Chronobiology is the study of biological rhythms. There are a number of chronobiological effects which may have important clinical implications for antitumor therapies. For example, chronobiological effects on the replication of some types of tumor cells, the expression of certain drug toxicities, and the number of cytotoxic effector cells have been described. Interferon therapies are currently being evaluated in clinical trials for their potential as antitumor agents. This proposal focuses on possible chronobiological effects which may effect the potencies of various interferon therapies. We propose to evaluate the chronobiological effects on tumor growth of interferons administered (1) as single agent therapy; (2) as multiple interferon therapies (IFN-gamma plus IFN-alpha or IFN- beta); (3) as multiple agent therapies with hyperthermia; and, as multiple agent therapies with phenytoin. These studies will be performed both in vitro, using B-16 melanoma cells in cloning studies, and in vivo, using the B-16 melanoma/C57/B1/6 tumor system. Simultaneous treatments and various sequential treatments will be compared to identify the most potent treatment protocol. We also propose to evaluate the chronobiological effects on IFN-mediated bone marrow suppression of colony stimulating factor administration. These studies will be performed both in vitro using bone marrow colony growth assays and in vivo using total white blood cell counts as an indicator of bone marrow suppression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA050752-02
Application #
3195414
Study Section
Special Emphasis Panel (SRC (50))
Project Start
1990-04-06
Project End
1995-02-28
Budget Start
1991-03-01
Budget End
1992-02-29
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Fleischmann Jr, W R; Koren, S (1999) Systemic effects of orally administered interferons and interleukin-2. J Interferon Cytokine Res 19:829-39
Wu, T Y; Fleischmann Jr, W R (1998) Efficacy of B16 melanoma cells exposed in vitro to long-term IFN-alpha treatment (B16alpha cells) as a tumor vaccine in mice. J Interferon Cytokine Res 18:829-39
Fleischmann, C M; Wu, T Y; Fleischmann Jr, W R (1997) B16 melanoma cells exposed in vitro to long-term IFN-alpha treatment (B16 alpha cells) as activators of tumor immunity in mice. J Interferon Cytokine Res 17:37-43
Fleischmann, C M; Stanton, G J; Fleischmann Jr, W R (1996) Enhanced in vivo sensitivity of in vitro interferon-treated B16 melanoma cells to CD8 cells and activated macrophages. J Interferon Cytokine Res 16:805-12
Fleischmann, C M; Fleischmann Jr, W R (1995) Enhanced in vitro macrophage cytotoxicity against interferon-treated B16 melanoma cells. J Biol Regul Homeost Agents 9:139-45
Koren, S; Fleischmann Jr, W R (1994) Modulation of peripheral leukocyte counts and bone marrow function in mice by oral administration of interleukin-2. J Interferon Res 14:343-7
Fleischmann Jr, W R; Fleischmann, C M (1994) Enhancement of MuIFN-gamma antitumor effects by hyperthermia: sequence dependence and time dependence of hyperthermia. J Biol Regul Homeost Agents 8:101-7
Fleischmann, C M; Stanton, G J; Fleischmann Jr, W R (1994) Enhanced in vivo sensitivity to interferon with in vitro resistant B16 tumor cells in mice. Cancer Immunol Immunother 39:148-54
Koren, S; Fleischmann Jr, W R (1993) Optimal circadian timing reduces the myelosuppressive activity of recombinant murine interferon-gamma administered to mice. J Interferon Res 13:187-95
Koren, S; Fleischmann Jr, W R (1993) Circadian variations in myelosuppressive activity of interferon-alpha in mice: identification of an optimal treatment time associated with reduced myelosuppressive activity. Exp Hematol 21:552-9

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