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Cell kill is a function of the dose (for alkylating agents, kill increases linearly with dose) and the schedule of drug administration. For most cancer drugs, cell kill correlates with a specific pharmacokinetic parameter, the area under the drug concentration multiplied by the time curve (C × T, or AUC) ( Fig. 8-2 ).
- Cited Cause of Fractional Killing: Cell Cycle Effects
- Lack of Cell Cycle Effect in Drugs Documented to Be Cell Cycle Phase Specific
- Cell-To-Cell Variation in Protein Levels
The fractional killing of tumors in response to treatment is assumed to be due to the cell cycle specificity of chemotherapy drugs. Cytarabine, a DNA-synthesis inhibitor also known as ara-C, is cited as the classic cell cycle phase-specific agent. Chemotherapy dosing schedules have been optimized based on the fact that cytarabine is only expected t...
Very little direct information is available on whether cells undergo apoptosis from a certain point in the cell cycle. One study which did address this topic used flow cytometry or elutriation of synchronized cells treated with actinomycin D1, camptothecin, or aphidicolin, each of which had been documented to exert its effects in a particular phase...
A recent paper by Spencer et al. raises the possibility that cell-to-cell variability in protein concentrations may contribute to fractional killing in the case of treatment with TRAIL(TNF-related apoptosis inducing ligand). TRAIL is a ligand native to the human body that is currently being developed as a cancer treatment. Spencer et al. observed f...
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The clonal theory views leukemia as replacement of the marrow by the progeny of a cell inherently incapable of normal maturation. The cell kill rationale of therapy is a logical outgrowth of this theory.
- John E. Kurnick, William A. Robinson
- 1972
May 15, 2014 · For example if one drug can kill 90% of the cells and another call kill 90% of the cells, using them both would kill 99%, a two-log kill. 2. The log-kill hypothesis almost immediately generated many ideas concerning the best way to discover, test, and use anticancer drugs.
- Larry Norton
- 2014
Jun 24, 2013 · The cell kill hypothesis states that a specific dose of drug kills a constant fraction of cells rather than a specific number. Its incremental success, therefore, depends on the number of cells at the start of the treatment.
Jan 1, 2017 · Definition. The log-kill hypothesis proposes a model for the effect of cytotoxic chemotherapy on tumor size. It states that a given dose of chemotherapy kills the same fraction of tumor cells regardless of the size of the tumor at the time of treatment.
Programmed Cell Death (Apoptosis) The cells of a multicellular organism are members of a highly organized community. The number of cells in this community is tightly regulated—not simply by controlling the rate of cell division, but also by controlling the rate of cell death.
