Abstract

Whereas the clinical and prognostic relevance of cell cycle kinetic properties of neoplastic cells was a subject embroiled in controversy in the past, the relatively recent introduction of monoclonal antibodies to thymidine analogues such as bromodeoxyuridine (BrdU) and iododeoxyuridine (IUdR) has dramatically altered our perceptions. It is now not only possible to characterize large numbers of patients with myeloid disorders for detailed cell cycle kinetics, but given their impressive prognostic value and the fact that data are available in a prompt fashion, this information can provide the basis for prospective manipulations of the biologic properties of leukemia cells. The goal of this project is to explore the phenomena of proliferation in patients with acute myeloid leukemia (AML). New methods have been developed to investigate the cell cycle kinetics in biopsies using two DNA specific probes i.e., Iudr and BrdU in vivo. The effects of chemotherapy as well as cytokines can also be measured by the sequential administration of these agents. These incisive studies will surely lead to an improve understanding of biology and are already forming the basis for the design of our future therapeutic protocols in these disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA060085-05
Application #
2100701
Study Section
Special Emphasis Panel (SRC)
Project Start
1992-08-01
Project End
1997-05-31
Budget Start
1995-06-01
Budget End
1996-05-31
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
Rush University Medical Center
Department
Type
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60612

  Publications

Ali, A; Mundle, S D; Ragasa, D et al. (1999) Sequential activation of caspase-1 and caspase-3-like proteases during apoptosis in myelodysplastic syndromes. J Hematother Stem Cell Res 8:343-56
Mundle, S; Venugopal, P; Shetty, V et al. (1999) The relative extent and propensity of CD34+ vs. CD34- cells to undergo apoptosis in myelodysplastic marrows. Int J Hematol 69:152-9
Preisler, H D; Bi, S; Venugopal, P et al. (1997) Cytokines, molecular biological abnormalities, and acute myelogenous leukemia. Leuk Res 21:299-312
Handa, H; Hegde, U P; Kotelnikov, V M et al. (1997) Bcl-2 and c-myc expression, cell cycle kinetics and apoptosis during the progression of chronic myelogenous leukemia from diagnosis to blastic phase. Leuk Res 21:479-89
Raza, A; Alvi, S; Borok, R Z et al. (1997) Excessive proliferation matched by excessive apoptosis in myelodysplastic syndromes: the cause-effect relationship. Leuk Lymphoma 27:111-8
Raza, A; Alvi, S; Broady-Robinson, L et al. (1997) Cell cycle kinetic studies in 68 patients with myelodysplastic syndromes following intravenous iodo- and/or bromodeoxyuridine. Exp Hematol 25:530-5
Handa, H; Hegde, U P; Kotelnikov, V M et al. (1997) The effects of 13-cis retinoic acid and interferon-alpha in chronic myelogenous leukemia cells in vivo in patients. Leuk Res 21:1087-96
Preisler, H D; Raza, A; Bonomi, P et al. (1997) Regrowth resistance as a likely significant contributor to treatment failure in drug-sensitive neoplastic diseases. Cancer Invest 15:358-68
Raza, A; Gregory, S A; Preisler, H D (1996) The myelodysplastic syndromes in 1996: complex stem cell disorders confounded by dual actions of cytokines. Leuk Res 20:881-90
Raza, A; Mundle, S; Shetty, V et al. (1996) A paradigm shift in myelodysplastic syndromes. Leukemia 10:1648-52

Showing the most recent 10 out of 18 publications