Diagnosis and treatment of malignant neoplasms

Abstract

The invention features a method for diagnosing a malignant neoplasm in a mammal by contacting a bodily fluid from the mammal with an antibody which binds to an human aspartyl (asparaginyl) beta-hydroxylase (HAAH) polypeptide and methods of treating malignant neoplasms by inhibiting HAAH.

1 . An antisense sequence which is complementary to the 5′ portion of the AAH sequence comprising cggaccgtgca (nucleotides 1-11 of SEQ ID NO:3). 
     
     
         2 . A method of inhibiting tumor growth in a mammal, comprising administering to said mammal a compound which inhibits expression of alpha-ketoglutarate-dependent dioxygenase aspartyl (asparaginyl) beta-hydroxylase (AAH), wherein said compound is a nucleic acid comprising an antisense sequence which is complementary to the 5′ portion of the AAH sequence comprising cggaccgtgca (nucleotides 1-11 of SEQ ID NO:3) in a pharmaceutically acceptable carrier, said antisense sequence consisting of 10 nucleotides in length and wherein said tumor overexpresses AAH compared to normal noncancerous cells. 
     
     
         3 . The method of  claim 2 , wherein said tumor is derived from endodermal tissue. 
     
     
         4 . The method of  claim 2 , wherein said tumor is selected from colon cancer, breast cancer, pancreatic cancer, liver cancer, and cancer of the bile ducts. 
     
     
         5 . The method of  claim 2 , wherein said tumor is selected from a CNS tumor, a glioblastoma, a neuroblastoma, a cholangiocarcinoma, or a hepatocellular carcinoma. 
     
     
         6 . A method of inhibiting tumor growth in a mammal, comprising administering to said mammal a nucleic acid in a pharmaceutically acceptable carrier, wherein said nucleic acid comprises an antisense sequence which is complementary to a 5′ portion of the AAH sequence of SEQ ID NO:3 and comprises a sequence complementary to the initiating ATG methionine-encoding codon of said SEQ ID NO:3, said antisense sequence consisting of between 10-50 nucleotides, inclusive, in length and wherein said tumor overexpresses AAH compared to normal noncancerous cells. 
     
     
         7 . The method of  claim 6 , wherein said tumor is derived from endodermal tissue. 
     
     
         8 . The method of  claim 6 , wherein said tumor is selected from the group consisting of colon cancer, breast cancer, pancreatic cancer, liver cancer, and cancer of the bile duct. 
     
     
         9 . The method of  claim 6 , wherein said tumor is selected from a CNS tumor, a glioblastoma, a neuroblastoma, a cholangiocarcinoma, or a hepatocellular carcinoma. 
     
     
         10 . A method of inhibiting tumor growth in a mammal, comprising administering to said mammal a compound which inhibits expression of alpha-ketoglutarate-dependent dioxygenase aspartyl (asparaginyl) beta-hydroxylase (AAH) in a pharmaceutically acceptable carrier, wherein said compound is a nucleic acid comprising an antisense sequence which is complementary to the 5′ AAH sequence cggaccgtgca of SEQ ID NO:3, wherein said tumor overexpresses AAH compared to normal noncancerous cells, and wherein the length of said antisense sequence consists of between 10-50 nucleotides, inclusive. 
     
     
         11 . The method of  claim 10 , wherein the length of said antisense sequence consists of between 10-20 nucleotides, inclusive. 
     
     
         12 . The method of  claim 10 , wherein said antisense sequence comprises a portion that is complementary to a 5′ region of SEQ ID NO:3 which includes the ATG initiating methionine-encoding codon. 
     
     
         13 . The method of  claim 10 , wherein said antisense sequence consists of between 10-20 nucleotides in length, inclusive.