Pharmacodiagnosis Test 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 No 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 No 183 and SEQ ID No 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 No 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 No 1 and the sequences 181 to 185.   
     
     
         3 . The Liv21 human complex is further comprising:
 The nucleotide sequences of any one or ribonucleotide sequence SEQ ID No 119 to 126 or 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 92 to 118, and
 GUGGCAUGGUCGUUACCAA dTdT 
 DTdT CACCGUACCAGCAAUGGUU 
 GGACAUUAUUCUAAGUGAA dTdT 
   
     
     
         4 . Liv21 human complex according to  claim 1 , further comprises at least one of:
 Any one of the nucleotide sequences SEQ ID No. 123, 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 said sequences SEQ ID No: 1 to 185.   
     
     
         5 . Liv21 human complex according to any one of  claims 1  to  3 , characterized in that it interacts with at least one of the partners associated, said at least one of these being associated partners 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, p73, 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 . 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 according to  claim 1 . 
     
     
         7 . 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 according to  claim 2 . 
     
     
         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 said complex sequence of these Liv21 human complex and associated partners according to  claim 3 . 
     
     
         9 . 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 said complex sequence of these Liv21 human complex and associated partners according to  claim 4 . 
     
     
         10 . Detection method according to  claim 5 , comprises at least 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 or human Liv21 complex and its content partners, and at least one control and   A step of detecting the expression products of gene expression said complex Liv21 or said human Liv21 complex and its associated partners, said products being comprised of expression of messenger RNA, or peptides, or proteins.   
     
     
         11 . Method detection according to  claim 10 , wherein screening a candidate compound is capable of modulating the activity of said human complex Liv21, and in that it further comprises:
 a step of contacting said biological material with said candidate compound, and a step of selecting said candidate compound.   
     
     
         12 . Method according to  claim 11 , wherein said biological sample is taken from a cancer patient and in a healthy patient, and in that said material comprises nuclear cell extracts, cell extracts and cytoplasmic or cell extracts membrane, and in that it 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 . Method according to  claim 12 , and further comprises a step of determining said radio sub-expression and overexpression of said gene products:
 cell nuclear extracts and cytoplasmic cell extracts, cell extracts or membrane, and that it further comprises a step of analyzing combined radio said biological material taken from a cancer patient and in a healthy patient   
     
     
         14 . Method according to any one of  claim 10 , characterized in that it uses a biochip on which is deposited at least one sequence-specific probes from said complex Liv21 human according to  claim 1 . 
     
     
         15 . 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 disease. 
     
     
         16 . Method of treating cancers using an siRNA selected from siRNA SEQ ID NO: 91 to 118. 
     
     
         17 . Method of treating cancers by injection of a peptide selected from a vectorized peptide of SEQ ID No: 215 to 220.