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6th ESACP Congress, Heidelberg, April 7-11, 1999 |
A009
New methods adaptable to flow- and laser scanning- cytometry habe been
developed to identify apoptotic cells and reveal whether apoptosis is
selective to particular phases of the cell cycle. These methods enabled us
to characterize several antitumor drugs of different classes in terms of
their cell cycle specificity in vitro. Using these methods it was possible
to assess apoptosis and correlate it with the cell cycle position in clinical
samples during treatment of acute leukemias (AML, ALL, CML in blastic crisis).
These in vitro and clinical observations provided rationale for new antitumor
strategies. The respective strategies are based on: (i)drug combinations and
sequences that recruit cells to the sensitive phase of the cycle; (ii)
suppression of normal cells proliferation by agents that arrest in Go phase
combined with the drugs that target other phases of the cycle: the cells that
are unable to postmitotically enter Go, namely the tumor cells, are then
preferentially undergoing apoptosis; (iii) potentiation of apoptosis when
DNA damaging drugs are followed by inducers of differentiation, and (iv)
suppression of induction of cell survival genes which are triggered by
nuclear factor kappa B, selectively in tumor cells. Some of these strategies
are being tested in clinical trials in our Institute.
CELL CYCLE SPECIFICITY IN INDUCTION OF APOPTOSIS BY ANTITUMOR AGENTS
Darzynkiewicz Z
Brander Cancer Research Institute, Hawthorne, N.Y. USA