다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.

Inflammation and cancer

Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Integrins: versatility, modulation, and signaling in cell adhesion.

Glycomics -- Essentials of Glycobiology

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

N-glycolylneuraminic acid (Neu5Gc) is a non-human sialic acid derived from the diet (primarily red meat) that can be metabolically incorporated into human tissues despite being an antigen. Since this incorporation occurs in the face of circulating anti-Neu5Gc antibodies, we hypothesized that this generates an antibody-antigen reaction and leads to inflammation termed “xenosialitis”. Although red meat consumption is prominently associated with cancer development, pathological mechanisms behind this link are yet to be conclusively proven. The purpose of our research is to investigate the relationship between “xenosialitis”, inflammation and cancer. We used a Cmah null mouse model (mimicking the human lack of Neu5Gc) to provide evidence for such inflammation and cancer promotion. Anti-Neu5Gc antibodies were generated by immunizing Cmah null mice, with chimpanzee red blood cell membranes, or with human red blood cell membranes as controls. Pooled immune or control sera were repeatedly adsorbed with human red blood cells, and the resulting polyclonal antisera passively transferred into additional Cmah null mice that were on a diet with or without Neu5Gc. Mice fed with Neu5Gc and injected with anti-Neu5Gc antibodies showed dose-dependent elevation in acute phase proteins (Serum Amyloid A and Haptoglobin) in the serum as compared to controls. Such C57BL/6 mice are prone to developing hepatic adenomas and occasional carcinomas. Cmah null but not wild-type C57BL/6 mice immunized with chimpanzee red blood cell membranes and fed with Neu5Gc developed a higher frequency of hepatocellular cancer and liver histology showed Neu5Gc accumulation and foci of inflammation. In conclusion, Neu5Gc that has metabolically incorporated into tissues from the diet interacts with anti-Neu5Gc antibodies, generating xenosialitis. Potential correlations of human anti-Neu5Gc antibody levels with red meat consumption and cancer risk are being investigated. Methods to flush out the xenogenic Neu5Gc are being pursued. Similar mechanisms may be operative in other chronic inflammatory processes in diseases epidemiologically associated with red meat consumption, such as atherosclerosis.

Citation Format: Annie N. Samraj, Heinz Laubli, Oliver Pearce, Patrick Secrest, Andrea E. Garcia-Bingman, Nissi Varki, Ajit Varki. A diet-derived sialic acid promotes inflammation and hepatocellular cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-156. doi:10.1158/1538-7445.AM2014-LB-156

Abstract LB-156: A diet-derived sialic acid promotes inflammation and hepatocellular cancer

Sialic acids are abundant acidic sugars decorating the cell surfaces of vertebrates and their close relatives, but rarely found in other taxa – with the striking exception of certain bacterial commensals and pathogens of vertebrates. Siglecs are a family of sialic acid recognizing receptors in mammals that mediate a variety of functions in different biological processes. The CD33-related Siglecs (CD33rSiglecs) are prominent on immune cells and play a role in distinguishing self and non-self by recognizing sialoglycans as “self-associated molecular patterns.” Some pathogenic microorganisms exploit this self-recognition system by molecular mimicry of ligands or by direct binding, thus averting detection and elimination by the innate immune system. A subset of CD33rSiglecs with cell-activating properties may have evolved to counter such exploitation by T. Angata (*) Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan e-mail: angata@gate.sinica.edu.tw A. Varki Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA # Springer Japan 2015 N. Taniguchi et al. (eds.), Glycoscience: Biology and Medicine, DOI 10.1007/978-4-431-54841-6_211 633 pathogens. In keeping with this, some show extreme sequence identity in their binding domains with respective inhibitory counterparts. Human null polymorphisms have been described for some CD33rSiglecs, which may be explained by counteracting evolutionary selective forces imposed by different pathogens. Two CD33rSiglecs appear to have been inactivated in our ancestors, just prior to the origin of the human species. Environmental factors associated with civilization may have also played a role in shaping the genetics and functions of these receptors.

Siglec Interactions with Pathogens

The Selectins. A Family of Sialic Acid-Binding Lectins Directly Involved in Intercellular Adhesion.

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Ajit Varki

Papers

Glycomics -- Essentials of Glycobiology

Abstract LB-156: A diet-derived sialic acid promotes inflammation and hepatocellular cancer

Siglec Interactions with Pathogens

The Selectins. A Family of Sialic Acid-Binding Lectins Directly Involved in Intercellular Adhesion.

Fate of 'retired' research chimps.