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R.D. Braun, J.L. Chunta; Hypoxia in an Orthotopic Xenograft Model of Human Choroidal Melanoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2226.
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Most medium–sized choroidal melanomas are treated by enucleation or eye–sparing radiation therapy. While radiation therapy is as effective as enucleation in terms of long–term survival, it has been only marginally successful in saving patient vision. It should be possible to minimize peripheral damage and increase vision retention by optimizing the radiation treatment. One way to achieve this is to increase the radiosensitivity of the tumor by raising local oxygen levels. Most tumors are poorly oxygenated, i.e., they are hypoxic and are inherently radioresistant. The purpose of this initial study was to determine whether hypoxia exists in an orthotopic human choroidal melanoma xenograft model.
Orthotopic xenografts were grown by implanting human choroidal melanoma C918 spheroids into the suprachoroidal space of nude, athymic WAG/Nij–rnu rats. After 3 weeks, rats were anesthetized with urethane, and tumor oxygen tension (PO2) was measured with recessed, polarographic oxygen microelectrodes. Two to four tracks were recorded by withdrawing the electrode through the tumor while the rat was breathing air. These measurements were used to create PO2 histograms.
PO2 histograms were measured in 10 rats. A total of 90 + 31 points (mean + SD) were measured in each tumor. Under air–breathing conditions, orthotopic C918 xenografts were very hypoxic. The mean hypoxic fraction (%PO2 values < 5 mm Hg) in the 10 tumors was 43.7 + 27.2 %. The average median PO2 was 8.2 + 5.9 mm Hg.
The C918 orthotopic xenograft tumor is inherently hypoxic. Therefore, this model can be used to test methods to improve tumor oxygenation and to determine the resultant radiation response.
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