Progastrin and liver pathologies
Progastrin levels are determined to diagnose one or more liver pathologies.
1. A method of diagnosing whether a subject suffers from liver cancer and at least one other liver pathology selected from hepatitis C and cirrhosis, comprising the steps of:
(a) identifying, using an anti-hPG antibody, whether said subject previously diagnosed with liver cancer has a serum or plasma human progastrin (hPG) concentration above a threshold value, where the threshold value is at least about 100 pM, and
(b) testing said patient for at least one other liver pathology selected from hepatitis C and cirrhosis,
thereby diagnosing whether the subject suffers from liver cancer and at least one other liver pathology selected from hepatitis C and cirrhosis.
2. The method of claim 1 , in which the threshold value is 400 pM.
3. The method of claim 1 , in which the threshold value is 500 pM.
4. A method of diagnosing whether a subject suffers from a combination of two or more liver pathologies selected from hepatitis C, cirrhosis, and liver cancer comprising the steps of:
(a) identifying, using a first anti-hPG antibody, whether said subject previously diagnosed with at least one liver pathology selected from hepatitis C, cirrhosis, and liver cancer has a serum or plasma human progastrin (hPG) concentration above a threshold value, where the threshold value is at least about 400 pM, and
(b) testing said patient for at least one other liver pathology selected from liver cancer, hepatitis C and cirrhosis,
thereby diagnosing whether the subject suffers from at least two liver pathologies selected from liver cancer, hepatitis C and cirrhosis.
5. The method of claim 4 , in which the threshold value is 400 pM.
6. The method of claim 4 , in which the threshold value is 500 pM.
7. The method of claim 4 , further comprising using a second antibody specific for a different epitope of hPG than the first antibody and determining the concentration of hPG based upon the amount of hPG bound by both antibodies.
8. The method of claim 7 , wherein at least one of said antibodies is coupled to a detectable marker.
9. The method of any one of claims 4 , 5 , and 7 , wherein said first anti-hPG antibody is a monoclonal antibody.
10. The method of claim 9 , wherein said first anti-hPG antibody binds a C-terminal epitope of hPG.
11. The method of claim 9 , wherein said first anti-hPG antibody binds an N-terminal epitope of hPG.
12. A method of diagnosing whether a subject suffers from a combination of liver cancer and at least one other liver pathology selected from hepatitis C and cirrhosis comprising the step of:
identifying, using a first anti-hPG antibody, whether said subject has a serum or plasma hPG concentration above a threshold value, where the threshold value is at least about 100 pM, wherein a serum concentration above the threshold value indicates that the subject suffers from a combination of liver cancer and at least one other liver pathology selected from hepatitis C and cirrhosis, and
wherein said anti-hPG antibody has a light chain CDR1 domain comprising the amino acid sequence of SEQ ID NO: 50, a light chain CDR2 domain comprising the amino acid sequence of SEQ ID NO: 53, a light chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 57, a heavy chain CDR1 domain comprising the amino acid sequence of SEQ ID NO: 39, a heavy chain CDR2 domain comprising the amino acid sequence of SEQ ID NO: 43, and a heavy chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 47.
13. A method of diagnosing whether a subject suffers from a combination of two or more liver pathologies selected from hepatitis C, cirrhosis, and liver cancer comprising the step of:
identifying, using a first anti-hPG antibody, whether said subject has a serum or plasma hPG concentration above a threshold value, where the threshold value is at least about 400 pM, wherein a serum concentration above the threshold indicates that the subject suffers from a combination of two or more liver pathologies selected from hepatitis C, cirrhosis, and liver cancer, and
wherein said anti-hPG antibody has a light chain CDR1 domain comprising the amino acid sequence of SEQ ID NO: 50, a light chain CDR2 domain comprising the amino acid sequence of SEQ ID NO: 53, a light chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 57, a heavy chain CDR1 domain comprising the amino acid sequence of SEQ ID NO: 39, a heavy chain CDR2 domain comprising the amino acid sequence of SEQ ID NO: 43, and a heavy chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 47.
14. The method of claim 12 or 13 , wherein said anti-hPG antibody is a Fab′, F(ab′) 2 , Fv, rIgG, or scFv.
15. The method of claim 12 or 13 , wherein said anti-hPG antibody is an IgA 1 , IgA 2 , IgD, IgE, IgG 1 , IgG 2 , IgG 3 , IgG 4 , or IgM.
16. The method of claim 15 , wherein said anti-hPG antibody is an IgG 1 .
17. The method of claim 12 or 13 , wherein said anti-hPG antibody is a monoclonal antibody.
18. The method of claim 17 , wherein said monoclonal anti-hPG antibody is a mouse monoclonal antibody.
19. The method of claim 18 , wherein said mouse monoclonal anti-hPG antibody has a light chain variable region comprising the amino acid sequence of SEQ ID NO: 65 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61.
20. The method of claim 17 , wherein said monoclonal anti-hPG antibody is a humanized monoclonal anti-hPG antibody.
21. The method of claim 20 , wherein said first anti-hPG antibody has a light chain variable region comprising the amino acid sequence of SEQ ID NO: 85 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 84.
22. The method of claim 20 , wherein said first anti-hPG antibody has a light chain variable region comprising the amino acid sequence of SEQ ID NO: 87 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 86.
23. The method of claim 20 , wherein said first anti-hPG antibody has a light chain variable region comprising the amino acid sequence of SEQ ID NO: 89 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 88.
24. The method of claim 12 or 13 , further comprising using a second antibody specific for a different epitope of hPG than the first antibody and determining the concentration of hPG based upon the amount of hPG bound by both antibodies.
25. The method of claim 12 or 13 , wherein said antibody is coupled to a detectable marker.
26. The method of claim 24 , wherein at least one of said antibodies is coupled to a detectable marker.
27. The method of claim 24 , wherein said second anti-hPG antibody binds a C-terminal epitope of hPG.
28. The method of claim 26 , wherein said detectable marker is horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase.
29. The method of claim 26 , wherein said detectable marker is umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluroescein, dansyl chloride, or phycoerythrin.
30. The method of claim 26 , wherein said detectable marker is luminol, luciferase, luciferin, or aequorin.
31. The method of claim 26 , wherein said detectable marker is 125 I, 131 I, 111 In, or 99 Tc.