YEARS

1998-2001

AUTHORS

Thomas E. Witzig

TITLE

APOPTOSIS AND %S AS PROGNOSTIC FACTORS FOR COLON CANCER

ABSTRACT

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.

FUNDED PUBLICATIONS

  • Prognostic value of proliferation, apoptosis, defective DNA mismatch repair, and p53 overexpression in patients with resected Dukes' B2 or C colon cancer: a North Central Cancer Treatment Group Study.
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    18 TRIPLES      15 PREDICATES      19 URIs      7 LITERALS

    Subject Predicate Object
    1 grants:ca4fb1223e5d79a1b9738c192cdde9da sg:abstract 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.
    2 sg:endYear 2001
    3 sg:hasContribution contributions:361c2f23eb419b298cca2eec77ff2b6b
    4 sg:hasFieldOfResearchCode anzsrc-for:06
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    7 anzsrc-for:1112
    8 sg:hasFundedPublication articles:c83003592cff8060a07b935f7cc7880b
    9 sg:hasFundingOrganization grid-institutes:grid.48336.3a
    10 sg:hasRecipientOrganization grid-institutes:grid.66875.3a
    11 sg:language English
    12 sg:license http://scigraph.springernature.com/explorer/license/
    13 sg:scigraphId ca4fb1223e5d79a1b9738c192cdde9da
    14 sg:startYear 1998
    15 sg:title APOPTOSIS AND %S AS PROGNOSTIC FACTORS FOR COLON CANCER
    16 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=2896670
    17 rdf:type sg:Grant
    18 rdfs:label Grant: APOPTOSIS AND %S AS PROGNOSTIC FACTORS FOR COLON CANCER
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