JP2016518129A - 細胞ベースの薬物スクリーニングアッセイの方法及びその使用 - Google Patents
細胞ベースの薬物スクリーニングアッセイの方法及びその使用 Download PDFInfo
- Publication number
- JP2016518129A JP2016518129A JP2016509438A JP2016509438A JP2016518129A JP 2016518129 A JP2016518129 A JP 2016518129A JP 2016509438 A JP2016509438 A JP 2016509438A JP 2016509438 A JP2016509438 A JP 2016509438A JP 2016518129 A JP2016518129 A JP 2016518129A
- Authority
- JP
- Japan
- Prior art keywords
- cell
- drug
- cells
- ent
- environment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000007878 drug screening assay Methods 0.000 title claims abstract description 4
- 238000000034 method Methods 0.000 title claims description 31
- 210000004027 cell Anatomy 0.000 claims abstract description 205
- 238000011282 treatment Methods 0.000 claims abstract description 45
- 238000012544 monitoring process Methods 0.000 claims abstract description 25
- 229940088679 drug related substance Drugs 0.000 claims abstract description 22
- 239000008186 active pharmaceutical agent Substances 0.000 claims abstract description 21
- 230000000694 effects Effects 0.000 claims abstract description 17
- 230000009471 action Effects 0.000 claims abstract description 6
- 238000012258 culturing Methods 0.000 claims abstract description 6
- 210000004748 cultured cell Anatomy 0.000 claims abstract description 4
- 229940079593 drug Drugs 0.000 claims description 72
- 239000003814 drug Substances 0.000 claims description 72
- 206010028980 Neoplasm Diseases 0.000 claims description 55
- 201000011510 cancer Diseases 0.000 claims description 47
- 206010021143 Hypoxia Diseases 0.000 claims description 26
- 230000012010 growth Effects 0.000 claims description 25
- 230000014509 gene expression Effects 0.000 claims description 22
- 239000011159 matrix material Substances 0.000 claims description 22
- 206010009944 Colon cancer Diseases 0.000 claims description 20
- 208000029742 colonic neoplasm Diseases 0.000 claims description 20
- 230000010261 cell growth Effects 0.000 claims description 18
- 238000011084 recovery Methods 0.000 claims description 15
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 14
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 14
- 201000002528 pancreatic cancer Diseases 0.000 claims description 14
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 14
- 206010033128 Ovarian cancer Diseases 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 12
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 11
- 238000004113 cell culture Methods 0.000 claims description 11
- 108090000623 proteins and genes Proteins 0.000 claims description 11
- 238000004458 analytical method Methods 0.000 claims description 10
- 102000004169 proteins and genes Human genes 0.000 claims description 10
- 230000002503 metabolic effect Effects 0.000 claims description 9
- 230000007954 hypoxia Effects 0.000 claims description 8
- 235000018102 proteins Nutrition 0.000 claims description 7
- 229920002477 rna polymer Polymers 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 238000000684 flow cytometry Methods 0.000 claims description 5
- 238000004949 mass spectrometry Methods 0.000 claims description 5
- -1 linker compound Chemical class 0.000 claims description 4
- 210000000130 stem cell Anatomy 0.000 claims description 4
- 238000006116 polymerization reaction Methods 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 2
- 235000018417 cysteine Nutrition 0.000 claims description 2
- 238000003364 immunohistochemistry Methods 0.000 claims description 2
- 231100000682 maximum tolerated dose Toxicity 0.000 claims description 2
- 239000002105 nanoparticle Substances 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 238000011002 quantification Methods 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- 230000002491 angiogenic effect Effects 0.000 claims 1
- 238000005266 casting Methods 0.000 claims 1
- 230000024245 cell differentiation Effects 0.000 claims 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical group C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 claims 1
- 238000003556 assay Methods 0.000 description 19
- 230000001146 hypoxic effect Effects 0.000 description 18
- 230000001766 physiological effect Effects 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 9
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 8
- 238000007877 drug screening Methods 0.000 description 8
- 229960002949 fluorouracil Drugs 0.000 description 8
- 229960005277 gemcitabine Drugs 0.000 description 8
- 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 8
- 238000012216 screening Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 229940041181 antineoplastic drug Drugs 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 229960002378 oftasceine Drugs 0.000 description 4
- 108700012439 CA9 Proteins 0.000 description 3
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 description 3
- 102100034671 L-lactate dehydrogenase A chain Human genes 0.000 description 3
- 108091006296 SLC2A1 Proteins 0.000 description 3
- 230000003698 anagen phase Effects 0.000 description 3
- 230000033115 angiogenesis Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 238000009509 drug development Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000000691 measurement method Methods 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000002611 ovarian Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000012605 2D cell culture Methods 0.000 description 2
- 102100035656 BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 Human genes 0.000 description 2
- 102000058063 Glucose Transporter Type 1 Human genes 0.000 description 2
- 101000803294 Homo sapiens BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 Proteins 0.000 description 2
- 101001090713 Homo sapiens L-lactate dehydrogenase A chain Proteins 0.000 description 2
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012136 culture method Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940000406 drug candidate Drugs 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- 238000003255 drug test Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000002165 resonance energy transfer Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 238000012604 3D cell culture Methods 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 1
- 108050009527 Hypoxia-inducible factor-1 alpha Proteins 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 108010088350 Lactate Dehydrogenase 5 Proteins 0.000 description 1
- 101100380295 Mus musculus Asah1 gene Proteins 0.000 description 1
- 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 1
- 101150006573 PAN1 gene Proteins 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 1
- 208000037842 advanced-stage tumor Diseases 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 238000007707 calorimetry Methods 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000023549 cell-cell signaling Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000009643 clonogenic assay Methods 0.000 description 1
- 231100000096 clonogenic assay Toxicity 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000005757 colony formation Effects 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 230000000729 hypotrophic effect Effects 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000000575 proteomic method Methods 0.000 description 1
- 230000029219 regulation of pH Effects 0.000 description 1
- 230000008672 reprogramming Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/10—Screening for compounds of potential therapeutic value involving cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- General Engineering & Computer Science (AREA)
- Oncology (AREA)
Abstract
Description
Claims (13)
- 細胞ベースの薬物スクリーニングアッセイの方法であって、
−培養環境において細胞集団を培養するステップと、
−前記細胞型、前記細胞の生理学的特性、形成組織の生理学的特性、原薬の作用様式、及び前記培養環境のうちの少なくとも1つに依存して少なくとも2つの監視時点を定義するステップと、
−少なくとも1つの処理時点で前記培養細胞に原薬を適用するステップと、
−少なくとも前記2つの監視時点で細胞または形成組織に対する前記原薬の効果を監視するステップと、を含む、前記方法。 - 前記監視時点が、
−特定の細胞の早期に関連性のある時点、好ましくは、前記環境において前記細胞を培養してから4〜7日後、
−進行期の時点、好ましくは、前記環境において前記細胞を培養してから14〜17日後、
かつ
特定の生理学的特性、例えば、低酸素または細胞成長動態の変化の有無によって定義される時点、
及び
−薬物不使用の回復期後に薬物有効性を測定することに関連性のある時点、からなる群から選択される、請求項1に記載の前記方法。 - 細胞増殖の監視が、前記薬物適用の終了後1〜7日以上続く、請求項1及び2に記載の前記方法。
- 細胞が、ある環境において培養され、前記環境が、ビニルスルホン末端基を持つ多分岐状ポリエチレングリコール、及び三次元マトリックスへの重合を可能にする少なくとも2つのシステインまたは一般的にチオール基を含むペプチドを優先的に含む、構造化合物及びリンカー化合物を含む、請求項1〜3に記載の前記方法。
- 前記三次元環境が、前記被包された細胞の三次元成長、優先的にはスフェロイド成長を促進する、請求項4に記載の前記方法。
- 前記三次元環境が、ゲル鋳込デバイスまたは標準細胞培養デバイス、好ましくは、384ウェルプレート等の受容器において鋳込される、請求項4及び5に記載の前記方法。
- 前記細胞が、任意の細胞型、細胞株、分化細胞、ならびに結腸癌細胞、膵臓癌細胞、及び卵巣癌細胞等の癌細胞からなる群から選択される、請求項1〜6に記載の前記方法。
- 前記細胞が、前記成長が前記薬物処理によって促進される細胞である、請求項1〜6に記載の前記方法。
- 前記原薬が、
(i)任意の化学、天然、または合成物質、及び既知の薬物スクリーンの任意の物質、または
(ii)i)に従う物質の任意の組み合わせ、
(iii)溶液中の、または任意の担体、ナノ粒子、もしくは送達デバイスと組み合わされるかいずれかの、i)またはii)に従う任意の物質(複数可)、からなる群から選択される、請求項1〜8に記載の前記方法。 - 細胞特性の監視が、
代謝活性、
及び/またはフローサイトメトリー、
及び/またはDNA量、
及び/またはタンパク質定量、
及び/または細胞計数、
及び/または画像に基づく分析、
及び/または低酸素及び血管形成マーカのレベル、
及び/またはリボ核酸(RNA)レベル、
及び/またはタンパク質発現レベル、
及び/または質量分析法、
及び/または免疫組織化学的検査によってアッセイされる、請求項1〜9に記載の前記方法。 - 原薬の最大耐量が、所与の細胞型に対して決定される、請求項1〜10に記載の前記方法。
- 原薬の最小有効量が、所与の細胞型に対して決定される、請求項1〜11に記載の前記方法。
- (i)適用された物質に関する分化細胞の初期化と、
(ii)適用された物質に関する幹細胞の分化と、を評価するための、請求項1〜12に記載の前記方法の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP13165419.6 | 2013-04-25 | ||
EP13165419.6A EP2796873A1 (en) | 2013-04-25 | 2013-04-25 | Method for a cell-based drug screening assay and the use thereof |
PCT/EP2014/058152 WO2014173907A1 (en) | 2013-04-25 | 2014-04-22 | Method for a cell-based drug screening assay and the use thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016518129A true JP2016518129A (ja) | 2016-06-23 |
JP6484219B2 JP6484219B2 (ja) | 2019-03-13 |
Family
ID=48326111
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016509438A Active JP6484219B2 (ja) | 2013-04-25 | 2014-04-22 | 細胞ベースの薬物スクリーニングアッセイの方法及びその使用 |
Country Status (14)
Country | Link |
---|---|
US (1) | US20160077081A1 (ja) |
EP (2) | EP2796873A1 (ja) |
JP (1) | JP6484219B2 (ja) |
KR (1) | KR102255944B1 (ja) |
CN (1) | CN105143883B (ja) |
AU (1) | AU2014257584B2 (ja) |
BR (1) | BR112015026601B1 (ja) |
CA (1) | CA2910146C (ja) |
ES (1) | ES2729341T3 (ja) |
IL (1) | IL242172B (ja) |
MX (1) | MX366369B (ja) |
RU (1) | RU2702643C2 (ja) |
SG (1) | SG11201508611WA (ja) |
WO (1) | WO2014173907A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020071484A1 (ja) * | 2018-10-05 | 2020-04-09 | 国立大学法人名古屋大学 | 化学物質のスクリーニング方法、プログラム、制御装置、及び培養観察装置 |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011140441A2 (en) | 2010-05-06 | 2011-11-10 | Children's Hospital Medical Center | Methods and systems for converting precursor cells into intestinal tissues through directed differentiation |
CA2949834A1 (en) | 2014-05-28 | 2015-12-03 | James Macormack Wells | Methods and systems for converting precursor cells into gastric tissues through directed differentiation |
WO2016061464A1 (en) | 2014-10-17 | 2016-04-21 | Children's Hospital Center, D/B/A Cincinnati Children's Hospital Medical Center | In vivo model of human small intetine using pluripotent stem cells and methods of making and using same |
JP2016136848A (ja) * | 2015-01-26 | 2016-08-04 | 富士フイルム株式会社 | 薬剤の評価方法及び薬剤スクリーニング方法 |
GB201514864D0 (en) * | 2015-08-20 | 2015-10-07 | Insphero Ag | An in vitro 3D cell culture model-based tumor relapse assay |
EP3452578B1 (en) | 2016-05-05 | 2022-08-10 | Children's Hospital Medical Center | Methods for the in vitro manufacture of gastric fundus tissue and compositions related to same |
KR101916801B1 (ko) * | 2016-08-12 | 2018-11-08 | 경북대학교 산학협력단 | 3차원 생체 모사 시스템을 이용한 맥락막 혈관신생을 수반하는 질환의 치료제 스크리닝 방법 |
IT201600099380A1 (it) * | 2016-10-04 | 2018-04-04 | Univ Bologna Alma Mater Studiorum | Composizioni, dispositivi e metodi per il controllo in vitro del microambiente chimico in colture cellulari |
AU2017373767B2 (en) | 2016-12-05 | 2021-09-16 | Children's Hospital Medical Center | Colonic organoids and methods of making and using same |
GB201818885D0 (en) * | 2018-11-20 | 2019-01-02 | Precomb Therapeutics Ag | 3d human cancer model-based combinatiorial drug development method |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002501609A (ja) * | 1996-07-12 | 2002-01-15 | プリシジョン セラピューティクス,アイエヌシー. | 化学治療剤を含む活性薬剤の正確な効能アッセイ方法 |
JP2004533500A (ja) * | 2001-04-03 | 2004-11-04 | バイオセプト インコーポレイテッド | 生細胞および有機分子をカプセル封入するための方法およびゲル組成物 |
US20110004414A1 (en) * | 2009-06-06 | 2011-01-06 | Ceetox, Inc. | Method for Predicting Respiratory Toxicity of Compounds |
WO2011131642A1 (en) * | 2010-04-22 | 2011-10-27 | Qgel Sa | Hydrogel precursor formulation and production process thereof |
WO2012046797A1 (ja) * | 2010-10-06 | 2012-04-12 | ファーマロジカルズ・リサーチ プライベート リミテッド | 癌幹細胞集団及びその作製方法 |
WO2013039087A1 (ja) * | 2011-09-12 | 2013-03-21 | 国立大学法人 熊本大学 | 物質のスクリーニング方法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2005253923A1 (en) * | 2004-06-08 | 2005-12-29 | Primegen Biotech Llc | Therapeutic reprogramming, hybrid stem cells and maturation |
US20090324596A1 (en) * | 2008-06-30 | 2009-12-31 | The Trustees Of Princeton University | Methods of identifying and treating poor-prognosis cancers |
EP2342317B1 (en) | 2008-09-22 | 2012-12-19 | University Of Zurich Prorektorat Forschung | Hanging drop plate |
WO2010083385A2 (en) * | 2009-01-15 | 2010-07-22 | The General Hospital Corporation | Compounds for reducing drug resistance and uses thereof |
-
2013
- 2013-04-25 EP EP13165419.6A patent/EP2796873A1/en not_active Withdrawn
-
2014
- 2014-04-22 JP JP2016509438A patent/JP6484219B2/ja active Active
- 2014-04-22 CA CA2910146A patent/CA2910146C/en active Active
- 2014-04-22 MX MX2015014892A patent/MX366369B/es active IP Right Grant
- 2014-04-22 ES ES14718624T patent/ES2729341T3/es active Active
- 2014-04-22 AU AU2014257584A patent/AU2014257584B2/en active Active
- 2014-04-22 SG SG11201508611WA patent/SG11201508611WA/en unknown
- 2014-04-22 KR KR1020157033467A patent/KR102255944B1/ko active IP Right Grant
- 2014-04-22 RU RU2015150203A patent/RU2702643C2/ru active
- 2014-04-22 BR BR112015026601-0A patent/BR112015026601B1/pt active IP Right Grant
- 2014-04-22 WO PCT/EP2014/058152 patent/WO2014173907A1/en active Application Filing
- 2014-04-22 CN CN201480022749.4A patent/CN105143883B/zh active Active
- 2014-04-22 US US14/786,637 patent/US20160077081A1/en active Pending
- 2014-04-22 EP EP14718624.1A patent/EP2989460B1/en active Active
-
2015
- 2015-10-20 IL IL242172A patent/IL242172B/en active IP Right Grant
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002501609A (ja) * | 1996-07-12 | 2002-01-15 | プリシジョン セラピューティクス,アイエヌシー. | 化学治療剤を含む活性薬剤の正確な効能アッセイ方法 |
US20100120070A1 (en) * | 1996-07-12 | 2010-05-13 | Kornblith Paul L | Precise efficacy assay methods for active agents including chemotherapeutic agents |
JP2004533500A (ja) * | 2001-04-03 | 2004-11-04 | バイオセプト インコーポレイテッド | 生細胞および有機分子をカプセル封入するための方法およびゲル組成物 |
US20110004414A1 (en) * | 2009-06-06 | 2011-01-06 | Ceetox, Inc. | Method for Predicting Respiratory Toxicity of Compounds |
WO2011131642A1 (en) * | 2010-04-22 | 2011-10-27 | Qgel Sa | Hydrogel precursor formulation and production process thereof |
WO2012046797A1 (ja) * | 2010-10-06 | 2012-04-12 | ファーマロジカルズ・リサーチ プライベート リミテッド | 癌幹細胞集団及びその作製方法 |
WO2013039087A1 (ja) * | 2011-09-12 | 2013-03-21 | 国立大学法人 熊本大学 | 物質のスクリーニング方法 |
Non-Patent Citations (4)
Title |
---|
BIOMATERIALS, vol. 31, JPN6018002988, 2010, pages 8494 - 8506, ISSN: 0003896074 * |
JOURNAL OF BIOMOLECULAR SCREENING, vol. 9, no. 4, JPN6018002993, 2004, pages 273 - 285, ISSN: 0003896076 * |
NATURE PROTOCOLS, vol. 4, no. 3, JPN6018002987, 2009, pages 309 - 324, ISSN: 0003896073 * |
再生歯誌, vol. 2, no. 3, JPN6018002991, 2005, pages 166 - 181, ISSN: 0003896075 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020071484A1 (ja) * | 2018-10-05 | 2020-04-09 | 国立大学法人名古屋大学 | 化学物質のスクリーニング方法、プログラム、制御装置、及び培養観察装置 |
JP7405373B2 (ja) | 2018-10-05 | 2023-12-26 | 国立大学法人東海国立大学機構 | 化学物質のスクリーニング方法、プログラム、制御装置、及び培養観察装置 |
Also Published As
Publication number | Publication date |
---|---|
EP2989460A1 (en) | 2016-03-02 |
IL242172B (en) | 2019-03-31 |
MX2015014892A (es) | 2016-03-07 |
MX366369B (es) | 2019-07-05 |
BR112015026601A2 (pt) | 2017-07-25 |
RU2702643C2 (ru) | 2019-10-09 |
AU2014257584A1 (en) | 2015-11-05 |
CN105143883B (zh) | 2018-10-23 |
US20160077081A1 (en) | 2016-03-17 |
CA2910146A1 (en) | 2014-10-30 |
KR20160003761A (ko) | 2016-01-11 |
KR102255944B1 (ko) | 2021-05-25 |
EP2796873A1 (en) | 2014-10-29 |
WO2014173907A1 (en) | 2014-10-30 |
ES2729341T3 (es) | 2019-10-31 |
AU2014257584B2 (en) | 2020-05-14 |
CN105143883A (zh) | 2015-12-09 |
EP2989460B1 (en) | 2019-03-06 |
CA2910146C (en) | 2024-04-09 |
BR112015026601B1 (pt) | 2023-11-21 |
RU2015150203A (ru) | 2017-05-31 |
SG11201508611WA (en) | 2015-11-27 |
JP6484219B2 (ja) | 2019-03-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6484219B2 (ja) | 細胞ベースの薬物スクリーニングアッセイの方法及びその使用 | |
Huang et al. | Characterization of triple-negative breast cancer MDA-MB-231 cell spheroid model | |
Pijuan et al. | In vitro cell migration, invasion, and adhesion assays: from cell imaging to data analysis | |
Yankaskas et al. | A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens | |
Wang et al. | High-efficiency isolation and rapid identification of heterogeneous circulating tumor cells (CTCs) using dual-antibody-modified fluorescent-magnetic nanoparticles | |
Kim et al. | Detection of pathogenic biofilms with bacterial amyloid targeting fluorescent probe, CDy11 | |
Somasundaram et al. | Inducible nitric oxide synthase-derived extracellular nitric oxide flux regulates proinflammatory responses at the single cell level | |
Cutrona et al. | A High‐Throughput Automated Confocal Microscopy Platform for Quantitative Phenotyping of Nanoparticle Uptake and Transport in Spheroids | |
Cao et al. | In situ programmable DNA circuit-promoted electrochemical characterization of stemlike phenotype in breast cancer | |
US20230375527A1 (en) | Methods and kits for predicting cancer prognosis and metastasis | |
Willey et al. | Patient-derived xenografts as a model system for radiation research | |
Clough et al. | Neutrally charged self-assembling peptide hydrogel recapitulates in vitro mechanisms of breast cancer progression | |
Santi et al. | Production of 3D tumor models of head and neck squamous cell carcinomas for nanotheranostics assessment | |
Singh et al. | Controlled three-dimensional tumor microenvironments recapitulate phenotypic features and differential drug response in early vs advanced stage breast cancer | |
Shelper et al. | Assessing drug efficacy in a miniaturized pancreatic cancer in vitro 3D cell culture model | |
Li et al. | Assay establishment and validation of a high-throughput organoid-based drug screening platform | |
Close et al. | Detection and impact of hypoxic regions in multicellular tumor spheroid cultures formed by head and neck squamous cell carcinoma cells lines | |
Cromwell et al. | Multifunctional profiling of triple-negative breast cancer patient-derived tumoroids for disease modeling | |
Sohrabi et al. | Microenvironmental stiffness induces metabolic reprogramming in glioblastoma | |
Frtús et al. | Mechanical Regulation of Mitochondrial Dynamics and Function in a 3D-Engineered Liver Tumor Microenvironment | |
US20200063108A1 (en) | Three-dimensional tissue structures | |
Thakuri et al. | Microprinted tumor spheroids enable anti-cancer drug screening | |
Seidlits et al. | Effects Of Matrix Stiffness On Glioblastoma Metabolism | |
González-Callejo et al. | 3D Bioprinted Tumor-Stroma Models of Triple-Negative Breast Cancer Stem Cells for Preclinical Targeted Therapy Evaluation | |
Rainu et al. | Dual-Sensitive Fluorescent Nanoprobes for Simultaneously Monitoring In Situ Changes in pH and Matrix Metalloproteinase Expression in Stiffness-Tunable Three-Dimensional In Vitro Scaffolds |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170301 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20180122 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180206 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180501 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181016 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190122 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190215 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6484219 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |