoting tumor aggressiveness and offer a preclinical proof-of-concept to target this pathway as a strategy to treat head and neck cancer. 相似文献
45.
Systemic exosomal siRNA delivery reduced alpha‐synuclein aggregates in brains of transgenic mice
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J. Mark Cooper PhD P.B. Oscar Wiklander MD Joel Z. Nordin MD Raya Al‐Shawi PhD Matthew J. Wood MD Mansi Vithlani PhD Anthony H. V. Schapira DSc J. Paul Simons PhD Samir El‐Andaloussi PhD Lydia Alvarez‐Erviti PhD 《Movement disorders》2014,29(12):1476-1485
Alpha‐synuclein (α‐Syn) aggregates are the main component of Lewy bodies, which are the characteristic pathological feature in Parkinson's disease (PD) brain. Evidence that α‐Syn aggregation can be propagated between neurones has led to the suggestion that this mechanism is responsible for the stepwise progression of PD pathology. Decreasing α‐Syn expression is predicted to attenuate this process and is thus an attractive approach to delay or halt PD progression. We have used α‐Syn small interfering RNA (siRNA) to reduce total and aggregated α‐Syn levels in mouse brains. To achieve widespread delivery of siRNAs to the brain we have peripherally injected modified exosomes expressing Ravies virus glycoprotein loaded with siRNA. Normal mice were analyzed 3 or 7 days after injection. To evaluate whether this approach can decrease α‐Syn aggregates, we repeated the treatment using transgenic mice expressing the human phosphorylation‐mimic S129D α‐Syn, which exhibits aggregation. In normal mice we detected significantly reduced α‐Syn messenger RNA (mRNA) and protein levels throughout the brain 3 and 7 days after treatment with RVG‐exosomes loaded with siRNA to α‐Syn. In S129D α‐Syn transgenic mice we found a decreased α‐Syn mRNA and protein levels throughout the brain 7 days after injection. This resulted in significant reductions in intraneuronal protein aggregates, including in dopaminergic neurones of the substantia nigra. This study highlights the therapeutic potential of RVG‐exosome delivery of siRNA to delay and reverse brain α‐Syn pathological conditions. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. 相似文献
46.
In several economic fields, such as those related to health or education, the individuals' characteristics are measured by bounded variables. Accordingly, these characteristics may be indistinctly represented by achievements or shortfalls. A difficulty arises when inequality needs to be assessed. One may focus either on achievements or on shortfalls but the respective inequality rankings may lead to contradictory results. In this note we propose a procedure to define indicators that measure equally the achievement and shortfall inequality. Specifically, we derive measures which are invariant under ratio-scale or translation transformations, and a decomposable measure is also obtained. As the indicators proposed depend on the distribution bounds, families of indices that guarantee the same inequality rankings regardless of the distribution maximal levels are identified. 相似文献
47.
June Ho Shin Luhua Zhang Oihana Murillo-Sauca Junmo Kim Holbrook E. K. Kohrt Jack D. Bui John B. Sunwoo 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(30):12391-12396
The aryl hydrocarbon receptor (AhR) has become increasingly recognized for its role in the differentiation and activity of immune cell subsets; however, its role in regulating the activity of natural killer (NK) cells has not been described. Here, we show that AhR expression is induced in murine NK cells upon cytokine stimulation. We show that in the absence of AhR, NK cells have reduced cytolytic activity and reduced capacity to control RMA-S tumor formation in vivo, despite having normal development and maturation markers. Although AhR was first identified to bind the xenobiotic compound dioxin, AhR is now known to bind a variety of natural exogenous (e.g., dietary) and endogenous ligands. We show that activation of AhR with an endogenous tryptophan derivative, 6-formylindolo[3,2-b]carbazole, potentiates NK cell IFN-γ production and cytolytic activity. Further, administration of 6-formylindolo[3,2-b]carbazole in vivo enhances NK cell control of tumors in an NK cell- and AhR-dependent manner. Finally, similar effects on NK cell potency occur with AhR dietary ligands, potentially explaining the numerous associations that have been observed in the past between diet and NK cell function. Our studies introduce AhR as another regulator of NK cell activity in vivo. 相似文献