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

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Vascular endothelial growth factor (VEGF) is a key regulator of physiological angiogenesis during embryogenesis, skeletal growth and reproductive functions. VEGF has also been implicated in pathological angiogenesis associated with tumors, intraocular neovascular disorders and other conditions. The biological effects of VEGF are mediated by two receptor tyrosine kinases (RTKs), VEGFR-1 and VEGFR-2, which differ considerably in signaling properties. Non-signaling co-receptors also modulate VEGF RTK signaling. Currently, several VEGF inhibitors are undergoing clinical testing in several malignancies. VEGF inhibition is also being tested as a strategy for the prevention of angiogenesis, vascular leakage and visual loss in age-related macular degeneration.

The biology of VEGF and its receptors.

Putative endothelial cell (EC) progenitors or angioblasts were isolated from human peripheral blood by magnetic bead selection on the basis of cell surface antigen expression In vitro, these cells differentiated into ECs In animal models of ischemia, heterologous, homologous, and autologous EC progenitors incorporated into sites of active angiogenesis These findings suggest that EC progenitors may be useful for augmenting collateral vessel growth to ischemic tissues (therapeutic angiogenesis) and for delivering anti- or pro-angiogenic agents, respectively, to sites of pathologic or utilitarian angiogenesis

http://science.sciencemag.org/content/sci/275/5302/964.full.pdf

Isolation of putative progenitor endothelial cells for angiogenesis.

Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis

Recent studies have revealed the importance of long noncoding RNAs (lncRNAs) as tissue-specific regulators of gene expression. There is ample evidence that distinct types of vasculature undergo tight transcriptional control to preserve their structure, identity, and functions. We determined, for the first time, the global lineage-specific lncRNAome of human dermal blood and lymphatic endothelial cells (BECs and LECs), combining RNA-Seq and CAGE-Seq. A subsequent genome-wide antisense oligonucleotide-knockdown screen of a robust set of BEC- and LEC-specific lncRNAs identified LETR1 as a critical gatekeeper of the global LEC transcriptome. Deep RNA-DNA, RNA-protein, and phenotype rescue analyses revealed that LETR1 acts as a nuclear trans-acting lncRNA modulating, via key epigenetic factors, the expression of essential target genes, including KLF4 and SEMA3C, governing the growth and migratory ability of LECs. Together, our study provides new evidence supporting the intriguing concept that every cell type expresses precise lncRNA signatures to control lineage-specific regulatory programs.

/pdf/lesr2-is-a-lymphatic-endothelial-specific-lncrna-that-29xb046nol.pdf

LESR2 is a lymphatic endothelial-specific lncRNA that governs cell proliferation and migration through KLF4 and SEMA3C

It is well established that cancers need to induce increased vascularization (tumor angiogenesis) to sustain their neoplastic growth and to mediate tissue invasion. This is achieved by upregulation of angiogenic growth factors, in particular VEGF-A, and by downregulation of endogenous angiogenesis inhibitors, in particular thrombospondins (TSPs). Indeed, enhanced production of VEGF-A by squamous cell carcinomas promotes skin cancer invasion (Detmar et al., 2000), whereas overexpression of TSP-1 or of TSP-2 inhibits skin carcinogenesis (Hawighorst et al., 2002; Streit et al., 1999). Tumor metastasis to regional (sentinel) lymph nodes represents the first step of tumor dissemination in most human cancers and serves as a major prognostic indicator for disease progression. However, little is known about the mechanisms how tumor cells gain entry into the lymphatic system, and it has been generally thought that lymphatic endothelium only plays a passive role during this process and that lymphatic invasion only occurs once stroma-infiltrating tumor cells happen upon preexisting peritumoral lymphatic vessels. In this respect, we have previously shown that tumors can actively induce the formation of lymphatic vessels (leading to the new concept of tumor lymphangiogenesis) (Skobe et al., 2001) and that tumor lymphangiogenesis was correlated with lymph node metastasis in an orthotopic breast cancer model. Our studies in human cutaneous malignant melanomas demonstrated the presence of both intratumoral and peritumoral lymphangiogenesis in cutaneous melanoma. They also showed that primary melanomas that later metastasized were characterized by increased lymphangiogenesis – compared to non-metastatic tumors – and that the degree of tumor lymphangiogenesis can serve as a novel predictor of lymph node metastasis and overall patient survival, independently of tumor thickness (Dadras et al., 2003). More recently, we found that the extent of lymphatic vessel growth in primary human cutaneous melanomas was the most sensitive parameter for predicting whether these tumors had already metastasized to the sentinel (draining) lymph node at the time of surgery (Dadras et al., 2005).

Angiogenesis and lymphangiogenesis in cutaneous cancer

lymphangiogenesis in draining lymph nodes VEGF-A produced by chronically inflamed tissue induces

This invention describes compositions comprising indocyanine green and poly(N-vinylpyrrolidone) and methods of making the same as well as applications thereof for diagnostic and therapeutic uses. One of those applications is the structural and functional assessment of the lymphatic system by fluorescence imaging.

Compositions for circulatory system visualization

The present invention relates to a method of evaluating cellulite using fibulin-3 and/or sarcoglycan gamma as an indicator in a harvested skin sample, and a method of evaluating a drug for improving, preventing or treating cellulite using fibulin-3 and/or sarcoglycan gamma as an indicator in cultured cells.

Michael Detmar

Papers

LESR2 is a lymphatic endothelial-specific lncRNA that governs cell proliferation and migration through KLF4 and SEMA3C

Angiogenesis and lymphangiogenesis in cutaneous cancer

lymphangiogenesis in draining lymph nodes VEGF-A produced by chronically inflamed tissue induces

Compositions for circulatory system visualization

Method of evaluating cellulite and method of evaluating cellulite-effective drug using fibulin-3 and/or sarcoglycan gamma as an indicator