CA2713469A1

CA2713469A1 - Methods and compositions relating to carcinoma stem cells

Methods and compositions relating to carcinoma stem cells Download PDF

Info

Publication number: CA2713469A1
Authority: CA; Canada
Prior art keywords: mir; cells; cell; mirna; cancer
Prior art date: 2008-02-01
Legal status : Abandoned

Application number

CA2713469A

Other languages

English (en)

French (fr)

Inventor

Michael Clarke

Yohei Shimono

Current Assignee

Leland Stanford Junior University

Original Assignee

Individual

Priority date

2008-02-01

Filing date

2009-01-30

Publication date

2009-08-06

2009-01-30 Application filed by Individual filed Critical Individual

2009-08-06 Publication of CA2713469A1 publication Critical patent/CA2713469A1/en

Status Abandoned legal-status Critical Current

Links

210000000130 stem cell Anatomy 0.000 title claims abstract description 128
238000000034 method Methods 0.000 title claims abstract description 88
201000009030 Carcinoma Diseases 0.000 title description 26
239000000203 mixture Substances 0.000 title description 7
210000004027 cell Anatomy 0.000 claims abstract description 415
206010028980 Neoplasm Diseases 0.000 claims abstract description 231
239000002679 microRNA Substances 0.000 claims abstract description 217
201000011510 cancer Diseases 0.000 claims abstract description 131
108091070501 miRNA Proteins 0.000 claims abstract description 122
230000014509 gene expression Effects 0.000 claims abstract description 120
208000026310 Breast neoplasm Diseases 0.000 claims abstract description 110
108700011259 MicroRNAs Proteins 0.000 claims abstract description 109
206010006187 Breast cancer Diseases 0.000 claims abstract description 108
108090000623 proteins and genes Proteins 0.000 claims description 86
239000003795 chemical substances by application Substances 0.000 claims description 64
108091074450 miR-200c stem-loop Proteins 0.000 claims description 57
102000004169 proteins and genes Human genes 0.000 claims description 46
230000000694 effects Effects 0.000 claims description 41
108091029500 miR-183 stem-loop Proteins 0.000 claims description 37
230000001105 regulatory effect Effects 0.000 claims description 30
101000868273 Homo sapiens CD44 antigen Proteins 0.000 claims description 26
238000011282 treatment Methods 0.000 claims description 26
102100032912 CD44 antigen Human genes 0.000 claims description 25
231100001221 nontumorigenic Toxicity 0.000 claims description 24
238000001727 in vivo Methods 0.000 claims description 20
108091089775 miR-200b stem-loop Proteins 0.000 claims description 18
238000000338 in vitro Methods 0.000 claims description 17
108091059199 miR-200a stem-loop Proteins 0.000 claims description 17
239000003153 chemical reaction reagent Substances 0.000 claims description 16
238000007901 in situ hybridization Methods 0.000 claims description 13
238000012216 screening Methods 0.000 claims description 12
108091058688 miR-141 stem-loop Proteins 0.000 claims description 11
108091023796 miR-182 stem-loop Proteins 0.000 claims description 11
108091059135 miR-429 stem-loop Proteins 0.000 claims description 11
238000003753 real-time PCR Methods 0.000 claims description 10
108091028049 Mir-221 microRNA Proteins 0.000 claims description 9
108091027559 Mir-96 microRNA Proteins 0.000 claims description 9
108091086713 miR-96 stem-loop Proteins 0.000 claims description 9
108091070961 miR-96-3 stem-loop Proteins 0.000 claims description 9
108091033773 MiR-155 Proteins 0.000 claims description 8
230000007423 decrease Effects 0.000 claims description 6
108091026807 MiR-214 Proteins 0.000 claims description 5
108091028076 Mir-127 Proteins 0.000 claims description 5
108091034117 Oligonucleotide Proteins 0.000 claims description 5
239000000074 antisense oligonucleotide Substances 0.000 claims description 5
238000012230 antisense oligonucleotides Methods 0.000 claims description 5
108091079658 miR-142-1 stem-loop Proteins 0.000 claims description 5
108091071830 miR-142-2 stem-loop Proteins 0.000 claims description 5
108091043612 miR-146b stem-loop Proteins 0.000 claims description 5
108091025686 miR-199a stem-loop Proteins 0.000 claims description 5
108091092012 miR-199b stem-loop Proteins 0.000 claims description 5
108091080321 miR-222 stem-loop Proteins 0.000 claims description 5
108091028080 MiR-132 Proteins 0.000 claims description 4
108091046841 MiR-150 Proteins 0.000 claims description 4
108091028108 MiR-212 Proteins 0.000 claims description 4
108091093085 MiR-338 Proteins 0.000 claims description 4
108091028066 Mir-126 Proteins 0.000 claims description 4
108091062140 Mir-223 Proteins 0.000 claims description 4
108091060585 Mir-31 Proteins 0.000 claims description 4
108091091360 miR-125b stem-loop Proteins 0.000 claims description 4
108091028466 miR-130b stem-loop Proteins 0.000 claims description 4
108091032320 miR-146 stem-loop Proteins 0.000 claims description 4
108091024530 miR-146a stem-loop Proteins 0.000 claims description 4
108091039097 miR-193b stem-loop Proteins 0.000 claims description 4
108091064378 miR-196b stem-loop Proteins 0.000 claims description 4
108091053935 miR-212 stem-loop Proteins 0.000 claims description 4
108091028397 miR-212-1 stem-loop Proteins 0.000 claims description 4
108091028945 miR-212-2 stem-loop Proteins 0.000 claims description 4
108091061917 miR-221 stem-loop Proteins 0.000 claims description 4
108091063489 miR-221-1 stem-loop Proteins 0.000 claims description 4
108091055391 miR-221-2 stem-loop Proteins 0.000 claims description 4
108091031076 miR-221-3 stem-loop Proteins 0.000 claims description 4
108091079013 miR-34b Proteins 0.000 claims description 4
108091084018 miR-34b stem-loop Proteins 0.000 claims description 4
108091063470 miR-34b-1 stem-loop Proteins 0.000 claims description 4
108091049916 miR-34b-2 stem-loop Proteins 0.000 claims description 4
108091057222 miR-34b-3 stem-loop Proteins 0.000 claims description 4
108091092639 miR-34b-4 stem-loop Proteins 0.000 claims description 4
108091028761 miR-409 stem-loop Proteins 0.000 claims description 4
108091029445 miR-432 stem-loop Proteins 0.000 claims description 4
108091031190 miR-495 stem-loop Proteins 0.000 claims description 4
108091046338 miR-521 stem-loop Proteins 0.000 claims description 4
108091043430 miR-521-1 stem-loop Proteins 0.000 claims description 4
108091044256 miR-521-2 stem-loop Proteins 0.000 claims description 4
108091048420 miR-521-3 stem-loop Proteins 0.000 claims description 4
239000002246 antineoplastic agent Substances 0.000 claims description 3
108091028043 Nucleic acid sequence Proteins 0.000 claims description 2
229940127089 cytotoxic agent Drugs 0.000 claims description 2
230000037041 intracellular level Effects 0.000 claims 1
239000002157 polynucleotide Substances 0.000 abstract description 27
102000040430 polynucleotide Human genes 0.000 abstract description 26
108091033319 polynucleotide Proteins 0.000 abstract description 26
230000001225 therapeutic effect Effects 0.000 abstract description 10
210000000069 breast epithelial cell Anatomy 0.000 abstract description 5
238000009509 drug development Methods 0.000 abstract description 3
239000000523 sample Substances 0.000 description 41
230000000381 tumorigenic effect Effects 0.000 description 38
210000001519 tissue Anatomy 0.000 description 36
231100000588 tumorigenic Toxicity 0.000 description 36
101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 description 33
102100024270 Transcription factor SOX-2 Human genes 0.000 description 32
241000713666 Lentivirus Species 0.000 description 28
108091032973 (ribonucleotides)n+m Proteins 0.000 description 24
150000001875 compounds Chemical class 0.000 description 24
238000004458 analytical method Methods 0.000 description 23
201000009051 Embryonal Carcinoma Diseases 0.000 description 22
210000000481 breast Anatomy 0.000 description 21
230000004069 differentiation Effects 0.000 description 21
239000013598 vector Substances 0.000 description 21
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
238000002560 therapeutic procedure Methods 0.000 description 19
238000003556 assay Methods 0.000 description 18
201000010099 disease Diseases 0.000 description 17
238000000684 flow cytometry Methods 0.000 description 17
241001465754 Metazoa Species 0.000 description 15
150000007523 nucleic acids Chemical class 0.000 description 15
238000001514 detection method Methods 0.000 description 14
210000004216 mammary stem cell Anatomy 0.000 description 14
102000039446 nucleic acids Human genes 0.000 description 14
108020004707 nucleic acids Proteins 0.000 description 14
241000699670 Mus sp. Species 0.000 description 13
241000894007 species Species 0.000 description 13
238000003745 diagnosis Methods 0.000 description 12
230000007705 epithelial mesenchymal transition Effects 0.000 description 12
238000002493 microarray Methods 0.000 description 12
108020005345 3' Untranslated Regions Proteins 0.000 description 11
101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 11
241000699666 Mus <mouse, genus> Species 0.000 description 11
102100038081 Signal transducer CD24 Human genes 0.000 description 11
238000011161 development Methods 0.000 description 11
230000018109 developmental process Effects 0.000 description 11
239000012634 fragment Substances 0.000 description 11
239000002953 phosphate buffered saline Substances 0.000 description 11
238000013456 study Methods 0.000 description 11
208000024891 symptom Diseases 0.000 description 11
108060001084 Luciferase Proteins 0.000 description 10
108091027967 Small hairpin RNA Proteins 0.000 description 10
230000006870 function Effects 0.000 description 10
230000001965 increasing effect Effects 0.000 description 10
239000002609 medium Substances 0.000 description 10
108020004999 messenger RNA Proteins 0.000 description 10
239000002773 nucleotide Substances 0.000 description 10
125000003729 nucleotide group Chemical group 0.000 description 10
238000010186 staining Methods 0.000 description 10
239000000126 substance Substances 0.000 description 10
238000012360 testing method Methods 0.000 description 10
230000000692 anti-sense effect Effects 0.000 description 9
230000033228 biological regulation Effects 0.000 description 9
230000002401 inhibitory effect Effects 0.000 description 9
230000003211 malignant effect Effects 0.000 description 9
210000000056 organ Anatomy 0.000 description 9
102000040650 (ribonucleotides)n+m Human genes 0.000 description 8
239000005089 Luciferase Substances 0.000 description 8
238000001574 biopsy Methods 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
230000003915 cell function Effects 0.000 description 8
238000002512 chemotherapy Methods 0.000 description 8
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound 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 8
230000000295 complement effect Effects 0.000 description 8
230000003247 decreasing effect Effects 0.000 description 8
239000003814 drug Substances 0.000 description 8
210000001671 embryonic stem cell Anatomy 0.000 description 8
238000002474 experimental method Methods 0.000 description 8
239000005090 green fluorescent protein Substances 0.000 description 8
230000037361 pathway Effects 0.000 description 8
238000003752 polymerase chain reaction Methods 0.000 description 8
108090000765 processed proteins & peptides Proteins 0.000 description 8
239000000047 product Substances 0.000 description 8
239000004055 small Interfering RNA Substances 0.000 description 8
108020004414 DNA Proteins 0.000 description 7
108091027977 Mir-200 Proteins 0.000 description 7
210000004369 blood Anatomy 0.000 description 7
239000008280 blood Substances 0.000 description 7
230000010261 cell growth Effects 0.000 description 7
230000003828 downregulation Effects 0.000 description 7
229940079593 drug Drugs 0.000 description 7
239000007924 injection Substances 0.000 description 7
238000002347 injection Methods 0.000 description 7
239000003550 marker Substances 0.000 description 7
239000000463 material Substances 0.000 description 7
206010061289 metastatic neoplasm Diseases 0.000 description 7
102000004196 processed proteins & peptides Human genes 0.000 description 7
238000003757 reverse transcription PCR Methods 0.000 description 7
229920002477 rna polymer Polymers 0.000 description 7
238000012384 transportation and delivery Methods 0.000 description 7
208000005623 Carcinogenesis Diseases 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
206010027476 Metastases Diseases 0.000 description 6
238000011579 SCID mouse model Methods 0.000 description 6
230000027455 binding Effects 0.000 description 6
230000036952 cancer formation Effects 0.000 description 6
231100000504 carcinogenesis Toxicity 0.000 description 6
230000009368 gene silencing by RNA Effects 0.000 description 6
230000012010 growth Effects 0.000 description 6
238000009396 hybridization Methods 0.000 description 6
230000000977 initiatory effect Effects 0.000 description 6
230000036210 malignancy Effects 0.000 description 6
230000035772 mutation Effects 0.000 description 6
239000013642 negative control Substances 0.000 description 6
229920001184 polypeptide Polymers 0.000 description 6
230000008569 process Effects 0.000 description 6
238000004393 prognosis Methods 0.000 description 6
230000035755 proliferation Effects 0.000 description 6
230000004083 survival effect Effects 0.000 description 6
238000001890 transfection Methods 0.000 description 6
102000000905 Cadherin Human genes 0.000 description 5
108050007957 Cadherin Proteins 0.000 description 5
101100297347 Caenorhabditis elegans pgl-3 gene Proteins 0.000 description 5
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
101000872170 Homo sapiens Polycomb complex protein BMI-1 Proteins 0.000 description 5
241001529936 Murinae Species 0.000 description 5
102100033566 Polycomb complex protein BMI-1 Human genes 0.000 description 5
108091030071 RNAI Proteins 0.000 description 5
IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 5
238000013459 approach Methods 0.000 description 5
230000004071 biological effect Effects 0.000 description 5
210000004556 brain Anatomy 0.000 description 5
230000005907 cancer growth Effects 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
210000000349 chromosome Anatomy 0.000 description 5
238000005755 formation reaction Methods 0.000 description 5
238000011534 incubation Methods 0.000 description 5
230000003993 interaction Effects 0.000 description 5
239000002502 liposome Substances 0.000 description 5
210000004072 lung Anatomy 0.000 description 5
230000001537 neural effect Effects 0.000 description 5
238000000926 separation method Methods 0.000 description 5
239000000243 solution Substances 0.000 description 5
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 5
231100000419 toxicity Toxicity 0.000 description 5
230000001988 toxicity Effects 0.000 description 5
238000013518 transcription Methods 0.000 description 5
230000035897 transcription Effects 0.000 description 5
238000013519 translation Methods 0.000 description 5
210000004881 tumor cell Anatomy 0.000 description 5
230000004614 tumor growth Effects 0.000 description 5
238000001262 western blot Methods 0.000 description 5
108020000948 Antisense Oligonucleotides Proteins 0.000 description 4
208000009458 Carcinoma in Situ Diseases 0.000 description 4
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
101000785626 Homo sapiens Zinc finger E-box-binding homeobox 1 Proteins 0.000 description 4
101000723833 Homo sapiens Zinc finger E-box-binding homeobox 2 Proteins 0.000 description 4
102100033420 Keratin, type I cytoskeletal 19 Human genes 0.000 description 4
102100023972 Keratin, type II cytoskeletal 8 Human genes 0.000 description 4
229920001213 Polysorbate 20 Polymers 0.000 description 4
241000700159 Rattus Species 0.000 description 4
108010052090 Renilla Luciferases Proteins 0.000 description 4
210000001744 T-lymphocyte Anatomy 0.000 description 4
102100026457 Zinc finger E-box-binding homeobox 1 Human genes 0.000 description 4
102100028458 Zinc finger E-box-binding homeobox 2 Human genes 0.000 description 4
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 description 4
210000000577 adipose tissue Anatomy 0.000 description 4
238000010171 animal model Methods 0.000 description 4
201000008275 breast carcinoma Diseases 0.000 description 4
230000024245 cell differentiation Effects 0.000 description 4
230000001413 cellular effect Effects 0.000 description 4
238000012512 characterization method Methods 0.000 description 4
235000012000 cholesterol Nutrition 0.000 description 4
230000021615 conjugation Effects 0.000 description 4
238000012217 deletion Methods 0.000 description 4
230000037430 deletion Effects 0.000 description 4
210000003527 eukaryotic cell Anatomy 0.000 description 4
239000012091 fetal bovine serum Substances 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
125000000623 heterocyclic group Chemical group 0.000 description 4
238000001794 hormone therapy Methods 0.000 description 4
201000004933 in situ carcinoma Diseases 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
239000012188 paraffin wax Substances 0.000 description 4
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
230000002062 proliferating effect Effects 0.000 description 4
238000001959 radiotherapy Methods 0.000 description 4
230000004044 response Effects 0.000 description 4
238000007423 screening assay Methods 0.000 description 4
210000002966 serum Anatomy 0.000 description 4
239000007787 solid Substances 0.000 description 4
230000023895 stem cell maintenance Effects 0.000 description 4
239000000758 substrate Substances 0.000 description 4
235000000346 sugar Nutrition 0.000 description 4
238000001356 surgical procedure Methods 0.000 description 4
230000002103 transcriptional effect Effects 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
102000051485 Bcl-2 family Human genes 0.000 description 3
108700038897 Bcl-2 family Proteins 0.000 description 3
-1 Bcl-w Proteins 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
206010009944 Colon cancer Diseases 0.000 description 3
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
206010053759 Growth retardation Diseases 0.000 description 3
241000282412 Homo Species 0.000 description 3
101001081567 Homo sapiens Insulin-like growth factor-binding protein 1 Proteins 0.000 description 3
101000998011 Homo sapiens Keratin, type I cytoskeletal 19 Proteins 0.000 description 3
102100027636 Insulin-like growth factor-binding protein 1 Human genes 0.000 description 3
108010052014 Liberase Proteins 0.000 description 3
101150022024 MYCN gene Proteins 0.000 description 3
241000124008 Mammalia Species 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
108700026495 N-Myc Proto-Oncogene Proteins 0.000 description 3
102000043276 Oncogene Human genes 0.000 description 3
108700020796 Oncogene Proteins 0.000 description 3
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 3
102000040945 Transcription factor Human genes 0.000 description 3
108091023040 Transcription factor Proteins 0.000 description 3
241000700605 Viruses Species 0.000 description 3
230000002159 abnormal effect Effects 0.000 description 3
230000003321 amplification Effects 0.000 description 3
239000000872 buffer Substances 0.000 description 3
238000004113 cell culture Methods 0.000 description 3
210000003169 central nervous system Anatomy 0.000 description 3
238000007385 chemical modification Methods 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
210000002919 epithelial cell Anatomy 0.000 description 3
239000013604 expression vector Substances 0.000 description 3
230000004547 gene signature Effects 0.000 description 3
230000030279 gene silencing Effects 0.000 description 3
230000002962 histologic effect Effects 0.000 description 3
208000015181 infectious disease Diseases 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
238000000370 laser capture micro-dissection Methods 0.000 description 3
150000002611 lead compounds Chemical class 0.000 description 3
108091023663 let-7 stem-loop Proteins 0.000 description 3
108091063478 let-7-1 stem-loop Proteins 0.000 description 3
108091049777 let-7-2 stem-loop Proteins 0.000 description 3
210000001165 lymph node Anatomy 0.000 description 3
238000012423 maintenance Methods 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
230000007246 mechanism Effects 0.000 description 3
230000001394 metastastic effect Effects 0.000 description 3
229930014626 natural product Natural products 0.000 description 3
238000003199 nucleic acid amplification method Methods 0.000 description 3
150000002894 organic compounds Chemical class 0.000 description 3
239000013641 positive control Substances 0.000 description 3
239000002243 precursor Substances 0.000 description 3
230000009467 reduction Effects 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 3
238000011160 research Methods 0.000 description 3
210000002536 stromal cell Anatomy 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
230000008685 targeting Effects 0.000 description 3
239000003981 vehicle Substances 0.000 description 3
230000035899 viability Effects 0.000 description 3
230000003612 virological effect Effects 0.000 description 3
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 2
FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
239000012103 Alexa Fluor 488 Substances 0.000 description 2
APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 2
108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 2
102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 2
208000003950 B-cell lymphoma Diseases 0.000 description 2
206010055113 Breast cancer metastatic Diseases 0.000 description 2
241000283707 Capra Species 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
108091026890 Coding region Proteins 0.000 description 2
102000053602 DNA Human genes 0.000 description 2
239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 2
101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
208000005726 Inflammatory Breast Neoplasms Diseases 0.000 description 2
206010021980 Inflammatory carcinoma of the breast Diseases 0.000 description 2
102100032816 Integrin alpha-6 Human genes 0.000 description 2
102000018697 Membrane Proteins Human genes 0.000 description 2
108010052285 Membrane Proteins Proteins 0.000 description 2
102000055056 N-Myc Proto-Oncogene Human genes 0.000 description 2
208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 2
238000000636 Northern blotting Methods 0.000 description 2
229930012538 Paclitaxel Natural products 0.000 description 2
241000288906 Primates Species 0.000 description 2
108010007568 Protamines Proteins 0.000 description 2
102000007327 Protamines Human genes 0.000 description 2
238000011529 RT qPCR Methods 0.000 description 2
102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
108700008625 Reporter Genes Proteins 0.000 description 2
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
108020004459 Small interfering RNA Proteins 0.000 description 2
108091008874 T cell receptors Proteins 0.000 description 2
102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
230000001594 aberrant effect Effects 0.000 description 2
230000002411 adverse Effects 0.000 description 2
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 2
229960003942 amphotericin b Drugs 0.000 description 2
230000001028 anti-proliverative effect Effects 0.000 description 2
239000000427 antigen Substances 0.000 description 2
108091007433 antigens Proteins 0.000 description 2
102000036639 antigens Human genes 0.000 description 2
238000000149 argon plasma sintering Methods 0.000 description 2
238000003491 array Methods 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
210000003719 b-lymphocyte Anatomy 0.000 description 2
230000008901 benefit Effects 0.000 description 2
210000000988 bone and bone Anatomy 0.000 description 2
150000001720 carbohydrates Chemical class 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
238000000423 cell based assay Methods 0.000 description 2
239000013592 cell lysate Substances 0.000 description 2
210000000170 cell membrane Anatomy 0.000 description 2
230000004663 cell proliferation Effects 0.000 description 2
239000002458 cell surface marker Substances 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
125000003636 chemical group Chemical group 0.000 description 2
229940044683 chemotherapy drug Drugs 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
230000003021 clonogenic effect Effects 0.000 description 2
230000005757 colony formation Effects 0.000 description 2
239000002299 complementary DNA Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
229960004397 cyclophosphamide Drugs 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
239000000975 dye Substances 0.000 description 2
230000002900 effect on cell Effects 0.000 description 2
201000002246 embryonal cancer Diseases 0.000 description 2
239000003623 enhancer Substances 0.000 description 2
210000000981 epithelium Anatomy 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
150000004665 fatty acids Chemical class 0.000 description 2
239000012894 fetal calf serum Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
238000001415 gene therapy Methods 0.000 description 2
230000002068 genetic effect Effects 0.000 description 2
230000000762 glandular Effects 0.000 description 2
231100000001 growth retardation Toxicity 0.000 description 2
210000005260 human cell Anatomy 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
238000010166 immunofluorescence Methods 0.000 description 2
210000004263 induced pluripotent stem cell Anatomy 0.000 description 2
230000001939 inductive effect Effects 0.000 description 2
201000004653 inflammatory breast carcinoma Diseases 0.000 description 2
238000011221 initial treatment Methods 0.000 description 2
238000003780 insertion Methods 0.000 description 2
230000037431 insertion Effects 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
230000002452 interceptive effect Effects 0.000 description 2
230000009545 invasion Effects 0.000 description 2
208000028867 ischemia Diseases 0.000 description 2
238000002372 labelling Methods 0.000 description 2
239000007788 liquid Substances 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
239000006166 lysate Substances 0.000 description 2
230000002934 lysing effect Effects 0.000 description 2
210000004962 mammalian cell Anatomy 0.000 description 2
210000005075 mammary gland Anatomy 0.000 description 2
230000004066 metabolic change Effects 0.000 description 2
230000009401 metastasis Effects 0.000 description 2
108091031103 miR-181a stem-loop Proteins 0.000 description 2
108091046591 miR-181a-4 stem-loop Proteins 0.000 description 2
108091049627 miR-181a-5 stem-loop Proteins 0.000 description 2
230000000897 modulatory effect Effects 0.000 description 2
238000012544 monitoring process Methods 0.000 description 2
210000002569 neuron Anatomy 0.000 description 2
108091027963 non-coding RNA Proteins 0.000 description 2
102000042567 non-coding RNA Human genes 0.000 description 2
229960001592 paclitaxel Drugs 0.000 description 2
230000036961 partial effect Effects 0.000 description 2
239000013610 patient sample Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
238000000053 physical method Methods 0.000 description 2
239000013612 plasmid Substances 0.000 description 2
238000010837 poor prognosis Methods 0.000 description 2
230000002265 prevention Effects 0.000 description 2
238000012545 processing Methods 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
229940048914 protamine Drugs 0.000 description 2
150000003212 purines Chemical class 0.000 description 2
150000003230 pyrimidines Chemical class 0.000 description 2
230000004043 responsiveness Effects 0.000 description 2
230000007017 scission Effects 0.000 description 2
230000019491 signal transduction Effects 0.000 description 2
210000003491 skin Anatomy 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000001509 sodium citrate Substances 0.000 description 2
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
206010041823 squamous cell carcinoma Diseases 0.000 description 2
150000003431 steroids Chemical class 0.000 description 2
229960005322 streptomycin Drugs 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
230000001629 suppression Effects 0.000 description 2
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
230000005026 transcription initiation Effects 0.000 description 2
108091006107 transcriptional repressors Proteins 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
HFJMJLXCBVKXNY-IVZWLZJFSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-prop-1-ynylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C#CC)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 HFJMJLXCBVKXNY-IVZWLZJFSA-N 0.000 description 1
MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 1
CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
ZRFXOICDDKDRNA-IVZWLZJFSA-N 4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-prop-1-ynylpyrimidin-2-one Chemical compound O=C1N=C(N)C(C#CC)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 ZRFXOICDDKDRNA-IVZWLZJFSA-N 0.000 description 1
CKTSBUTUHBMZGZ-ULQXZJNLSA-N 4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-tritiopyrimidin-2-one Chemical compound O=C1N=C(N)C([3H])=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-ULQXZJNLSA-N 0.000 description 1
KISUPFXQEHWGAR-RRKCRQDMSA-N 4-amino-5-bromo-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(Br)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 KISUPFXQEHWGAR-RRKCRQDMSA-N 0.000 description 1
LUCHPKXVUGJYGU-XLPZGREQSA-N 5-methyl-2'-deoxycytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 LUCHPKXVUGJYGU-XLPZGREQSA-N 0.000 description 1
108091027075 5S-rRNA precursor Proteins 0.000 description 1
208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
239000012110 Alexa Fluor 594 Substances 0.000 description 1
102000002260 Alkaline Phosphatase Human genes 0.000 description 1
108020004774 Alkaline Phosphatase Proteins 0.000 description 1
102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
108090001008 Avidin Proteins 0.000 description 1
108700010154 BRCA2 Genes Proteins 0.000 description 1
206010004146 Basal cell carcinoma Diseases 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
208000003174 Brain Neoplasms Diseases 0.000 description 1
101150008921 Brca2 gene Proteins 0.000 description 1
241000244203 Caenorhabditis elegans Species 0.000 description 1
241000282465 Canis Species 0.000 description 1
GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
108090000565 Capsid Proteins Proteins 0.000 description 1
102000014914 Carrier Proteins Human genes 0.000 description 1
102100023321 Ceruloplasmin Human genes 0.000 description 1
108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 1
108010077544 Chromatin Proteins 0.000 description 1
208000001333 Colorectal Neoplasms Diseases 0.000 description 1
241000699800 Cricetinae Species 0.000 description 1
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
238000012270 DNA recombination Methods 0.000 description 1
CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
206010059866 Drug resistance Diseases 0.000 description 1
238000003718 Dual-Luciferase Reporter Assay System Methods 0.000 description 1
208000006402 Ductal Carcinoma Diseases 0.000 description 1
102100023387 Endoribonuclease Dicer Human genes 0.000 description 1
241000283074 Equus asinus Species 0.000 description 1
241000283073 Equus caballus Species 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
241000282324 Felis Species 0.000 description 1
102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
108090000331 Firefly luciferases Proteins 0.000 description 1
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
102000004315 Forkhead Transcription Factors Human genes 0.000 description 1
108090000852 Forkhead Transcription Factors Proteins 0.000 description 1
101710113436 GTPase KRas Proteins 0.000 description 1
102100030708 GTPase KRas Human genes 0.000 description 1
208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
229920002527 Glycogen Polymers 0.000 description 1
108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
239000012981 Hank's balanced salt solution Substances 0.000 description 1
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
101000907904 Homo sapiens Endoribonuclease Dicer Proteins 0.000 description 1
101000584612 Homo sapiens GTPase KRas Proteins 0.000 description 1
101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
101001056180 Homo sapiens Induced myeloid leukemia cell differentiation protein Mcl-1 Proteins 0.000 description 1
101000869796 Homo sapiens Microprocessor complex subunit DGCR8 Proteins 0.000 description 1
101001126417 Homo sapiens Platelet-derived growth factor receptor alpha Proteins 0.000 description 1
101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
101000610551 Homo sapiens Prominin-1 Proteins 0.000 description 1
101001120822 Homo sapiens Putative microRNA 17 host gene protein Proteins 0.000 description 1
101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 1
101000800133 Homo sapiens Thyroglobulin Proteins 0.000 description 1
101000636213 Homo sapiens Transcriptional activator Myb Proteins 0.000 description 1
101000633054 Homo sapiens Zinc finger protein SNAI2 Proteins 0.000 description 1
241000701024 Human betaherpesvirus 5 Species 0.000 description 1
108060003951 Immunoglobulin Proteins 0.000 description 1
102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 description 1
102100023915 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
206010069755 K-ras gene mutation Diseases 0.000 description 1
102100040445 Keratin, type I cytoskeletal 14 Human genes 0.000 description 1
108010066321 Keratin-14 Proteins 0.000 description 1
108010066302 Keratin-19 Proteins 0.000 description 1
108010070511 Keratin-8 Proteins 0.000 description 1
102000011782 Keratins Human genes 0.000 description 1
108010076876 Keratins Proteins 0.000 description 1
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
239000012097 Lipofectamine 2000 Substances 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
208000007433 Lymphatic Metastasis Diseases 0.000 description 1
206010026673 Malignant Pleural Effusion Diseases 0.000 description 1
102100025169 Max-binding protein MNT Human genes 0.000 description 1
108091028141 MiR-203 Proteins 0.000 description 1
102100032459 Microprocessor complex subunit DGCR8 Human genes 0.000 description 1
208000034450 Multilocular cystic renal neoplasm of low malignant potential Diseases 0.000 description 1
108091057508 Myc family Proteins 0.000 description 1
201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
206010061309 Neoplasm progression Diseases 0.000 description 1
101710163270 Nuclease Proteins 0.000 description 1
102000015636 Oligopeptides Human genes 0.000 description 1
108010038807 Oligopeptides Proteins 0.000 description 1
108700026244 Open Reading Frames Proteins 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
206010033128 Ovarian cancer Diseases 0.000 description 1
108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
241001494479 Pecora Species 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
108091093037 Peptide nucleic acid Proteins 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
108010004729 Phycoerythrin Proteins 0.000 description 1
102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
102100030485 Platelet-derived growth factor receptor alpha Human genes 0.000 description 1
102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
108010022429 Polycomb-Group Proteins Proteins 0.000 description 1
102000012425 Polycomb-Group Proteins Human genes 0.000 description 1
102100040120 Prominin-1 Human genes 0.000 description 1
108700020978 Proto-Oncogene Proteins 0.000 description 1
102000052575 Proto-Oncogene Human genes 0.000 description 1
108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 1
102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 1
102100026055 Putative microRNA 17 host gene protein Human genes 0.000 description 1
108020004518 RNA Probes Proteins 0.000 description 1
238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
239000003391 RNA probe Substances 0.000 description 1
101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 1
108700005075 Regulator Genes Proteins 0.000 description 1
208000006265 Renal cell carcinoma Diseases 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
239000012722 SDS sample buffer Substances 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
102000039471 Small Nuclear RNA Human genes 0.000 description 1
108020003224 Small Nucleolar RNA Proteins 0.000 description 1
102000042773 Small Nucleolar RNA Human genes 0.000 description 1
206010041067 Small cell lung cancer Diseases 0.000 description 1
206010068771 Soft tissue neoplasm Diseases 0.000 description 1
208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 1
102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 1
108010090804 Streptavidin Proteins 0.000 description 1
101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
208000034972 Sudden Infant Death Diseases 0.000 description 1
206010042440 Sudden infant death syndrome Diseases 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
229940123237 Taxane Drugs 0.000 description 1
102100030780 Transcriptional activator Myb Human genes 0.000 description 1
102000004243 Tubulin Human genes 0.000 description 1
108090000704 Tubulin Proteins 0.000 description 1
102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
102100029570 Zinc finger protein SNAI2 Human genes 0.000 description 1
230000035508 accumulation Effects 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
238000007792 addition Methods 0.000 description 1
208000009956 adenocarcinoma Diseases 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
238000009098 adjuvant therapy Methods 0.000 description 1
229940009456 adriamycin Drugs 0.000 description 1
210000004504 adult stem cell Anatomy 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
238000003314 affinity selection Methods 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
230000006909 anti-apoptosis Effects 0.000 description 1
230000002424 anti-apoptotic effect Effects 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
238000002617 apheresis Methods 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
239000003855 balanced salt solution Substances 0.000 description 1
108700000711 bcl-X Proteins 0.000 description 1
102000055104 bcl-X Human genes 0.000 description 1
239000011324 bead Substances 0.000 description 1
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
108091008324 binding proteins Proteins 0.000 description 1
239000013060 biological fluid Substances 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
239000012472 biological sample Substances 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin Substances 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
210000001124 body fluid Anatomy 0.000 description 1
210000001185 bone marrow Anatomy 0.000 description 1
UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
239000006172 buffering agent Substances 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
239000012830 cancer therapeutic Substances 0.000 description 1
229960004117 capecitabine Drugs 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000007910 cell fusion Effects 0.000 description 1
239000002771 cell marker Substances 0.000 description 1
230000012292 cell migration Effects 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
230000010001 cellular homeostasis Effects 0.000 description 1
230000030570 cellular localization Effects 0.000 description 1
210000001175 cerebrospinal fluid Anatomy 0.000 description 1
230000008859 change Effects 0.000 description 1
210000003483 chromatin Anatomy 0.000 description 1
230000002759 chromosomal effect Effects 0.000 description 1
238000010367 cloning Methods 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
238000010293 colony formation assay Methods 0.000 description 1
238000009096 combination chemotherapy Methods 0.000 description 1
238000002591 computed tomography Methods 0.000 description 1
238000004590 computer program Methods 0.000 description 1
238000004624 confocal microscopy Methods 0.000 description 1
239000013068 control sample Substances 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
238000011443 conventional therapy Methods 0.000 description 1
230000009260 cross reactivity Effects 0.000 description 1
210000004748 cultured cell Anatomy 0.000 description 1
230000001351 cycling effect Effects 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
239000002254 cytotoxic agent Substances 0.000 description 1
231100000599 cytotoxic agent Toxicity 0.000 description 1
238000011393 cytotoxic chemotherapy Methods 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
238000007405 data analysis Methods 0.000 description 1
230000034994 death Effects 0.000 description 1
230000007547 defect Effects 0.000 description 1
MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 1
239000003599 detergent Substances 0.000 description 1
230000029087 digestion Effects 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical group P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
230000006806 disease prevention Effects 0.000 description 1
230000005750 disease progression Effects 0.000 description 1
BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000009826 distribution Methods 0.000 description 1
NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical class OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
229960003668 docetaxel Drugs 0.000 description 1
229960004679 doxorubicin Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000008482 dysregulation Effects 0.000 description 1
238000004520 electroporation Methods 0.000 description 1
231100001129 embryonic lethality Toxicity 0.000 description 1
230000012202 endocytosis Effects 0.000 description 1
230000003511 endothelial effect Effects 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
238000007387 excisional biopsy Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
230000003176 fibrotic effect Effects 0.000 description 1
GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
238000000799 fluorescence microscopy Methods 0.000 description 1
238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
229960002949 fluorouracil Drugs 0.000 description 1
235000013305 food Nutrition 0.000 description 1
230000005714 functional activity Effects 0.000 description 1
238000002825 functional assay Methods 0.000 description 1
230000002538 fungal effect Effects 0.000 description 1
229960005277 gemcitabine Drugs 0.000 description 1
SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
238000011223 gene expression profiling Methods 0.000 description 1
238000012252 genetic analysis Methods 0.000 description 1
210000004602 germ cell Anatomy 0.000 description 1
229940096919 glycogen Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
210000004524 haematopoietic cell Anatomy 0.000 description 1
201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 1
210000003958 hematopoietic stem cell Anatomy 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
206010073071 hepatocellular carcinoma Diseases 0.000 description 1
231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
238000013537 high throughput screening Methods 0.000 description 1
230000001744 histochemical effect Effects 0.000 description 1
108091008039 hormone receptors Proteins 0.000 description 1
102000048851 human CD44 Human genes 0.000 description 1
102000047444 human SOX2 Human genes 0.000 description 1
102000047688 human TG Human genes 0.000 description 1
210000004408 hybridoma Anatomy 0.000 description 1
230000001900 immune effect Effects 0.000 description 1
238000003018 immunoassay Methods 0.000 description 1
102000018358 immunoglobulin Human genes 0.000 description 1
238000012151 immunohistochemical method Methods 0.000 description 1
238000003364 immunohistochemistry Methods 0.000 description 1
238000007386 incisional biopsy Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
239000000411 inducer Substances 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
102000028416 insulin-like growth factor binding Human genes 0.000 description 1
108091022911 insulin-like growth factor binding Proteins 0.000 description 1
230000010354 integration Effects 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
208000030776 invasive breast carcinoma Diseases 0.000 description 1
208000024312 invasive carcinoma Diseases 0.000 description 1
229960002725 isoflurane Drugs 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
230000003902 lesion Effects 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
210000000265 leukocyte Anatomy 0.000 description 1
239000003446 ligand Substances 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
238000003468 luciferase reporter gene assay Methods 0.000 description 1
HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
201000005249 lung adenocarcinoma Diseases 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
201000009546 lung large cell carcinoma Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
201000000966 lung oat cell carcinoma Diseases 0.000 description 1
210000002751 lymph Anatomy 0.000 description 1
230000001926 lymphatic effect Effects 0.000 description 1
210000001161 mammalian embryo Anatomy 0.000 description 1
230000008176 mammary development Effects 0.000 description 1
108010082117 matrigel Proteins 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 1
239000012528 membrane Substances 0.000 description 1
210000005033 mesothelial cell Anatomy 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
108091043187 miR-30a stem-loop Proteins 0.000 description 1
238000010208 microarray analysis Methods 0.000 description 1
244000005700 microbiome Species 0.000 description 1
238000000520 microinjection Methods 0.000 description 1
210000003470 mitochondria Anatomy 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000009456 molecular mechanism Effects 0.000 description 1
201000010274 multilocular clear cell renal cell carcinoma Diseases 0.000 description 1
238000002703 mutagenesis Methods 0.000 description 1
231100000350 mutagenesis Toxicity 0.000 description 1
201000011216 nasopharynx carcinoma Diseases 0.000 description 1
238000013188 needle biopsy Methods 0.000 description 1
210000005170 neoplastic cell Anatomy 0.000 description 1
210000001178 neural stem cell Anatomy 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000010606 normalization Methods 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
229920002113 octoxynol Polymers 0.000 description 1
239000002674 ointment Substances 0.000 description 1
238000002515 oligonucleotide synthesis Methods 0.000 description 1
231100000590 oncogenic Toxicity 0.000 description 1
230000002246 oncogenic effect Effects 0.000 description 1
238000011275 oncology therapy Methods 0.000 description 1
230000005305 organ development Effects 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
239000003002 pH adjusting agent Substances 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
238000004091 panning Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000007170 pathology Effects 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
229940056360 penicillin g Drugs 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
230000035699 permeability Effects 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
239000002831 pharmacologic agent Substances 0.000 description 1
RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
150000004713 phosphodiesters Chemical group 0.000 description 1
SXADIBFZNXBEGI-UHFFFAOYSA-N phosphoramidous acid Chemical group NP(O)O SXADIBFZNXBEGI-UHFFFAOYSA-N 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
108060006184 phycobiliprotein Proteins 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
239000013600 plasmid vector Substances 0.000 description 1
210000001778 pluripotent stem cell Anatomy 0.000 description 1
238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
229920002981 polyvinylidene fluoride Polymers 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
230000000861 pro-apoptotic effect Effects 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
108700042226 ras Genes Proteins 0.000 description 1
108010014186 ras Proteins Proteins 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000010188 recombinant method Methods 0.000 description 1
208000016691 refractory malignant neoplasm Diseases 0.000 description 1
230000023276 regulation of development, heterochronic Effects 0.000 description 1
230000030198 regulation of embryonic development Effects 0.000 description 1
230000014493 regulation of gene expression Effects 0.000 description 1
230000037425 regulation of transcription Effects 0.000 description 1
230000009712 regulation of translation Effects 0.000 description 1
230000008439 repair process Effects 0.000 description 1
230000002629 repopulating effect Effects 0.000 description 1
230000008672 reprogramming Effects 0.000 description 1
238000002271 resection Methods 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
230000001177 retroviral effect Effects 0.000 description 1
238000010839 reverse transcription Methods 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
238000010845 search algorithm Methods 0.000 description 1
230000009758 senescence Effects 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
235000020183 skimmed milk Nutrition 0.000 description 1
208000000649 small cell carcinoma Diseases 0.000 description 1
208000000587 small cell lung carcinoma Diseases 0.000 description 1
108091029842 small nuclear ribonucleic acid Proteins 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
238000005063 solubilization Methods 0.000 description 1
230000007928 solubilization Effects 0.000 description 1
210000001082 somatic cell Anatomy 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
230000007480 spreading Effects 0.000 description 1
238000003892 spreading Methods 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000012192 staining solution Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000024642 stem cell division Effects 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
210000001179 synovial fluid Anatomy 0.000 description 1
238000012385 systemic delivery Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
238000009121 systemic therapy Methods 0.000 description 1
238000012353 t test Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000030968 tissue homeostasis Effects 0.000 description 1
230000025934 tissue morphogenesis Effects 0.000 description 1
238000004448 titration Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
108091006106 transcriptional activators Proteins 0.000 description 1
108091008023 transcriptional regulators Proteins 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000009261 transgenic effect Effects 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
206010044412 transitional cell carcinoma Diseases 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
238000011277 treatment modality Methods 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
230000005740 tumor formation Effects 0.000 description 1
210000005102 tumor initiating cell Anatomy 0.000 description 1
239000000439 tumor marker Substances 0.000 description 1
230000005751 tumor progression Effects 0.000 description 1
241000701161 unidentified adenovirus Species 0.000 description 1
241001430294 unidentified retrovirus Species 0.000 description 1
230000003827 upregulation Effects 0.000 description 1
229960005486 vaccine Drugs 0.000 description 1
238000010200 validation analysis Methods 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
229960002066 vinorelbine Drugs 0.000 description 1
GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1