Methods for Identifying Fragile Histidine Triad (FHIT) Interaction and Uses Thereof

Abstract

Provided herein are methods and compositions for the diagnosis, prognosis and treatment of a cancer associated disorders using the Fhit gene.

What is claimed is: 
     
         1 . A method of sensitizing at least one cell to a chemotherapeutic agent comprising:
 exposing the at least one cell to an exogenous fragile histidine triad (Fhit) gene product in an amount sufficient to sensitize the at least one cell; and thereafter,   administering a chemotherapeutic agent to the at least one sensitized cell.   
     
     
         2 . The method of  claim 1 , wherein the cell is a cancer cell. 
     
     
         3 . The method of  claim 2 , wherein the cancer cell comprises one or more of: a lung cancer cell, a colon cancer cell, or a gastric cancer cell. 
     
     
         4 . The method of  claim 1 , wherein the cell is a human cell. 
     
     
         5 . The method of  claim 1 , wherein the chemotherapeutic agent comprises one or more of: paclitaxel or cisplatin. 
     
     
         6 . The method of  claim 1 , wherein the Fhit gene product comprises Fhit-His6. 
     
     
         7 . The method of  claim 3 , wherein the Fhit-His6, comprises an adenovirus carrying a FHIT-His6 cDNA. 
     
     
         8 . The method of  claim 1 , wherein the Fhit gene product comprises a recombinant adenovirus carrying fragile histidine triad (Fhit) FHIT cDNA modified at its 3′ with a sequence encoding a histidine-six epitope tag (AdFHIT-His6). 
     
     
         9 . The method of  claim 1 , wherein the amount of Fhit gene product is administered in an amount sufficient to mediate an apoptotic process in the cell. 
     
     
         10 . The method of  claim 1 , wherein the amount of Fhit gene product is administered in an amount sufficient to cause generation of reactive oxygen species (ROS) in the cell. 
     
     
         11 . The method of  claim 1 , wherein the amount of Fhit gene product is administered to a sufficient amount to:
 allow the Fhit gene product to enter mitochondria in the cell;   interact with Fdxr protein in the cell;   cause an increase in Fdxr protein level in the cell that is associated with generation of reactive oxygen species (ROS); and/or,   cause a change in an apoptotic process in the cell.   
     
     
         12 . A pharmaceutical composition for treating a cancer associated disorder, comprising at least one isolated Fhit gene product, and a pharmaceutically-acceptable carrier. 
     
     
         13 . The pharmaceutical composition of  claim 12 , further comprising at least one chemotherapeutic composition present in a dosage form that contacts at least one cell at a time subsequent to the at least one isolated Fhit gene product. 
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the chemotherapeutic composition comprises one or more of: paclitaxel or cisplatin. 
     
     
         15 . The pharmaceutical composition of  claim 14 , the paclitaxel is present in an amount between about 50 ng/ml to about 500 ng/ml. 
     
     
         16 . The pharmaceutical composition of  claim 14 , the paclitaxel is present in an amount of: 50 ng/ml, 100 ng/ml, or 500 ng/ml. 
     
     
         17 . The pharmaceutical composition of  claim 14 , wherein the cisplatin is present in an amount between about 0.05 mM to about 0.2 mM. 
     
     
         18 . The pharmaceutical composition of  claim 14 , the cisplatin is present in an amount of: 0.05 mM, 0.1 mM, or 0.2 mM. 
     
     
         19 . The pharmaceutical composition of  claim 14 , wherein the cancer comprises one or more of: a lung cancer, a colon cancer, or a gastric cancer.