Compositions and Methods for Treating and Preventing Pancreatitis, Renal Injury and Cancer

Abstract

The present invention includes compositions and methods for detecting, treating and preventing renal and pancreatic diseases and disorders.

1 . A method of treating or preventing a renal disease or disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising at least one PMCA4b activator. 
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the PMCA4b activator is a renalase polypeptide. 
     
     
         4 . The method of  claim 3 , wherein the renalase polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 8 and SEQ ID NO: 9. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the PMCA4b activator is a renalase polypeptide fragment. 
     
     
         7 . The method of  claim 6 , wherein the renalase polypeptide fragment comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the at least one PMCA4b activator is administered one time or repeatedly. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the at least one PMCA4b activator is administered locally, regionally or systemically. 
     
     
         13 . The method of  claim 1 , wherein the PMCA4b activator is an activator of PMCA4b expression, an activator of PMCA4b activity, or a combination thereof. 
     
     
         14 . The method of  claim 1 , wherein the renal disease or disorder is selected from the group consisting of acute kidney injury (AKI), chronic kidney disease (CKD), renal ischemic injury, renal reperfusion injury, renal ischemic-reperfusion injury, toxic renal injury, renal tubular necrosis, renal tubular inflammation, renal tubular apoptosis, hypertension, and any combination thereof. 
     
     
         15 . (canceled) 
     
     
         16 . A method of treating or preventing cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising at least one PMCA4b inhibitor. 
     
     
         17 . The method of  claim 16 , wherein the PMCA4b inhibitor is at least one selected from the group consisting of a chemical compound, a protein, a peptide, a peptidomemetic, an antibody, a ribozyme, a small molecule chemical compound, and an antisense nucleic acid molecule. 
     
     
         18 . The method of  claim 16 , wherein the PMCA4b inhibitor is one selected from the group consisting of caloxin 1b and cisplatin. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 16 , wherein the cancer is selected from the group consisting of brain cancer, bladder cancer, breast cancer, cervical cancer, colorectal cancer, liver cancer, kidney cancer, lymphoma, leukemia, lung cancer, melanoma, metastatic melanoma, mesothelioma, neuroblastoma, ovarian cancer, prostate cancer, pancreatic cancer, renal cancer, skin cancer, thymoma, sarcoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, uterine cancer, and any combination thereof. 
     
     
         21 . (canceled) 
     
     
         22 . A method of treating or preventing a pancreatic disease or disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising at least one agent, wherein the at least one agent is at least one selected from the group consisting of a renalase polypeptide, a renalase polypeptide fragment, and an activator of renalase. 
     
     
         23 . The method of  claim 22 , wherein the renalase polypeptide is a recombinant renalase polypeptide. 
     
     
         24 . The method of  claim 22 , wherein the renalase polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 8 and SEQ ID NO: 9. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 22 , wherein the renalase polypeptide fragment comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5. 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 22 , wherein the activator of renalase is an activator of renalase expression, an activator of renalase activity, or a combination thereof. 
     
     
         33 . (canceled) 
     
     
         34 . The method of  claim 22 , wherein the pancreatic disease or disorder is at least one selected from the group consisting of acute pancreatitis and chronic pancreatitis. 
     
     
         35 . A method of diagnosing a pancreatic disease or disorder in a subject in need thereof, the method comprising:
 a. determining the level of renalase in a biological sample of the subject,   b. comparing the level of renalase in the biological sample of the subject with a comparator control, and   c. diagnosing the subject with a pancreatic disease or disorder when the level of renalase in the biological sample of subject is reduced when compared with the level of renalase of the comparator control.   
     
     
         36 . The method of  claim 35 , comprising the further step of administering a treatment to the subject that was diagnosed as having a pancreatic disease or disorder. 
     
     
         37 . The method of  claim 35 , wherein the level of renalase in the biological sample is determined by measuring at least one of the group consisting of the level of renalase mRNA in the biological sample, the level of renalase polypeptide in the biological sample, and an enzymatic activity of renalase polypeptide in the biological sample. 
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . The method of  claim 35 , wherein the comparator control is at least one selected from the group consisting of: a positive control, a negative control, a historical control, a historical norm, or the level of a reference molecule in the biological sample. 
     
     
         41 . The method of  claim 35 , wherein the pancreatic disease or disorder is at least one selected from the group consisting of acute pancreatitis and chronic pancreatitis. 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . (canceled) 
     
     
         46 . (canceled) 
     
     
         47 . (canceled) 
     
     
         48 . (canceled) 
     
     
         49 . (canceled)