DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE
NATIONAL CANCER INSTITUTE
ANNUAL REPORT October 1, 1982 through September 30, 1983 CONTENTS DIVISION OF CANCER TREATMENT
NOTICE OF INTRAMURAL RESEARCH PROJECT
PROJECT NUMBER
Z01-CM-6402-13-CP
PERIOD COVERED
October 1, 1982 to September 30, 1983
TITLE OF PROJECT (80 character! or lest. Title must fit on one line between the borders.)
Tumor Growth Kinetics and Chemotherapy
PRINCIPAL INVESTIGATOR (List other professional personnel on subsequent pages.) (Name, title, laboratory, and Institute affiliation)
Stanley E. Shackney, M.D.
COOPERATING UNITS (If any) . . .
Laboratory of Applied Clinical Engineering Branch Medicine Branch
LAB/BRANCH
Clinical Pharmacology Branch
SECTION
Cellular Kinetics Section
INSTITUTE AND LOCATION
NCI, National Cancer Institute, Bethesda, MD 20205
TOTAL MANYEARS: 5
PROFESSIONAL: 3
CHECK APPROPRIATE BOX(ES>
(a) Human subjects I I (a1) Minors (a2) Interviews
[XI (b) Human tissues
(c) Neither
SUMMARY OF WORK (Use standard unreduced type. Do not exceed the space provided.)
Studies have focused on: a) schedul ing considerations for tubulin binding agents , specifically vincristine . The results favor infusions over pulse doses, and indicate schedule-dependent synergism with hydroxyurea and adriamycin, respectively, b) Defining the relationship between cell proliferation and the quantitative expression of specialized gene products. An inverse relationship was found between the rate of cell proliferation and the quantitative expression of immunologic surface markers in an early B cell line; similarly, an inverse relationship was observed between cell proliferation and cell content of estrogen receptor, c) Studying the mechanisms underlying clonal evolution as they may relate to clinical and histologic transformation of the lymphomas and as they may relate to the development of drug resistance. Flow cytometry studies in the non-Hodgkin's lymphomas suggest that clonal evolution is fueled by a sequence of i) cell tetraploidization ii) long term cytogenetic instability of the tetraploid line, iii) progre'ssive chromosome from the tetraploid line, and iv) overgrowth of aneup1oi"a cell lines that are produced by this process.