Kari Alitalo

Bio: Kari Alitalo is an academic researcher from University of Helsinki. The author has contributed to research in topics: Angiogenesis & Vascular endothelial growth factor C. The author has an hindex of 174, co-authored 817 publications receiving 114231 citations. Previous affiliations of Kari Alitalo include Mount Sinai Hospital, Toronto & Cornell University.

A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains.

Abstract: Endothelial cell surfaces play key roles in several important physiological and pathological processes such as blood clotting, angiogenic responses, and inflammation. Here we describe the cloning and characterization of tie, a novel type of human endothelial cell surface receptor tyrosine kinase. The extracellular domain of the predicted tie protein product has an exceptional multidomain structure consisting of a cluster of three epidermal growth factor homology motifs embedded between two immunoglobulinlike loops, which are followed by three fibronectin type III repeats next to the transmembrane region. Additionally, a cDNA form lacking the first of the three epidermal growth factor homology domains was isolated, suggesting that alternative splicing creates different tie-type receptors. Cells transfected with tie cDNA expression vector produce glycosylated polypeptides of 117 kDa which are reactive to antisera raised against the tie carboxy terminus. The tie gene was located in chromosomal region 1p33 to 1p34. Expression of the tie gene appeared to be restricted in some cell lines; large amounts of tie mRNA were detected in endothelial cell lines and in some myeloid leukemia cell lines with erythroid and megakaryoblastoid characteristics. In addition, mRNA in situ studies further indicated the endothelial expression of the tie gene. The tie receptor tyrosine kinase may have evolved for multiple protein-protein interactions, possibly including cell adhesion to the vascular endothelium.

Tie receptors: new modulators of angiogenic and lymphangiogenic responses

Abstract: Angiogenesis is required for normal embryonic vascular development and aberrant angiogenesis contributes to several diseases, including cancer, diabetes and tissue ischaemia. What are the molecular mechanisms that regulate this important process? The Tie family of receptors and their ligands, the angiopoietins, are beginning to provide insight into how vessels make decisions such as whether to grow or regress--processes that are important not only during development but throughout an organism's life.

Signaling and Functions of Angiopoietin-1 in Vascular Protection

Abstract: Angiopoietin-1 (Ang1) has powerful vascular protective effects: suppressing plasma leakage, inhibiting vascular inflammation, and preventing endothelial death. Preclinical studies indicate that Ang1 may be therapeutically useful in a number of situations, including treatment of edema, endotoxemia, and transplant arteriosclerosis. However, the ligand has also been implicated in vessel remodeling, induction of angiogenesis and pulmonary hypertension, indicating that strategies to minimize any deleterious effects while optimizing vessel protection are likely to be needed. This review surveys the published data on vascular protective effects of Ang1 and highlights the therapeutic potential of this ligand, as well as possible limitations to its use. We also consider the data on Ang1 receptors and speculate on how to maximize therapeutic benefit by targeting the Tie receptors.

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

Abstract: 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。

Inflammation and cancer

Abstract: 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.

Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene

Abstract: The HER-2/neu oncogene is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene has been shown to be amplified in human breast cancer cell lines. In the current study, alterations of the gene in 189 primary human breast cancers were investigated. HER-2/neu was found to be amplified from 2- to greater than 20-fold in 30% of the tumors. Correlation of gene amplification with several disease parameters was evaluated. Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer. It retained its significance even when adjustments were made for other known prognostic factors. Moreover, HER-2/neu amplification had greater prognostic value than most currently used prognostic factors, including hormonal-receptor status, in lymph node-positive disease. These data indicate that this gene may play a role in the biologic behavior and/or pathogenesis of human breast cancer.