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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.



PHS 6040 (Rev. 1/83)



GPO 895-100



511



Z01-CM-06402-13-CP
Other Professional Personnel

Hamza Mujagic, M.D. CPB, COP, DCT, NCI

William Schuette ACES, BEIB, NIH

Marc Lippman, M.D. MB, COP, DCT, NCI

Raymond Jakesz, M.D. MB, COP, DCT, NCI

Jon Minford, M.D. LMPH, COP, DCT, NCI

Leonard Zwelling, M.D. LMPH, COP, DCT, NCI

Richard Fisher, M.D. MB, COP, DCT, NCI

Susan Bates, M.D. MB, COP, DCT, NCI