Method of modulating or examining Ku70 levels in cells

• US 20030073661A1
• Filed: 09/19/2002
• Published: 04/17/2003
• Est. Priority Date: 09/24/2001
• Status: Abandoned Application

• Current Assignee: Blood Center Research Foundation
• Original Assignee: Blood Center Research Foundation
• Inventors: Sun, Weiyong, Matsuyama, Shigemi
• Application Number:
  US10/247,045
• Publication Number:
  US 20030073661A1
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/111 spanning the whole gene, or a large part of it
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

A method of predicting whether cells would respond to therapies which are mediated through Bax-regulated apoptosis is disclosed. In one embodiment, the method comprises the step of: (a) examining the intensity of the expression of the Bax protein or mRNA in a cell relative to a control, and (b) based on that intensity level, predicting whether cells will respond to therapies which are mediated through Bax-regulated apoptosis, wherein a high Bax level indicates that one may lower Ku70 levels and increase sensitivity to apoptosis. In another embodiment, the invention is a method of sensitizing cells to cancer therapy, comprising the step of reducing the cell'"'"'s native Ku70 protein level. In another embodiment the invention is method of treating cell death-related diseases comprising the step of increasing cellular Ku70 protein level.

Claims

1. A method of predicting whether cancer cells would respond to therapies which are mediated through Bax-regulated apoptosis, comprising the step of:

(a) examining the intensity of the expression of the Bax gene in cancer cells relative to a control, and (b) predicting whether the cells will respond to therapies which are mediated through Bax-regulated apoptosis, wherein a high Bax level indicates that one may lower Ku70 levels and increase sensitivity to apoptosis.

2. The method of claim 1 wherein one additionally examines the intensity of expression of the Ku70 gene in the cells.

3. The method of claim 2 wherein one examines the Bax and Ku70 protein level.

4. The method of claim 2 wherein one examines the Bax and Ku70 mRNA level.

5. A method of sensitizing cells to cancer therapy, comprising the step of reducing the cells'"'"' native Ku70 protein level sufficiently so that the cell is more sensitive to cancer therapy.

6. The method of claim 5 wherein the reduction is through antisense mRNA methods.

7. The method of claim 5 wherein the cells are selected from the group consisting of glioma cells, colon cancer cells, prostatic cancer cells, fibrosarcoma cells, and cervical cancer cells.

8. The method of claim 5 wherein the reduction is through inhibiting Ku70 gene transcription.

9. The method of claim 5 wherein the reduction is through the use of reversed full-length Ku70 RNA.

10. The method of claim 5 wherein the reduction is through the use of a plasmid encoding antisense Ku70 RNA.

11. The method of claim 5 wherein the reduction is through the use of a viral vector encoding antisense Ku70 RNA.

12. A method of treating cell death-related diseases comprising the step of increasing cellular Ku70 protein level in cells sufficiently so that the cells are more resistant to cytotoxic stimuli.

13. The method of claim 12 wherein the increase is via the introduction and expression of heterologous DNA sequences encoding Ku70 within the cells.

14. The method of claim 12 wherein the cells are selected from the group consisting of platelets, white blood cells and stem cells.

15. The method of claim 12 wherein the cells are part of an organ.

16. The method of claim 12 wherein the cells are within a human patient.