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Author

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.


Papers
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Journal ArticleDOI
TL;DR: The data suggest that VEGF-D may be beneficial in early-stage tumors since it suppresses the pro-tumorigenic inflammation, while at later stages VEGf-D-induced tumor lymphatics provide a route for metastasis.

11 citations

Journal ArticleDOI
TL;DR: The chimeric receptor showed strict ligand‐dependent tyrosine kinase and signal transducing activities for the induction of growth‐regulated biochemical activities and DNA synthesis in resting cells, establishing similarities between the signal pathways of the EGF receptor and the neu tyrosINE kinase.
Abstract: The effects of a ligand regulated neu tyrosine kinase were examined in NIH 3T3 cells. A chimeric construct encoding the human EGF receptor extracellular domain fused to the tyrosine kinase domain of the rat neu cDNA was expressed under the transcriptional control of the Moloney murine leukemia virus LTR promoter. This resulted in higher levels of expression of the chimeric receptor than were previously obtained from the SV40 virus early promoter in the same cells. The chimeric receptor showed strict ligand-dependent tyrosine kinase and signal transducing activities for the induction of growth-regulated biochemical activities and DNA synthesis in resting cells. The ligand-activated cells became morphologically transformed and grew in agar in the presence of EGF and TGF beta as efficiently as did the ligand-independent neu oncogene-transformed cells. Our results establish similarities between the signal pathways of the EGF receptor and the neu tyrosine kinase.

11 citations

Journal Article
03 Aug 1995-Oncogene
TL;DR: The results indicate that the suppressive activity of Max requires C-terminal acidic and basic regions and an intact leucine zipper, and Surprisingly, delta Max does not require the DNA-binding basic region for enhancement of transformation and has no effect on Myc-induced transcription activation from Myc/Max-binding site-containing promoter construct.
Abstract: The DNA-binding, transcriptional activation and transforming activities of the Myc protein require dimerization with Max. Max can form also homodimers which are able to bind the same DNA sequence as Myc/Max heterodimers and suppress Myc-induced transcription and transformation. We have recently identified a naturally occurring truncated form of Max, delta Max, which in a rat embryo fibroblast enhances transformation by Myc and Ras. Like Max, this delta Max protein contains a b-HLH-Zip domain, except that the end of the leucine zipper is replaced by five delta Max-specific amino acid residues. Delta Max also lacks the C-terminal sequences of Max including a nuclear localisation signal. Here we have dissected the regions responsible for the specific effects of Max and delta Max in Ras-Myc cotransformation of rat embryo fibroblasts. Our results indicate that the suppressive activity of Max requires C-terminal acidic and basic regions and an intact leucine zipper. Replacement of the end of the leucine zipper with the delta Max-specific sequence is responsible for the enhancement of transformation by delta Max. Surprisingly, delta Max does not require the DNA-binding basic region for enhancement of transformation and has no effect on Myc-induced transcription activation from Myc/Max-binding site-containing promoter construct.

10 citations

Journal ArticleDOI
TL;DR: Two cases of clear-cell sarcoma of tendons and aponeuroses are reported and some integrative remarks based on earlier reports of 33 cases and the present two cases are presented.
Abstract: Two cases of clear-cell sarcoma of tendons and aponeuroses are reported. The first patient was a 19-year-old man with a tumor in the medial collateral ligament of the knee. The tumor was enucleated, and after postoperative radiotherapy a wide local excision was done. The patient was symptomless 4½ years after the operation. The other patient was a man aged 68 with a tumor between the medial malleolus and the Achilles tendon. He also received postoperative radiotherapy after enucleation. Three months later a metastasis was noticed in the ipsilateral para-iliac nodes. The patient died 16 months after the operation. The histology and clinical course of the two cases are analyzed. Some integrative remarks based on earlier reports of 33 cases and the present two cases are presented.

10 citations

Journal ArticleDOI
TL;DR: An important crosstalk between the VEGF-C and Ang signaling pathways is revealed and new avenues for therapeutic manipulation of lymphangiogenesis by targeting Ang2/Tie/PI3K signaling are suggested.
Abstract: Vascular endothelial growth factor C (VEGF-C) induces lymphangiogenesis via VEGF receptor 3 (VEGFR3), which is encoded by the most frequently mutated gene in human primary lymphedema. Angiopoietins (Angs) and their Tie receptors regulate lymphatic vessel development, and mutations of the ANGPT2 gene were recently found in human primary lymphedema. However, the mechanistic basis of Ang2 activity in lymphangiogenesis is not fully understood. Here, we used gene deletion, blocking Abs, transgene induction, and gene transfer to study how Ang2, its Tie2 receptor, and Tie1 regulate lymphatic vessels. We discovered that VEGF-C–induced Ang2 secretion from lymphatic endothelial cells (LECs) was involved in full Akt activation downstream of phosphoinositide 3 kinase (PI3K). Neonatal deletion of genes encoding the Tie receptors or Ang2 in LECs, or administration of an Ang2-blocking Ab decreased VEGFR3 presentation on LECs and inhibited lymphangiogenesis. A similar effect was observed in LECs upon deletion of the PI3K catalytic p110α subunit or with small-molecule inhibition of a constitutively active PI3K located downstream of Ang2. Deletion of Tie receptors or blockade of Ang2 decreased VEGF-C–induced lymphangiogenesis also in adult mice. Our results reveal an important crosstalk between the VEGF-C and Ang signaling pathways and suggest new avenues for therapeutic manipulation of lymphangiogenesis by targeting Ang2/Tie/PI3K signaling.

10 citations


Cited by
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Journal ArticleDOI
04 Mar 2011-Cell
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.

51,099 citations

Journal ArticleDOI
07 Jan 2000-Cell
TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.

28,811 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组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�ly.
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。

18,940 citations

Journal ArticleDOI
19 Dec 2002-Nature
TL;DR: 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.
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.

12,395 citations

Journal ArticleDOI
09 Jan 1987-Science
TL;DR: Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer, and had greater prognostic value than most currently used prognostic factors in lymph node-positive disease.
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.

11,597 citations