Contributions of cell kill and posttreatment tumor growth rates to the repopulation of intracerebral 9L tumors after chemotherapy: An MRI study

被引:70
作者
Ross, BD
Zhao, YJ
Neal, ER
Stegman, LD
Ercolani, M
Ben-Yoseph, O
Chenevert, TL
机构
[1] Univ Michigan, Med Ctr, Dept Radiol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Med Ctr, Dept Biol Chem, Ann Arbor, MI 48109 USA
关键词
D O I
10.1073/pnas.95.12.7012
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The drought of progress in clinical brain tumor therapy provides an impetus for developing new treatments as well as methods for testing therapeutics in animal models. The inability of traditional assays to simultaneously measure tumor size, location, growth kinetics, and cell kill achieved by a treatment complicates the interpretation of therapy experiments in animal models. To address these issues, tumor volume measurements obtained from serial magnetic resonance images were used to noninvasively estimate cell kill values in individual rats with intracerebral 9L tumors after treatment with 0.5, 1, or 2 x LD10 doses of 1,3-bis(2-chloroethyl)-1-nitrosourea. The calculated cell kill values Were consistently lower than those reported using traditional assays. A dose-dependent increase in 9L tumor doubling time after treatment was observed that significantly contributed to the time required for surviving cells to repopulate the tumor mass. This study reveals that increases in animal survival are not exclusively attributable to the fraction of tumor cells killed but rather are a function of the cell kill and repopulation kinetics, both of which vary with treatment dose.
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页码:7012 / 7017
页数:6
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