CA2765770A1

CA2765770A1 - Agents and uses thereof

Agents and uses thereof Download PDF

Info

Publication number: CA2765770A1
Authority: CA; Canada
Prior art keywords: sox11; agent; agent according; lymphoma; cancer
Prior art date: 2009-06-19
Legal status : Abandoned

Application number

CA2765770A

Other languages

English (en)

French (fr)

Inventor

Carl Arne Krister Borrebaeck

Sara Charlotte Andersson Ek

Current Assignee

Immunovia AB

Original Assignee

Immunovia AB

Priority date

2009-06-19

Filing date

2010-06-18

Publication date

2010-12-23

2010-06-18 Application filed by Immunovia AB filed Critical Immunovia AB

2010-12-23 Publication of CA2765770A1 publication Critical patent/CA2765770A1/en

Status Abandoned legal-status Critical Current

Links

101150020367 SOX11 gene Proteins 0.000 claims abstract description 233
239000003795 chemical substances by application Substances 0.000 claims abstract description 181
206010028980 Neoplasm Diseases 0.000 claims abstract description 100
238000000034 method Methods 0.000 claims abstract description 60
206010025323 Lymphomas Diseases 0.000 claims abstract description 36
239000003814 drug Substances 0.000 claims abstract description 20
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
230000003213 activating effect Effects 0.000 claims abstract description 13
238000011282 treatment Methods 0.000 claims abstract description 13
210000004027 cell Anatomy 0.000 claims description 196
208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 104
201000011510 cancer Diseases 0.000 claims description 65
230000011987 methylation Effects 0.000 claims description 39
238000007069 methylation reaction Methods 0.000 claims description 39
108020004414 DNA Proteins 0.000 claims description 37
239000012634 fragment Substances 0.000 claims description 36
102000004196 processed proteins & peptides Human genes 0.000 claims description 34
108090000765 processed proteins & peptides Proteins 0.000 claims description 34
229920001184 polypeptide Polymers 0.000 claims description 33
206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 32
230000035755 proliferation Effects 0.000 claims description 32
208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 30
108020004999 messenger RNA Proteins 0.000 claims description 29
230000027455 binding Effects 0.000 claims description 28
238000009739 binding Methods 0.000 claims description 28
208000003950 B-cell lymphoma Diseases 0.000 claims description 27
201000003444 follicular lymphoma Diseases 0.000 claims description 26
239000000203 mixture Substances 0.000 claims description 22
102000039446 nucleic acids Human genes 0.000 claims description 21
108020004707 nucleic acids Proteins 0.000 claims description 21
150000007523 nucleic acids Chemical class 0.000 claims description 21
150000001413 amino acids Chemical class 0.000 claims description 17
239000013598 vector Substances 0.000 claims description 17
230000001965 increasing effect Effects 0.000 claims description 16
208000032839 leukemia Diseases 0.000 claims description 16
241000701161 unidentified adenovirus Species 0.000 claims description 15
239000000427 antigen Substances 0.000 claims description 14
108091007433 antigens Proteins 0.000 claims description 14
102000036639 antigens Human genes 0.000 claims description 14
230000008685 targeting Effects 0.000 claims description 14
108700039691 Genetic Promoter Regions Proteins 0.000 claims description 13
210000003169 central nervous system Anatomy 0.000 claims description 12
238000013518 transcription Methods 0.000 claims description 12
230000035897 transcription Effects 0.000 claims description 12
238000009472 formulation Methods 0.000 claims description 11
230000004927 fusion Effects 0.000 claims description 11
208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 claims description 10
206010033128 Ovarian cancer Diseases 0.000 claims description 10
210000000952 spleen Anatomy 0.000 claims description 9
241001430294 unidentified retrovirus Species 0.000 claims description 9
241000700605 Viruses Species 0.000 claims description 8
210000003491 skin Anatomy 0.000 claims description 8
210000004369 blood Anatomy 0.000 claims description 7
239000008280 blood Substances 0.000 claims description 7
239000002299 complementary DNA Substances 0.000 claims description 7
238000001415 gene therapy Methods 0.000 claims description 7
230000002401 inhibitory effect Effects 0.000 claims description 7
230000001404 mediated effect Effects 0.000 claims description 7
239000002773 nucleotide Substances 0.000 claims description 7
125000003729 nucleotide group Chemical group 0.000 claims description 7
239000000651 prodrug Substances 0.000 claims description 7
229940002612 prodrug Drugs 0.000 claims description 7
239000000546 pharmaceutical excipient Substances 0.000 claims description 6
206010000871 Acute monocytic leukaemia Diseases 0.000 claims description 5
230000004071 biological effect Effects 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
210000001989 nasopharynx Anatomy 0.000 claims description 5
238000007911 parenteral administration Methods 0.000 claims description 5
230000011664 signaling Effects 0.000 claims description 5
241000700588 Human alphaherpesvirus 1 Species 0.000 claims description 4
102100026459 POU domain, class 3, transcription factor 2 Human genes 0.000 claims description 4
102100026456 POU domain, class 3, transcription factor 3 Human genes 0.000 claims description 4
101710133393 POU domain, class 3, transcription factor 3 Proteins 0.000 claims description 4
210000001185 bone marrow Anatomy 0.000 claims description 4
210000000481 breast Anatomy 0.000 claims description 4
230000004611 cancer cell death Effects 0.000 claims description 4
210000002569 neuron Anatomy 0.000 claims description 4
239000013612 plasmid Substances 0.000 claims description 4
108010072897 transcription factor Brn-2 Proteins 0.000 claims description 4
238000013519 translation Methods 0.000 claims description 4
241000702421 Dependoparvovirus Species 0.000 claims description 3
210000000013 bile duct Anatomy 0.000 claims description 3
210000000988 bone and bone Anatomy 0.000 claims description 3
210000004556 brain Anatomy 0.000 claims description 3
230000030833 cell death Effects 0.000 claims description 3
210000001072 colon Anatomy 0.000 claims description 3
210000000232 gallbladder Anatomy 0.000 claims description 3
210000001035 gastrointestinal tract Anatomy 0.000 claims description 3
210000004907 gland Anatomy 0.000 claims description 3
210000003734 kidney Anatomy 0.000 claims description 3
210000004185 liver Anatomy 0.000 claims description 3
210000004072 lung Anatomy 0.000 claims description 3
210000002751 lymph Anatomy 0.000 claims description 3
210000000056 organ Anatomy 0.000 claims description 3
210000002307 prostate Anatomy 0.000 claims description 3
230000001850 reproductive effect Effects 0.000 claims description 3
210000002784 stomach Anatomy 0.000 claims description 3
FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 2
208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 2
241000714192 Human spumaretrovirus Species 0.000 claims description 2
108010067060 Immunoglobulin Variable Region Proteins 0.000 claims description 2
102000017727 Immunoglobulin Variable Region Human genes 0.000 claims description 2
241000713666 Lentivirus Species 0.000 claims description 2
241000702263 Reovirus sp. Species 0.000 claims description 2
210000002919 epithelial cell Anatomy 0.000 claims description 2
239000002479 lipoplex Substances 0.000 claims description 2
150000003384 small molecules Chemical class 0.000 claims description 2
108091032973 (ribonucleotides)n+m Proteins 0.000 claims 1
101001007348 Arachis hypogaea Galactose-binding lectin Proteins 0.000 claims 1
230000014509 gene expression Effects 0.000 description 69
108090000623 proteins and genes Proteins 0.000 description 59
102000004169 proteins and genes Human genes 0.000 description 42
101000825086 Homo sapiens Transcription factor SOX-11 Proteins 0.000 description 40
102000053602 DNA Human genes 0.000 description 36
102100022415 Transcription factor SOX-11 Human genes 0.000 description 36
235000018102 proteins Nutrition 0.000 description 36
241000282414 Homo sapiens Species 0.000 description 33
108010058546 Cyclin D1 Proteins 0.000 description 29
102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 29
208000011691 Burkitt lymphomas Diseases 0.000 description 28
108091034117 Oligonucleotide Proteins 0.000 description 27
238000004458 analytical method Methods 0.000 description 26
230000000694 effects Effects 0.000 description 25
230000002018 overexpression Effects 0.000 description 20
150000001875 compounds Chemical class 0.000 description 18
238000003197 gene knockdown Methods 0.000 description 17
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 16
229940024606 amino acid Drugs 0.000 description 15
238000001727 in vivo Methods 0.000 description 15
108020004459 Small interfering RNA Proteins 0.000 description 14
235000001014 amino acid Nutrition 0.000 description 14
210000003719 b-lymphocyte Anatomy 0.000 description 14
238000002474 experimental method Methods 0.000 description 14
150000003839 salts Chemical class 0.000 description 14
230000000875 corresponding effect Effects 0.000 description 12
210000002741 palatine tonsil Anatomy 0.000 description 12
238000012163 sequencing technique Methods 0.000 description 12
230000004083 survival effect Effects 0.000 description 12
108700028369 Alleles Proteins 0.000 description 11
102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 11
108091029523 CpG island Proteins 0.000 description 11
101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 11
241001465754 Metazoa Species 0.000 description 11
206010042971 T-cell lymphoma Diseases 0.000 description 11
229940079593 drug Drugs 0.000 description 11
230000006870 function Effects 0.000 description 11
201000009277 hairy cell leukemia Diseases 0.000 description 11
239000002245 particle Substances 0.000 description 11
238000010186 staining Methods 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
101000652332 Homo sapiens Transcription factor SOX-1 Proteins 0.000 description 10
238000011529 RT qPCR Methods 0.000 description 10
208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 10
102100030248 Transcription factor SOX-1 Human genes 0.000 description 10
239000002253 acid Substances 0.000 description 10
239000002585 base Substances 0.000 description 10
239000000523 sample Substances 0.000 description 10
239000000243 solution Substances 0.000 description 10
210000001519 tissue Anatomy 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
230000001177 retroviral effect Effects 0.000 description 9
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 8
230000007067 DNA methylation Effects 0.000 description 8
102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 8
102100034343 Integrase Human genes 0.000 description 8
101100310657 Mus musculus Sox1 gene Proteins 0.000 description 8
206010035226 Plasma cell myeloma Diseases 0.000 description 8
108010092799 RNA-directed DNA polymerase Proteins 0.000 description 8
RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 8
230000015556 catabolic process Effects 0.000 description 8
201000010099 disease Diseases 0.000 description 8
230000002068 genetic effect Effects 0.000 description 8
108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 8
210000004881 tumor cell Anatomy 0.000 description 8
238000001262 western blot Methods 0.000 description 8
108010021625 Immunoglobulin Fragments Proteins 0.000 description 7
102000008394 Immunoglobulin Fragments Human genes 0.000 description 7
208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 7
210000001744 T-lymphocyte Anatomy 0.000 description 7
102000040945 Transcription factor Human genes 0.000 description 7
108091023040 Transcription factor Proteins 0.000 description 7
238000003556 assay Methods 0.000 description 7
239000000872 buffer Substances 0.000 description 7
230000007423 decrease Effects 0.000 description 7
239000007924 injection Substances 0.000 description 7
238000002347 injection Methods 0.000 description 7
230000003211 malignant effect Effects 0.000 description 7
201000000050 myeloid neoplasm Diseases 0.000 description 7
210000004940 nucleus Anatomy 0.000 description 7
229920002477 rna polymer Polymers 0.000 description 7
239000000725 suspension Substances 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
238000013459 approach Methods 0.000 description 6
238000001369 bisulfite sequencing Methods 0.000 description 6
230000003247 decreasing effect Effects 0.000 description 6
238000006731 degradation reaction Methods 0.000 description 6
238000009826 distribution Methods 0.000 description 6
230000030279 gene silencing Effects 0.000 description 6
239000002609 medium Substances 0.000 description 6
RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 6
238000011144 upstream manufacturing Methods 0.000 description 6
108010047041 Complementarity Determining Regions Proteins 0.000 description 5
208000017604 Hodgkin disease Diseases 0.000 description 5
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 5
241000699670 Mus sp. Species 0.000 description 5
241000283973 Oryctolagus cuniculus Species 0.000 description 5
108010082046 SOXC Transcription Factors Proteins 0.000 description 5
102000003703 SOXC Transcription Factors Human genes 0.000 description 5
102000014307 Transcription factor SOX-11 Human genes 0.000 description 5
108050003311 Transcription factor SOX-11 Proteins 0.000 description 5
230000004913 activation Effects 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
230000002596 correlated effect Effects 0.000 description 5
238000000684 flow cytometry Methods 0.000 description 5
230000012010 growth Effects 0.000 description 5
230000001976 improved effect Effects 0.000 description 5
238000000338 in vitro Methods 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
239000002502 liposome Substances 0.000 description 5
201000011649 lymphoblastic lymphoma Diseases 0.000 description 5
238000004519 manufacturing process Methods 0.000 description 5
230000009826 neoplastic cell growth Effects 0.000 description 5
230000001537 neural effect Effects 0.000 description 5
150000008298 phosphoramidates Chemical class 0.000 description 5
239000000843 powder Substances 0.000 description 5
239000003826 tablet Substances 0.000 description 5
230000001225 therapeutic effect Effects 0.000 description 5
230000005945 translocation Effects 0.000 description 5
230000004614 tumor growth Effects 0.000 description 5
IPDRTIBDOPMMIQ-VAOFZXAKSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)-2-methyloxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@]1(C)O[C@H](CO)[C@@H](O)C1 IPDRTIBDOPMMIQ-VAOFZXAKSA-N 0.000 description 4
206010073478 Anaplastic large-cell lymphoma Diseases 0.000 description 4
208000025321 B-lymphoblastic leukemia/lymphoma Diseases 0.000 description 4
102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 4
108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
101100356020 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) recA gene Proteins 0.000 description 4
238000009015 Human TaqMan MicroRNA Assay kit Methods 0.000 description 4
241000701044 Human gammaherpesvirus 4 Species 0.000 description 4
208000030289 Lymphoproliferative disease Diseases 0.000 description 4
241000699666 Mus <mouse, genus> Species 0.000 description 4
101100042680 Mus musculus Slc7a1 gene Proteins 0.000 description 4
101710163270 Nuclease Proteins 0.000 description 4
229910019142 PO4 Inorganic materials 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
108700009124 Transcription Initiation Site Proteins 0.000 description 4
230000001594 aberrant effect Effects 0.000 description 4
239000000443 aerosol Substances 0.000 description 4
230000010261 cell growth Effects 0.000 description 4
230000008859 change Effects 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 4
230000000295 complement effect Effects 0.000 description 4
230000001086 cytosolic effect Effects 0.000 description 4
230000017858 demethylation Effects 0.000 description 4
238000010520 demethylation reaction Methods 0.000 description 4
238000012377 drug delivery Methods 0.000 description 4
229940088598 enzyme Drugs 0.000 description 4
239000000499 gel Substances 0.000 description 4
238000010874 in vitro model Methods 0.000 description 4
-1 ketyl Chemical class 0.000 description 4
230000000670 limiting effect Effects 0.000 description 4
239000007788 liquid Substances 0.000 description 4
230000036210 malignancy Effects 0.000 description 4
239000003550 marker Substances 0.000 description 4
239000000463 material Substances 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
239000010452 phosphate Substances 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
239000000047 product Substances 0.000 description 4
230000035945 sensitivity Effects 0.000 description 4
239000008107 starch Substances 0.000 description 4
229940032147 starch Drugs 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
238000012360 testing method Methods 0.000 description 4
238000002560 therapeutic procedure Methods 0.000 description 4
108020005345 3' Untranslated Regions Proteins 0.000 description 3
108091093088 Amplicon Proteins 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
102100032218 Cytokine-inducible SH2-containing protein Human genes 0.000 description 3
238000002965 ELISA Methods 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
208000016937 Extranodal nasal NK/T cell lymphoma Diseases 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
206010018338 Glioma Diseases 0.000 description 3
208000021519 Hodgkin lymphoma Diseases 0.000 description 3
208000010747 Hodgkins lymphoma Diseases 0.000 description 3
101000943420 Homo sapiens Cytokine-inducible SH2-containing protein Proteins 0.000 description 3
241000713772 Human immunodeficiency virus 1 Species 0.000 description 3
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
229930182816 L-glutamine Natural products 0.000 description 3
235000010643 Leucaena leucocephala Nutrition 0.000 description 3
240000007472 Leucaena leucocephala Species 0.000 description 3
241001529936 Murinae Species 0.000 description 3
101100366227 Mus musculus Sox11 gene Proteins 0.000 description 3
101100043050 Mus musculus Sox4 gene Proteins 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
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 3
102000004338 Transferrin Human genes 0.000 description 3
108090000901 Transferrin Proteins 0.000 description 3
102000001742 Tumor Suppressor Proteins Human genes 0.000 description 3
229930003779 Vitamin B12 Natural products 0.000 description 3
239000012190 activator Substances 0.000 description 3
125000000539 amino acid group Chemical group 0.000 description 3
238000010804 cDNA synthesis Methods 0.000 description 3
239000002775 capsule Substances 0.000 description 3
238000004113 cell culture Methods 0.000 description 3
230000001413 cellular effect Effects 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
230000034994 death Effects 0.000 description 3
230000004069 differentiation Effects 0.000 description 3
230000007783 downstream signaling Effects 0.000 description 3
230000009977 dual effect Effects 0.000 description 3
239000012091 fetal bovine serum Substances 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
238000009396 hybridization Methods 0.000 description 3
210000004408 hybridoma Anatomy 0.000 description 3
238000012744 immunostaining Methods 0.000 description 3
230000003993 interaction Effects 0.000 description 3
239000008101 lactose Substances 0.000 description 3
210000004698 lymphocyte Anatomy 0.000 description 3
239000006166 lysate Substances 0.000 description 3
208000021937 marginal zone lymphoma Diseases 0.000 description 3
208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 description 3
239000012528 membrane Substances 0.000 description 3
YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 3
230000000877 morphologic effect Effects 0.000 description 3
201000005962 mycosis fungoides Diseases 0.000 description 3
239000002674 ointment Substances 0.000 description 3
235000019271 petrolatum Nutrition 0.000 description 3
150000004713 phosphodiesters Chemical class 0.000 description 3
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
229920000656 polylysine Polymers 0.000 description 3
102000054765 polymorphisms of proteins Human genes 0.000 description 3
102000040430 polynucleotide Human genes 0.000 description 3
108091033319 polynucleotide Proteins 0.000 description 3
239000002157 polynucleotide Substances 0.000 description 3
239000013641 positive control Substances 0.000 description 3
208000017426 precursor B-cell acute lymphoblastic leukemia Diseases 0.000 description 3
229950010131 puromycin Drugs 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
239000007921 spray Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000000758 substrate Substances 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
230000001052 transient effect Effects 0.000 description 3
230000004565 tumor cell growth Effects 0.000 description 3
235000019163 vitamin B12 Nutrition 0.000 description 3
239000011715 vitamin B12 Substances 0.000 description 3
108090000663 Annexin A1 Proteins 0.000 description 2
102100040006 Annexin A1 Human genes 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
108091029430 CpG site Proteins 0.000 description 2
QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 2
230000004568 DNA-binding Effects 0.000 description 2
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 2
239000004471 Glycine Substances 0.000 description 2
108091093094 Glycol nucleic acid Proteins 0.000 description 2
229920000209 Hexadimethrine bromide Polymers 0.000 description 2
101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 2
102000002265 Human Growth Hormone Human genes 0.000 description 2
108010000521 Human Growth Hormone Proteins 0.000 description 2
239000000854 Human Growth Hormone Substances 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
102100027629 Kinesin-like protein KIF11 Human genes 0.000 description 2
QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 2
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
208000006404 Large Granular Lymphocytic Leukemia Diseases 0.000 description 2
208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 description 2
206010024305 Leukaemia monocytic Diseases 0.000 description 2
102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 2
208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
201000003791 MALT lymphoma Diseases 0.000 description 2
208000000172 Medulloblastoma Diseases 0.000 description 2
208000035489 Monocytic Acute Leukemia Diseases 0.000 description 2
101100490437 Mus musculus Acvrl1 gene Proteins 0.000 description 2
238000011789 NOD SCID mouse Methods 0.000 description 2
206010029461 Nodal marginal zone B-cell lymphomas Diseases 0.000 description 2
239000002033 PVDF binder Substances 0.000 description 2
102000057297 Pepsin A Human genes 0.000 description 2
108090000284 Pepsin A Proteins 0.000 description 2
108091093037 Peptide nucleic acid Proteins 0.000 description 2
239000004264 Petrolatum Substances 0.000 description 2
208000007452 Plasmacytoma Diseases 0.000 description 2
239000004698 Polyethylene Substances 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
238000001190 Q-PCR Methods 0.000 description 2
238000002123 RNA extraction Methods 0.000 description 2
239000012980 RPMI-1640 medium Substances 0.000 description 2
241000283984 Rodentia Species 0.000 description 2
238000012300 Sequence Analysis Methods 0.000 description 2
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
101150023247 Tefm gene Proteins 0.000 description 2
108091046915 Threose nucleic acid Proteins 0.000 description 2
108700025716 Tumor Suppressor Genes Proteins 0.000 description 2
108010040002 Tumor Suppressor Proteins Proteins 0.000 description 2
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
230000002159 abnormal effect Effects 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
229960003767 alanine Drugs 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
230000003321 amplification Effects 0.000 description 2
230000000692 anti-sense effect Effects 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
238000003491 array Methods 0.000 description 2
239000011324 bead Substances 0.000 description 2
230000008901 benefit Effects 0.000 description 2
230000033228 biological regulation Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 2
230000036760 body temperature Effects 0.000 description 2
230000004663 cell proliferation Effects 0.000 description 2
238000001516 cell proliferation assay Methods 0.000 description 2
208000013056 classic Hodgkin lymphoma Diseases 0.000 description 2
238000010367 cloning Methods 0.000 description 2
210000000795 conjunctiva Anatomy 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
239000006071 cream Substances 0.000 description 2
230000002950 deficient Effects 0.000 description 2
239000012649 demethylating agent Substances 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
210000004207 dermis Anatomy 0.000 description 2
238000001514 detection method Methods 0.000 description 2
NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical class OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
230000000431 effect on proliferation Effects 0.000 description 2
239000012636 effector Substances 0.000 description 2
238000004520 electroporation Methods 0.000 description 2
238000005516 engineering process Methods 0.000 description 2
230000006718 epigenetic regulation Effects 0.000 description 2
239000000284 extract Substances 0.000 description 2
238000001125 extrusion Methods 0.000 description 2
230000002349 favourable effect Effects 0.000 description 2
239000000835 fiber Substances 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
102000055387 human SOX11 Human genes 0.000 description 2
239000001863 hydroxypropyl cellulose Substances 0.000 description 2
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
229940071676 hydroxypropylcellulose Drugs 0.000 description 2
230000002163 immunogen Effects 0.000 description 2
238000007901 in situ hybridization Methods 0.000 description 2
238000010348 incorporation Methods 0.000 description 2
230000006698 induction Effects 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
229940029329 intrinsic factor Drugs 0.000 description 2
230000003902 lesion Effects 0.000 description 2
238000011068 loading method Methods 0.000 description 2
239000006210 lotion Substances 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
208000003747 lymphoid leukemia Diseases 0.000 description 2
229920002521 macromolecule 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
210000003519 mature b lymphocyte Anatomy 0.000 description 2
238000005259 measurement Methods 0.000 description 2
239000004005 microsphere Substances 0.000 description 2
235000013336 milk Nutrition 0.000 description 2
239000008267 milk Substances 0.000 description 2
210000004080 milk Anatomy 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
238000007479 molecular analysis Methods 0.000 description 2
201000006894 monocytic leukemia Diseases 0.000 description 2
210000004877 mucosa Anatomy 0.000 description 2
239000013642 negative control Substances 0.000 description 2
238000006386 neutralization reaction Methods 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
201000006039 nodal marginal zone lymphoma Diseases 0.000 description 2
238000003199 nucleic acid amplification method Methods 0.000 description 2
229940111202 pepsin Drugs 0.000 description 2
230000002093 peripheral effect Effects 0.000 description 2
229940066842 petrolatum Drugs 0.000 description 2
239000008024 pharmaceutical diluent Substances 0.000 description 2
229940124531 pharmaceutical excipient Drugs 0.000 description 2
229920002981 polyvinylidene fluoride Polymers 0.000 description 2
239000011148 porous material Substances 0.000 description 2
230000002035 prolonged effect Effects 0.000 description 2
239000003380 propellant Substances 0.000 description 2
239000003531 protein hydrolysate Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
238000011002 quantification Methods 0.000 description 2
238000002708 random mutagenesis Methods 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
238000011160 research Methods 0.000 description 2
230000004044 response Effects 0.000 description 2
230000019491 signal transduction Effects 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
229910021653 sulphate ion Inorganic materials 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
238000001890 transfection Methods 0.000 description 2
239000012581 transferrin Substances 0.000 description 2
RTKIYFITIVXBLE-QEQCGCAPSA-N trichostatin A Chemical compound ONC(=O)/C=C/C(/C)=C/[C@@H](C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-QEQCGCAPSA-N 0.000 description 2
238000005199 ultracentrifugation Methods 0.000 description 2
230000004580 weight loss Effects 0.000 description 2
NDQQRRVKUBPTHQ-QBIQUQHTSA-N (2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO NDQQRRVKUBPTHQ-QBIQUQHTSA-N 0.000 description 1
101150084750 1 gene Proteins 0.000 description 1
YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
HSTOKWSFWGCZMH-UHFFFAOYSA-N 3,3'-diaminobenzidine Chemical compound C1=C(N)C(N)=CC=C1C1=CC=C(N)C(N)=C1 HSTOKWSFWGCZMH-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
FICVQGAXQTVNNK-JHYUDYDFSA-N 4-amino-1-[(2r,4s,5s)-4-hydroxy-5-(hydroxyamino)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](NO)[C@@H](O)C1 FICVQGAXQTVNNK-JHYUDYDFSA-N 0.000 description 1
UZOVYGYOLBIAJR-UHFFFAOYSA-N 4-isocyanato-4'-methyldiphenylmethane Chemical compound C1=CC(C)=CC=C1CC1=CC=C(N=C=O)C=C1 UZOVYGYOLBIAJR-UHFFFAOYSA-N 0.000 description 1
LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 1
208000017726 ALK-positive large B-cell lymphoma Diseases 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
208000016683 Adult T-cell leukemia/lymphoma Diseases 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
208000012791 Alpha-heavy chain disease Diseases 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
206010002412 Angiocentric lymphomas Diseases 0.000 description 1
102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
208000010566 B-cell lymphoma, unclassifiable, with features intermediate between diffuse large b-cell lymphoma and classical Hodgkin lymphoma Diseases 0.000 description 1
208000012526 B-cell neoplasm Diseases 0.000 description 1
208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 description 1
102100038080 B-cell receptor CD22 Human genes 0.000 description 1
102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
108091012583 BCL2 Proteins 0.000 description 1
201000004085 CLL/SLL Diseases 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
241000283707 Capra Species 0.000 description 1
101800005309 Carboxy-terminal peptide Proteins 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
208000033816 Chronic lymphoproliferative disorder of natural killer cells Diseases 0.000 description 1
108091026890 Coding region Proteins 0.000 description 1
108010026206 Conalbumin Proteins 0.000 description 1
108091035707 Consensus sequence Proteins 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
102000016736 Cyclin Human genes 0.000 description 1
108050006400 Cyclin Proteins 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
108010009540 DNA (Cytosine-5-)-Methyltransferase 1 Proteins 0.000 description 1
102100036279 DNA (cytosine-5)-methyltransferase 1 Human genes 0.000 description 1
102000004594 DNA Polymerase I Human genes 0.000 description 1
108010017826 DNA Polymerase I Proteins 0.000 description 1
230000026641 DNA hypermethylation Effects 0.000 description 1
230000033616 DNA repair Effects 0.000 description 1
102000052510 DNA-Binding Proteins Human genes 0.000 description 1
101710096438 DNA-binding protein Proteins 0.000 description 1
102000007260 Deoxyribonuclease I Human genes 0.000 description 1
108010008532 Deoxyribonuclease I Proteins 0.000 description 1
102000016911 Deoxyribonucleases Human genes 0.000 description 1
108010053770 Deoxyribonucleases Proteins 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
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 1
239000004150 EU approved colour Substances 0.000 description 1
208000002460 Enteropathy-Associated T-Cell Lymphoma Diseases 0.000 description 1
241000283086 Equidae Species 0.000 description 1
208000033371 Extranodal NK/T-cell lymphoma, nasal type Diseases 0.000 description 1
206010061850 Extranodal marginal zone B-cell lymphoma (MALT type) Diseases 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
241000287828 Gallus gallus Species 0.000 description 1
208000012841 Gamma-heavy chain disease Diseases 0.000 description 1
208000032612 Glial tumor Diseases 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
201000000439 HCL-V Diseases 0.000 description 1
208000035481 HHV-8-associated multicentric Castleman disease Diseases 0.000 description 1
208000010956 Hairy cell leukemia variant Diseases 0.000 description 1
208000002250 Hematologic Neoplasms Diseases 0.000 description 1
239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
102000006947 Histones Human genes 0.000 description 1
108010033040 Histones Proteins 0.000 description 1
208000025795 Hodgkin lymphoma, lymphocytic depletion Diseases 0.000 description 1
241000282412 Homo Species 0.000 description 1
101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
101000803294 Homo sapiens BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 Proteins 0.000 description 1
101000766306 Homo sapiens Serotransferrin Proteins 0.000 description 1
101000642514 Homo sapiens Transcription factor SOX-4 Proteins 0.000 description 1
101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
108060003951 Immunoglobulin Proteins 0.000 description 1
108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
150000008575 L-amino acids Chemical class 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
206010023791 Large granular lymphocytosis Diseases 0.000 description 1
206010052178 Lymphocytic lymphoma Diseases 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
241000940612 Medina Species 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
108060004795 Methyltransferase Proteins 0.000 description 1
102000016397 Methyltransferase Human genes 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
208000012799 Mu-heavy chain disease Diseases 0.000 description 1
208000034578 Multiple myelomas Diseases 0.000 description 1
AFQNEJIPKKLOCL-UHFFFAOYSA-N N-{1-amino-6-[(5-nitro-2-furoyl)amino]-1-oxohexan-2-yl}-26-(indol-3-yl)-23-oxo-4,7,10,13,16,19-hexaoxa-22-azahexacosan-1-amide Chemical compound C=1NC2=CC=CC=C2C=1CCCC(=O)NCCOCCOCCOCCOCCOCCOCCC(=O)NC(C(=O)N)CCCCNC(=O)C1=CC=C([N+]([O-])=O)O1 AFQNEJIPKKLOCL-UHFFFAOYSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
108091061960 Naked DNA Proteins 0.000 description 1
206010061309 Neoplasm progression Diseases 0.000 description 1
108090000028 Neprilysin Proteins 0.000 description 1
102000003729 Neprilysin Human genes 0.000 description 1
206010029260 Neuroblastoma Diseases 0.000 description 1
206010060860 Neurological symptom Diseases 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
208000019569 Nodular lymphocyte predominant Hodgkin lymphoma Diseases 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
108700020796 Oncogene Proteins 0.000 description 1
108090000526 Papain Proteins 0.000 description 1
238000001358 Pearson's chi-squared test Methods 0.000 description 1
101710173835 Penton protein Proteins 0.000 description 1
208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 1
108010039918 Polylysine Proteins 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
208000009052 Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
208000017414 Precursor T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
208000032758 Precursor T-lymphoblastic lymphoma/leukaemia Diseases 0.000 description 1
206010065857 Primary Effusion Lymphoma Diseases 0.000 description 1
208000024588 Primary cutaneous follicle center lymphoma Diseases 0.000 description 1
206010036711 Primary mediastinal large B-cell lymphomas Diseases 0.000 description 1
208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 description 1
208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 description 1
108010059712 Pronase Proteins 0.000 description 1
102000007327 Protamines Human genes 0.000 description 1
108010007568 Protamines Proteins 0.000 description 1
239000004365 Protease Substances 0.000 description 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
241000125945 Protoparvovirus Species 0.000 description 1
238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
206010038997 Retroviral infections Diseases 0.000 description 1
102000017100 SOX Transcription Factors Human genes 0.000 description 1
108010013721 SOX Transcription Factors Proteins 0.000 description 1
DYAHQFWOVKZOOW-UHFFFAOYSA-N Sarin Chemical compound CC(C)OP(C)(F)=O DYAHQFWOVKZOOW-UHFFFAOYSA-N 0.000 description 1
208000009359 Sezary Syndrome Diseases 0.000 description 1
208000021388 Sezary disease Diseases 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
239000004147 Sorbitan trioleate Substances 0.000 description 1
PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
238000002105 Southern blotting Methods 0.000 description 1
208000011783 Splenic diffuse red pulp small B-cell lymphoma Diseases 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
208000010502 Subcutaneous panniculitis-like T-cell lymphoma Diseases 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 compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
239000005864 Sulphur Substances 0.000 description 1
241000282898 Sus scrofa Species 0.000 description 1
208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 1
208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
201000011648 T-cell childhood lymphoblastic lymphoma Diseases 0.000 description 1
201000008717 T-cell large granular lymphocyte leukemia Diseases 0.000 description 1
208000026651 T-cell prolymphocytic leukemia Diseases 0.000 description 1
208000011778 T-cell/histiocyte rich large B cell lymphoma Diseases 0.000 description 1
208000020982 T-lymphoblastic lymphoma Diseases 0.000 description 1
108091036066 Three prime untranslated region Proteins 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102100036693 Transcription factor SOX-4 Human genes 0.000 description 1
RTKIYFITIVXBLE-UHFFFAOYSA-N Trichostatin A Natural products ONC(=O)C=CC(C)=CC(C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-UHFFFAOYSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
241000700618 Vaccinia virus Species 0.000 description 1
206010046865 Vaccinia virus infection Diseases 0.000 description 1
208000016025 Waldenstroem macroglobulinemia Diseases 0.000 description 1
208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
101100043968 Xenopus laevis sox11-a gene Proteins 0.000 description 1
101100043969 Xenopus laevis sox11-b gene Proteins 0.000 description 1
101100257371 Xenopus laevis sox3-b gene Proteins 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
210000001015 abdomen Anatomy 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000009471 action Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
201000006966 adult T-cell leukemia Diseases 0.000 description 1
208000015230 aggressive NK-cell leukemia Diseases 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
230000004075 alteration Effects 0.000 description 1
239000012491 analyte Substances 0.000 description 1
206010002449 angioimmunoblastic T-cell lymphoma Diseases 0.000 description 1
238000010171 animal model Methods 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
238000000137 annealing Methods 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000002424 anti-apoptotic effect Effects 0.000 description 1
230000003466 anti-cipated effect Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
235000019445 benzyl alcohol Nutrition 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
239000011230 binding agent Substances 0.000 description 1
229920002988 biodegradable polymer Polymers 0.000 description 1
239000004621 biodegradable polymer Substances 0.000 description 1
239000012620 biological material Substances 0.000 description 1
229920001222 biopolymer Polymers 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000000981 bystander Effects 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 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
244000309466 calf Species 0.000 description 1
230000009702 cancer cell proliferation Effects 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000022159 cartilage development Effects 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
210000004534 cecum Anatomy 0.000 description 1
230000022131 cell cycle Effects 0.000 description 1
230000003915 cell function Effects 0.000 description 1
239000013592 cell lysate Substances 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
229940081733 cetearyl alcohol Drugs 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
150000005829 chemical entities Chemical class 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
230000002759 chromosomal effect Effects 0.000 description 1
210000000349 chromosome Anatomy 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
208000037976 chronic inflammation Diseases 0.000 description 1
230000006020 chronic inflammation Effects 0.000 description 1
208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
208000023738 chronic lymphocytic leukemia/small lymphocytic lymphoma Diseases 0.000 description 1
208000014620 chronic lymphoproliferative disorder of NK-cells Diseases 0.000 description 1
238000011509 clonal analysis Methods 0.000 description 1
230000008045 co-localization Effects 0.000 description 1
238000000975 co-precipitation Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000004040 coloring Methods 0.000 description 1
239000002131 composite material Substances 0.000 description 1
238000004590 computer program Methods 0.000 description 1
230000001268 conjugating effect Effects 0.000 description 1
238000011109 contamination Methods 0.000 description 1
238000010924 continuous production Methods 0.000 description 1
239000013068 control sample Substances 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
229960001681 croscarmellose sodium Drugs 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
239000012228 culture supernatant Substances 0.000 description 1
230000001351 cycling effect Effects 0.000 description 1
230000009089 cytolysis Effects 0.000 description 1
210000000805 cytoplasm Anatomy 0.000 description 1
238000012303 cytoplasmic staining Methods 0.000 description 1
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical class NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
230000006735 deficit Effects 0.000 description 1
238000004925 denaturation Methods 0.000 description 1
230000036425 denaturation Effects 0.000 description 1
239000007933 dermal patch Substances 0.000 description 1
238000013461 design Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
238000002405 diagnostic procedure Methods 0.000 description 1
235000019700 dicalcium phosphate Nutrition 0.000 description 1
229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
229940042935 dichlorodifluoromethane Drugs 0.000 description 1
229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
208000011782 diffuse large B-cell lymphoma of the central nervous system Diseases 0.000 description 1
230000029087 digestion Effects 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
229940112141 dry powder inhaler Drugs 0.000 description 1
238000010410 dusting Methods 0.000 description 1
239000000975 dye Substances 0.000 description 1
230000008482 dysregulation Effects 0.000 description 1
230000002900 effect on cell Effects 0.000 description 1
230000001819 effect on gene Effects 0.000 description 1
230000005684 electric field Effects 0.000 description 1
230000009881 electrostatic interaction Effects 0.000 description 1
230000013020 embryo development Effects 0.000 description 1
210000001671 embryonic stem cell Anatomy 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000008387 emulsifying waxe Substances 0.000 description 1
210000001163 endosome Anatomy 0.000 description 1
208000037902 enteropathy Diseases 0.000 description 1
108700004025 env Genes Proteins 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
230000001973 epigenetic effect Effects 0.000 description 1
230000007608 epigenetic mechanism Effects 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
238000010195 expression analysis Methods 0.000 description 1
201000006569 extramedullary plasmacytoma Diseases 0.000 description 1
230000008175 fetal development Effects 0.000 description 1
230000001605 fetal effect Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000000834 fixative Substances 0.000 description 1
MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
239000007850 fluorescent dye Substances 0.000 description 1
239000012909 foetal bovine serum Substances 0.000 description 1
230000003325 follicular Effects 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
238000011223 gene expression profiling Methods 0.000 description 1
230000009368 gene silencing by RNA Effects 0.000 description 1
239000011521 glass Substances 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229940049654 glyceryl behenate Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
208000025750 heavy chain disease Diseases 0.000 description 1
230000009033 hematopoietic malignancy Effects 0.000 description 1
206010066957 hepatosplenic T-cell lymphoma Diseases 0.000 description 1
208000029824 high grade glioma Diseases 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
230000006197 histone deacetylation Effects 0.000 description 1
208000017728 hydroa vacciniforme-like lymphoma Diseases 0.000 description 1
150000005828 hydrofluoroalkanes Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000006607 hypermethylation Effects 0.000 description 1
206010020718 hyperplasia Diseases 0.000 description 1
210000003405 ileum Anatomy 0.000 description 1
238000003018 immunoassay Methods 0.000 description 1
102000018358 immunoglobulin Human genes 0.000 description 1
238000003364 immunohistochemistry Methods 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
201000006747 infectious mononucleosis Diseases 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000010354 integration Effects 0.000 description 1
230000016507 interphase Effects 0.000 description 1
208000028774 intestinal disease Diseases 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
239000007926 intracavernous injection Substances 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
208000026876 intravascular large B-cell lymphoma Diseases 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000011835 investigation Methods 0.000 description 1
238000001038 ionspray mass spectrometry Methods 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
238000002865 local sequence alignment Methods 0.000 description 1
230000033001 locomotion Effects 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
208000037515 lymphocytic depletion Hodgkin lymphoma Diseases 0.000 description 1
208000037652 lymphocytic-histiocytic predominance Hodgkin lymphoma Diseases 0.000 description 1
208000019420 lymphoid neoplasm Diseases 0.000 description 1
210000003563 lymphoid tissue Anatomy 0.000 description 1
208000006116 lymphomatoid granulomatosis Diseases 0.000 description 1
208000007282 lymphomatoid papulosis Diseases 0.000 description 1
201000007919 lymphoplasmacytic lymphoma Diseases 0.000 description 1
239000012139 lysis buffer Substances 0.000 description 1
210000003712 lysosome Anatomy 0.000 description 1
230000001868 lysosomic effect Effects 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
201000011614 malignant glioma Diseases 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
201000007924 marginal zone B-cell lymphoma Diseases 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
201000000638 mature B-cell neoplasm Diseases 0.000 description 1
210000001939 mature NK cell Anatomy 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
208000037524 mixed cellularity Hodgkin lymphoma Diseases 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
238000010172 mouse model Methods 0.000 description 1
239000002324 mouth wash Substances 0.000 description 1
208000015325 multicentric Castleman disease Diseases 0.000 description 1
230000035772 mutation Effects 0.000 description 1
210000000822 natural killer cell Anatomy 0.000 description 1
229910052754 neon Inorganic materials 0.000 description 1
GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
208000010915 neoplasm of mature B-cells Diseases 0.000 description 1
208000021119 neoplasm of mature T-cells or NK-cells Diseases 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
230000004766 neurogenesis Effects 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
208000025275 nodular sclerosis classical Hodgkin lymphoma Diseases 0.000 description 1
230000001293 nucleolytic effect Effects 0.000 description 1
229940063149 nutropin Drugs 0.000 description 1
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 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
230000005868 ontogenesis Effects 0.000 description 1
229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
238000004806 packaging method and process Methods 0.000 description 1
229940055729 papain Drugs 0.000 description 1
235000019834 papain Nutrition 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
235000010603 pastilles Nutrition 0.000 description 1
230000037361 pathway Effects 0.000 description 1
230000035515 penetration Effects 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
239000000816 peptidomimetic Substances 0.000 description 1
230000035699 permeability Effects 0.000 description 1
230000002688 persistence Effects 0.000 description 1
238000002823 phage display Methods 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
150000003014 phosphoric acid esters Chemical class 0.000 description 1
238000000053 physical method Methods 0.000 description 1
208000007525 plasmablastic lymphoma Diseases 0.000 description 1
239000013600 plasmid vector Substances 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
239000004417 polycarbonate Substances 0.000 description 1
229920000515 polycarbonate Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
229940113124 polysorbate 60 Drugs 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
208000000814 primary cutaneous anaplastic large cell lymphoma Diseases 0.000 description 1
230000000861 pro-apoptotic effect Effects 0.000 description 1
210000001948 pro-b lymphocyte Anatomy 0.000 description 1
230000008569 process Effects 0.000 description 1
238000004393 prognosis Methods 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
229940048914 protamine Drugs 0.000 description 1
238000001742 protein purification Methods 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
238000003908 quality control method Methods 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000003753 real-time PCR Methods 0.000 description 1
230000010837 receptor-mediated endocytosis Effects 0.000 description 1
230000007115 recruitment Effects 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000000306 recurrent effect Effects 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000008844 regulatory mechanism Effects 0.000 description 1
230000010076 replication Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
238000010839 reverse transcription Methods 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
210000003079 salivary gland Anatomy 0.000 description 1
238000013077 scoring method Methods 0.000 description 1
238000012216 screening Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
230000007781 signaling event Effects 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
108010062513 snake venom phosphodiesterase I Proteins 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
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 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
229940080313 sodium starch Drugs 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
201000006576 solitary osseous plasmacytoma Diseases 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000001587 sorbitan monostearate Substances 0.000 description 1
235000011076 sorbitan monostearate Nutrition 0.000 description 1
229940035048 sorbitan monostearate Drugs 0.000 description 1
235000019337 sorbitan trioleate Nutrition 0.000 description 1
229960000391 sorbitan trioleate Drugs 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
210000003594 spinal ganglia Anatomy 0.000 description 1
206010062113 splenic marginal zone lymphoma Diseases 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
210000000434 stratum corneum Anatomy 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
125000001174 sulfone group Chemical group 0.000 description 1
239000013589 supplement Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
210000001550 testis Anatomy 0.000 description 1
MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
210000000779 thoracic wall Anatomy 0.000 description 1
210000001541 thymus gland Anatomy 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
208000019632 tonsillar lymphoma Diseases 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000014616 translation Effects 0.000 description 1
230000032258 transport Effects 0.000 description 1
238000011269 treatment regimen 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
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
230000005751 tumor progression Effects 0.000 description 1
238000000108 ultra-filtration Methods 0.000 description 1
241000712461 unidentified influenza virus Species 0.000 description 1
230000003827 upregulation Effects 0.000 description 1
229940035893 uracil Drugs 0.000 description 1
208000007089 vaccinia Diseases 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
230000029812 viral genome replication Effects 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
239000003871 white petrolatum Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1