EXPERIMENTAL AND CLINICAL STUDIES IN COLORECTAL CANCER

Project: Research project

Project Details

Description

The overall goal of this proposal is to evaluate the prevalence and
prognostic value of "cancer associated" markers in normal,
premalignant and malignant human colorectal tissue.
Importantly, the ability of these markers to predict the
development of metachronous lesions in patients with resected
colorectal cancer and premalignant adenomatous polyps will be
analyzed. In a prospective study, biopsies of normal rectum,
sigmoid and ascending colon will be obtained during colonoscopy.
Regional differences in mucus glycoproteins (lectin binding),
calcium activated proteins and cellular proliferation (ornithine
decarboxylase activity and polyamine levels) will be determined
and compared among and between patients with and without
adenomatous polyps. Analysis of regional differences in these
parameters may help explain the predilection of tumors to occur
in the distal colon and rectum. Similar observation will be made
on resected adenomatous polyps and colorectal cancer. Patients
with resected polyps or cancer will then undergo surveillance
colonoscopy to document metachronous neoplastic lesions. The
parameters used to assess cellular growth and differentiation will
be correlated with recurrence of neoplastic disease and survival.
In a retrospective study, lectin binding and flow cytometric
analysis of paraffin embedded adenomatous polyps will be
determined in patients who have undergone surveillance
colonoscopy. The direct clinical benefit of this study is to
determine the need and timing of surveillance colonoscopy in
patients with a history of colonic adenomatous polyps and cancer.
The more fundamental benefit will be to elucidate potential
biochemical changes that hallmark transformation of normal to
premalignant to malignant colorectal tissue.

Parallel observations of changes in calcium binding proteins,
mucus glycoproteins and cellular proliferation will be made in
dimethylhydrazine-induced colon carcinoma in the rat. Regional
and sequential changes will be measured during carcinogenesis.
The proposed studies will provide direct comparisons of changes
that occur in human colon neoplasia and animal models of
carcinogenesis.
StatusFinished
Effective start/end date1/1/901/1/90

Funding

  • National Cancer Institute

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