Project: Research project

Project Details


The growth of a colon cancer is determined by the rates of malignant
cell proliferation and natural apoptosis. Because of molecular genetic
changes in the cancer cell both of these processes can be disrupted and
lead to tumor growth. We hypothesize that the rate of colon cancer cell
apoptosis is an important determinant of net cancer cell growth and that
a measure of the percent cells in apoptosis will provide additional
prognostic information to the cell proliferation rate. The overall
goals of this proposal are to measure the rates of basal apoptosis and
cell proliferation on specimens of colon adenocarcinomas and relate
these measurements to prognosis and the molecular genetic abnormalities
determined on the same tumor sample. Paraffin-embedded tissue from
patients that participated in randomized, controlled NCCTG clinical
trials which now have adequate follow-up data to correlate these
measurements to colon cancer recurrence and survival. Cell
proliferation and DNA ploidy will be measured using state-of-the-art
flow cytometry hardware and software. Apoptosis will be measured with
a TUNEL technique. We propose to utilize the cell proliferation
(percent S and percent G2M phases) and percent apoptosis measurements
to develop a formula - the colon cancer growth index (CCGI) - that
better predicts prognosis. The second hypothesis to be tested is that
the alterations of cancer cell proliferation and apoptosis are the
consequences of genetic abnormalities and that these genetic
abnormalities will differentially affect proliferation and apoptosis.
This study offers the unique opportunity to study the cell proliferation
and apoptosis rates of colon cancers that have already been studied for
molecular abnormalities by Dr. Steven Thibodeau in a previous study
(NCCTG 93-46-55). By performing these assays on clinical material, we
aim to translate these findings into prognostic tools that can be used
in the clinic to formulate new treatment strategies based on the
knowledge of apoptosis and cell proliferation of colon cancers.
StatusNot started


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