Claims
- 1. A method for predicting the response of a cancer cell to treatment with an NSAID comprising:
(a) providing a cancer cell; (b) contacting said cancer cell with an NSAID; and (c) determining the NSAID's effect on the expression of a plurality of NSAID-modulated genes, wherein an effect similar to that seen in NSAID-responsive cancer cells is predictive that said cancer cell also would be responsive to NSAID treatment.
- 2. The method of claim 1, wherein said cancer cell is selected from the group consisting of a brain cancer cell, a head & neck cancer cell, an esophageal cancer cell, a lung cancer cell, a thyroid cancer cell, a stomach cancer cell, a colon cancer cell, a liver cancer cell, a kidney cancer cell, a prostate cancer cell, a breast cancer cell, a cervical cancer cell, an ovarian cancer cell, a testicular cancer cell, a rectal cancer cell, a skin cancer cell or a blood cancer cell.
- 3. The method of claim 1, wherein said NSAID is a non-steroidal anti-inflammatory drug.
- 4. The method of claim 1, wherein said plurality of NSAID-modulated genes comprises at least one gene selected from the group consisting of the genes listed in Table 1 and Table 2.
- 5. The method of claim 4, wherein said plurality of NSAID-modulated genes comprises at least one gene selected from the group consisting of SEQ. ID. NO: 1, SEQ. ID. NO: 2, SEQ. ID. NO: 3, SEQ. ID. NO: 6, SEQ. ID. NO: 7, SEQ. ID. NO: 18, SEQ. ID. NO: 31, SEQ. ID. NO: 32, SEQ. ID. NO: 33, SEQ. ID. NO: 38, SEQ. ID. NO: 39, or SEQ. ID. NO: 42.
- 6. The method of claim 4, wherein the plurality comprises at least two genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 7. The method of claim 7, wherein the plurality comprises at least three genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 8. The method of claim 7, wherein the plurality comprises at least five genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 9. The method of claim 4, wherein the plurality comprises at least one gene that is not listed in Table 1 or Table 2.
- 10. The method of claim 1, wherein the plurality comprises at least one gene listed in Table 5.
- 11. The method of claim 1, wherein determining comprises quantitating a mRNA for NSAID-modulated genes.
- 12. The method of claim 11, wherein quantitating comprises Northern analysis.
- 13. The method of claim 11, wherein quantitating comprises densitometric scanning of a one- or two-dimensional gel.
- 14. The method of claim 11, wherein quantitating comprises nucleic acid amplification.
- 15. The method of claim 14, wherein nucleic acid amplification comprises quantitative RT-PCR.
- 16. The method of claim 11, wherein quantitating comprises nucleic acid hybrizidation.
- 17. The method of claim 14, wherein hybridization comprises a nucleic acid array.
- 18. The method of claim 17, wherein said nucleic acid array is disposed on a chip or wafer.
- 19. The method of claim 18, wherein said chip is a glass or membrane that carries nucleic acid.
- 20. The method of claim 1, wherein determining comprises quantitating NSAID-modulated polypeptides.
- 21. The method of claim 20, wherein quantitating comprises densitometric scanning of a one- or two-dimensional gel.
- 22. The method of claim 20, wherein quantitating comprises immunologic detection of said polypeptides.
- 23. The method of claim 22, wherein immunologic detection comprises Western blot, ELISA, or RIA.
- 24. The method of claim 1, wherein said cancer cell is obtained from a subject in need of cancer therapy.
- 25. The method of claim 24, further comprising treating said subject.
- 26. The method of claim 1, further comprising treating a cancer cell known to be responsive to said NSAID with said NSAID, and comparing the expression of the same plurality of NSAID-modulated genes with the results of step (c).
- 27. A method for predicting the efficacy of an NSAID in cancer therapy comprising:
(a) providing a cancer cell; (b) contacting said cancer cell with an NSAID; and (c) determining the NSAID's effect on the expression of a plurality of NSAID-modulated genes, wherein an effect similar to that seen in NSAID-responsive cancer cells treated with known cancer-therapeutic NSAIDs is predictive that said NSAID also would be efficacious in cancer therapy.
- 28. The method of claim 27, wherein said cancer cell is selected from the group consisting of a brain cancer cell, a head & neck cancer cell, an esophageal cancer cell, a lung cancer cell, a thyroid cancer cell, a stomach cancer cell, a colon cancer cell, a liver cancer cell, a kidney cancer cell, a prostate cancer cell, a breast cancer cell, a cervical cancer cell, an ovarian cancer cell, a testicular cancer cell, a rectal cancer cell, a skin cancer cell or a blood cancer cell.
- 29. The method of claim 27, wherein said NSAID is a non-steroidal anti-inflammatory drug.
- 30. The method of claim 27, wherein said plurality of NSAID-modulated genes are selected from the group consisting of the genes listed in Table 1 and Table 2.
- 31. The method of claim 30, wherein the plurality comprises at least one gene selected from the group consisting of the genes listed in Table 1 and Table 2.
- 32. The method of claim 31, wherein said plurality of genes comprises at least one gene selected from the group consisting of SEQ. ID. NO: 1, SEQ. ID. NO: 2, SEQ. ID. NO: 3, SEQ. ID. NO: 6, SEQ. ID. NO: 7, SEQ. ID. NO: 18, SEQ. ID. NO: 31, SEQ. ID. NO: 32, SEQ. ID. NO: 33, SEQ. ID. NO: 38, SEQ. ID. NO: 39, or SEQ. ID. NO: 42.
- 33. The method of claim 30, wherein the plurality comprises at least two genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 34. The method of claim 33, wherein the plurality comprises at least three genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 35. The method of claim 34, wherein the plurality comprises at least five genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 36. The method of claim 30, wherein the plurality comprises at least one gene that is not listed in Table 1 or Table 2.
- 37. The method of claim 27, wherein the plurality comprises at least one gene listed in Table 5.
- 38. The method of claim 27, wherein determining comprises quantitating a mRNA for NSAID-modulated genes.
- 39. The method of claim 38, wherein quantitating comprises Northern analysis.
- 40. The method of claim 38, wherein quantitating comprises densitometric scanning of a one- or two-dimensional gel.
- 41. The method of claim 38, wherein quantitating comprises nucleic acid amplification.
- 42. The method of claim 41, wherein nucleic acid amplification comprises quantitative RT-PCR.
- 43. The method of claim 38, wherein quantitating comprises nucleic acid hybrizidation.
- 44. The method of claim 41, wherein hybridization comprises a nucleic acid array.
- 45. The method of claim 44, wherein said nucleic acid array is disposed on a chip or wafer.
- 46. The method of claim 45, wherein said chip is a glass or membrane that carries nucleic acid.
- 47. The method of claim 27, wherein determining comprises quantitating NSAID-modulated polypeptides.
- 48. The method of claim 47, wherein quantitating comprises densitometric scanning of a one- or two-dimensional gel.
- 49. The method of claim 47, wherein quantitating comprises immunologic detection of said polypeptides.
- 50. The method of claim 49, wherein immunologic detection comprises Western blot, ELISA, or RIA.
- 51. The method of claim 27, wherein said cancer cell is obtained from a subject in need of cancer therapy.
- 52. The method of claim 51, further comprising treating said subject.
- 53. The method of claim 27, further comprising treating a cancer cell, known to be responsive to said NSAID, with said NSAID, and comparing the expression of the same plurality of NSAID-modulated genes with the results of step (c).
- 54. The method of claim 53, wherein the NSAID is aspirin, sulindac or celecoxib.
- 55. A method for treating a subject with cancer comprising administering to said subject a composition that modulates the levels of one or more of NSAID-modulated polypeptides.
- 56. The method of claim 55, wherein said composition increases the level of one or more of NSAID-stimulated polypeptides.
- 57. The method of claim 56, wherein said one or more NSAID-stimulated polypeptides are translation products of the NSAID-stimulated genes.
- 58. The method of claim 55, wherein said composition decreases the level of one or more of NSAID-inhibited polypeptides.
- 59. The method of claim 58, wherein said one or more NSAID-inhibited polypeptides are translation products of the NSAID-inhibited genes.
- 60. The method of claim 55, further comprising administering to said subject two compositions, wherein a first composition increases the level of one or more of NSAID-stimulated polypeptides, and a second composition decreases the level of one or more of NSAID-inhibited polypeptides.
- 61. The method of claim 55, wherein said cancer is selected from the group consisting of a brain cancer, a head & neck cancer, an esophageal cancer, a lung cancer, a thyroid cancer, a stomach cancer, a colon cancer, a liver cancer, a kidney cancer, a prostate cancer, a breast cancer, a cervical cancer, an ovarian cancer, a testicular cancer, a rectal cancer, a skin cancer or a blood cancer.
- 62. The method of claim 55, wherein said composition is an expression cassette comprising a nucleic acid encoding one of said NSAID-modulated polypeptides, and a promoter active cells of said subject.
- 63. The method of claim 62, wherein said nucleic acid encodes an NSAID-stimulated polypeptides and is positioned sense to said promoter.
- 64. The method of claim 62, wherein said nucleic acid encodes an NSAID-inhibited polypeptides and is positioned anti-sense to said promoter.
- 65. The method of claim 62, wherein said expression cassette is incorporated in non-viral expression vector.
- 66. The method of claim 62, wherein said expression cassette is incorporated in viral expression vector.
- 67. The method of claim 66, wherein said viral expression vector is an adenoviral expression vector, a herpesviral expression vector, a retroviral expression vector, a vaccinia viral expression vector, an adeno-associated viral expression vector or a polyoma viral expression vector.
- 68. The method of claim 62, wherein said promoter is a constitutive promoter, a tumor specific promoter or an inducible promoter.
- 69. The method of claim 62, wherein said expression cassette further comprises a polyadenylation signal.
- 70. The method of claim 58, wherein said composition is an expression cassette comprising a nucleic acid encoding ribozyme that cleaves the mRNA encoding one of said NSAID-inhibited polypeptides, and promoter active cells of said subject.
- 71. The method of claim 58, wherein said composition is an expression cassette comprising a nucleic acid encoding single chain antibody that binds one of said NSAID-inhibited polypeptides, and promoter active cells of said subject.
- 72. The method of claim 55, wherein said composition is a small molecule.
- 73. The method of claim 55, further comprising treating said subject with chemotherapy, radiotherapy, immunotherapy or surgery.
- 74. The method of claim 55, further comprising monitoring the level of one or more NSAID-modulated polypeptides or transcript.
- 75. A method of screening compounds for NSAID-like activity comprising:
(a) providing a cell; (b) contacting said cell with a candidate compound; and (c) determining the candidate compound's effect on the expression of a plurality of NSAID-modulated genes, wherein an effect similar to that seen in cells treated with known NSAIDs is predictive that said candidate compound exhibits NSAID-like activity.
- 76. The method of claim 75, wherein said plurality of NSAID-modulated genes are selected from the group consisting of the genes listed in Table 1 and Table 2.
- 77. The method of claim 76, wherein the plurality comprises at least one gene selected from the group consisting of the genes listed in Table 1 and Table 2.
- 78. The method of claim 77, wherein said plurality of genes comprises at least one gene selected from the group consisting of SEQ. ID. NO: 1, SEQ. ID. NO: 2, SEQ. ID. NO: 3, SEQ. ID. NO: 6, SEQ. ID. NO: 7, SEQ. ID. NO: 18, SEQ. ID. NO: 31, SEQ. ID. NO: 32, SEQ. ID. NO: 33, SEQ. ID. NO: 38, SEQ. ID. NO: 39, or SEQ. ID. NO: 42.
- 79. The method of claim 76, wherein the plurality comprises at least two genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 80. The method of claim 79, wherein the plurality comprises at least three genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 81. The method of claim 80, wherein the plurality comprises at least five genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 82. The method of claim 76, wherein the plurality comprises at least one gene that is not listed in Table 1 or Table 2.
- 83. The method of claim 75, wherein the plurality comprises at least one gene listed in Table 5.
- 84. The method of claim 75, further comprising determining the expression of a plurality of NSAID-modulated genes in the absence of said candidate compound.
- 85. The method of claim 75, further comprising determining the expression of a plurality of NSAID-modulated genes in a similar cell following treatment with a known NSAID.
- 86. The method of claim 75, wherein said cell is a cancer cell.
- 87. The method of claim 75, wherein determining comprises quantitating a mRNA for NSAID-modulated genes.
- 88. The method of claim 87, wherein quantitating comprises nucleic acid amplification.
- 89. The method of claim 87, wherein quantitating comprises, nucleic acid hybrizidation.
- 90. The method of claim 89, wherein hybridization comprises a nucleic acid array disposed on a chip or wafer.
- 91. The method of claim 87, wherein determining comprises quantitating NSAID-modulated polypeptides.
- 92. A nucleic acid array comprising a plurality of nucleic acid segments, each segment comprising at least 15 consecutive bases of a nucleic acid encoding a different NSAID-modulated polypeptide.
- 93. The nucleic acid array of claim 92, wherein said nucleic acid array is disposed on a chip or wafer.
- 94. The nucleic acid array of claim 92, wherein said plurality of NSAID-modulated genes are selected from the group consisting of the genes listed in Table I and Table 2.
- 95. The method of claim 94, wherein the plurality comprises at least one gene selected from the group consisting of the genes listed in Table 1 and Table 2.
- 96. The method of claim 95, wherein said plurality of genes comprises at least one gene selected from the group consisting of SEQ. ID. NO: 1, SEQ. ID. NO: 2, SEQ. ID. NO: 3, SEQ. ID. NO: 6, SEQ. ID. NO: 7, SEQ. ID. NO: 18, SEQ. ID. NO: 31, SEQ. ID. NO: 32, SEQ. ID. NO: 33, SEQ. ID. NO: 38, SEQ. ID. NO: 39, or SEQ. ID. NO: 42.
- 97. The method of claim 94, wherein the plurality comprises at least two genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 98. The method of claim 97, wherein the plurality comprises at least three genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 99. The method of claim 98, wherein the plurality comprises at least five genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 100. The method of claim 94, wherein the plurality comprises at least one gene that is not listed in Table 1 or Table 2.
- 101. The method of claim 92, wherein the plurality comprises at least one gene listed in Table 5.
- 102. A kit comprising a chip comprising a nucleic acid array comprising a plurality of nucleic acid segments, each segment comprising at least 15 consecutive bases of a nucleic acid encoding a different NSAID-modulated polypeptide.
- 103. The kit of claim 102, wherein said plurality of NSAID-modulated genes are selected from the group consisting of the genes listed in Table 1 and Table 2.
- 104. The method of claim 103, wherein the plurality comprises at least one gene selected from the group consisting of the genes listed in Table 1 and Table 2.
- 105. The method of claim 104, wherein said plurality of genes comprises at least one gene selected from the group consisting of SEQ. ID. NO: 1, SEQ. ID. NO: 2, SEQ. ID. NO: 3, SEQ. ID. NO: 6, SEQ. ID. NO: 7, SEQ. ID. NO: 18, SEQ. ID. NO: 31, SEQ. ID. NO: 32, SEQ. ID. NO: 33, SEQ. ID. NO: 38, SEQ. ID. NO: 39, or SEQ. ID. NO: 42.
- 106. The method of claim 103, wherein the plurality comprises at least two genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 107. The method of claim 108, wherein the plurality comprises at least three genes selected from the group consisting of the genes listed in Table 1 and Table 2.
- 108. The method of claim 107, wherein the plurality comprises at least five genes selected from the group consisting of the genes listed in Table I and Table 2.
- 109. The method of claim 103, wherein the plurality comprises at least one gene that is not listed in Table 1 or Table 2.
- 110. The method of claim 102, wherein the plurality comprises at least one gene listed in Table 5.
Parent Case Info
[0001] The present application claims priority to co-pending U.S. Provisional Patent Application Serial No. 60/308,370 filed on Jul. 27, 2001. The entire text of the above-referenced disclosure is specifically incorporated herein by reference without disclaimer. The government owns rights in the present invention pursuant to grant numbers DK47297, P0 CA77839, P30 CA68485 from United States Public Health Services.
Provisional Applications (1)
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Number |
Date |
Country |
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60308370 |
Jul 2001 |
US |