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National Cancer Institute - NCI Division of Cancer Treatment and ...

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DTP oversees animal-production facilities that produce<br />

inbred <strong>and</strong> hybrid strains <strong>of</strong> rats, mice, <strong>and</strong> guinea pigs.<br />

This program provides researchers nationwide with<br />

genetically defined, pathogen-free laboratory animals.<br />

Animal Production<br />

http://dtp.nci.nih.gov/branches/btb/<br />

services.html#AnimalProduction<br />

DTP’s Biological Testing Branch oversees<br />

animal-production facilities that produce<br />

inbred <strong>and</strong> hybrid strains <strong>of</strong> rats, mice,<br />

<strong>and</strong> guinea pigs. This program provides<br />

researchers nationwide with genetically<br />

defined, pathogen-free laboratory animals<br />

as well as animal-related services such<br />

as jugular vein cannulations, vasectomies,<br />

ovariectomies, <strong>and</strong> castrations. In 2005,<br />

the branch distributed 1,473,062 rodents<br />

to about 1700 investigators at 240<br />

institutions.<br />

In Vitro Screening: The Human<br />

Tumor Cell Line Assay<br />

http://dtp.nci.nih.gov/branches/btb/<br />

ivclsp.html<br />

In 1985, the hypothesis was put forward<br />

that a human tumor cell line screen<br />

could help investigators discover celltype–specific<br />

agents with clinical activity<br />

against solid tumors. The emerging reality<br />

was that while correlation <strong>of</strong> in vitro histology<br />

to clinical activity is poor, the pattern<br />

<strong>of</strong> cellular sensitivity <strong>and</strong> resistance <strong>of</strong><br />

the cell lines to the drug correlated with<br />

molecular target expression.<br />

In response, DTP developed a cell-line–<br />

based screen representing the major<br />

classes <strong>of</strong> solid tumors. That allowed<br />

relatively inexpensive <strong>and</strong> rapid testing<br />

<strong>of</strong> potential therapeutic agents against<br />

broad panels <strong>of</strong> human tumors that<br />

could be adapted to the needs <strong>of</strong> natural<br />

product screening.<br />

106 ■ P R O G R A M A C C O M P L I S H M E N T S 2 0 0 6<br />

■ ■ ■<br />

Since April 1990, DTP has used the human<br />

tumor cell line in vitro screen as its primary<br />

assay with follow-up in vivo evaluation in<br />

the hollow fiber assay. The screen is currently<br />

composed <strong>of</strong> 59 human tumor cell<br />

lines, representing leukemia, melanoma,<br />

<strong>and</strong> cancers <strong>of</strong> the lung, colon, brain, ovary,<br />

breast, prostate, <strong>and</strong> kidney. These cell<br />

lines were selected partly on pragmatic<br />

terms: those selected behaved best under<br />

typical assay conditions. The screen was<br />

designed so that for each compound<br />

tested, both the absolute <strong>and</strong> the relative<br />

sensitivities <strong>of</strong> individual cell lines were<br />

reproducible to the extent that a characteristic<br />

pr<strong>of</strong>ile or fingerprint <strong>of</strong> cellular<br />

response was generated.<br />

Although the particular inhibitory<br />

response <strong>of</strong> a single cell line might be<br />

relatively uninformative, the pattern <strong>of</strong><br />

response <strong>of</strong> the cell lines as a group can<br />

be used to rank a compound according<br />

to the likelihood <strong>of</strong> sharing common<br />

mechanisms. The COMPARE algorithm<br />

(a computer program) qualifies this<br />

pattern <strong>and</strong> searches an inventory <strong>of</strong><br />

screened agents to compile a list <strong>of</strong> the<br />

compounds that have the most similar<br />

patterns <strong>of</strong> cellular sensitivity <strong>and</strong><br />

resistance.<br />

Extramural researchers who wish to<br />

access this service should complete an<br />

online submission form: http://dtp.nci.<br />

nih.gov/compsub/index.html. Pure compounds<br />

must be <strong>of</strong> known molecular<br />

structure, <strong>and</strong> the investigator is required<br />

to enter the molecular structure on the<br />

online submission form before sending<br />

samples <strong>of</strong> the test compound. Additional

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