Treatment targeting oncology and neurodegeneration

Abstract

The present invention relates to the field of medicine and biology. It concerns a new test for screening and therapeutic follow-up in oncology. More particularly, it relates to diagnostic and/or therapeutic tests in oncology and on neurodegenerative diseases. Molecular targeting by peptide vectors and antibodies or by small interfering RNAs (siRNAs) opens a new concept of interdependence for diagnostic and therapeutic tools.

1 . A Human Liv 21 complex characterized in that it comprises:
 a nucleotide sequences selected from SEQ ID N° 171 to 175 and SEQ ID 217 an siRNA sequence derived from one of the RNA sequences seq120 and 121 and 171 to 175 and all siRNA sequences (SEQ ID 91 to 118) a protein fraction comprising at least sequence SEQ ID 1 to 181 or a sequence having 90%, and preferably 80%, and more preferably 70% identity with said SEQ ID 1 to 181 and SEQ ID N° 183 and SEQ ID N° 215 to 220 or a sequence having 70, 80 or 90% identity with said sequence SEQ ID 183 and 215 to 220 and SEQ ID 230.   
     
     
         2 . Liv 21 human complex according to  claim 1 , further comprising:
 A nucleotide sequences SEQ ID N° 123, 124, 127 and the protein fractions comprising at least sequence SEQ ID No. 1 or a sequence having 70, 80 or 90% identity with said sequence SEQ ID N° 1 and the sequences 181 to 185.   
     
     
         3 . The Liv21 human complex according to  claim 1  further comprising: The nucleotide sequences of any one or ribonucleotide sequence SEQ ID N° 119 to 126 or 127, or a sequence having 90%, and preferably 80%, and more preferably 70% identity with said sequence SEQ ID N° 119 to 127, or sequence having 90%, and preferably 80%, and more preferably 70% identity with said sequence SEQ ID N° 119 to 127, or UUGGUAACGACCAUGCCAC or UUCACUUAGAAUAAUGUCC or UCUUUGUGAAUUUGACAAC or UCAAGGUCCAGGCUACAAC or
 any of the following siRNA sequences SEQ ID IN° 60 to 88 and 92 to 118, and 
 
       
         
           
                 
                 
               
                     
                   GUGGCAUGGUCGUUACCAA dTdT 
                 
                     
                     
                 
                     
                   DTdT CACCGUACCAGCAAUGGUU 
                 
                     
                     
                 
                     
                   GGACAUUAUUCUAAGUGAA dTdT 
                 
             
                
                
                
                
                
               
            
           
         
       
     
     
         4 . Liv21 human complex according to  claim 1 , further comprising at least one of:
 Any one of the nucleotide sequences SEQ ID No. 123, 124 and SEQ ID N° 127 to 149 or   Any one of amino acid sequences SEQ ID N° 1 to 118 and SEQ ID N° 150 to 170 and SEQ ID N° 180 to 185: or a sequence having 90%, and preferably 80%, and more preferably 70% identity with said sequences SEQ ID N°: 1 to 185.   
     
     
         5 . Liv21 human complex according to  claim 1 , characterized in that it interacts with at least one associated partners, said at least one associated partners being selected from the group consisting of; any of the following proteins: RBP2, TNF alpha crb2, cmd2, cycE/cdk2, cdk1, CREB1 and p300, Rb, p107, p130 of family of pocket proteins, NFkB, cdc2A, mdm2, p21, p53, p65, p′73, CyclinA and D1, BCAS3, BCAS4, Solute Carrier; or a antibody of any one of the following proteins: RBP2, E2F4, E2F1, E2F2, SUMO, HDAC1, crb2, Int2, cmd2, cycE/cdk2, cdk1, CREB1 and p300, Rb, p107, p130 of family of pocket proteins, NFkB, cdc2A, mdm2, p21, p53, p65, Ki67, CAF1, CyclinA and D1, CHUK, BCAS3, BCAS4,Solute Carrier. 
     
     
         6 . A method of detecting the complex human Liv21, characterized in that it comprises the implementation of at least one probe specific for at least one sequence of said human Liv21 complex selected from:
 a nucleotide sequences selected from SEQ ID NO: 171 to 175 and. SEQ ID NO: 217   a siRNA sequence derived from one of the RNA sequences SEQ ID NO: 120 and SEQ ID NO: 121 and SEQ ID NO: 171 to 175 and all siRNA sequences (SEQ ID NO: 91 to 118)   a protein fraction comprising at least sequence SEQ ID NO: 1 to 181 or a sequence having 90%, and preferably 80%, and more preferably 70% identity with said SEQ ID NO: 1 to 181 and SEQ ID NO: 183 and SEQ ID NO: 215 to 220 or a sequence having 70, 80 or 90% identity with said sequence SEQ ID NO: 183 and 215 to 220 and SEQ ID NO: 230, or   nucleotide sequences SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 127 and the protein fractions comprising at least sequence SEQ ID NO: 1 or a sequence having 70, 80 or 90% identity with said sequence SEQ ID NO: 1 and the sequences SEQ ID NO: 181 to 185,   a nucleotide sequences of any one or ribonucleotide sequence SEQ ID NO: 119 to 126 or SEQ ID NO: 127,   or a sequence having 90%, and preferably 80%, and more preferably 70% identity with said sequence SEQ ID NO: 119 to 127,   or a sequence having 90%, and preferably 80%, and more preferably 70% identity with said sequence SEQ ID NO: 119 to 127, or UUGGUAACGACCAUGCCAC or UUCACUUAGAAUAAUGUCC or UCUUUGUGAAUUUGACAAC or UCAAGGUCCAGGCUACAAC or   any of the following siRNA sequences SEQ ID NO: 60 to 88 and SEQ ID NO: 92 to 118, and   
       
         
           
                 
                 
               
                     
                   
                     GUGGCAUGGUCGUUACCAA dTdT 
                   
                 
                     
                     
                 
                     
                   
                     dTdT CACCGUACCAGCAAUGGUU 
                   
                 
                     
                     
                 
                     
                   
                     GGACAUUAUUCUAAGUGAA dTdT, 
                   
                 
             
                
                
                
                
                
               
            
           
         
         any one of the nucleotide sequences SEQ ID NO: 123, SEQ ID NO: 124 and SEQ ID NO: 127 to 149 or 
         any one of amino acid sequences SEQ ID NO: 1 to 118 and SEQ ID NO: 150 to 170 and SEQ ID NO: 180 to 185: or a sequence having 90%, and preferably 80%, and more preferably 70% identity with the sequences SEQ ID NO: 1 to 185. 
       
     
     
         7 . (canceled) 
     
     
         8 . Method of detecting the human complex Liv21 according to  claim 6 , further comprising the implementation of at least one probe specific for at least one of associated partners selected from the group consisting of:
 any of the following proteins: RBP2, TNF alpha crb2, cmd2, cycE/cdk2, cdk1, CREBI and p300, Rb, p1 07, p130 of family of pocket proteins, NFkB, cdc2A, mdm2, p21, p52, p65, p73, CyclinA and D1, BCAS3, BCAS4, Solute Carrier; or   a antibody of any one of the following proteins: RBP2, E2E4, E2F1, E2F2, SUMO, HDACI, crb2, Int2, cmd2, cycE/cdk2, cdk1, CREBI and p300, Rb, p1 07, p130 of family of pocket proteins, NFkB, cdc2A, mdm2, p21, p53, p65, Ki67, CAFI, CyclinA and DI, CHUK, BCAS3 BCAS4, Solute Carrier.   
     
     
         9 . (canceled) 
     
     
         10 . The method of detecting the human complex Liv21 according to  claim 6 , comprising the following steps:
 A step of extracting biological material from a biological sample taken. from a patient,   A step of contacting said biological material with at least said specific probe of any one of said. sequences of said human complex Liv21 and its associated partners, and at least one control and   A step of detecting the expression products of gene expression said human Liv21 complex and its associated partners, said products being comprised of expression of messenger RNA, or peptides, or proteins.   
     
     
         11 . Method of detecting the human complex Liv 21 according to  claim 10 , comprising a step of screening a candidate compound capable of modulating the activity of said human. complex Liv21, wherein said step of screening comprises a step of contacting said biological material with said candidate compound, and a step of selecting said candidate compound. 
     
     
         12 . Method of detecting the human complex Liv21 according to  claim 11 , wherein said biological sample is taken from a cancer patient and from a healthy patient, and wherein said biological material comprises nuclear cell extracts, cell extracts and cytoplasmic or cell extracts membrane, and wherein the emthod further comprises a step of determining the sub-expression and overexpression of the gene products of said complex or said complex Liv21 or said Liv21 human. complex and. associated partners said biological extracts. 
     
     
         13 . The method of detecting the human complex. Liv21 according to  claim 12  further comprising a step of determining ratios of said sub-expression and overexpression of the gene products of said cell nuclear extracts and said cytoplasmic cell extracts, or said membrane cell extracts, and wherein the method further comprises a step of combined analysis of said ratios of said biological material taken from a cancer patient and in a healthy patient 
     
     
         14 . The method of detecting the human complex Liv21 according to  claim 10 , characterized in that it uses a biochip on which is deposited at least one sequence-specific probe from said human Liv21 complex comprising
 a nucleotide sequences selected from SE ID NO: 171 to 175 and SEQ ID NO: 217   a siRNA sequence derived from one of the RNA sequences SEQ ID NO: 120 and SEQ ID NO: 121 and SEQ ID NO: 171 to 175 and   all siRNA sequences (SEQ ID NO: 91 to 118 and SEQ ID NO: 248 to 303)   a protein fraction comprising at least sequence SEQ ID NO: 1 to 181 or a sequence having 90%, and preferably 80%, and more preferably 70% identity with said SEQ ID NO: 1 to 181 and SEQ ID NO: 183 and SEQ ID NO: 215 to 220 or a sequence having 70, 80 or 90% identity with said sequence SEQ ID NO: 183 and 215 to 220 and SEQ ID NO: 230,   a nucleotide sequences SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 127 and the protein fractions comprising at least. sequence SEQ ID NO: 1 or a sequence having 70, 80 or 90% identity with said sequence SEQ ID NO: 1 and the sequences SEQ ID NO: 181 to 185,   a nucleotide sequences of any one or ribonucleotide sequence SEQ ID NO: 119 to 126 or SEQ ID NO: 127,   or a sequence having 90%, and preferably 80%, and more preferably 70% identity with said sequence SEQ ID NO: 119 to 127,   or a sequence having 90%, and preferably 80%, and more preferably 70% identity with said sequence SEQ ID NO: 119 to 127, or UUGGUAACGACCAUGCCAC or UUCACUUAGAAUAAUGUCC or UCUUUGUGAAUUUGACAAC or UCAAGGUCCAGGCUACAAC or   any of the following siRNA sequences SEQ ID NO: 60 to 88 and SEQ ID NO: 92 to 118, and   
       
         
           
                 
                 
               
                     
                   
                     GUGGCAUGGUCGUUACCAA dTdT 
                   
                 
                     
                     
                 
                     
                   
                     dTdT CACCGUACCAGCAAUGGUU 
                   
                 
                     
                     
                 
                     
                   
                     GGACAUUAUUCUAAGUGAA dTdT, 
                   
                 
             
                
                
                
                
                
               
            
           
         
         any one of the nucleotide sequences SEQ ID NO: 123, SEQ ID NO: 124 and SEQ ID NO: 127 to 149 or 
         any one of amino acid sequences SEQ ID NO: 1 to 118 and SEQ ID NO: 150 to 170 and SEQ ID NO: 180 to 185: or a sequence having 90%, and preferably 80%, and more preferably 70% identity with the sequences SEQ ID NO: 1 to 185. 
       
     
     
         15 . The method according to  claim 10 , characterized in that it applies to brain cancer, neuroblastoma, glioblastoma, without being limited there and breast cancer, bladder, skin and prostate and Alzheimer's disease. 
     
     
         16 . (canceled) 
     
     
         17 . A method of treating cancers comprising the injection of a peptide selected from a vectorized peptide of SEQ ID N°: 215 to 220. 
     
     
         18 . The method according to  claim 6 , wherein said probe is specific of the SEC) ID NO: 150 or to a sequence having 90%, and preferably 80%, and more preferably 70% identity with the SEQ ID NO:150. 
     
     
         19 . The method according to  claim 14 , wherein said sequence-specific probe is specific of the SEQ ID NO: 150 or to a sequence having 90%, and preferably 80%, and more preferably 70% identity with the SEQ ID NO: 150.