CA2734179A1 - Micro-rna-based compositions and methods for the diagnosis, prognosis and treatment of multiple myeloma - Google Patents
Micro-rna-based compositions and methods for the diagnosis, prognosis and treatment of multiple myeloma Download PDFInfo
- Publication number
- CA2734179A1 CA2734179A1 CA2734179A CA2734179A CA2734179A1 CA 2734179 A1 CA2734179 A1 CA 2734179A1 CA 2734179 A CA2734179 A CA 2734179A CA 2734179 A CA2734179 A CA 2734179A CA 2734179 A1 CA2734179 A1 CA 2734179A1
- Authority
- CA
- Canada
- Prior art keywords
- mir
- gene product
- subject
- cells
- expression
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 206010035226 Plasma cell myeloma Diseases 0.000 title claims abstract description 290
- 238000000034 method Methods 0.000 title claims abstract description 163
- 208000034578 Multiple myelomas Diseases 0.000 title claims abstract description 48
- 238000011282 treatment Methods 0.000 title claims abstract description 26
- 239000000203 mixture Substances 0.000 title claims abstract description 11
- 108091070501 miRNA Proteins 0.000 title claims description 153
- 238000004393 prognosis Methods 0.000 title abstract description 19
- 238000003745 diagnosis Methods 0.000 title abstract description 7
- 201000000050 myeloid neoplasm Diseases 0.000 claims abstract description 242
- 230000014509 gene expression Effects 0.000 claims abstract description 212
- 230000001575 pathological effect Effects 0.000 claims abstract description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 310
- 239000000523 sample Substances 0.000 claims description 118
- 206010028980 Neoplasm Diseases 0.000 claims description 103
- 239000002679 microRNA Substances 0.000 claims description 99
- 201000011510 cancer Diseases 0.000 claims description 85
- 201000005328 monoclonal gammopathy of uncertain significance Diseases 0.000 claims description 79
- 208000010190 Monoclonal Gammopathy of Undetermined Significance Diseases 0.000 claims description 75
- 108091050874 miR-19a stem-loop Proteins 0.000 claims description 56
- 108091086850 miR-19a-1 stem-loop Proteins 0.000 claims description 56
- 108091088468 miR-19a-2 stem-loop Proteins 0.000 claims description 56
- 238000012360 testing method Methods 0.000 claims description 54
- 150000001875 compounds Chemical class 0.000 claims description 53
- 108091037787 miR-19b stem-loop Proteins 0.000 claims description 53
- 239000003795 chemical substances by application Substances 0.000 claims description 51
- 108091031103 miR-181a stem-loop Proteins 0.000 claims description 49
- 108091046591 miR-181a-4 stem-loop Proteins 0.000 claims description 49
- 108091049627 miR-181a-5 stem-loop Proteins 0.000 claims description 49
- 108091024082 miR-32 stem-loop Proteins 0.000 claims description 40
- 238000009396 hybridization Methods 0.000 claims description 39
- 108010006198 p300-CBP-associated factor Proteins 0.000 claims description 39
- 108091034117 Oligonucleotide Proteins 0.000 claims description 37
- 230000002401 inhibitory effect Effects 0.000 claims description 35
- 108091043222 miR-181b stem-loop Proteins 0.000 claims description 35
- 102000004169 proteins and genes Human genes 0.000 claims description 34
- 108091062762 miR-21 stem-loop Proteins 0.000 claims description 33
- 108091041631 miR-21-1 stem-loop Proteins 0.000 claims description 33
- 108091044442 miR-21-2 stem-loop Proteins 0.000 claims description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 201000010099 disease Diseases 0.000 claims description 30
- 239000003550 marker Substances 0.000 claims description 29
- 230000004083 survival effect Effects 0.000 claims description 29
- 238000002493 microarray Methods 0.000 claims description 28
- 230000000694 effects Effects 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 26
- 230000001105 regulatory effect Effects 0.000 claims description 25
- 108700027336 Suppressor of Cytokine Signaling 1 Proteins 0.000 claims description 22
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 claims description 21
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 claims description 21
- 230000000692 anti-sense effect Effects 0.000 claims description 21
- 102100024779 Suppressor of cytokine signaling 1 Human genes 0.000 claims description 19
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 18
- 239000003153 chemical reaction reagent Substances 0.000 claims description 17
- 229940046166 oligodeoxynucleotide Drugs 0.000 claims description 17
- 230000035755 proliferation Effects 0.000 claims description 17
- 239000013068 control sample Substances 0.000 claims description 16
- 108091085564 miR-25 stem-loop Proteins 0.000 claims description 16
- 108091080167 miR-25-1 stem-loop Proteins 0.000 claims description 16
- 108091083056 miR-25-2 stem-loop Proteins 0.000 claims description 16
- 230000004075 alteration Effects 0.000 claims description 15
- 108091045790 miR-106b stem-loop Proteins 0.000 claims description 15
- 108091064157 miR-106a stem-loop Proteins 0.000 claims description 13
- 241000282414 Homo sapiens Species 0.000 claims description 12
- 108090001005 Interleukin-6 Proteins 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 238000000338 in vitro Methods 0.000 claims description 12
- 230000006907 apoptotic process Effects 0.000 claims description 11
- 239000000758 substrate Substances 0.000 claims description 11
- 230000002441 reversible effect Effects 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 9
- 108091091751 miR-17 stem-loop Proteins 0.000 claims description 9
- 108091069239 miR-17-2 stem-loop Proteins 0.000 claims description 9
- 239000003112 inhibitor Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 238000012216 screening Methods 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 230000004614 tumor growth Effects 0.000 claims description 7
- 230000008506 pathogenesis Effects 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 230000009466 transformation Effects 0.000 claims description 6
- 230000033228 biological regulation Effects 0.000 claims description 5
- 230000000670 limiting effect Effects 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 101001120822 Homo sapiens Putative microRNA 17 host gene protein Proteins 0.000 claims description 4
- 102100026055 Putative microRNA 17 host gene protein Human genes 0.000 claims description 4
- 230000002411 adverse Effects 0.000 claims description 4
- 230000001276 controlling effect Effects 0.000 claims description 4
- 230000004044 response Effects 0.000 claims description 4
- 230000019491 signal transduction Effects 0.000 claims description 4
- 230000008685 targeting Effects 0.000 claims description 4
- 239000002246 antineoplastic agent Substances 0.000 claims description 3
- 230000000903 blocking effect Effects 0.000 claims description 3
- 230000000977 initiatory effect Effects 0.000 claims description 3
- 230000001717 pathogenic effect Effects 0.000 claims description 3
- 230000001737 promoting effect Effects 0.000 claims description 3
- 230000011664 signaling Effects 0.000 claims description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims description 2
- 229940124660 anti-multiple myeloma Drugs 0.000 claims description 2
- 230000002222 downregulating effect Effects 0.000 claims description 2
- 230000001632 homeopathic effect Effects 0.000 claims description 2
- 230000037353 metabolic pathway Effects 0.000 claims description 2
- 108091042832 miR-191a stem-loop Proteins 0.000 claims description 2
- 108091027592 miR-191b stem-loop Proteins 0.000 claims description 2
- 239000002417 nutraceutical Substances 0.000 claims description 2
- 235000021436 nutraceutical agent Nutrition 0.000 claims description 2
- 230000007170 pathology Effects 0.000 claims description 2
- 239000003183 carcinogenic agent Substances 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 255
- 150000007523 nucleic acids Chemical class 0.000 description 77
- 108700011259 MicroRNAs Proteins 0.000 description 64
- 239000000090 biomarker Substances 0.000 description 59
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 58
- 102000039446 nucleic acids Human genes 0.000 description 57
- 108020004707 nucleic acids Proteins 0.000 description 57
- 210000004180 plasmocyte Anatomy 0.000 description 54
- 210000001519 tissue Anatomy 0.000 description 47
- 239000002502 liposome Substances 0.000 description 33
- 239000002773 nucleotide Substances 0.000 description 26
- 125000003729 nucleotide group Chemical group 0.000 description 26
- 108091049730 miR-1792 stem-loop Proteins 0.000 description 24
- 108020004999 messenger RNA Proteins 0.000 description 23
- 108020004459 Small interfering RNA Proteins 0.000 description 22
- 238000001890 transfection Methods 0.000 description 22
- 239000013598 vector Substances 0.000 description 22
- 239000013603 viral vector Substances 0.000 description 20
- 239000013612 plasmid Substances 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 17
- 230000000295 complement effect Effects 0.000 description 17
- 230000005764 inhibitory process Effects 0.000 description 14
- 108091028043 Nucleic acid sequence Proteins 0.000 description 13
- 238000011529 RT qPCR Methods 0.000 description 13
- 238000009739 binding Methods 0.000 description 12
- 108020004414 DNA Proteins 0.000 description 11
- 102000004889 Interleukin-6 Human genes 0.000 description 11
- 230000027455 binding Effects 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 11
- -1 miR-106b--25 cluster Proteins 0.000 description 11
- 238000001514 detection method Methods 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 108020005345 3' Untranslated Regions Proteins 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 239000011324 bead Substances 0.000 description 9
- 230000000875 corresponding effect Effects 0.000 description 9
- 230000007774 longterm Effects 0.000 description 9
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 230000037396 body weight Effects 0.000 description 8
- 230000003247 decreasing effect Effects 0.000 description 8
- 108091059456 miR-92-1 stem-loop Proteins 0.000 description 8
- 230000014207 opsonization Effects 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- 239000002243 precursor Substances 0.000 description 8
- 238000001262 western blot Methods 0.000 description 8
- 108060001084 Luciferase Proteins 0.000 description 7
- 239000005089 Luciferase Substances 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 238000000636 Northern blotting Methods 0.000 description 7
- 239000000427 antigen Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 230000002074 deregulated effect Effects 0.000 description 7
- 230000002255 enzymatic effect Effects 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 108091084336 miR-92-2 stem-loop Proteins 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
- 101710163270 Nuclease Proteins 0.000 description 6
- 230000003042 antagnostic effect Effects 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 238000001574 biopsy Methods 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000001185 bone marrow Anatomy 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 238000000326 densiometry Methods 0.000 description 6
- 230000003828 downregulation Effects 0.000 description 6
- 238000003119 immunoblot Methods 0.000 description 6
- 238000007901 in situ hybridization Methods 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 238000010606 normalization Methods 0.000 description 6
- 238000003499 nucleic acid array Methods 0.000 description 6
- 230000002246 oncogenic effect Effects 0.000 description 6
- 239000013610 patient sample Substances 0.000 description 6
- 239000013600 plasmid vector Substances 0.000 description 6
- 229920001451 polypropylene glycol Polymers 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000003757 reverse transcription PCR Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 239000013607 AAV vector Substances 0.000 description 5
- 102000007469 Actins Human genes 0.000 description 5
- 108010085238 Actins Proteins 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 108091032902 miR-93 stem-loop Proteins 0.000 description 5
- 238000010208 microarray analysis Methods 0.000 description 5
- 231100000590 oncogenic Toxicity 0.000 description 5
- 230000002018 overexpression Effects 0.000 description 5
- 230000000861 pro-apoptotic effect Effects 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 238000002271 resection Methods 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 241000701161 unidentified adenovirus Species 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- BDUHCSBCVGXTJM-WUFINQPMSA-N 4-[[(4S,5R)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazol-1-yl]-oxomethyl]-2-piperazinone Chemical compound CC(C)OC1=CC(OC)=CC=C1C1=N[C@@H](C=2C=CC(Cl)=CC=2)[C@@H](C=2C=CC(Cl)=CC=2)N1C(=O)N1CC(=O)NCC1 BDUHCSBCVGXTJM-WUFINQPMSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 108090000331 Firefly luciferases Proteins 0.000 description 4
- 108090000246 Histone acetyltransferases Proteins 0.000 description 4
- 102000003893 Histone acetyltransferases Human genes 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 230000002424 anti-apoptotic effect Effects 0.000 description 4
- 239000012472 biological sample Substances 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical group C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 238000000151 deposition Methods 0.000 description 4
- 239000007850 fluorescent dye Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 4
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000005017 polysaccharide Substances 0.000 description 4
- 150000004804 polysaccharides Chemical class 0.000 description 4
- 238000010837 poor prognosis Methods 0.000 description 4
- 125000002652 ribonucleotide group Chemical group 0.000 description 4
- 239000004055 small Interfering RNA Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- KWVJHCQQUFDPLU-YEUCEMRASA-N 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KWVJHCQQUFDPLU-YEUCEMRASA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 108090000565 Capsid Proteins Proteins 0.000 description 3
- 102100023321 Ceruloplasmin Human genes 0.000 description 3
- 239000003298 DNA probe Substances 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 3
- 206010064912 Malignant transformation Diseases 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 3
- 102100032543 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN Human genes 0.000 description 3
- 101710132081 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN Proteins 0.000 description 3
- 241000288906 Primates Species 0.000 description 3
- 108020004518 RNA Probes Proteins 0.000 description 3
- 239000003391 RNA probe Substances 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 108091028664 Ribonucleotide Proteins 0.000 description 3
- 102000058018 Suppressor of Cytokine Signaling 1 Human genes 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 235000020958 biotin Nutrition 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 210000000234 capsid Anatomy 0.000 description 3
- 239000013592 cell lysate Substances 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 210000004748 cultured cell Anatomy 0.000 description 3
- 239000005547 deoxyribonucleotide Substances 0.000 description 3
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 230000036212 malign transformation Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 108091051741 miR-10625-1 stem-loop Proteins 0.000 description 3
- 108091047481 miR-10625-2 stem-loop Proteins 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 239000002853 nucleic acid probe Substances 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 238000000611 regression analysis Methods 0.000 description 3
- 239000002336 ribonucleotide Substances 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000012353 t test Methods 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- 238000010200 validation analysis Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- 108090001008 Avidin Proteins 0.000 description 2
- 102000051485 Bcl-2 family Human genes 0.000 description 2
- 108700038897 Bcl-2 family Proteins 0.000 description 2
- 101100297347 Caenorhabditis elegans pgl-3 gene Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 102100032257 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 208000004463 Follicular Adenocarcinoma Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101000611943 Homo sapiens Programmed cell death protein 4 Proteins 0.000 description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
- 102100034349 Integrase Human genes 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 108010043958 Peptoids Proteins 0.000 description 2
- 102100040992 Programmed cell death protein 4 Human genes 0.000 description 2
- 238000002123 RNA extraction Methods 0.000 description 2
- 108010052090 Renilla Luciferases Proteins 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 241000906446 Theraps Species 0.000 description 2
- 241000711975 Vesicular stomatitis virus Species 0.000 description 2
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000003491 array Methods 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000009702 cancer cell proliferation Effects 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000011712 cell development Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000012829 chemotherapy agent Substances 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 239000000834 fixative Substances 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 150000002270 gangliosides Chemical class 0.000 description 2
- 230000030279 gene silencing Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000000126 in silico method Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 229920001427 mPEG Polymers 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 108091049679 miR-20a stem-loop Proteins 0.000 description 2
- 108091027963 non-coding RNA Proteins 0.000 description 2
- 102000042567 non-coding RNA Human genes 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 229920001542 oligosaccharide Chemical class 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 229920000962 poly(amidoamine) Polymers 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000005760 tumorsuppression Effects 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 239000012130 whole-cell lysate Substances 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- CERZMXAJYMMUDR-QBTAGHCHSA-N 5-amino-3,5-dideoxy-D-glycero-D-galacto-non-2-ulopyranosonic acid Chemical compound N[C@@H]1[C@@H](O)CC(O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO CERZMXAJYMMUDR-QBTAGHCHSA-N 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 1
- 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 208000012526 B-cell neoplasm Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-YMDCURPLSA-N D-galactopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-YMDCURPLSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-VANFPWTGSA-N D-mannopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-VANFPWTGSA-N 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 101100447432 Danio rerio gapdh-2 gene Proteins 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 1
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 101150112014 Gapdh gene Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000904152 Homo sapiens Transcription factor E2F1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000282596 Hylobatidae Species 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 101710203526 Integrase Proteins 0.000 description 1
- 230000004163 JAK-STAT signaling pathway Effects 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000254158 Lampyridae Species 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 108091008065 MIR21 Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 108020005093 RNA Precursors Proteins 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 206010038111 Recurrent cancer Diseases 0.000 description 1
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 101150045565 Socs1 gene Proteins 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 238000012233 TRIzol extraction Methods 0.000 description 1
- 102100024026 Transcription factor E2F1 Human genes 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 1
- 102000015098 Tumor Suppressor Protein p53 Human genes 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000010817 Wright-Giemsa staining Methods 0.000 description 1
- MMXKIWIWQPKTIK-KPRKPIBOSA-N [(2r,3s,5r)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl [(2r,3s,5r)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-(phosphonooxymethyl)oxolan-3-yl] hydrogen phosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(O)=O)[C@@H](O)C1 MMXKIWIWQPKTIK-KPRKPIBOSA-N 0.000 description 1
- FPKBIYKAYFGTKG-UHFFFAOYSA-N [5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[2-[[[2-[[[5-(2-amino-6-oxo-1H-purin-9-yl)-2-(hydroxymethyl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]oxolan-3-yl] [3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methyl hydrogen phosphate Chemical compound Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O FPKBIYKAYFGTKG-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001745 anti-biotin effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 108700021042 biotin binding protein Proteins 0.000 description 1
- 102000043871 biotin binding protein Human genes 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 235000010633 broth Nutrition 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000011692 calcium ascorbate Substances 0.000 description 1
- 235000010376 calcium ascorbate Nutrition 0.000 description 1
- 229940047036 calcium ascorbate Drugs 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229960002713 calcium chloride Drugs 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
- 235000013927 calcium gluconate Nutrition 0.000 description 1
- 229960004494 calcium gluconate Drugs 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- BLORRZQTHNGFTI-ZZMNMWMASA-L calcium-L-ascorbate Chemical compound [Ca+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] BLORRZQTHNGFTI-ZZMNMWMASA-L 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- BHRQIJRLOVHRKH-UHFFFAOYSA-L calcium;2-[bis[2-[bis(carboxylatomethyl)amino]ethyl]amino]acetate;hydron Chemical compound [Ca+2].OC(=O)CN(CC(O)=O)CCN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O BHRQIJRLOVHRKH-UHFFFAOYSA-L 0.000 description 1
- 238000004422 calculation algorithm Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 150000004653 carbonic acids Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007960 cellular response to stress Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 238000013170 computed tomography imaging Methods 0.000 description 1
- 230000006552 constitutive activation Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical class O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000007387 excisional biopsy Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000011536 extraction buffer Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 230000003116 impacting effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 230000002687 intercalation Effects 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 150000008040 ionic compounds Chemical class 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000008206 lipophilic material Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 108091007431 miR-29 Proteins 0.000 description 1
- 108091029997 miR-328 stem-loop Proteins 0.000 description 1
- 108091050164 miR-92 stem-loop Proteins 0.000 description 1
- 238000003253 miRNA assay Methods 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 1
- CERZMXAJYMMUDR-UHFFFAOYSA-N neuraminic acid Natural products NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO CERZMXAJYMMUDR-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 238000001558 permutation test Methods 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical group 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000088 plastic resin Substances 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 102000016914 ras Proteins Human genes 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 239000002342 ribonucleoside Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000007727 signaling mechanism Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 230000004654 survival pathway Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 108091008023 transcriptional regulators Proteins 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000009752 translational inhibition Effects 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940073585 tromethamine hydrochloride Drugs 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
- C12N2310/141—MicroRNAs, miRNAs
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/112—Disease subtyping, staging or classification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8803608P | 2008-08-12 | 2008-08-12 | |
| US61/088,036 | 2008-08-12 | ||
| PCT/US2009/053586 WO2010019694A1 (en) | 2008-08-12 | 2009-08-12 | Micro-rna-based compositions and methods for the diagnosis, prognosis and treatment of multiple myeloma |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2734179A1 true CA2734179A1 (en) | 2010-02-18 |
Family
ID=41669274
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2734179A Abandoned CA2734179A1 (en) | 2008-08-12 | 2009-08-12 | Micro-rna-based compositions and methods for the diagnosis, prognosis and treatment of multiple myeloma |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20110152357A1 (enExample) |
| EP (1) | EP2323677A4 (enExample) |
| JP (1) | JP2012500389A (enExample) |
| CN (1) | CN102149401A (enExample) |
| AU (1) | AU2009281969A1 (enExample) |
| CA (1) | CA2734179A1 (enExample) |
| WO (1) | WO2010019694A1 (enExample) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105902559A (zh) | 2005-08-01 | 2016-08-31 | 俄亥俄州立大学研究基金会 | 用于乳腺癌的诊断、预后和治疗的基于MicroRNA的方法和组合物 |
| WO2007033023A2 (en) | 2005-09-12 | 2007-03-22 | The Ohio State University Research Foundation | Compositions and methods for the diagnosis and therapy of bcl2-associated cancers |
| EP2487254B1 (en) | 2006-01-05 | 2015-07-29 | The Ohio State University Research Foundation | MicroRNA-based methods and compositions for the diagnosis and treatment of solid cancers |
| JP5490413B2 (ja) | 2006-01-05 | 2014-05-14 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイション | 膵内分泌腫瘍及び膵腺房腫瘍におけるマイクロｒｎａ発現異常 |
| EP2514434B1 (en) | 2006-01-05 | 2015-10-21 | The Ohio State University Research Foundation | MicroRNA-based methods for the diagnosis, prognosis and treatment of lung cancer |
| ES2446362T3 (es) | 2006-03-20 | 2014-03-07 | The Ohio State University Research Foundation | Huellas de microARN durante megacariocipoyesis humana |
| EP2436787B1 (en) | 2006-07-13 | 2016-01-20 | The Ohio State University Research Foundation | MIR-21 for diagnosing poor survival prognosis colon adenocarcinoma. |
| JP5426383B2 (ja) | 2006-09-19 | 2014-02-26 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイション | 慢性リンパ球性白血病におけるｍｉＲ−２９およびｍｉＲ−１８１によって制御されるＴＣＬ１発現 |
| CA2667617A1 (en) | 2006-11-01 | 2008-05-08 | The Ohio State University Research Foundation | Microrna expression signature for predicting survival and metastases in hepatocellular carcinoma |
| CN101627134B (zh) | 2007-01-31 | 2013-11-06 | 俄亥俄州立大学研究基金会 | 用于急性髓细胞白血病（aml）的诊断、预后和治疗的基于微rna的方法和组合物 |
| JP5690588B2 (ja) | 2007-06-08 | 2015-03-25 | アメリカ合衆国 | 肝細胞癌のサブタイプを決定し、肝癌幹細胞を検出するための方法 |
| US8053186B2 (en) | 2007-06-15 | 2011-11-08 | The Ohio State University Research Foundation | Oncogenic ALL-1 fusion proteins for targeting Drosha-mediated microRNA processing |
| JP2010535782A (ja) | 2007-07-31 | 2010-11-25 | ズィ、オハイオウ、ステイト、ユーニヴァーサティ、リサーチ、ファウンデイシャン | Ｄｎｍｔ３ａ及びｄｎｍｔ３ｂを標的にすることによるメチル化を元に戻す方法 |
| ES2570359T3 (es) | 2007-08-03 | 2016-05-18 | Univ Ohio State Res Found | Regiones ultraconservadas que codifican ARNnc |
| JP5770472B2 (ja) | 2007-08-22 | 2015-08-26 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイションＴｈｅ Ｏｈｉｏ Ｓｔａｔｅ Ｕｎｉｖｅｒｓｉｔｙ Ｒｅｓｅａｒｃｈ Ｆｏｕｎｄａｔｉｏｎ | ヒト急性白血病におけるｅｐｈａ７及びｅｒｋリン酸化の調節解除を誘発するための方法及び組成物 |
| CN102137927B (zh) | 2007-10-26 | 2014-03-12 | 俄亥俄州立大学研究基金会 | 鉴定脆性组氨酸三联体(Fhit)相互作用的方法及其用途 |
| AU2009257410B2 (en) | 2008-06-11 | 2014-03-06 | Fudan University | Use of miR-26 family as a predictive marker of hepatocellular carcinoma and responsiveness to therapy |
| CN102803511A (zh) | 2009-11-23 | 2012-11-28 | 俄亥俄州立大学 | 用于影响肿瘤细胞生长、迁移和侵袭的材料和方法 |
| CN102241773B (zh) * | 2010-05-13 | 2014-05-14 | 四川大学 | 抗骨髓瘤细胞多克隆抗体及其制备方法 |
| AU2011326032B2 (en) | 2010-11-12 | 2016-10-06 | The Ohio State University Research Foundation | Materials and methods related to microRNA-21, mismatch repair, and colorectal cancer |
| WO2012068147A1 (en) | 2010-11-15 | 2012-05-24 | The Ohio State University Research Foundation | Controlled release mucoadhesive systems |
| GB2486424A (en) * | 2010-12-13 | 2012-06-20 | Univ Sussex | Markers for plasma cell disorders |
| CA2828772A1 (en) | 2011-03-07 | 2012-09-13 | The Ohio State University | Mutator activity induced by microrna-155 (mir-155) links inflammation and cancer |
| JP2014511677A (ja) * | 2011-03-22 | 2014-05-19 | コーネル・ユニバーシティー | 鑑別困難な良性甲状腺病変と悪性甲状腺病変との識別法 |
| US8945829B2 (en) | 2011-03-22 | 2015-02-03 | Cornell University | Distinguishing benign and malignant indeterminate thyroid lesions |
| US9249468B2 (en) | 2011-10-14 | 2016-02-02 | The Ohio State University | Methods and materials related to ovarian cancer |
| AU2012347470B2 (en) | 2011-12-09 | 2017-02-02 | Medtronic Ireland Manufacturing Unlimited Company | Therapeutic neuromodulation of the hepatic system |
| AU2012352265B2 (en) | 2011-12-13 | 2017-02-16 | Ohio State Innovation Foundation | Methods and compositions related to miR-21 and miR-29a, exosome inhibition, and cancer metastasis |
| CN105936932A (zh) | 2012-01-20 | 2016-09-14 | 俄亥俄州立大学 | 浸润性和预后的乳腺癌生物标志物标签 |
| US10047401B2 (en) | 2012-08-20 | 2018-08-14 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Expression protein-coding and noncoding genes as prognostic classifiers in early stage lung cancer |
| US9944991B2 (en) | 2012-11-02 | 2018-04-17 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for diagnosis, prognosis and treatment of hematological malignancies |
| CN108603232A (zh) * | 2015-12-03 | 2018-09-28 | 阿尔佛雷德医疗集团 | 监测骨髓瘤的治疗或进展 |
| CN105603087B (zh) * | 2016-02-01 | 2019-03-01 | 中国医学科学院血液病医院（血液学研究所） | 检测多发性骨髓瘤克隆进化的基因探针组合物及试剂盒 |
| EP3481403B1 (en) * | 2016-07-06 | 2022-02-09 | Youhealth Biotech, Limited | Solid tumor methylation markers and uses thereof |
| CN110223733B (zh) * | 2019-04-22 | 2022-02-01 | 福建医科大学附属第一医院 | 一种多发性骨髓瘤预后基因的筛查方法 |
| CN113795581A (zh) * | 2019-05-03 | 2021-12-14 | 迪克纳制药公司 | 具有缩短的有义链的双链核酸抑制剂分子 |
| US20210002698A1 (en) * | 2019-07-02 | 2021-01-07 | Quark Biosciences Taiwan, Inc. | miRNA Receptivity Analysis of the Endometrium |
| CN110564852A (zh) * | 2019-08-06 | 2019-12-13 | 中国医学科学院血液病医院(中国医学科学院血液学研究所) | 与人类多发性骨髓瘤相关的miRNAs表达图谱模型、构建方法及应用 |
| CN113186163A (zh) * | 2021-01-18 | 2021-07-30 | 南昌五元生物科技有限公司 | 一种基于p53突变筛选肿瘤类器官的培养方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005078139A2 (en) * | 2004-02-09 | 2005-08-25 | Thomas Jefferson University | DIAGNOSIS AND TREATMENT OF CANCERS WITH MicroRNA LOCATED IN OR NEAR CANCER-ASSOCIATED CHROMOSOMAL FEATURES |
| EP2474616B1 (en) * | 2004-05-28 | 2015-07-08 | Asuragen, Inc. | Methods and compositions involving microRNA |
| EP1838852A2 (en) * | 2004-11-12 | 2007-10-03 | Asuragen, Inc. | Methods and compositions involving mirna and mirna inhibitor molecules |
| US20060185027A1 (en) * | 2004-12-23 | 2006-08-17 | David Bartel | Systems and methods for identifying miRNA targets and for altering miRNA and target expression |
| CA2607256A1 (en) * | 2005-05-02 | 2006-11-09 | Cold Spring Harbor Laboratory | Composition and methods for cancer diagnosis utilizing the mir 17-92 cluster |
| ES2446362T3 (es) * | 2006-03-20 | 2014-03-07 | The Ohio State University Research Foundation | Huellas de microARN durante megacariocipoyesis humana |
| EP2436787B1 (en) * | 2006-07-13 | 2016-01-20 | The Ohio State University Research Foundation | MIR-21 for diagnosing poor survival prognosis colon adenocarcinoma. |
| CA2663962A1 (en) * | 2006-09-19 | 2008-03-27 | Asuragen, Inc. | Mir-15, mir-26, mir-31,mir-145, mir-147, mir-188, mir-215, mir-216, mir-331, mmu-mir-292-3p regulated genes and pathways as targets for therapeutic intervention |
| US8765702B2 (en) * | 2007-02-27 | 2014-07-01 | Rosetta Genomics Ltd. | Composition and methods for modulating cell proliferation and cell death |
| EP2126584B1 (en) * | 2007-03-16 | 2012-12-19 | CovalX AG | Direct mass spectrometric analysis of drug candidates targeting protein complexes |
| EP3708682B1 (en) * | 2008-02-01 | 2022-11-23 | The General Hospital Corporation | Use of microvesicles in diagnosis and prognosis of medical diseases and conditions |
-
2009
- 2009-08-12 EP EP09807241A patent/EP2323677A4/en not_active Withdrawn
- 2009-08-12 CN CN2009801354566A patent/CN102149401A/zh active Pending
- 2009-08-12 US US13/058,662 patent/US20110152357A1/en not_active Abandoned
- 2009-08-12 CA CA2734179A patent/CA2734179A1/en not_active Abandoned
- 2009-08-12 AU AU2009281969A patent/AU2009281969A1/en not_active Abandoned
- 2009-08-12 JP JP2011523144A patent/JP2012500389A/ja active Pending
- 2009-08-12 WO PCT/US2009/053586 patent/WO2010019694A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP2323677A4 (en) | 2013-01-09 |
| WO2010019694A1 (en) | 2010-02-18 |
| JP2012500389A (ja) | 2012-01-05 |
| US20110152357A1 (en) | 2011-06-23 |
| AU2009281969A1 (en) | 2010-02-18 |
| CN102149401A (zh) | 2011-08-10 |
| EP2323677A1 (en) | 2011-05-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20110152357A1 (en) | Micro-RNA-Based Compositions and Methods for the Diagnosis, Prognosis and Treatment of Multiple Myeloma | |
| US8071292B2 (en) | Leukemia diagnostic methods | |
| US9574239B2 (en) | MicroRNA signatures in human ovarian cancer | |
| CN101627134B (zh) | 用于急性髓细胞白血病（aml）的诊断、预后和治疗的基于微rna的方法和组合物 | |
| CN101809169B (zh) | 通过靶向dnmt3a和dnmt3b恢复甲基化的方法 | |
| JP5489459B2 (ja) | 乳癌の診断、予後及び治療のためのマイクロｒｎａに基づいた方法及び組成物 | |
| AU2008310704B2 (en) | Methods and compositions for the diagnosis and treatment of esphageal adenocarcinomas | |
| JP2010503420A5 (enExample) | ||
| AU2015202920B2 (en) | MicroRNA signatures in human ovarian cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20140730 |
|
| FZDE | Discontinued |
Effective date: 20180316 |