TWI847369B - 新穎腸膜明串珠菌菌株 - Google Patents
新穎腸膜明串珠菌菌株 Download PDFInfo
- Publication number
- TWI847369B TWI847369B TW111143885A TW111143885A TWI847369B TW I847369 B TWI847369 B TW I847369B TW 111143885 A TW111143885 A TW 111143885A TW 111143885 A TW111143885 A TW 111143885A TW I847369 B TWI847369 B TW I847369B
- Authority
- TW
- Taiwan
- Prior art keywords
- cjrs
- cells
- strain
- cancer
- cell
- Prior art date
Links
- 241000192130 Leuconostoc mesenteroides Species 0.000 title claims description 16
- 241000192132 Leuconostoc Species 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 82
- 206010028980 Neoplasm Diseases 0.000 description 32
- 239000000203 mixture Substances 0.000 description 30
- 210000001744 T-lymphocyte Anatomy 0.000 description 26
- 201000011510 cancer Diseases 0.000 description 23
- 239000003814 drug Substances 0.000 description 22
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 22
- 230000028327 secretion Effects 0.000 description 21
- 241000699666 Mus <mouse, genus> Species 0.000 description 20
- 239000003674 animal food additive Substances 0.000 description 16
- 229940079593 drug Drugs 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 14
- 210000004989 spleen cell Anatomy 0.000 description 14
- 241000894006 Bacteria Species 0.000 description 13
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 13
- 239000002953 phosphate buffered saline Substances 0.000 description 13
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 12
- 210000002865 immune cell Anatomy 0.000 description 12
- 201000005202 lung cancer Diseases 0.000 description 12
- 208000020816 lung neoplasm Diseases 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- 239000004310 lactic acid Substances 0.000 description 11
- 235000014655 lactic acid Nutrition 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 239000002246 antineoplastic agent Substances 0.000 description 10
- 239000012091 fetal bovine serum Substances 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 108010034798 CDC2 Protein Kinase Proteins 0.000 description 9
- 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 9
- 230000001093 anti-cancer Effects 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 235000013305 food Nutrition 0.000 description 9
- 102000004889 Interleukin-6 Human genes 0.000 description 8
- 108090001005 Interleukin-6 Proteins 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 238000002626 targeted therapy Methods 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 239000003242 anti bacterial agent Substances 0.000 description 7
- 229940088710 antibiotic agent Drugs 0.000 description 7
- 230000025084 cell cycle arrest Effects 0.000 description 7
- 238000003501 co-culture Methods 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 235000013336 milk Nutrition 0.000 description 7
- 239000008267 milk Substances 0.000 description 7
- 210000004080 milk Anatomy 0.000 description 7
- 235000012149 noodles Nutrition 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- 102000008178 Cyclin B1 Human genes 0.000 description 6
- 108010060385 Cyclin B1 Proteins 0.000 description 6
- 102000008070 Interferon-gamma Human genes 0.000 description 6
- 108010074328 Interferon-gamma Proteins 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 230000003115 biocidal effect Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 6
- 229960003130 interferon gamma Drugs 0.000 description 6
- 229940100601 interleukin-6 Drugs 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 210000004985 myeloid-derived suppressor cell Anatomy 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- WWSJZGAPAVMETJ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-ethoxypyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OCC WWSJZGAPAVMETJ-UHFFFAOYSA-N 0.000 description 5
- 206010000050 Abdominal adhesions Diseases 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 239000003833 bile salt Substances 0.000 description 5
- 238000011260 co-administration Methods 0.000 description 5
- 235000013373 food additive Nutrition 0.000 description 5
- 239000002778 food additive Substances 0.000 description 5
- 230000015784 hyperosmotic salinity response Effects 0.000 description 5
- 210000002540 macrophage Anatomy 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 4
- 102100022338 Integrin alpha-M Human genes 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 102000006995 beta-Glucosidase Human genes 0.000 description 4
- 108010047754 beta-Glucosidase Proteins 0.000 description 4
- 230000022131 cell cycle Effects 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- 230000002949 hemolytic effect Effects 0.000 description 4
- 210000005008 immunosuppressive cell Anatomy 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 235000021109 kimchi Nutrition 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 235000015067 sauces Nutrition 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
- 241000251468 Actinopterygii Species 0.000 description 3
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 3
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 3
- PHEDXBVPIONUQT-UHFFFAOYSA-N Cocarcinogen A1 Natural products CCCCCCCCCCCCCC(=O)OC1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(C)=O)C2(C)C PHEDXBVPIONUQT-UHFFFAOYSA-N 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- 244000046052 Phaseolus vulgaris Species 0.000 description 3
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 3
- 241000286209 Phasianidae Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 230000001464 adherent effect Effects 0.000 description 3
- 238000011319 anticancer therapy Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 235000015155 buttermilk Nutrition 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229960001484 edetic acid Drugs 0.000 description 3
- 235000015243 ice cream Nutrition 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 230000001875 tumorinhibitory effect Effects 0.000 description 3
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 2
- 101710168331 ALK tyrosine kinase receptor Proteins 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 102100026189 Beta-galactosidase Human genes 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 206010071119 Hormone-dependent prostate cancer Diseases 0.000 description 2
- 102100024295 Maltase-glucoamylase Human genes 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 2
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 2
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 2
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 2
- 229940123237 Taxane Drugs 0.000 description 2
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 2
- 229940122803 Vinca alkaloid Drugs 0.000 description 2
- 239000005862 Whey Substances 0.000 description 2
- 102000007544 Whey Proteins Human genes 0.000 description 2
- 108010046377 Whey Proteins Proteins 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 108010028144 alpha-Glucosidases Proteins 0.000 description 2
- 238000011224 anti-cancer immunotherapy Methods 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000002543 antimycotic Substances 0.000 description 2
- 238000003782 apoptosis assay Methods 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 230000004611 cancer cell death Effects 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 235000014171 carbonated beverage Nutrition 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 235000013351 cheese Nutrition 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 235000013365 dairy product Nutrition 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 235000021107 fermented food Nutrition 0.000 description 2
- 235000013332 fish product Nutrition 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 230000002434 immunopotentiative effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- -1 pH adjusters Substances 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 244000144977 poultry Species 0.000 description 2
- 235000013594 poultry meat Nutrition 0.000 description 2
- 230000022983 regulation of cell cycle Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 235000013580 sausages Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- 235000013618 yogurt Nutrition 0.000 description 2
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 1
- CTRPRMNBTVRDFH-UHFFFAOYSA-N 2-n-methyl-1,3,5-triazine-2,4,6-triamine Chemical compound CNC1=NC(N)=NC(N)=N1 CTRPRMNBTVRDFH-UHFFFAOYSA-N 0.000 description 1
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 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
- 206010061424 Anal cancer Diseases 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 235000007319 Avena orientalis Nutrition 0.000 description 1
- 244000075850 Avena orientalis Species 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 208000005440 Basal Cell Neoplasms Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 241000901050 Bifidobacterium animalis subsp. lactis Species 0.000 description 1
- 241000186016 Bifidobacterium bifidum Species 0.000 description 1
- 241000186015 Bifidobacterium longum subsp. infantis Species 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 239000005996 Blood meal Substances 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 240000002791 Brassica napus Species 0.000 description 1
- 235000004977 Brassica sinapistrum Nutrition 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101000715943 Caenorhabditis elegans Cyclin-dependent kinase 4 homolog Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 240000004160 Capsicum annuum Species 0.000 description 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
- 235000007862 Capsicum baccatum Nutrition 0.000 description 1
- 241001609213 Carassius carassius Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241001107116 Castanospermum australe Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102000005483 Cell Cycle Proteins Human genes 0.000 description 1
- 108010031896 Cell Cycle Proteins Proteins 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 241000195649 Chlorella <Chlorellales> Species 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000252233 Cyprinus carpio Species 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 208000021994 Diffuse astrocytoma Diseases 0.000 description 1
- 235000011511 Diospyros Nutrition 0.000 description 1
- 244000236655 Diospyros kaki Species 0.000 description 1
- 206010061825 Duodenal neoplasm Diseases 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 208000017259 Extragonadal germ cell tumor Diseases 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 235000019733 Fish meal Nutrition 0.000 description 1
- 230000035519 G0 Phase Effects 0.000 description 1
- 230000010190 G1 phase Effects 0.000 description 1
- 230000004668 G2/M phase Effects 0.000 description 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 235000018142 Hedysarum alpinum var americanum Nutrition 0.000 description 1
- 240000006461 Hedysarum alpinum var. americanum Species 0.000 description 1
- 244000020551 Helianthus annuus Species 0.000 description 1
- 235000003222 Helianthus annuus Nutrition 0.000 description 1
- 208000008051 Hereditary Nonpolyposis Colorectal Neoplasms Diseases 0.000 description 1
- 208000017095 Hereditary nonpolyposis colon cancer Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 description 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 101000863873 Homo sapiens Tyrosine-protein phosphatase non-receptor type substrate 1 Proteins 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 208000005726 Inflammatory Breast Neoplasms Diseases 0.000 description 1
- 206010021980 Inflammatory carcinoma of the breast Diseases 0.000 description 1
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 description 1
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 description 1
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 1
- 102100022297 Integrin alpha-X Human genes 0.000 description 1
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 206010073094 Intraductal proliferative breast lesion Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 description 1
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 201000005027 Lynch syndrome Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
- 206010034811 Pharyngeal cancer Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 1
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
- 201000005746 Pituitary adenoma Diseases 0.000 description 1
- 206010061538 Pituitary tumour benign Diseases 0.000 description 1
- 108010064851 Plant Proteins Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 229940123924 Protein kinase C inhibitor Drugs 0.000 description 1
- 102000015690 Proto-Oncogene Proteins c-bcr Human genes 0.000 description 1
- 108010024221 Proto-Oncogene Proteins c-bcr Proteins 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 241000277331 Salmonidae Species 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 206010054184 Small intestine carcinoma Diseases 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 101710165436 Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 102100029948 Tyrosine-protein phosphatase non-receptor type substrate 1 Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 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
- 229940124532 absorption promoter Drugs 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 201000000452 adenoid squamous cell carcinoma Diseases 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 235000021120 animal protein Nutrition 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000000781 anti-lymphocytic effect Effects 0.000 description 1
- 230000001399 anti-metabolic effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 235000015241 bacon Nutrition 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 229940002008 bifidobacterium bifidum Drugs 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 235000021279 black bean Nutrition 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 239000006161 blood agar Substances 0.000 description 1
- 229940036811 bone meal Drugs 0.000 description 1
- 239000002374 bone meal Substances 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- KQNZDYYTLMIZCT-KQPMLPITSA-N brefeldin A Chemical compound O[C@@H]1\C=C\C(=O)O[C@@H](C)CCC\C=C\[C@@H]2C[C@H](O)C[C@H]21 KQNZDYYTLMIZCT-KQPMLPITSA-N 0.000 description 1
- JUMGSHROWPPKFX-UHFFFAOYSA-N brefeldin-A Natural products CC1CCCC=CC2(C)CC(O)CC2(C)C(O)C=CC(=O)O1 JUMGSHROWPPKFX-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- BMQGVNUXMIRLCK-OAGWZNDDSA-N cabazitaxel Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@H](OC)C2=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=3C=CC=CC=3)C[C@]1(O)C2(C)C)C)OC)C(=O)C1=CC=CC=C1 BMQGVNUXMIRLCK-OAGWZNDDSA-N 0.000 description 1
- 229960001573 cabazitaxel Drugs 0.000 description 1
- 235000012970 cakes Nutrition 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 239000001728 capsicum frutescens Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001765 catechin Chemical class 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 229960005110 cerivastatin Drugs 0.000 description 1
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 229940045110 chitosan Drugs 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000012136 culture method Methods 0.000 description 1
- 235000015140 cultured milk Nutrition 0.000 description 1
- 235000021438 curry Nutrition 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000011850 desserts Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- CQAIPTBBCVQRMD-UHFFFAOYSA-L dipotassium;phosphono phosphate Chemical compound [K+].[K+].OP(O)(=O)OP([O-])([O-])=O CQAIPTBBCVQRMD-UHFFFAOYSA-L 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 235000021463 dry cake Nutrition 0.000 description 1
- 201000000312 duodenum cancer Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 201000011523 endocrine gland cancer Diseases 0.000 description 1
- 201000003914 endometrial carcinoma Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 201000008819 extrahepatic bile duct carcinoma Diseases 0.000 description 1
- 208000020603 familial colorectal cancer Diseases 0.000 description 1
- 201000001169 fibrillary astrocytoma Diseases 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000004467 fishmeal Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000012757 fluorescence staining Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000010610 frozen noodles Nutrition 0.000 description 1
- 235000021456 frozen pasta Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 235000020251 goat milk Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000020688 green tea extract Nutrition 0.000 description 1
- 229940094952 green tea extract Drugs 0.000 description 1
- 239000007952 growth promoter Substances 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 230000008821 health effect Effects 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 201000004653 inflammatory breast carcinoma Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 1
- 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 1
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 235000015094 jam Nutrition 0.000 description 1
- 235000008960 ketchup Nutrition 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229950005692 larotaxel Drugs 0.000 description 1
- SEFGUGYLLVNFIJ-QDRLFVHASA-N larotaxel dihydrate Chemical compound O.O.O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@@]23[C@H]1[C@@]1(CO[C@@H]1C[C@@H]2C3)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 SEFGUGYLLVNFIJ-QDRLFVHASA-N 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 229940069445 licorice extract Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 235000020121 low-fat milk Nutrition 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 208000006178 malignant mesothelioma Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 235000013622 meat product Nutrition 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical class CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 201000010879 mucinous adenocarcinoma Diseases 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 235000019462 natural additive Nutrition 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 238000009099 neoadjuvant therapy Methods 0.000 description 1
- 208000025189 neoplasm of testis Diseases 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 244000309459 oncolytic virus Species 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 208000021284 ovarian germ cell tumor Diseases 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 description 1
- 230000009996 pancreatic endocrine effect Effects 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 239000000467 phytic acid Substances 0.000 description 1
- 235000002949 phytic acid Nutrition 0.000 description 1
- 229940068041 phytic acid Drugs 0.000 description 1
- 201000007315 pineal gland astrocytoma Diseases 0.000 description 1
- 229960002797 pitavastatin Drugs 0.000 description 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
- 208000021310 pituitary gland adenoma Diseases 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- OQZCJRJRGMMSGK-UHFFFAOYSA-M potassium metaphosphate Polymers [K+].[O-]P(=O)=O OQZCJRJRGMMSGK-UHFFFAOYSA-M 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 235000014059 processed cheese Nutrition 0.000 description 1
- 235000020991 processed meat Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 239000003881 protein kinase C inhibitor Substances 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 208000013368 pseudoglandular squamous cell carcinoma Diseases 0.000 description 1
- 239000000649 purine antagonist Substances 0.000 description 1
- 239000003790 pyrimidine antagonist Substances 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 208000010639 renal pelvis urothelial carcinoma Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 230000005070 ripening Effects 0.000 description 1
- 229940092258 rosemary extract Drugs 0.000 description 1
- 235000020748 rosemary extract Nutrition 0.000 description 1
- 239000001233 rosmarinus officinalis l. extract Substances 0.000 description 1
- 235000021108 sauerkraut Nutrition 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000008137 solubility enhancer Substances 0.000 description 1
- 235000013322 soy milk Nutrition 0.000 description 1
- 235000013555 soy sauce Nutrition 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- 235000021404 traditional food Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 201000000334 ureter transitional cell carcinoma Diseases 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 208000037965 uterine sarcoma Diseases 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
本發明係有關一種新穎腸膜明串珠菌菌株。
Description
本發明係有關一種新穎腸膜明串珠菌(Leuconostoc mesenteroides)菌株。
乳酸菌是一種微生物群,其在微生物產業中佔有重要的地位。傳統乳酸菌發酵食品包括韓國泡菜(kimchi)、優格、起司、酪乳、酸菜等,由乳酸菌發酵的乳酸也被應用於未加熱香腸的熟成及保存。
尤其,在傳統發酵食品之韓國泡菜中發現了多種乳酸菌,其中包含腸膜明串珠菌(Leuconostoc mesenteroides)。
此外,已有報告指出乳酸菌展現多項促進健康的效果,例如:整腸、抑制壞菌、免疫調節、降低血液膽固醇、抗癌作用等(韓國發明專利第10-2307603號)。
本發明的其中一態樣是提供一種腸膜明串珠菌CJRS-10671(韓國寄存編號:KCCM13059P)菌株。
本發明的另外一態樣是提供一種腸膜明串珠菌CJRS-10672(韓國寄存編號:KCCM13060P)菌株。
以下將藉由具體實施例描述本發明。在本發明中的每一個說明與實施例也可以應用於其他說明與其他實施例。亦即,本發明中各項要件的全部組合都落在本發明的範圍內。另外,本發明的範圍不受以下具體描述的限制。此外,發明所屬技術領域中具有通常知識者可由常規實驗瞭解或確認本說明書所揭示的具體實施例中的多項均等內容。再者,該些均等內容應當落入本發明的範圍內。
根據本發明的一態樣提供一種腸膜明串珠菌CJRS-10671(韓國寄存編號:KCCM13059P)菌株。
根據本發明的另一態樣提供一種腸膜明串珠菌CJRS-10672(韓國寄存編號:KCCM13060P)菌株。
本發明之技術用語「腸膜明串珠菌」是指具有圓球狀的乳酸菌,且已知為具備發酵益生菌或例如韓國泡菜的食物之功能的乳酸菌。
本發明的腸膜明串珠菌菌株可以是選自於韓國寄存編號為KCCM13059P的CJRS-10671菌株或韓國寄存編號為KCCM13060P的CJRS-10672菌株中的至少一種。
本發明的CJRS-10671菌株可具有β-半乳糖苷酶(β-galactosidase)、α-葡萄糖苷酶(α-glucosidase)以及β-葡萄糖苷酶(β-glucosidase)的高酵素活性,以及本發明的CJRS-10672菌株可具有β-葡萄糖苷酶的酵素活性。
另外,本發明的菌株可具有整腸功效和免疫增強功效。
根據本發明的再一態樣提供一種含有CJRS-10671菌株(韓國寄存編號為KCCM13059P)或CJRS-10672菌株(韓國寄存編號為KCCM13060P)的組合物,韓國寄存編號KCCM13059P或韓國寄存編號KCCM13060P的菌株
之培養物,或衍生自韓國寄存編號KCCM13059P或韓國寄存編號KCCM13060P的菌株之物質。
本發明的組合物可以是食物或飼料。
本發明的菌株可呈現為活細胞或死細胞,且可以乾燥或冷凍乾燥的形式呈現。
本發明的培養物可包括活細胞培養物(即,在培養基質中培養活細胞所得到的產物)、藉由滅殺活細胞培養物中的活細胞所得到的培養物、或培養濾液(即,藉由從培養物中移除死細胞或活細胞後所得到的產物)。衍生自本發明的菌株的組成可包括藉由細胞破碎所得到的細胞質破片(cytoplasmic fraction),其含有細胞外囊泡(extracellular vesicles,EVs)或類似物。此外,適於被包含於醫藥組合物之乳酸菌的形式及其形成方法、菌株衍生組成物的分離方法等,是發明所屬技術領域中具有通常知識者所習知的。
具體而言,本發明的菌株可以是以0.1%至10%接種於MRS液體培養基中,並在25℃至40℃下培養4至72小時後所得到的菌株。
本發明的菌株可具有抗癌症、抗發炎和增強免疫的功效。
在本發明中,癌症可包括本領域已知的任何類型的癌症,但不以此為限,其舉例可包括肺癌(例如:非小細胞肺癌、小細胞肺癌、惡性間皮瘤)、間皮瘤、胰臟癌(例如:胰管腺癌、胰臟內分泌腫瘤)、咽癌、喉癌、食道癌、胃癌(例如:乳突狀腺癌、黏液性腺癌、腺樣鱗狀細胞癌)、十二指腸癌、小腸癌、結直腸癌(例如:結腸癌、直腸癌、肛門癌、家族性結直腸癌、遺傳性非瘜肉病性結直腸癌、胃腸道間質瘤)、乳癌(例如:浸潤性乳腺管癌、非浸潤性乳腺管癌、發炎性乳癌)、卵巢癌(例如:卵巢上皮癌、生殖腺外生殖細胞瘤、卵巢生殖細胞腫瘤、卵巢低惡性瘤)、睪丸腫瘤、前列腺癌(例如:賀爾蒙依賴性前列腺癌、非賀爾蒙依賴性前列腺癌)、肝癌(例如:肝細胞癌、
原發性肝癌、肝外膽管癌)、甲狀腺癌(例如:甲狀腺髓質癌)、腎癌(例如:腎細胞癌、腎盂與輸尿管移行細胞癌)、子宮癌(例如:子宮頸癌、子宮內膜癌、子宮肉瘤)、腦瘤(例如:髓母細胞瘤、膠質細胞瘤、松果體星細胞瘤、纖維性星細胞瘤、瀰散性星細胞劉、退化性星細胞瘤、垂體腺瘤)、視網膜母細胞瘤、皮膚癌(例如:基底細胞瘤、惡性黑色素瘤)、肉瘤(例如:橫紋肌肉瘤、平滑肌肉瘤、軟組織肉瘤)、惡性骨腫瘤、膀胱癌、血液腫瘤(例如:多發性骨髓瘤、白血病、惡性淋巴瘤、何杰金氏淋巴瘤、慢性骨髓性增生疾病)、原發部位不明癌等,但不限於此,且具體來說,可以是肺癌或結直腸癌。
本發明的菌株或組合物可以表現出抗癌功效。具體而言,抗癌功效可包括癌細胞滅殺或抑制腫瘤生長的功效(實例9以及實例10-1)。
舉例來說,本發明的菌株或組合物可以抑制癌細胞的細胞週期,進而表現癌細胞滅殺或抑制腫瘤生長的功效,進而產生抗癌功效(實例8)。
再舉例而言,本發明的菌株或組合物可藉由增加免疫增強細胞激素之IL-6、IL-12p70以及干擾素-γ(IFN γ)的分泌,以展現抗發炎或增強免疫的功效(實例7)。
在本發明中,本發明的菌株或組合物可以和抗癌劑聯合施用。
抗癌劑的舉例可包括基於紫杉烷(taxane-based)的抗癌劑、他汀類藥物(statins)、烷化劑、鉑類藥物、抗代謝藥物、抗生素、基於長春花生物鹼(vinca alkaloid-based)的抗癌劑、標靶治療劑、抗癌免疫治療劑、癌症疫苗、細胞治療劑、溶瘤病毒及其組合,但不以此為限,具體來說,所述抗癌劑可以是抗癌免疫治療劑。
基於紫杉烷(taxane-based)的抗癌劑的舉例可為紫杉醇(paclitaxel)、多烯紫杉醇(docetaxel)、拉羅他賽(larotaxel)、卡巴他賽(cabazitaxel)等,但不以此為限。
他汀類藥物的舉例可以是辛伐他汀(simvastatin)、阿托伐他汀(atorvastatin)、洛伐他汀(lovastatin)、氟伐他汀(fluvastatin)、西立伐他汀(cerivastatin)、匹伐他汀(pitavastatin)等,但不以此為限。
烷化劑的舉例可以是氮芥類藥物、乙烯亞胺基類藥物和甲基三聚氰胺類藥物、甲基肼衍生物、烷基磺酸類藥物、亞硝基脲類藥物、三嗪類藥物等,但不以此為限。
鉑類藥物的舉例可以是順鉑、卡鉑、奧沙利鉑等,但不限於此。
抗代謝物的舉例可以是基於葉酸拮抗劑的藥物、基於嘌呤拮抗劑的藥物、基於嘧啶拮抗劑的藥物等,但不以此為限。
抗生素的舉例可以是依妥普賽(etoposide)、拓普替康(topotecan)、伊立替康(irinotecan)、艾達黴素(idarubicin)、泛艾黴素(epirubicin)、放線菌素(dactinomycin)、艾黴素(doxorubicin)、阿黴素(adriamycin)、道諾黴素(daunorubicin)、博來黴素(bleomycin)、絲裂黴素C(mitomycin C)、米托蒽醌(mitoxantrone)等,但不以此為限。
基於長春花生物鹼的抗癌藥物的舉例可以是長春花新鹼(vincristine)、長春花鹼(vinblastine)、溫諾平(vinorelbine)等,但不以此為限。
標靶治療劑的舉例可以是表皮生長因子受體(EGFR)標靶治療劑、人類表皮生長因子受體2(HER2)標靶治療劑、CD20(B細胞標記)標靶治療劑、CD33(骨髓細胞表面抗原)標靶治療劑、CD52(分化簇52)標靶治療劑、CD30(腫瘤壞死因子受體超家族成員8)標靶治療劑、斷裂點簇集區蛋白酪氨酸蛋白激酶(BCR-ABL)/酪氨酸激酶受體(c-Kit)標靶治療劑、間變性淋巴瘤受體酪氨酸激酶(ALK)標靶治療劑、抗血管生成標靶治療劑、哺乳類雷帕黴素靶蛋白(mTOR)標靶治療劑、細胞週期蛋白依賴性激酶4/6
(CDK4/6)標靶治療劑、聚(ADP-核糖)聚合酶(PARP)標靶治療劑、蛋白酶體抑制劑、酪氨酸激酶拮抗劑、蛋白激酶C抑制劑、法尼基轉移酶抑制劑等,但不限於此。
抗癌免疫治療劑的實例可以是抗程式化細胞死亡蛋白1(抗-PD-1)、抗程式化細胞死亡配體1(抗PD-L1)、細胞毒性T淋巴細胞相關抗原4(CTLA4)、CTLA4/B7-1/B7-2相互作用抑制劑、分化簇47/信號調節蛋白(CD47/SIRP)相互作用抑制劑、抗T細胞免疫球蛋白及黏蛋白結構域3(抗Tim3)、抗淋巴細胞活化基因3(抗LAG3)等,但不以此為限。
具體地,本發明的抗癌劑可以是,但不限於,抗PD-1免疫治療劑。
在本發明中,聯合施用(co-administration)可以是同時、依序或反序施用菌株或組合物與抗癌劑,但施用順序不受限制,只要兩者以能夠表現出兩者藥理作用的施用間隔施用,即屬於本發明的範圍。所述菌株或組合物與抗癌劑可以分別製備成調配物,也可以製備成一構造(formation),但不以此為限。
在本發明中,本發明的菌株或組合物的施用可以與抗癌治療一起進行。抗癌治療的舉例可以是放射性治療、新輔助治療、化療、標靶治療、光動力治療等,但不以此為限,且可包括本領域已知的所有類型的抗癌治療。
本發明的食品組合物可以是食品添加劑的形式。
食品組合物還可以含有食品添加劑,其作為「食品添加劑」的適用性,除非另有規定,係根據食品藥品安全部批准的《食品添加劑法典》之通則和通用測試方法,依據相應項目的標準和準則決定。
《食品添加劑法典》所列項目可包括,例如:化學合成產品(例如:酮、甘氨酸、檸檬酸鉀、菸鹼酸以及肉桂酸)、天然添加劑(例如:柿子
色素、甘草根萃取物、結晶纖維素以及瓜爾豆膠)以及混合製劑(例如:L-谷氨酸鈉製劑,用於添加到麵條中的鹼劑、防腐劑製劑以及焦油色製劑)。
含有本發明的活性成分的食品的舉例可包括:甜食(例如:麵包、年糕、乾蛋糕、糖果、巧克力、口香糖以及果醬)、冰淇淋產品(例如:冰淇淋、冷凍甜點以及冰淇淋粉)、乳製品(例如:牛奶、低脂牛奶、乳糖降解牛奶、加工牛奶、山羊奶、發酵乳、酪乳、濃縮乳、牛奶奶油、酪乳、天然乳酪、加工乳酪、奶粉以及乳清)、肉製品(例如:加工肉製品、加工蛋製品以及漢堡)、魚肉製品(例如:魚餅以及魚肉加工產品),例如:火腿、香腸以及培根、麵條(例如:拉麵、乾麵、鮮麵、速食炸麵、糊化乾麵、改性熟麵、冷凍麵條、以及義大利麵)、飲料(例如:水果飲料、蔬菜飲料、碳酸飲料、豆漿、乳酸菌飲料(包含優酪乳)以及混合飲料)、調味食品(例如:醬油、發酵豆醬、紅辣椒醬、黑豆醬、快速發酵豆瓣醬、混合醬、醋、醬汁、番茄醬、咖哩以及淋醬)以及發酵食品,但不以此為限。
除上述外,本發明的食品組合物可包含各種營養物質、維生素、電解質、調味劑、著色劑、果膠酸及其鹽類、海藻酸及其鹽類、有機酸、保護膠體增稠劑、pH調整劑、安定劑、防腐劑、甘油、醇類、碳酸飲料中使用的碳酸化劑等。此外,本發明的食品組合物可包含用於製造天然果汁、果汁飲料和蔬菜飲料的果肉。該些成分可單獨使用,也可以組合使用。
除了飼料組合物之外,飼料組合物可以是飼料添加劑組合物的形式。
當組合物被製造為飼料添加劑時,其可以被製成為20%至90%的高濃縮溶液,或呈粉末或顆粒之形式。所述飼料添加劑還可包含以下任意一種或一種或多種:有機酸(例如:檸檬酸、延胡索酸、己二酸、乳酸以及蘋果酸)、磷酸鹽(例如:磷酸鈉、磷酸鉀、酸性焦磷酸鹽和多磷酸鹽)或天然抗
氧化劑(例如:多酚、兒茶素、α生殖酚、迷迭香萃取物、維生素C、綠茶萃取物、甘草萃取物、殼聚糖、鞣酸以及植酸)。當組合物被製造為飼料時,組合物可以普通飼料形式配製,並且可以一起包含普通飼料成分。
所述飼料和飼料添加劑還可以包含:穀物(例如:粉狀或顆粒狀的小麥、燕麥、大麥、玉米以及稻米)、植物蛋白飼料(例如:以油菜、豆類和向日葵為主要成分的飼料)、動物蛋白飼料(例如:血粉、肉粉、骨粉以及魚粉)以及糖與乳製品(例如:包括各種類型的奶粉和乳清粉之乾燥組分),並且除上述外,還可以包含營養補充劑、消化與吸收促進劑、生長促進劑等。
所述飼料添加劑可以單獨施用於動物,也可以與食用載體中的其它飼料添加劑結合施用。所述飼料添加劑藉由直接與動物飼料混合而作為追肥,或作為與飼料分開的口服製劑而可容易地施用於動物。當飼料添加劑與動物飼料分開施用時,可將飼料添加劑製備為速釋或緩釋製劑,與本領域公知的醫藥上可接受的食用載體組合。所述食用載體可以是固體或液體,例如:玉米澱粉、乳糖、蔗糖、豆片、花生油、橄欖油、芝麻油以及丙二醇。當使用固體載體時,飼料添加劑可以是片劑、膠囊、粉末、片劑、錠劑或非分散追肥的形式。當使用液體載體時,飼料添加劑可以是明膠軟膠囊、糖漿、懸浮液、乳液或溶液的配方。
飼料和飼料添加劑可含有佐劑,例如:防腐劑、安定劑、保濕劑、乳化劑及溶液促進劑。飼料添加劑可以藉由浸泡、噴灑或混合而添加到動物飼料中使用。
本發明的飼料或飼料添加劑可應用於許多動物的飼料,包括哺乳動物、家禽和魚類。
本發明的飼料或飼料添加劑可用於:哺乳動物(例如:豬、牛、馬、綿羊、兔子、山羊、囓齒動物)、實驗齧齒動物(包括:大鼠、倉鼠以及
天竺鼠)、寵物(例如:狗與貓)、家禽(例如:雞、火雞、鴨、鵝、雉雞以及鵪鶉)、以及魚類(例如:鯉魚、鲫魚以及鱒魚),但不以此為限。
根據本發明的又一態樣提供了一種用於預防或治療癌症的方法,其包括向受試者施用本發明的菌株或組合物。
本發明的菌株或組合物可提供作為用於預防或治療癌症的藥物組合物,且所述菌株、組合物與癌症如上所述。
本發明的治療方法包括對疑似患有癌症的受試者施用一醫藥上有效劑量的本發明的菌株或組合物。受試者可以指任何哺乳動物,包括:狗、牛、馬、兔、小鼠、大鼠、雞與人類,但本發明的哺乳動物不以該些舉例為限。菌株或組合物可以藉由非經口、皮下、腹膜內、肺內和鼻內途徑施用。對於局部治療,如有必要時,菌株或組合物可以藉由包括病灶內施用的適當方法施用。非經口注射包括肌內、靜脈內、動脈內、腹膜內或皮下施用。較佳的製劑是靜脈注射、皮下注射、皮內注射、肌內注射或滴注的製劑。本發明的菌株或組合物的較佳劑量可依據受試者的狀況和體重、疾病的嚴重程度、藥物類型以及施用途徑和期間而變化,並且可以由發明所屬技術領域中具有通常知識者適當地決定。
根據本發明的新穎腸膜明串珠菌菌株表現出抗癌功效,並表現出免疫增強功效,例如:藉由增強CD8 T細胞效價來增加免疫增強細胞激素IL-6、IL-12p70以及IFN γ的分泌,因此,可應用於食品或飼料。
圖1顯示腸膜明串珠菌CJRS-10671菌株以及CJRS-10672菌株的酵素活性。
圖2顯示CJRS-10671菌株以及CJRS-10672菌株的溶血活性。
圖3顯示CJRS-10671菌株以及CJRS-10672菌株的腸黏附性。
圖4顯示於巨噬細胞株之CJRS-10671菌株以及CJRS-10672菌株所致的介白素-6(IL-6)分泌。
圖5顯示於人類周邊血單核細胞(PBMCs)之CJRS-10671菌株以及CJRS-10672菌株所致的IL-12p70分泌。
圖6顯示於小鼠脾臟細胞以及人類周邊血單核細胞中的CJRS-10671菌株以及CJRS-10672菌株所致之CD8 T細胞的干擾素γ(IFN γ)分泌能力。
圖7顯示CJRS-10671菌株以及CJRS-10672菌株所致的癌細胞的細胞週期停止。
圖8顯示CJRS-10671菌株以及CJRS-10672菌株所致的週期蛋白B1與週期蛋白依賴性激酶1(CDK1)的表現,週期蛋白B1與週期蛋白依賴性激酶1(CDK1)為癌細胞中之細胞週期停止相關因子。
圖9顯示CJRS-10671菌株以及CJRS-10672菌株所致的癌細胞死亡。
圖10顯示在小鼠肺癌模型(LLC1)中施用CJRS-10671以及CJRS-10672所致的腫瘤抑制功效。
圖11顯示在小鼠肺癌模型(LLC1)中施用CJRS-10671所致的CD8 T細胞的干擾素γ(IFN γ)分泌能力。
圖12顯示在小鼠肺癌模型(LLC1)中施用CJRS-10672所致的CD8 T細胞的干擾素γ(IFN γ)分泌能力。
圖13顯示在小鼠肺癌模型(LLC1)中施用CJRS-10671以及CJRS-10672所致的腫瘤組織中的CD8 T細胞的干擾素γ(IFN γ)分泌能力。
圖14顯示在小鼠肺癌模型(LLC1)中施用CJRS-10671以及CJRS-10672所致的髓源性抑制細胞(MDSC)作為免疫抑制細胞的變化。
圖15顯示在小鼠肺癌模型(LLC1)中施用CJRS-10671所致的免疫細胞變化分析。
圖16顯示在小鼠肺癌模型(LLC1)中施用CJRS-10672所致的免疫細胞變化分析。
有關本發明的詳細內容將參閱以下實例進行說明。然而,該些實例僅用於說明本發明的較佳實施例,因此並非旨在限制本發明的權利範圍。同時,本文中未敘述之技術事項可由本發明領域或本發明相似技術領域具有通常知識者充分理解與輕易實現。此外,於說明書全中引用許多論文與專利文件,並提供其引用。所引用論文及專利文獻之公開藉由引用其全文而納入本說明書中,並更清楚地解釋了本發明所屬技術領域的水準與細節。
實例1:腸膜明串珠菌菌株的糖發酵特性
使用Difco的MRS液體培養基與瓊脂培養基培養從韓國泡菜中分離出的腸膜明串珠菌CJRS-10671菌株以及CJRS-10672菌株。依據一協定(protocol)製備每一培養基,並在121℃下滅菌15分鐘。於實驗前2天,將每種菌株的備料以1%接種於MRS液體培養基中,並在37℃下靜態培養20小時,而後以2%再次接種於MRS液體培養基中(活化)並在37℃下培養20小時。
使用API 50 CHL試劑盒(生物梅里埃,法國)檢測以上述培養方式培養的CJRS-10671菌株及CJRS-10672菌株對於49種碳水化合物的糖發酵特性。具體而言,將繼代培養兩次的菌株以磷酸鹽緩衝鹽水(PBS)潤洗後,將每一菌株懸浮於API 50 CHL培養基中達到McFarland標準2.0,再接種至帶 材上,以37℃培養24小時。使用碳水化合物所導致的黃色會被解讀為顯示陽性反應,而沒有使用碳水化合物所導致的紫色會被解讀為顯示陰性反應。
實例2:菌株的酵素活性
為了分析實例1的CJRS-1067菌株及CJRS-10672菌株的生化特性,該等菌株使用API ZYM試劑盒(生物梅里埃,法國)測試了19種酵素活性。
結果如下表2及圖1所示,CJRS-10671在β-半乳糖苷酶、α-葡萄糖苷酶和β-葡萄糖苷酶中表現出高酵素活性,CJRS-10672則是在β-葡萄糖苷酶中表現出高酵素活性。
實例3:菌株的溶血活性
為了確認實施例1的CJRS-10671菌株及CJRS-10672菌株是否具有溶血活性,將菌株嵌接在補充有5%去纖維化綿羊血(MB細胞,韓國)的血瓊脂上,並在37℃下培養24小時,之後觀察菌落周圍是否形成清晰區域。
測試結果如圖2所示,在菌落周圍並沒有觀察到因血細胞溶解而產生的清晰區域,表示CJRS-10671菌株及CJRS-10672菌株並沒有溶血活性。
實例4:菌株的抗生素抗藥性
為了確認實例1的CJRS-10671菌株及CJRS-10672菌株的抗生素抗藥性,根據EFSA抗生素抗藥性測試指南進行抗生素抗藥性測試,以確認最低抑制濃度(minimum inhibitory concentration,MIC)。該測試指南規定了8種抗生素用於腸膜明串珠菌的臨界值標準。
MIC的測試結果,CJRS-10671菌株及CJRS-10672菌株符合其中5種抗生素的標準,但超出某些抗生素的MIC標準,因此,根據EFSA指南對於抗生素抗藥性是先天抗藥性還是後天抗藥性來進行遺傳分析。測試結果如下表3所示。根據EFSA指南,具有先天抗藥性的菌株是可以使用的,因為抗生素抗藥性基因並不可能從外部轉移其他細菌上。已有報告指出明串珠菌屬的菌
株對於氯黴菌(MICs4μg/mL)具有抗藥性,但已知此抗藥性可能是明串珠菌屬的先天抗藥性,不太可能是由水平基因轉移至其他細菌所引起的(AB Florez,2005)。
實例5:菌株的耐酸性和膽鹽耐受性
由於穩定到達腸道發揮功效在口服製劑中很重要,因此,對菌株的耐酸性和膽鹽耐受性進行評估,以確定其作為口服製劑的適用性。具體而言,耐酸性測試是將繼代培養兩次的菌株以1%接種於藉由1N HCL調整至pH 3.0的PBS溶液中,並在37℃培養2小時,而後在初始活細胞與培養後活細胞計數之間進行比較。
膽鹽耐受性之確認則是將活化的菌株以1%接種在含有1%牛膽汁(Difco,美國)的PBS溶液中,並在37℃培養2小時,而後在初始活細胞與培養後活細胞計數之間進行比較。
結果如表4所示,以初始活細胞計數100%作為基準,CJRS-10671菌株顯示耐酸性為95.7%,膽鹽耐受性為136.6%;以初始活細胞計數100%作為基準,CJRS-10672菌株顯示耐酸性為120.6%,膽鹽耐受性為67.9%。
實例6:菌株的腸黏附性
為了確認實例1的CJRS-10671菌株及CJRS-10672菌株在腸道環境中的穩定性與適應性,使用HT-29細胞株(韓國細胞庫,KCLB,首爾,韓國)作為腸上皮細胞以評估菌株的腸黏附性。
具體而言,將HT-29細胞株培養於補充有10%胎牛血清(FBS,Gibco,Carlsbad,CA,美國)、100U/mL青黴素以及0.1mg/mL鏈黴素的杜氏改良伊格爾最低限度必需培養基(Dulbecco’s modified Eagle’s minimal essential medium,DMEM)中,並在37℃及5%二氧化碳條件下培養。將HT-29細胞株以1.0×105顆細胞/孔的數量種於24孔盤中,待形成到約80%的單層細胞層,再用PBS潤洗2次以除去DMEM中所含的抗生素。用PBS潤洗繼代培養兩次的菌株並重新溶於不含抗生素的DMEM中,並以2×107CFU/孔的比例進行處理。在37℃及5%二氧化碳條件下培養2小時後,使用PBS潤洗去除未黏附的細胞,並藉由加入乙二胺四乙酸(EDTA,trypsin-ethylene-diamine-tetraacetic acid)而僅分離黏附的HT-29及菌株細胞,接下來,使用MRS瓊脂計數活細胞。腸黏附性的程度是以每100個HT-29細胞中之黏附菌株細胞的CFU數量表示,並使用雙叉雙歧桿菌(Bifidobacterium bifidum)、嬰兒雙歧桿菌(B.infantis)以及乳酸雙歧桿菌(B.lactis)ATCC型菌株作為對照組。
結果顯示,CJRS-10671菌株的腸黏附率為217±21個細菌/100個細胞,和對照組菌株的腸黏附率相當或更高(如圖3所示)。
實例7:菌株分泌免疫增強細胞激素
7-1.巨噬細胞株的介白素-6(interleukin-6,IL-6)分泌
確認IL-6(被稱為免疫增強細胞激素)的分泌是否是由實例1的CJRS-10671及CJRS-10672在免疫細胞中所誘發的。使用小鼠巨噬細胞株(Raw 264.7)以及人類單核球細胞(THP-1)作為免疫細胞。在實驗前一周將Raw 264.7細胞株繼代培養並維持於含有10%FBS以及1%抗生素-抗真菌劑的DMEM中,並在實驗前一天以6×104細胞/孔的細胞數量種在平的96孔盤中。在實驗前兩天將THP-1細胞株繼代培養並維持於含有10%FBS,1%青黴素-鏈黴素(PS)以及0.05mM的2-疏基乙醇(2-ME)的RPMI培養基中,並以8×104細胞/孔的細胞數量種在平的96孔盤中,接著再以25ng/mL的佛波醇12-十四酸酯13-乙酸酯(PMA,phorbol 12-myristate 13-acetate)處理俾誘導人類單核球細胞分化成人類巨噬細胞兩天。之後當細胞與CJRS-10671及CJRS-10672共培養時,是使用含有10%FBS的無抗生素培養基作為培養基。培養後,使用Novocyte儀器測量並計算CJRS-10671及CJRS-10672的總細胞數量,然後使用於以比例1:10與免疫細胞進行處理。在共培養24小時以後,將培養盤離心以沉澱細胞並獲得上清液,然後將其用於檢測細胞激素分泌。使用BD生物科學公司的BD細胞儀微球陣列(CBA)鼠/人彈性組製備分析樣品,且以BD Lyric(流式細胞儀)進行讀取,並藉由FCAP軟體分析結果。
結果顯示,CJRS-10671和CJRS-10672在與小鼠或人類巨噬細胞共培養時增加了IL-6的分泌(如圖4所示)。
7-2.人類外周血單核球細胞(PBMCs)中的IL-12p70分泌
確認IL-12p70(已知為免疫增強細胞激素)的分泌是否是由人
類PBMC中的CJRS-10671及CJRS-10672所誘發的。將人類PBMC以2×105細胞/孔的細胞數量種在96孔盤中。之後,當細胞與CJRS-10671及CJRS-10672共培養時,是使用含有10%FBS的無抗生素培養基作為培養基。培養後,使用Novocyte儀器測量並計算CJRS-10671及CJRS-10672的總細胞數量,然後使用於以比例1:10與免疫細胞進行處理。在共培養24小時後獲得上清液,且分析結果顯示,CJRS-10671和CJRS-10672在與人類PBMCs共培養時增加了IL-12p70的分泌(如圖5所示)。
7-3.小鼠脾細胞以及人類PBMCs中之CD8 T細胞的干擾素-γ(IFN γ)分泌
已知CD8 T細胞(細胞毒性T細胞)的IFN γ分泌能力對抗癌功效有很大影響。為了確認CJRS-10671菌株及CJRS-10672菌株對細胞毒性T細胞的IFN γ分泌能力,使用小鼠脾細胞和人類PBMCs檢測CD8+IFN γ+。
詳細來說,為了分離小鼠脾細胞,使用注射器將含有IV型膠原酶的Hanks平衡鹽溶液(HBSS)插入小鼠脾臟組織中使細胞流出。重複此過程數次後,使用注射器將剩餘組織切成小塊並在37℃培養25分鐘。加入0.5M EDTA後,於37℃再培養5分鐘。使用巴斯德移液管攪拌細胞,再用細胞過濾器過濾。經過1,500rpm離心3分鐘後,使用1X RBC裂解緩衝液移除紅血球,並將脾細胞懸浮於新鮮培養基中供實驗使用。
人類PBMCs購自STEMCELL科技,並在收到後儲存於液態氮桶中,待實驗時使用。在實驗當日,將庫存從液態氮桶中取出並於恆溫水浴中融化。加入補充有10%FBS的RPMI 1640,然後以1,500rpm離心5分鐘,然後在使用於實驗前將PBMCs懸浮於新鮮培養基中。
由於需要T細胞刺激劑來確認小鼠脾細胞分泌IFN γ的能力,因此,在與菌株共培養的前一天,將稀釋於PBS中的0.1μg/mL抗-CD3抗體以0.1
μg/mL的濃度,以每孔100μL體積被覆至平的96孔盤中。在共培養當天,經被覆盤在使用PBS潤洗兩次後製備完成,並依據協定分離出小鼠脾細胞,接著將5×105細胞/孔的細胞數量種於被覆有包含1μg/mL純化抗CD28抗體的96孔盤中。CJRS-10671菌株及CJRS-10672菌株使用無抗生素培養基以1:10的比例與脾細胞共培養。在共培養3天後,加入布雷非德菌素A(brefeldin A),接著加入高基氏體停止劑(Golgi-stop)3至4小時,接著使用BD轉錄因子緩衝液組檢測標記,並使用螢光抗體進行染色以製備分析樣品。使用BD Lyric(流式細胞儀)和Flowjo軟體分析樣品,並評估結果。
將人類PBMCs細胞以2×105細胞/孔的細胞數量播種,並採用與實例7-2相同的方式進行共培養。
結果顯示,CJRS-10671和CJRS-10672增加了小鼠脾細胞以及人類PBMCs中CD8 T細胞的IFN γ分泌能力(如圖6所示)。
實例8:菌株對癌細胞細胞週期的調節
8-1.癌細胞的細胞週期停止
檢測實例1的CJRS-10671菌株及CJRS-10672菌株在癌細胞株中的細胞週期調控。
使用路易斯肺癌LL/2(Lewis lung carcinoma LL/2)(LLC1)肺癌細胞株與小鼠癌-38(murine carcinoma-38,MC38)結直腸癌細胞株作為癌細胞株。實驗前一周,將LLC1與MC38細胞株培養並維持於含有10%FBS及1%抗生素-抗真菌劑的DMEM中。將LLC1以及MC38細胞株分別以2.4×105細胞/孔以及1.2×105細胞/孔的細胞數量種在6孔盤中。為了使細胞週期同步到G0/G1期,在培養24小時後以1X PBS潤洗該等盤兩次,再將該培養基與含有0.5%FBS的無抗生素培養基交換。以癌細胞株:菌株為1:10、1:100或1:1,000的比例加入CJRS-10671菌株及CJRS-10672菌株。在共培養24小時後,使用胰
蛋白酶-EDTA分離細胞並用1X PBS洗滌,然後加入5mL冰冷的75%EtOH使僅留下細胞,然後使其隔夜存於-20℃。之後進行Ki67和PI螢光染色,並使用BD Lyric(流式細胞儀)和Flowjo軟體分析細胞週期結果。使用沒有接受CJRS-10671菌株及CJRS-10672菌株處理的組別(非菌株處理組)作為控制組。
結果顯示,與非菌株處理組相比,在菌株處理組觀察到細胞週期停止效應,並且細胞週期停止效應主要是由CJRS-10671在G2/M期所誘導的(如圖7所示)。
8-2.週期蛋白B1與週期蛋白依賴性激酶1(CDK1)的表現,癌細胞週期停止相關因子
測試CJRS-10671菌株及CJRS-10672菌株對於週期蛋白B1與CDK1(其等為癌細胞株中的G2/M細胞週期調控相關因子)的表現變化。LLC1細胞與CJRS-10671菌株及CJRS-10672菌株採用與實例8-1相同的方式共培養24小時,接著使用TRIzol從細胞中萃取RNA。從中合成cDNA,並使用QuantStudio 5即時PCR系統進行PCR,以測量相對表現程度。使用沒有接受CJRS-10671菌株及CJRS-10672菌株處理的組別(非菌株處理組)作為控制組。
結果顯示,與G2/M細胞週期停止相關的週期蛋白B1和CDK1降低,以及,與非菌株處理組相比,LLC1中的週期蛋白B1與CDK1相對表現程度主要降低於菌株處理組(如圖8所示)。
實例9:菌株所致的癌細胞死亡
為了確認實例1的CJRS-10671菌株及CJRS-10672菌株對癌細胞株存活率的變化,將LLC1及MC38細胞分別以2.4×105細胞/孔以及1.2×105細胞/孔的細胞數量種在6孔盤中。在培養24小時後,將培養基更換為含有0.5%FBS的培養基,接著進行血清耗盡(serum starvation)24小時。以癌細胞株:菌株為1:10、1:100或1:1,000的比例使用CJRS-10671菌株及CJRS-10672
菌株進行處理。在共培養24小時後,使用胰蛋白酶-EDTA分離細胞並用1X PBS洗滌,且使用可固定細胞活性染劑510抗體進行螢光染色以區分死細胞與活細胞,並使用BD Lyric(流式細胞儀)和Flowjo軟體分析細胞存活結果。以細胞總數為100%,活細胞與死細胞的比例如圖所示。
結果顯示,與非菌株處理組相比,使用菌株處理組的細胞存活率降低(如圖9所示)。
實例10:小鼠肺癌(LLC1)模型中菌株的抗癌功效
10-1.腫瘤抑制功效
為了建構肺癌動物模型,將LLC1細胞株以4×105細胞/小鼠皮下注射到c57BL/6小鼠中。當腫瘤細胞注射後的腫瘤大小達到30至50mm3時,將小鼠分為以下組別:陰性控制組(腫瘤細胞注射後未予處理)、CJRS-10671或CJRS-10672樣品處理組、免疫檢查點抑制劑抗PD-1處理組(陽性控制組),以及CJRS-10671或CJRS-10672樣品與抗PD-1聯合處理組。將CJRS-10671或CJRS-10672樣品在100μL PBS中稀釋為每隻動物109CFU且在10天內共施用10次,以及每兩天以腹腔膜內施用抗PD-1(10mg/kg,BioXCell)。每週以卡尺測量腫瘤的大小3次,並在施用結束後的次日,犧牲小鼠以測量腫瘤重量並分析其血液與器官。
結果顯示,與單獨施用抗PD-1組相比,即使單獨施用CJRS-10671也減小了腫瘤大小,並且在聯合施用抗PD-1時表現了優異的腫瘤抑制功效。單獨施用CJRS-10672顯示出輕微的功效,但是當與抗PD-1聯合施用時表現了特別優異的腫瘤抑制功效(如圖10所示)。
10-2.CD8 T細胞的IFN γ分泌能力
在實例10-1的測試結束之後,從每組的脾組織中分離脾細胞,並以106細胞/孔種植於圓底的96孔盤中。使用刺激所有免疫細胞的PMA/離子
黴素刺激脾細胞3至4小時,然後進行表面標記染色與細胞內細胞激素染色(ICS)。之後,藉由FACS確定CD8 T細胞分泌的IFN γ量。為了進一步確認CD8 T細胞的效價,使用刺激T細胞的CD3/CD28(2μg/mL抗CD3抗體和2μg/mL抗CD28抗體)刺激同樣的經分離脾細胞1天,而後進行表面標記染色和ICS。之後,藉由FACS確定CD8 T細胞分泌的IFN γ量。
結果顯示,在CJRS-10671與抗PD-1聯合施用組中,CD8 T細胞分泌的IFN γ量在所有免疫細胞的刺激下顯著增加,並且CD8 T細胞分泌的IFN γ量即使在刺激T細胞時也趨於增加(如圖11所示)。在CJRS-10672與抗PD-1聯合施用組中,CD8 T細胞分泌的IFN γ量與單獨施用抗PD-1組在所有免疫細胞受到刺激時分泌的IFN γ量相似,但在刺激T細胞時,CD8 T細胞分泌的IFN γ量顯著增加(如圖12所示)。
10-3.癌組織中CD8 T細胞的IFN γ分泌能力
在實例10-1的測試結束之後,從每組的腫瘤組織中分離腫瘤浸潤淋巴細胞(TIL),接著以刺激T細胞的CD3/CD28(2μg/mL抗CD3抗體和2μg/mL抗CD28抗體)刺激1天,而後進行表面標記染色和ICS。然後,藉由FACS確定CD8 T細胞分泌的IFN γ量。
結果顯示,在CJRS-10671與抗PD-1聯合施用組以及CJRS-10672與抗PD-1聯合施用組中,在刺激T細胞後CD8 T細胞分泌的IFN γ量皆增加(如圖13所示)。
10-4.免疫抑制細胞的變化
在實施例10-1的測試結束後,藉由使用CD11b+Gr-1+標記及FACS的螢光染色來確定每組脾細胞與腫瘤細胞中已知為免疫抑制細胞的髓源性抑制細胞(MDSC)的變化。
結果顯示,陰性控制組中的脾細胞中的MDSC增加,但在CJRS-
10671與抗PD-1聯合施用組以及CJRS-10672與抗PD-1聯合施用組中則減少。此外,當在腫瘤中使用相同的標記時,與陰性控制組相比,CJRS-10671與抗PD-1聯合施用組以及CJRS-10672與抗PD-1聯合施用組中的MDSC顯著降低(如圖14所示)。
10-5.免疫細胞變化分析
在實例10-1的測試結束之後,從每組的脾組織中分離脾細胞,然後使用螢光抗體進行表面標記染色,以確認免疫細胞以及免疫抑制細胞的變化。不同類型之免疫細胞所使用的螢光標記如下:M1(CD11b+F4/80+CD86+)、M2(CD11b+F4/80+CD206+)、DC(IA-IE+CD11b+CD11c+)、B細胞(CD3-B220+)、NK細胞(CD3-NK1.1+)、NKT細胞(CD3+NK1.1+)以及調節T細胞Treg(CD4+CD25+Foxp3+)。使用BD Lyric(流式細胞儀)和Flowjo軟體分析樣品,接著將結果評估為%和#。
結果顯示,單獨施用或與抗PD-1聯合施用的CJRS-10671組以及CJRS-10672組中的M1、DC及NK T細胞的%和#值趨於增加(如圖15及圖16所示)。
CJRS-10671菌株以及CJRS-10672菌株於2021年10月19日寄存於《布達佩斯條約》下的保藏機構韓國微生物保藏中心,寄存編號分別為KCCM13059P以及KCCM13060P。
如上所述,與本發明所屬技術領域中具有通常知識者應能夠理解本發明可以以其他特定形式實現,而不背離其技術精神或其本質特徵。因此,上述實施例應被解釋為是示例性的,而不是對本發明有所限制。應當理解,從申請專利範圍及其均等內容的定義和範圍衍生的所有更改或修飾都落於本發明的範圍內。
Claims (2)
- 一種腸膜明串珠菌( Leuconostoc mesenteroides)CJRS-10671(韓國寄存編號:KCCM13059P)菌株。
- 一種腸膜明串珠菌( Leuconostoc mesenteroides)CJRS-10672(韓國寄存編號:KCCM13060P)菌株。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020210158920A KR20230072315A (ko) | 2021-11-17 | 2021-11-17 | 신규 류코노스톡 메센테로이데스 균주 |
KR10-2021-0158920 | 2021-11-17 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW202338083A TW202338083A (zh) | 2023-10-01 |
TWI847369B true TWI847369B (zh) | 2024-07-01 |
Family
ID=
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20100013184A (ko) | 2008-07-30 | 2010-02-09 | 한국식품연구원 | 항암활성이 있는 로이코노스톡 메센테로이데스 6-2 균주 및상기 균주를 포함하는 김치 |
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20100013184A (ko) | 2008-07-30 | 2010-02-09 | 한국식품연구원 | 항암활성이 있는 로이코노스톡 메센테로이데스 6-2 균주 및상기 균주를 포함하는 김치 |
Non-Patent Citations (1)
Title |
---|
期刊 Lee KW, et al. "Isolation of lactic acid bacteria with probiotic potentials from kimchi, traditional Korean fermented vegetable" Food Science and Technology 71: Elsevier 2016; 130-137 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI791111B (zh) | 具有預防或治療癌症的效果的新穎菌株 | |
CN101573138B (zh) | 能活化针对碳水化合物的细胞免疫的微生物及其部分 | |
EP4316499A1 (en) | Lactobacillus plantarum gb104 strain and composition comprising same for prevention or treatment of cancer | |
EP3858368B1 (en) | Antitumor effect potentiator | |
KR101880542B1 (ko) | 락테이트 금속염을 포함하는 암 치료용 약학 조성물 | |
JP2022550525A (ja) | 癌治療のための絶対嫌気性人体腸内微生物及びその用途 | |
JP2023540711A (ja) | 抗癌活性を有するラクトバチルス・プランタルム微生物、それを含む組成物、及びそれを利用した癌の予防方法または治療方法 | |
JP2024050573A (ja) | 腫瘍浸潤リンパ球(tils)を活性化する方法 | |
TWI847369B (zh) | 新穎腸膜明串珠菌菌株 | |
TWI847370B (zh) | 用以預防或治療癌症或發炎的包含新穎腸膜明串珠菌菌株之組成物及使用其預防或治療癌症或發炎的方法 | |
KR20210102090A (ko) | 미성숙 수지상 세포의 성숙화 유도를 이용한 암의 예방 또는 치료용 조성물 | |
JP7490554B2 (ja) | 免疫チェックポイント阻害療法を促進するための組成物 | |
US20220202754A1 (en) | Uses of pantothenic acid in preparation of a composition for treating and/or preventing tumors | |
EP4428224A1 (en) | Novel leuconostoc mesenteroides strain | |
EP4427757A1 (en) | Composition for preventing or treating cancer or inflammation comprising novel leuconostoc mesenteroides strain, and method for preventing or treating cancer or inflammation using same | |
KR20220058365A (ko) | 비피도박테리움 비피덤 kctc3357의 신규 용도 | |
TW202421178A (zh) | 包括植物乳桿菌菌株的用於改善腸道代謝物組成的組合物 | |
KR20230121536A (ko) | 락토바실러스 플란타룸 균주 및 항암제를 포함하는 병용 요법을 이용한 암 예방 또는 치료용 조성물 | |
KR102542476B1 (ko) | 오도리박터 스플란크니쿠스 또는 이의 배양액을 유효성분으로 포함하는 암 예방 또는 치료용 조성물 | |
EP4342535A1 (en) | Composition for inhibition of differentiation of osteoclast precursor cells into osteoclasts, and composition for improving bone metabolism | |
KR20240040601A (ko) | 락토바실러스 플란타룸 균주를 포함하는 장내 대사산물 조성의 개선을 위한 조성물 | |
JP2023539640A (ja) | 抗腫瘍細菌株、並びにそれを利用した組成物及びその方法 | |
Deng | Gut microbiota and cancer immunotherapy: mechanisms and modifications | |
KR20240123764A (ko) | 락토바실러스 플란타룸 균주 및 면역세포의 병용 요법을 이용한 암 예방 또는 치료용 조성물 | |
JP2012092044A (ja) | パパイア発酵物を有効成分とする末梢血単核球細胞の活性調節用組成物 |