Co-Localization of Hypoxia and Apoptosis in Irradiated and Untreated HCT116 Human Colon Carcinoma Xenografts

Koch, Cameron J.; Chasan, Jana E.; Jenkins, W. Timothy; Chan, Cecilia Y.; Laughlin, Kristine M.; Evans, Sydney M.

doi:10.1007/978-1-4615-4863-8_72

Cited by 4 publications

(2 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This spatial separation of apoptosis and hypoxia in experimental tumors in vivo confirms a previous report. 27 In contrast, a very strong and consistent overlap can be observed between markers of hypoxia and prominent EMAP II staining in perinecrotic areas of B16 melanomas. This is the first demonstration of a correlation between hypoxia and enhanced proEMAP II/p43 expression in a pathological setting in vivo (Figure 3, D-F).…”

Section: Discussionmentioning

confidence: 90%

Regulation of EMAP II by Hypoxia

Matschurat

Knies

Person

et al. 2003

The American Journal of Pathology

View full text Add to dashboard Cite

Endothelial-monocyte-activating polypeptide II (EMAP II) is a proinflammatory cytokine and a chemoattractant for monocytes and granulocytes. We have previously shown that EMAP II mRNA is strongly expressed at sites of apoptosis in the mouse embryo and that the mature protein is cleaved from its cellular precursor (proEMAP II/p43) by caspase activation to become released from cells. Here we demonstrate in vivo that EMAP II mRNA expression is strongly increased in tumor necrosis factor alpha (TNF)-treated murine meth A fibrosarcomas and in B16 melanomas, especially in close proximity to areas of tissue necrosis. Furthermore, by means of confocal microscopy, high level expression of proEMAP II/p43 protein correlated predominantly with hypoxic but also with apoptotic cells. In vitro, EMAP II mRNA levels were not increased by hypoxia. However, high amounts of mature EMAP II protein were detected in the supernatants of hypoxic tumor cells. Unlike in apoptotic cells, neither a broad-range caspase inhibitor nor an inhibitor specific for the internal cleavage site was able to inhibit processing of proEMAP II/p43 to the mature EMAP II protein. In conclusion, these data suggest that hypoxia and apoptosis provide two alternative mechanisms of EMAP II generation by tumor cells.

show abstract

Section: Discussionmentioning

confidence: 90%

Regulation of EMAP II by Hypoxia

Matschurat

Knies

Person

et al. 2003

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Thus EF5 binding was related to p O 2 in human cells, as shown in Table 1. The binding values can be converted to two-dimensional tissue oxygen maps and/or used to assess other spatial parameters within the tissue sections (31, 34, 35, 41). …”

Section: Methodsmentioning

confidence: 99%

Imaging and Analytical Methods as Applied to the Evaluation of Vasculature and Hypoxia in Human Brain Tumors

Evans

Jenkins

et al. 2008

Radiation Research

Self Cite

View full text Add to dashboard Cite

Tissue hypoxia results from the interaction of cellular respiration, vascular oxygen carrying capacity, and vessel distribution. We studied the relationship between tumor vasculature and regions of low pO 2 using quantitative analysis of binding of the 2-nitroimidazole EF5 given to patients intravenously (21 mg/kg) approximately 24 h preceding surgery. We describe new computer algorithms for determining EF5 binding as a function of radial distance from individual blood vessels and converting this value to tissue pO 2 . Tissues from six human brain tumors were assessed. In a hemangiopericytoma, a WHO Grade 2 and WHO Grade 3 glial brain tumor, all tissue pO 2 values calculated by EF5 binding were >20 mmHg (described as "physiologically oxygenated"). In these three tumors, EF5 binding gradients (measured as a function of distance from each observed vessel) were low, with small positive and negative values averaging close to zero. Much lower tissue oxygen levels were found, including near some vessels, in glioblastomas. Gradients of EF5 binding away from vessels were larger in glioblastomas than in the low-grade tumors, but positive and negative values again averaged to near zero. Based on these preliminary data, we hypothesize a new paradigm for tumor blood flow in human brain tumors whereby in-flowing and out-flowing blood patterns may have contrasting effects on average tissue EF5 (and by inference, oxygen) gradients. Our studies also imply that neither distance to the nearest blood vessel nor distance from each observed blood vessel provide reliable estimates of tissue pO 2 .

show abstract