Methods for measuring cell response to dna damaging agents using promyelocytic leukemia protein nuclear bodies
OwnerGraham Dellaire, David Bazett-Jonesinventors
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Abstract
Methods for assessing the potential efficacy of a DNA-damaging agent as a tumour treatment or for monitoring the efficacy of such treatment by determining promyelocytic leukemia protein nuclear body (PML NB) properties of the tumour are disclosed. PML NB properties, including morphology, number and biochemical composition, of cells or tissue are assessed following exposure to a DNA-damaging agent and compared to corresponding PML NB properties of cells or tissue not exposed to the DNA-damaging agent. The difference, or lack thereof, determines the efficacy of the DNA-damaging agent as a treatment for tumours or monitoring the efficacy of such treatment.
Claims30
A method for assessing or monitoring efficacy of a DNA-damaging agent in the treatment of a tumor in a subject, the method comprising:
- contacting tumor tissue with the DNA-damaging agent;
- determining the value of a selected promyelocytic leukemia nuclear body (PML NB) property in the tumor tissue at one or more time points after the contact with the DNA-damaging agent;
- and
- comparing the value of the selected property in the tumor tissue with the value of the selected property in control tissue;
- wherein a difference between the value of the selected property in the tumor tissue and the value of the property in the control tissue indicates efficacy for treatment of the tumor.
A method for assessing or monitoring efficacy of a DNA-damaging agent in the treatment of a tumor in a subject, the method comprising:
- contacting tumor tissue and normal tissue with the DNA-damaging agent;
- and
- determining the value of a selected PML NB property in the tumor tissue and in the normal tissue at one or more time points after the contact with the DNA-damaging agent
- wherein a difference in the response or in the timing of the response to the agent between the tumor and the normal tissue indicates that the agent lacks efficacy for treatment of the tumor.
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A method for monitoring the response of a cell or tissue to stress, the method comprising determining the level of at least one PML NB property in the cell or tissue before and after the stress, or comparing the post-stress level of at least one PML NB property in the cell or tissue to the level in a corresponding normal unstressed cell or tissue, wherein the greater the difference in the level of the at least one PML NB property in the stressed cell or tissue compared with the level in the cell or tissue before the stress, or with the level in a corresponding normal unstressed cell or tissue, the greater the response of the cell or tissue to the stress.
A method for monitoring oncogenesis and/or for assessing malignancy in a tissue in a subject, the method comprising determining the level of at least one PML NB property in the tissue, and comparing the level in the tissue to the level of the PML NB property in a control tissue, wherein a difference in the level of the property in the tissue of the subject relative to the level in the control tissue suggests increased oncogenesis and/or malignancy in the tissue of the subject.
Dependencies are inferred from the claim text.