This project is concerned with basic tumor biology. Human tumor cells and their normal counterparts are being isolated, some types for the first time, by Dr. Rheinwald. He is learning how their anaplastic and neoplastic properties are exhibited in culture. Normal and defective differentiation are also being studied by Dr. Gudas using molecular genetic techniques. The key role in growth regulation of normal and tumor cells by platelet-derived growth factor (PDGF) is being investigated at cellular, biochemical, and molecular genetic levels by Dr. Stiles, including possible relations to oncogenes. The importance of genetic rearrangements in human cancer has become increasingly more evident. Dr. Sager, one of the first to recognize this fact, is doing elegant experiments with human and rodent cells to study the mechanisms that bring about these changes. Along related lines, Dr. Maxam is probing gene structures and arrangements using sophisticated and delicate molecular techniques. Dr. Chen is identifying cancer cells using dyes novel for this purpose, Rhodamines. He has found these dyes to be selectively toxic to some tumor cells. Lethality of DNA-damaging agents toward human cells is increased greatly by preventing repair of the DNA lesions. Dr. Pardee is adding DNA repair inhibitors to chemotherapy with a view to improving the specificity and efficacy of the antineoplastic drugs. (V)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA022427-09
Application #
3092976
Study Section
(SRC)
Project Start
1978-03-01
Project End
1988-02-28
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
9
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Liang, P; Averboukh, L; Zhu, W et al. (1995) Molecular characterization of the murine thymidylate kinase gene. Cell Growth Differ 6:1333-8
Zou, Z; Anisowicz, A; Hendrix, M J et al. (1994) Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science 263:526-9
Dou, Q P; Zhao, S; Levin, A H et al. (1994) G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter. J Biol Chem 269:1306-13
Fridovich-Keil, J L; Markell, P J; Gudas, J M et al. (1993) DNA sequences required for serum-responsive regulation of expression from the mouse thymidine kinase promoter. Cell Growth Differ 4:679-87
DeFranco, C; Damon, D H; Endoh, M et al. (1993) Nerve growth factor induces transcription of NGFIA through complex regulatory elements that are also sensitive to serum and phorbol 12-myristate 13-acetate. Mol Endocrinol 7:365-79
DeFranco, C; Ro, M; Grossel, M et al. (1993) NGFIA (EGR1) contains transcription activating domains in both the amino terminal and carboxyl terminal regions of the protein. Biochem Biophys Res Commun 194:425-31
Keyomarsi, K; Samet, J; Molnar, G et al. (1993) The thymidylate synthase inhibitor, ICI D1694, overcomes translational detainment of the enzyme. J Biol Chem 268:15142-9
Sager, R; Anisowicz, A; Neveu, M et al. (1993) Identification by differential display of alpha 6 integrin as a candidate tumor suppressor gene. FASEB J 7:964-70
Dou, Q P; Levin, A H; Zhao, S et al. (1993) Cyclin E and cyclin A as candidates for the restriction point protein. Cancer Res 53:1493-7
Liang, P; Averboukh, L; Pardee, A B (1993) Distribution and cloning of eukaryotic mRNAs by means of differential display: refinements and optimization. Nucleic Acids Res 21:3269-75

Showing the most recent 10 out of 48 publications