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.

Damage and repair induced by bleomycin in the domain of human amplified MYC oncogenes.

Abstract: Growing monolayer COLO320 human cells having a 30- to 40-fold amplification of a MYC domain were pulse treated for 15 min with increasing doses of bleomycin (BLM). Cellular DNA was extracted at the end of the BLM treatment or after an interval of 30 min, during which the cells were allowed to repair the DNA damage at 37°C in culture medium without BLM. Damage and repair in total cellular DNA was assessed by alkaline unwinding and by neutral and alkaline gel electrophoresis. The response to BLM in the domain of MYC oncogene was evaluated by Southern blotting of Eco RI-digested DNAs separated by neutral or alkaline gel electrophoresis. We found that MYC domains from COLO320HSR showed a higher frequency of double-strand DNA breaks than MYC domains from COLO320DM cells. At the level of total cellular DNA, both cell lines showed the same frequency of double-strand nicks. No repair of double-strand breaks was observed. Total DNA from COLO320HSR cells was more sensitive to single-strand breakage than DNA from COLO320DM. At the gene level, the frequency of single-strand scissions was higher in COLO320DM than in COLO320HSR MYC domains. Both cell lines had good capability to close single-strand scissions. However, at high BLM doses the damage was more efficiently repaired by COLO320DM cells. We propose that chromatin organization in total cellular DNA and in the amplified MYC domain probably plays an important role in the DNA response to BLM.

Lymphatic endothelial cells materials and methods

Abstract: The present invention is directed to methods and compositions for isolating lymphatic endothelial cells from a mixed population of cells. More particularly, the inventors have found that certain antibodies that recognize the extracellular domain of VEGFR-3 can be used to specifically isolated lymphatic endothelial cells substantially free of other contaminating non-lymphatic endothelial cells. Methods and compositions for producing such cells and using such cells are described.

Zebrafish Tie-2 shares a redundant role with Tie-1 in heart development and regulates vessel integrity

Abstract: Tie-2 is a member of the receptor tyrosine kinase family and is required for vascular remodeling and maintenance of mammalian vessel integrity. A number of mutations in the human TIE2 gene have been identified in patients suffering from cutaneomucosal venous malformations and ventricular septal defects. How exactly Tie-2 signaling pathways play different roles in both vascular development and vascular stability is unknown. We have generated a zebrafish line carrying a stop mutation in the kinase domain of the Tie-2 receptor. Mutant embryos lack Tie-2 protein, but do not display any defect in heart and vessel development. Simultaneous loss of Tie-1 and Tie-2, however, leads to a cardiac phenotype. Our study shows that Tie-1 and Tie-2 are not required for early heart development, yet they have redundant roles for the maintenance of endocardial-myocardial connection in later stages. Tie-2 and its ligand Angiopoietin-1 have also been reported to play an important role in vessel stability. We used atorvastatin and simvastatin, drugs that cause bleeding in wild-type zebrafish larvae, to challenge vessel stability in tie-2 mutants. Interestingly, recent clinical studies have reported hemorrhagic stroke as a side effect of atorvastatin treatment. Exposure of embryos to statins revealed that tie-2 mutants are significantly protected from statin-induced bleeding. Furthermore, tie-2 mutants became less resistant to bleeding after VE-cadherin knockdown. Taken together, these data show that atorvastatin affects vessel stability through Tie-2, and that VE-cadherin and Tie-2 act in concert to allow vessel remodeling while playing a role in vessel stability. Our study introduces an additional vertebrate model to study in vivo the function of Tie-2 in development and disease.

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.