Claims
- 1. An isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof.
- 2. An isolated nucleic acid encoding a mammalian prostate cancer marker 1, and homologs, variants, mutants and fragments thereof.
- 3. The isolated nucleic acid of claim 1, wherein said nucleic acid shares greater than about 98% sequence identity with a nucleic acid encoding a human prostate cancer marker 1 (SEQ ID NO:1).
- 4. The isolated nucleic acid of claim 1, said nucleic acid further comprising a nucleic acid encoding a tag polypeptide covalently linked thereto.
- 5. The isolated nucleic acid of claim 4, wherein said tag polypeptide is selected from the group consisting of a myc tag polypeptide, a glutathione-S-transferase tag polypeptide, a green fluorescent protein tag polypeptide, a myc-pyruvate kinase tag polypeptide, a His6 tag polypeptide, an influenza virus hemagglutinin tag polypeptide, a flag tag polypeptide, and a maltose binding protein tag polypeptide.
- 6. The isolated nucleic acid of claim 1, said nucleic acid further comprising a nucleic acid encoding a promoter/regulatory sequence operably linked thereto.
- 7. A vector comprising a isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof.
- 8. The vector of claim 7, said vector further comprising a nucleic acid specifying a promoter/regulatory sequence operably linked thereto.
- 9. The vector of claim 8, wherein said isolated nucleic acid encoding a mammalian prostate cancer marker 1 is expressed when introduced into a cell.
- 10. A recombinant cell comprising an isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof.
- 11. A recombinant cell comprising the vector of claim 7.
- 12. A recombinant cell comprising the vector of claim 8.
- 13. An isolated nucleic acid complementary to an isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof, said complementary nucleic acid being in an antisense orientation.
- 14. The isolated nucleic acid of claim 13, wherein said isolated nucleic acid shares greater than about 98% identity with a nucleic acid complementary with a nucleic acid having the sequence of a human prostate cancer marker 1 (SEQ ID NO:1).
- 15. The isolated nucleic acid of claim 13, said isolated nucleic acid further comprising a nucleic acid specifying a promoter/regulatory sequence operably linked thereto.
- 16. The isolated nucleic acid of claim 15, wherein said isolated nucleic acid is expressed when introduced into a cell.
- 17. A vector comprising an isolated nucleic acid complementary to an isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof, said complementary nucleic acid being in an antisense orientation, wherein said isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof, shares greater than about 98% identity with a nucleic acid complementary with a nucleic acid having the sequence of a human prostate cancer marker 1 (SEQ ID NO:1).
- 18. A vector comprising an isolated nucleic acid complementary to an isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof, said complementary nucleic acid being in an antisense orientation, said isolated nucleic acid further comprising a nucleic acid specifying a promoter/regulatory sequence operably linked thereto, further wherein said isolated nucleic acid is expressed when introduced into a cell.
- 19. A recombinant cell comprising an isolated nucleic acid complementary to an isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof, said complementary nucleic acid being in an antisense orientation.
- 20. A recombinant cell comprising an isolated nucleic acid complementary to an isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof, said complementary nucleic acid being in an antisense orientation, wherein said isolated nucleic acid shares greater than about 98% identity with a nucleic acid complementary with a nucleic acid having the sequence of a human prostate cancer marker 1 (SEQ ID NO:1).
- 21. A recombinant cell comprising the vector of claim 17.
- 22. A recombinant cell comprising the vector of claim 18.
- 23. An isolated nucleic acid encoding a mammalian prostate cancer marker 1, wherein the amino acid sequence of said prostate cancer marker 1 shares greater than about 97% sequence identity with the amino acid sequence SEQ ID NO:2.
- 24. The nucleic acid of claim 23, said nucleic acid further comprising a nucleic acid encoding a tag polypeptide covalently linked thereto.
- 25. The nucleic acid of claim 24, wherein said tag polypeptide is selected from the group consisting of a myc tag polypeptide, a glutathione-S-transferase tag polypeptide, a green fluorescent protein tag polypeptide, a myc-pyruvate kinase tag polypeptide, a His6 tag polypeptide, an influenza virus hemagglutinin tag polypeptide, a flag tag polypeptide, and a maltose binding protein tag polypeptide.
- 26. The nucleic acid of claim 23, said nucleic acid further comprising a nucleic acid encoding a promoter/regulatory sequence operably linked thereto.
- 27. A vector comprising the nucleic acid of claim 23.
- 28. The vector of claim 27, said vector further comprising a nucleic acid specifying a promoter/regulatory sequence operably linked thereto.
- 29. The vector of claim 28, wherein said isolated nucleic acid encoding a mammalian prostate cancer marker 1 is expressed when introduced into a cell.
- 30. A recombinant cell comprising the isolated nucleic acid of claim 23.
- 31. A recombinant cell comprising the isolated nucleic acid of claim 24.
- 32. A recombinant cell comprising the vector of claim 27.
- 33. A recombinant cell comprising the vector of claim 28.
- 34. The recombinant cell of claim 33, wherein said vector is expressed when introduced into said cell.
- 35. An isolated nucleic acid complementary to the nucleic acid of claim 23, said complementary nucleic acid being in an antisense orientation.
- 36. The isolated nucleic acid of claim 35, said complementary nucleic acid further comprising a nucleic acid specifying a promoter/regulatory sequence operably linked thereto.
- 37. A vector comprising the isolated nucleic acid of claim 35.
- 38. A vector comprising the isolated nucleic acid of claim 36, wherein said isolated nucleic acid is expressed when introduced into a cell.
- 39. The isolated nucleic acid of claim 35, wherein said nucleic acid shares greater than about 98% identity with a nucleic acid complementary with a nucleic acid having the sequence of a human prostate cancer marker 1 (SEQ ID NO:1).
- 40. The isolated nucleic acid of claim 39, said isolated nucleic acid further comprising a nucleic acid specifying a promoter/regulatory sequence operably linked thereto.
- 41. A vector comprising the isolated nucleic acid of claim 39.
- 42. A vector comprising the isolated nucleic acid of claim 40.
- 43. The vector of claim 42, wherein said isolated nucleic acid is expressed when introduced into a cell.
- 44. A recombinant cell comprising the isolated nucleic acid of claim 39.
- 45. A recombinant cell comprising the isolated nucleic acid of claim 40.
- 46. The recombinant cell of claim 45, wherein said isolated nucleic acid is expressed in said cell.
- 47. An isolated polypeptide comprising a mammalian prostate cancer marker 1.
- 48. The isolated polypeptide of claim 47, wherein said mammalian prostate cancer marker 1 shares at least about 97% sequence identity with an amino acid of SEQ ID NO:2.
- 49. An isolated nucleic acid that specifically binds with a prostate cancer marker 1 polypeptide.
- 50. The isolated nucleic acid of claim 49, wherein said nucleic acid is a double-stranded DNA.
- 51. The isolated nucleic acid of claim 50, wherein said isolated nucleic acid comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence CACGGATG (SEQ ID NO:5), a nucleic acid sequence CACAATGA (SEQ ID NO:6), a nucleic acid sequence CACAATG (SEQ ID NO:7), and a nucleic acid sequence CACAATGTTTTTGT (SEQ ID NO:8).
- 52. An isolated nucleic acid that specifically binds with a mammalian leukemia cell break point cluster region binding protein.
- 53. The nucleic acid of claim 52, wherein said leukemia break point cluster region binding protein is selected from the group consisting of a Rag 1 protein and a Rag 2 protein.
- 54. The isolated nucleic acid of claim 53, wherein said isolated nucleic acid comprises a double-stranded DNA, said DNA comprising a nucleic acid sequence selected from the group consisting of a nucleic acid sequence CACGGATG (SEQ ID NO:5), and a nucleic acid sequence CACAATGA (SEQ ID NO:6).
- 55. An isolated nucleic acid that specifically binds with a prokaryotic break point cluster region binding protein.
- 56. The nucleic acid of claim 55, wherein said prokaryotic break point cluster region binding protein is selected from the group consisting of a RecA protein and a RecB protein.
- 57. The polypeptide of claim 47, wherein said polypeptide specifically binds with at least one of a nucleic acid selected from the group consisting of a nucleic acid consisting of the sequence CACGGATG (SEQ ID NO:5), a nucleic acid consisting of the sequence CACAATGA (SEQ ID NO:6), a nucleic acid consisting of the sequence CACAATG (SEQ ID NO:7), and a nucleic acid consisting of the sequence CACAATGTTTTTGT (SEQ ID NO:8).
- 58. An isolated enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a prostate cancer marker 1.
- 59. The isolated enzymatic nucleic acid of claim 58, said nucleic acid comprising a nucleic acid sequence selected from the group consisting of a sequence GATCTTCAGGCTAGCTACAACGAGTCCTTGA (SEQ ID NO:9), a sequence AAACTTTCGACGATCGCGTCTCATCAGAAGTCCCTA (SEQ ID NO:10), and a sequence GATCTAGGGACTTCTGATGAGACGCGATCGTCGAAA (SEQ ID NO:11).
- 60. An isolated enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a prostate cancer marker 1, wherein said nucleic acid encoding a prostate cancer marker 1 comprises a nucleic acid having the sequence SEQ ID NO:1, or a portion thereof.
- 61. A recombinant cell comprising the enzymatic nucleic acid of claim 60.
- 62. The enzymatic nucleic acid of claim 58, wherein said enzymatic nucleic acid comprises binding arms and further wherein said binding arms comprise a sequence complementary to SEQ ID NO:1, or a portion thereof.
- 63. The enzymatic nucleic acid of claim 58, said nucleic acid further comprising a nucleic acid specifying a promoter/regulatory sequence operably linked thereto.
- 64. A vector comprising the enzymatic nucleic acid of claim 58.
- 65. A vector comprising the enzymatic nucleic acid of claim 63.
- 66. The vector of claim 64, wherein said enzymatic nucleic acid is expressed when introduced into a cell.
- 67. The vector of claim 65, wherein said enzymatic nucleic acid is expressed when introduced into a cell.
- 68. A recombinant cell comprising the vector of claim 64.
- 69. A recombinant cell comprising the vector of claim 65.
- 70. The recombinant cell of claim 61, wherein said enzymatic nucleic acid is expressed therein.
- 71. The enzymatic nucleic acid of claim 60, wherein said enzymatic nucleic acid is in a hairpin motif.
- 72. The enzymatic nucleic acid of claim 60, wherein said enzymatic nucleic acid is in a hammerhead motif.
- 73. The enzymatic nucleic acid of claim 60, wherein said enzymatic nucleic acid comprises a stem II region of length greater than or equal to 2 base pairs.
- 74. An isolated enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a prostate cancer marker 1, wherein said nucleic acid encoding a prostate cancer marker 1 shares greater than about 98% sequence identity with a nucleic acid encoding a human prostate cancer marker 1 (SEQ ID NO:1).
- 75. A recombinant cell comprising the isolated nucleic acid of claim 74.
- 76. The recombinant cell of claim 75, wherein said isolated nucleic acid is expressed therein.
- 77. The enzymatic nucleic acid of claim 74, said enzymatic nucleic acid comprising binding arms wherein said binding arms comprise a sequence complementary to SEQ ID NO:1, or a portion thereof.
- 78. The enzymatic nucleic acid of claim 74, said nucleic acid further comprising a nucleic acid specifying a promoter/regulatory sequence operably linked thereto.
- 79. A vector comprising the enzymatic nucleic acid of claim 74.
- 80. A vector comprising the enzymatic nucleic acid of claim 78.
- 81. The vector of claim 79, wherein said enzymatic nucleic acid is expressed when introduced into a cell.
- 82. The vector of claim 80, wherein said enzymatic nucleic acid is expressed when introduced into a cell.
- 83. A recombinant cell comprising the vector of claim 79.
- 84. A recombinant cell comprising the vector of claim 80.
- 85. The recombinant cell of claim 84, wherein said enzymatic nucleic acid is expressed therein.
- 86. The enzymatic nucleic acid of claim 74, wherein said enzymatic nucleic acid is in a hairpin motif.
- 87. The enzymatic nucleic acid of claim 74, wherein said enzymatic nucleic acid is in a hammerhead motif.
- 88. The enzymatic nucleic acid of claim 74, wherein said enzymatic nucleic acid comprises a stem II region of length greater than or equal to 2 base pairs.
- 89. An isolated enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a prostate cancer marker 1, wherein the amino acid sequence of the prostate cancer marker 1 encoded by said nucleic acid encoding a prostate cancer marker 1 shares greater than about 97% sequence identity with the amino acid sequence SEQ ID NO:2.
- 90. A recombinant cell comprising the isolated enzymatic nucleic acid of claim 89.
- 91. The cell of claim 90, wherein said enzymatic nucleic acid is expressed therein.
- 92. The enzymatic nucleic acid of claim 89, wherein said enzymatic nucleic acid is in a hairpin motif.
- 93. The enzymatic nucleic acid of claim 89, wherein said enzymatic nucleic acid is in a hammerhead motif.
- 94. The enzymatic nucleic acid of claim 89, wherein said enzymatic nucleic acid comprises a stem II region of length greater than or equal to 2 base pairs.
- 95. An isolated enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a prostate cancer marker 1 consisting of a sequence selected from the group consisting of a sequence GATCTTCAGGCTAGCTACAACGAGTCCTTGA (SEQ ID NO:9), a sequence AAACTTTCGACGATCGCGTCTCATCAGAAGTCCCTA (SEQ ID NO:10), and a sequence GATCTAGGGACTTCTGATGAGACGCGATCGTCGAAA (SEQ ID NO:11).
- 96. A recombinant cell comprising the isolated nucleic acid of claim 95.
- 97. The cell of claim 96, wherein said isolated nucleic acid is expressed therein.
- 98. The enzymatic nucleic acid of claim 95, said enzymatic nucleic acid comprising binding arms wherein said binding arms comprise a sequence complementary to SEQ ID NO:1, or a portion thereof.
- 99. The enzymatic nucleic acid of claim 95, said nucleic acid further comprising a nucleic acid specifying a promoter/regulatory sequence operably linked thereto.
- 100. A vector comprising the enzymatic nucleic acid of claim 95.
- 101. A vector comprising the enzymatic nucleic acid of claim 99.
- 102. The vector of claim 100, wherein said enzymatic nucleic acid is expressed when introduced into a cell.
- 103. The vector of claim 100, wherein said enzymatic nucleic acid is expressed when introduced into a cell.
- 104. A recombinant cell comprising the vector of claim 100.
- 105. A recombinant cell comprising the vector of claim 101.
- 106. The enzymatic nucleic acid of claim 89, said enzymatic nucleic acid comprising binding arms wherein said binding arms comprise a sequence complementary to SEQ ID NO:1, or a portion thereof.
- 107. The enzymatic nucleic acid of claim 89, said nucleic acid further comprising a nucleic acid specifying a promoter/regulatory sequence operably linked thereto.
- 108. A vector comprising the enzymatic nucleic acid of claim 89.
- 109. A vector comprising the enzymatic nucleic acid of claim 107.
- 110. The vector of claim 108, wherein said enzymatic nucleic acid is expressed when introduced into a cell.
- 111. The vector of claim 109, wherein said enzymatic nucleic acid is expressed when introduced into a cell.
- 112. A recombinant cell comprising the vector of claim 108.
- 113. A recombinant cell comprising the vector of claim 109.
- 114. An antibody that specifically binds with a mammalian prostate cancer marker 1 polypeptide, or a fragment thereof.
- 115. The antibody of claim 114 wherein said antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a humanized antibody, a chimeric antibody, and a synthetic antibody.
- 116. A composition comprising an antibody that specifically binds with a mammalian prostate cancer marker 1 polypeptide, or a fragment thereof, and a pharmaceutically-acceptable carrier.
- 117. A composition comprising an isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof, and a pharmaceutically-acceptable carrier.
- 118. A composition comprising an isolated nucleic acid complementary to an isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof, said complementary nucleic acid being in an antisense orientation, and a pharmaceutically-acceptable carrier.
- 119. A composition comprising an isolated polypeptide comprising a mammalian prostate cancer marker 1, and a pharmaceutically-acceptable carrier.
- 120. A composition comprising an isolated nucleic acid that specifically binds with a prostate cancer marker 1 polypeptide and a pharmaceutically-acceptable carrier.
- 121. A composition comprising an isolated enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a prostate cancer marker 1, and a pharmaceutically-acceptable carrier.
- 122. A composition comprising an antibody that specifically binds with a mammalian prostate cancer marker 1 polypeptide, or a fragment thereof, and a pharmaceutically-acceptable carrier.
- 123. A transgenic non-human mammal comprising an isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof.
- 124. A transgenic non-human mammal comprising an isolated enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a prostate cancer marker 1.
- 125. A transgenic non-human mammal comprising an isolated nucleic acid complementary to an isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof, said complementary nucleic acid being in an antisense orientation.
- 126. A method of treating a disease mediated by mal-expression of a prostate cancer marker 1 in a mammal, said method comprising administering to a human afflicted with a disease mediated by mal-expression of a prostate cancer marker 1 expression-inhibiting amount of at least one substance selected from the group consisting of an isolated nucleic acid complementary to an isolated nucleic acid encoding a mammalian prostate cancer marker 1, or a fragment thereof, an isolated enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a prostate cancer marker 1, and an antibody that specifically binds with a mammalian prostate cancer marker 1.
- 127. The method of claim 126, wherein said disease is prostate cancer.
- 128. The method of claim 127, wherein said mammal is selected from the group consisting of a human and a dog.
- 129. The method of claim 127, further comprising administering an enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a polypeptide selected from a group consisting of a vascular epithelial growth factor 1 (VEGF-1) and a metalloproteinase 2 (MMP-2).
- 130. A method of diagnosing prostate cancer in a mammal, said method comprising obtaining a biological sample from said mammal, assessing the level of PCAM-1 in said biological sample, and comparing the level of PCAM-1 in said biological sample with the level of PCAM-1 in a biological sample obtained from a like mammal not afflicted with prostate cancer, wherein a higher level of PCAM-1 in said biological sample from said mammal compared with the level of PCAM-1 in said biological sample from said like mammal is an indication that said mammal is afflicted with prostate cancer, thereby diagnosing prostate cancer in said mammal.
- 131. The method of claim 130, wherein said mammal is selected from the group consisting of a human and a dog.
- 132. The method of claim 130, wherein said biological sample is selected from the group consisting of a prostate tissue sample, a blood sample, a urine sample, a sputum sample, a peritoneal cavity fluid sample, a perineal cavity fluid sample, a pleural cavity fluid sample, a semen sample, a prostatic fluid sample, a stool sample, and a bone marrow sample.
- 133. A method of diagnosing prostate cancer in a mammal, said method comprising obtaining a biological sample from said mammal, assessing the level of antibody that specifically binds with prostate cancer marker 1 in said biological sample, and comparing the level of antibody that specifically binds with prostate cancer marker 1 in said biological sample with the level of antibody that specifically binds with prostate cancer marker 1 in a biological sample obtained from a like mammal not afflicted with prostate cancer, wherein a higher level of antibody that specifically binds with prostate cancer marker 1 in said biological sample from said mammal compared with the level of antibody that specifically binds with prostate cancer marker 1 in said biological sample from said like mammal is an indication that said mammal is afflicted with prostate cancer, thereby diagnosing prostate cancer in a mammal.
- 134. The method of claim 133, wherein said mammal is selected from the group consisting of a human and a dog.
- 135. The method of claim 133, wherein said biological sample is selected from the group consisting of a prostate tissue sample, a blood sample, a urine sample, a sputum sample, a peritoneal cavity fluid sample, a perineal cavity fluid sample, a pleural cavity fluid sample, a semen sample, a prostatic fluid sample, a stool sample, and a bone marrow sample.
- 136. A method of identifying a test compound that affects expression of prostate cancer marker 1 in a cell, said method comprising contacting a cell with a test compound and comparing the level of prostate cancer marker 1 expression in said cell with the level of prostate cancer marker 1 expression in an otherwise identical cell not contacted with said test compound, wherein a higher or lower level of prostate cancer marker 1 expression in said cell contacted with said test compound compared with the level of prostate cancer marker 1 expression in said otherwise identical cell not contacted with said test compound is an indication that said test compound affects expression of prostate cancer marker 1 in a cell.
- 137. A compound identified by the method of claim 136.
- 138. A method of identifying a compound that reduces expression of prostate cancer marker 1 in a cell, said method comprising contacting a cell with a test compound and comparing the level of prostate cancer marker 1 expression in said cell with the level of prostate cancer marker 1 expression in an otherwise identical cell not contacted with said test compound, wherein a lower level of prostate cancer marker 1 expression in said cell contacted with said test compound compared with the level of prostate cancer marker 1 expression in said otherwise identical cell not contacted with said test compound is an indication that said test compound reduces expression of prostate cancer marker 1 in a cell.
- 139. A compound identified by the method of claim 138.
- 140. A method of identifying a compound that increases expression of prostate cancer marker 1 in a cell, said method comprising contacting a cell with a test compound and comparing the level of prostate cancer marker 1 expression in said cell with the level of prostate cancer marker 1 expression in an otherwise identical cell not contacted with said test compound, wherein a higher level of prostate cancer marker 1 expression in said cell contacted with said test compound compared with the level of prostate cancer marker 1 expression in said otherwise identical cell not contacted with said test compound is an indication that said test compound increases expression of prostate cancer marker 1 in a cell.
- 141. A compound identified by the method of claim 140.
- 142. A method of identifying a compound that affects binding of a prostate cancer marker 1 with a double-stranded nucleic acid that specifically binds with prostate cancer marker 1, said method comprising comparing the level of prostate cancer marker 1 binding with a double-stranded nucleic acid that specifically binds with a prostate cancer marker 1 in the presence of a compound with the level of prostate cancer marker 1 binding with said double-stranded nucleic acid that specifically binds with a prostate cancer marker 1 in the absence of said compound, wherein a higher or lower level of prostate cancer marker 1 binding with said double-stranded nucleic acid that specifically binds with a prostate cancer marker 1 in the presence of said compound compared with the level of prostate cancer marker 1 binding with said double-stranded nucleic acid that specifically binds with a prostate cancer marker 1 in the absence of said compound is an indication that said compound affects binding of a prostate cancer marker 1 with a double-stranded nucleic acid that specifically binds with prostate cancer marker 1, thereby identifying a compound that affects binding of a prostate cancer marker 1 with a double-stranded nucleic acid that specifically binds with prostate cancer marker 1.
- 143. The method of claim 142, wherein said double-stranded nucleic acid that specifically binds with prostate cancer marker 1 has a sequence selected from the group consisting of a sequence CACGGATG (SEQ ID NO:5), a sequence CACAATGA (SEQ ID NO:6), a sequence CACAATG (SEQ ID NO:7), and a sequence CACAATGTTTTTGT (SEQ ID NO:8).
- 144. The method of claim 142, wherein said prostate cancer marker 1 has a sequence that shares greater than about 97% amino acid homology with a sequence SEQ ID NO:2.
- 145. A compound identified by the method of claim 144.
- 146. A method of monitoring the treatment of a human having prostate cancer, said method comprising:
(a) assessing the level of prostate cancer marker 1 in a first biological sample obtained from said human to determine an initial level of prostate cancer marker 1; (b) administering an anti-prostate cancer therapy to said human; (c) assessing the level of prostate cancer marker 1 in a second otherwise identical biological sample obtained from said human during or after said therapy; (d) comparing said level of prostate cancer marker 1 in said first biological sample with said level of prostate cancer marker 1 in said second biological sample; and (e) correlating any reduction in level of prostate cancer marker 1 with the effectiveness of said anti-prostate cancer therapy, thereby monitoring the treatment of a human having prostate cancer.
- 147. The method of claim 146, said method further comprising repeating (b) through (e) during the course of said human's illness, anti-prostate cancer therapy, or any period or portion thereof.
- 148. The method of claim 146, wherein said level of prostate cancer marker 1 is assessed using a method selected from the group consisting of a method of detecting a nucleic acid encoding a prostate cancer marker 1, and a method of detecting a prostate cancer marker 1.
- 149. The method of claim 146, wherein said method of detecting a prostate cancer marker 1 is selected from the group consisting of a method of detecting an antibody that specifically binds with a prostate cancer marker 1, and a method of detecting binding of a double-stranded nucleic acid that specifically binds with a prostate cancer maker 1 wherein said nucleic acid is selected from the group consisting of a nucleic acid having the sequence SEQ ID NO:5, a nucleic acid having the sequence SEQ ID NO:6, a nucleic acid having the sequence SEQ ID NO:7, and a nucleic acid having the sequence SEQ ID NO:8.
- 150. A kit for alleviating a disease mediated by mal-expression of prostate cancer marker 1 in a mammal, said kit comprising a prostate cancer marker 1 expression-inhibiting amount of at least one molecule selected from the group consisting of an antibody that specifically binds with prostate cancer marker 1, an isolated nucleic acid complementary to a nucleic acid encoding a prostate cancer marker 1, said complementary nucleic acid being in an antisense orientation, and an isolated enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a prostate cancer marker 1, said kit further comprising an applicator, and an instructional material for the use thereof.
- 151. The kit of claim 150, wherein said disease is prostate cancer.
- 152. The kit of claim 150, wherein said isolated enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a prostate cancer marker 1 comprises a sequence selected from the group consisting of a sequence GATCTTCAGGCTAGCTACAACGAGTCCTTGA (SEQ ID NO:9), a sequence AAACTTTCGACGATCGCGTCTCATCAGAAGTCCCTA (SEQ ID NO:10), and a sequence GATCTAGGGACTTCTGATGAGACGCGATCGTCGAAA (SEQ ID NO:11).
- 153. The kit of claim 150, further comprising an enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a polypeptide selected from a group consisting of a vascular epithelial growth factor 1 (VEGF-1) and a metalloproteinase 2 (MMP-2).
- 154. A kit for treating a disease mediated by mal-expression of prostate cancer marker 1 in a mammal, said kit comprising a prostate cancer marker 1 expression-inhibiting amount of at least one molecule selected from the group consisting of an antibody that specifically binds with prostate cancer marker 1, an isolated nucleic acid complementary to a nucleic acid encoding a prostate cancer marker 1, said complementary nucleic acid being in an antisense orientation, and an isolated enzymatic nucleic acid which specifically cleaves RNA transcribed from a nucleic acid encoding a prostate cancer marker 1, said kit further comprising an applicator, and an instructional material for the use thereof.
- 155. A kit for assessing the level of prostate cancer marker 1 in a sample, said kit comprising a molecule that specifically binds with prostate cancer marker 1 polypeptide or with nucleic acid encoding a prostate cancer marker 1, said kit further comprising an applicator, and an instructional material for the use thereof.
- 156. The kit of claim 155, wherein said molecule that specifically binds with a prostate cancer marker 1 polypeptide is selected from the group consisting of an antibody that specifically binds with prostate cancer marker 1, and a double-stranded nucleic acid that specifically binds with prostate cancer marker 1.
- 157. The kit of claim 155, wherein said nucleic acid encoding prostate cancer marker 1 shares greater than about 98% sequence identity with a nucleic acid having the sequence SEQ ID NO:1.
- 158. The kit of claim 157, wherein said prostate cancer marker 1 polypeptide shares greater than about 97% sequence identity with an amino acid sequence SEQ ID NO:2.
- 159. The kit of claim 156, wherein said double-stranded nucleic acid that specifically binds with prostate cancer marker 1 comprises a sequence selected from the group consisting of a sequence CACGGATG (SEQ ID NO:5), a sequence CACAATGA (SEQ ID NO:6), a sequence CACAATG (SEQ ID NO:7), and a sequence CACAATGTTTTTGT (SEQ ID NO:8).
- 160. A kit for detecting prostate cancer marker 1 in a mammal, said kit comprising a molecule that specifically binds with prostate cancer marker 1 polypeptide or with a nucleic acid encoding a prostate cancer marker 1, said kit further comprising an applicator, and an instructional material for the use thereof.
- 161. The kit of claim 160, wherein said mammal is selected from the group consisting of a dog and a human.
- 162. The kit of claim 160, wherein said molecule that specifically binds with a prostate cancer marker 1 polypeptide is selected from the group consisting of an antibody that specifically binds with a prostate cancer marker 1, and a double-stranded nucleic acid that specifically binds with prostate cancer marker 1.
- 163. The kit of claim 162, wherein said double-stranded nucleic acid that specifically binds with prostate cancer marker 1 comprises a sequence selected from the group consisting of a sequence CACGGATG (SEQ ID NO:5), a sequence CACAATGA (SEQ ID NO:6), a sequence CACAATG (SEQ ID NO:7), and a sequence CACAATGTTTTTGT (SEQ ID NO:8).
- 164. The kit of claim 160, wherein said molecule that specifically binds with a nucleic acid encoding a prostate cancer marker 1 is selected from the group consisting of a nucleic acid complementary with a nucleic acid sharing greater than 98% sequence identity with sequence SEQ ID NO:1.
- 165. A Monte Carlo-like screening assay for identification of a double-stranded oligonucleotide that specifically binds with a DNA-binding protein, said assay comprising
(a) producing a semi-random double stranded oligonucleotide set wherein each double-stranded oligonucleotide comprises a random core nucleotide sequence flanked by a known sequence comprising at least two basepairs; and (b) detecting any oligonucleotide member of said set that specifically binds with a DNA-binding protein, thereby identifying a double-stranded oligonucleotide that specifically binds with a DNA-binding protein.
- 166. The assay of claim 165, wherein said detecting of (b) comprises a method selected from the group consisting of an electrophoretic mobility shift assay and a method of detecting a double-stranded oligonucleotide bound with a polypeptide.
- 167. The assay of claim 165, wherein said random core nucleotide sequence comprises from about 3 to 12 basepairs.
- 168. The assay of claim 165, wherein said double-stranded oligonucleotide ranges in length from about 7 to 16 basepairs.
- 169. The assay of claim 167, wherein said random core nucleotide sequence comprises a length selected from the group consisting of 7 basepairs, 8 basepairs, and 9 basepairs.
- 170. The assay of claim 165, said assay further comprising
(c) identifying the sequence of the double-stranded oligonucleotide that binds with the greatest affinity with a DNA-binding protein; (d) producing a semi-random double stranded oligonucleotide set wherein each double-stranded oligonucleotide consists of the known flanking sequence identified in (c), said oligonucleotide further comprising an additional known such that the unknown random core sequence consists of one less unknown basepair than the sequence identified in (c), and repeating (b) and (c).
- 171. The assay of claim 170, said assay further comprising repeating steps (c), (b) and (c) until the entire sequence of the double-stranded oligonucleotide that binds with the greatest affinity with a DNA-binding protein is identified.
- 172. An isolated double-stranded oligonucleotide that specifically binds with a DNA-binding protein identified by the assay of claim 165.
- 173. A method of identifying a double stranded-oligonucleotide that specifically binds with a DNA-binding protein associated with a tumor, said method comprising
(a) producing a semi-random double-stranded oligonucleotide set wherein each double-stranded oligonucleotide comprises a random core nucleotide sequence flanked by a known sequence comprising at least two basepairs; (b) mixing a double-stranded oligonucleotide member of said set with a sample containing a mixture comprising DNA-binding proteins prepared from a tumor cell or tissue under conditions in which one or more of said double-stranded oligonucleotides in said set specifically binds a DNA-binding protein; (c) mixing an identical double-stranded oligonucleotide member of said set with an otherwise identical sample containing a mixture comprising DNA-binding proteins prepared from an otherwise identical cell or tissue not comprising a tumor under conditions in which one or more of said double-stranded oligonucleotides in said set specifically binds with a DNA-binding protein; (d) detecting any specific oligonucleotide-protein binding in (a) and (b); and (e) identifying any double-stranded oligonucleotide that specifically binds with a DNA-binding protein in (b) but which does not specifically bind with a DNA-binding protein in (c), thereby identifying a double-stranded oligonucleotide that specifically binds with a DNA-binding protein associated with a tumor.
- 174. An isolated double-stranded oligonucleotide identified by the method of claim 173.
- 175. The method of claim 173, wherein said detecting of (d) comprises a method selected from the group consisting of an electrophoretic mobility shift assay and a method of detecting a labeled double-stranded oligonucleotide bound with a polypeptide.
- 176. The method of claim 173, wherein said random core nucleotide sequence comprises from about 3 to 12 basepairs.
- 177. The method of claim 173, wherein said double-stranded oligonucleotide ranges in length from about 7 to 16 basepairs.
- 178. The method of claim 176, wherein said random core nucleotide sequence comprises a length selected from the group consisting of 7 basepairs, 8 basepairs, and 9 basepairs.
- 179. The method of claim 173, said method further comprising
(f) identifying the sequence of the double-stranded oligonucleotide that binds with the greatest affinity with a DNA-binding protein in (e); (g) producing a semi-random double stranded oligonucleotide set wherein each double-stranded oligonucleotide consists of the known flanking sequence identified in (f), said oligonucleotide further comprising an additional known basepair adjacent to said unknown random core sequence such that said unknown random core sequence consists of one less unknown basepair than the sequence identified in (f); and (h) repeating (b) and (e).
- 180. The method of claim 179, said method further comprising repeating (b) through (h) until the entire sequence of the double-stranded oligonucleotide that binds with the greatest affinity with a DNA-binding protein is identified.
- 181. A Monte Carlo-like screening assay for identification of a double-stranded DNA-binding protein, said assay comprising
(a) producing a semi-random double stranded oligonucleotide set wherein each double-stranded oligonucleotide comprises a random core nucleotide sequence flanked by a known sequence comprising at least two basepairs; and (b) detecting any DNA-binding protein that specifically binds with an oligonucleotide member of said set, thereby identifying a double-stranded DNA-binding protein.
- 182. The assay of claim 181, wherein said detecting of (b) comprises a method selected from the group consisting of an electrophoretic mobility shift assay and a method of detecting a double-stranded oligonucleotide bound with a polypeptide.
- 183. The assay of claim 181, wherein said random core nucleotide sequence comprises from about 3 to 12 basepairs.
- 184. The assay of claim 181, wherein said double-stranded oligonucleotide ranges in length from about 7 to 16 basepairs.
- 185. The assay of claim 184, wherein said random core nucleotide sequence comprises a length selected from the group consisting of 7 basepairs, 8 basepairs, and 9 basepairs.
- 186. The assay of claim 181, said assay further comprising
(c) identifying the sequence of the double-stranded oligonucleotide that binds with the greatest affinity with a DNA-binding protein; (d) producing a semi-random double stranded oligonucleotide set wherein each double-stranded oligonucleotide consists of said known flanking sequence identified in (c), said oligonucleotide further comprising an additional known such that the unknown random core sequence consists of one less unknown basepair than the sequence identified in (c), and repeating (b) and (c).
- 187. The assay of claim 186, said assay further comprising repeating steps (c), (b) and (c) until the entire sequence of the double-stranded oligonucleotide that binds with the greatest affinity with a DNA-binding protein is identified.
- 188. An isolated double-stranded DNA-binding protein identified by the assay of claim 181.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation-in-part of PCT Application No. PCT/US00/25981, filed on Sep. 24, 2000, which is entitled to priority under 35 U.S.C. §119(e), to U.S. Provisional Application No. 60/155,865, filed on Sep. 24, 1999, all of which are hereby incorporated by reference in their entirety herein.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] This invention was supported in part by funds from the U.S. Government (National Institutes of Health—National Cancer Institutes Grant No. RFA CA99-007) and the U.S. Government may therefore have certain rights in the invention.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60155865 |
Sep 1999 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
PCT/US00/25981 |
Sep 2000 |
US |
Child |
09813380 |
Mar 2001 |
US |