Microenvironment of tumor

Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors a review. Cancer Res 49 6449-6465... 

One of the major features of solid tumors and even small deposits of tumor tissue is deficiency in the level of oxygen, because of an inadequate vascular supply. The adenosine elevation in response to hypoxia is not exclusive to tumor tissues, but, in this context, the adenosine elevation is localized to the tumor microenvironment, since the surrounding tissue is normally oxygenated. Adenosine is generated mainly by two enzymatic systems intra- or extracellularly localized 5 -nucleoti-dases and cytoplasmic S-adenosylhomocysteine hydrolase. The processes of adenosine elimination in the cell involve reactions catalyzed by adenosine deaminase and adenosine kinase (Shryock and Belardinelli 1997) yielding inosine or 5 -AMP,... 

Hobbs, S.K., Monsky, W., Yuan, F., Roberts, W.G., Griffith, L., Torchillin, V.P. et al. (1998) Regulation of transport pathways in tumor vessels Role of tumor type and microenviron-ment. Proc. Nat. Acad. Sci. USA, 95, 4607-4612. 

Molls M, Vaupel P (1998) The impact of the tumor environment on experimental and clinical radiation oncology and other therapeutic modalities. In Molls M, Vaupel P (eds) Blood perfusion and microenvironment of human tumors - implications for clinical radiooncology. Springer, Berlin Heidelberg New York... 

Activation and differentiation of cytotoxic T lymphocytes (CD8+ T cells) (CTLs) require interplay of various cytokines and cells. During the presentation of tumor-specific antigens by antigen-presenting cells (APCs) to helper T cells (CD4+ T cells), cytokines present in the microenvironment control the helper immune response to develop into either a cellular or a humoral response. CD4+ T cells have been classified into Thl and Th2 subsets according to the pattern of cytokines they produce. Thl clones secrete IL-12 and IFN-y, whereas Th2 clones secrete IL-4, IL-5, IL-6 and IL-10. Thl immune response is beneficial for the development of the cellular cytotoxic (CD8) immune response, whereas Th2 immune response is inhibitory to cytotoxic response. IFN-y is a type 1 interferon that also promotes Thl-type anti-tumor immunity, reduces tumor cell growth, and inhibits angiogenesis. 

This has led to the development of systems for site-specific delivery to tumor cells which exploit the unique microenvironment of the tumor. 

The invasion pathways, arrest and clearance of tumor cells in various tissues can be studied by injecting tumor cells into experimental animal models. In this case, a way of tracking single tumor cells within the circulatory system and the organ microenvironment is required. 

K. Regulation of transport pathways in tumor vessels role of tumor type and microenvironment. Proc. Natl. Acad. Sci. USA 1998, 95, 4607-4612. 

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