TW201414489A - 用於癌症標靶治療及預防癌症復發之含有基於血紅素的氧載體之醫藥組成物 - Google Patents
用於癌症標靶治療及預防癌症復發之含有基於血紅素的氧載體之醫藥組成物 Download PDFInfo
- Publication number
- TW201414489A TW201414489A TW102136951A TW102136951A TW201414489A TW 201414489 A TW201414489 A TW 201414489A TW 102136951 A TW102136951 A TW 102136951A TW 102136951 A TW102136951 A TW 102136951A TW 201414489 A TW201414489 A TW 201414489A
- Authority
- TW
- Taiwan
- Prior art keywords
- tumor
- cells
- heme
- cancer
- oxygen carrier
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 227
- 229910052760 oxygen Inorganic materials 0.000 title claims abstract description 110
- 239000001301 oxygen Substances 0.000 title claims abstract description 106
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 title claims abstract description 105
- 201000011510 cancer Diseases 0.000 title claims abstract description 90
- 102000001554 Hemoglobins Human genes 0.000 title claims abstract description 57
- 108010054147 Hemoglobins Proteins 0.000 title claims abstract description 57
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 28
- 230000008685 targeting Effects 0.000 title claims abstract description 7
- 238000011282 treatment Methods 0.000 title description 57
- 230000002265 prevention Effects 0.000 title description 5
- 210000004027 cell Anatomy 0.000 claims abstract description 208
- 206010021143 Hypoxia Diseases 0.000 claims abstract description 53
- 210000000130 stem cell Anatomy 0.000 claims abstract description 46
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 37
- 229940127089 cytotoxic agent Drugs 0.000 claims abstract description 37
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims abstract description 31
- 229960001467 bortezomib Drugs 0.000 claims abstract description 31
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims abstract description 30
- 230000001146 hypoxic effect Effects 0.000 claims abstract description 30
- 239000000203 mixture Substances 0.000 claims abstract description 24
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims abstract description 20
- 229960004316 cisplatin Drugs 0.000 claims abstract description 20
- 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 claims abstract description 18
- 230000007246 mechanism Effects 0.000 claims abstract description 12
- 108020003175 receptors Proteins 0.000 claims abstract description 11
- 102000005962 receptors Human genes 0.000 claims abstract description 11
- 230000001404 mediated effect Effects 0.000 claims abstract description 10
- 230000006907 apoptotic process Effects 0.000 claims abstract description 9
- 229960004679 doxorubicin Drugs 0.000 claims abstract description 9
- 150000003278 haem Chemical class 0.000 claims description 152
- 210000001519 tissue Anatomy 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 46
- 210000004185 liver Anatomy 0.000 claims description 32
- 108090000623 proteins and genes Proteins 0.000 claims description 29
- 229960002949 fluorouracil Drugs 0.000 claims description 28
- 230000006378 damage Effects 0.000 claims description 24
- 210000004072 lung Anatomy 0.000 claims description 19
- 102000004169 proteins and genes Human genes 0.000 claims description 15
- 239000000539 dimer Substances 0.000 claims description 13
- 210000004881 tumor cell Anatomy 0.000 claims description 12
- 239000000969 carrier Substances 0.000 claims description 10
- 238000001356 surgical procedure Methods 0.000 claims description 10
- 238000001959 radiotherapy Methods 0.000 claims description 9
- 230000002195 synergetic effect Effects 0.000 claims description 8
- 230000036542 oxidative stress Effects 0.000 claims description 7
- 239000012535 impurity Substances 0.000 claims description 6
- 230000035939 shock Effects 0.000 claims description 6
- 210000000481 breast Anatomy 0.000 claims description 5
- 238000009098 adjuvant therapy Methods 0.000 claims description 4
- 230000037396 body weight Effects 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 4
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims description 3
- 206010047139 Vasoconstriction Diseases 0.000 claims description 3
- 229960004308 acetylcysteine Drugs 0.000 claims description 3
- 230000036770 blood supply Effects 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 230000006395 clathrin-mediated endocytosis Effects 0.000 claims description 3
- 230000004807 localization Effects 0.000 claims description 3
- 230000001698 pyrogenic effect Effects 0.000 claims description 3
- 230000025033 vasoconstriction Effects 0.000 claims description 3
- 210000000805 cytoplasm Anatomy 0.000 claims description 2
- 238000001802 infusion Methods 0.000 claims description 2
- 230000001960 triggered effect Effects 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims 3
- 210000001072 colon Anatomy 0.000 claims 3
- 210000003128 head Anatomy 0.000 claims 3
- 210000001989 nasopharynx Anatomy 0.000 claims 3
- 210000003739 neck Anatomy 0.000 claims 3
- 239000002158 endotoxin Substances 0.000 claims 2
- 235000018102 proteins Nutrition 0.000 claims 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 1
- 235000018417 cysteine Nutrition 0.000 claims 1
- 238000004925 denaturation Methods 0.000 claims 1
- 230000036425 denaturation Effects 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 239000011159 matrix material Substances 0.000 claims 1
- 150000003904 phospholipids Chemical class 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 abstract description 49
- 230000009401 metastasis Effects 0.000 abstract description 47
- 101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 abstract description 11
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 abstract description 11
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract description 10
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 abstract description 10
- 230000030833 cell death Effects 0.000 abstract description 7
- 230000001939 inductive effect Effects 0.000 abstract description 4
- 108091027981 Response element Proteins 0.000 abstract description 2
- 210000005102 tumor initiating cell Anatomy 0.000 abstract 1
- 208000014018 liver neoplasm Diseases 0.000 description 64
- 241000700159 Rattus Species 0.000 description 50
- 201000007270 liver cancer Diseases 0.000 description 38
- 206010019695 Hepatic neoplasm Diseases 0.000 description 26
- 108020004414 DNA Proteins 0.000 description 25
- 108020001019 DNA Primers Proteins 0.000 description 24
- 239000003155 DNA primer Substances 0.000 description 24
- 238000012752 Hepatectomy Methods 0.000 description 22
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 22
- 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 22
- 230000007954 hypoxia Effects 0.000 description 22
- 230000004083 survival effect Effects 0.000 description 19
- 239000013615 primer Substances 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 208000027418 Wounds and injury Diseases 0.000 description 16
- 208000014674 injury Diseases 0.000 description 16
- 208000028867 ischemia Diseases 0.000 description 16
- 238000006213 oxygenation reaction Methods 0.000 description 16
- 102100032912 CD44 antigen Human genes 0.000 description 15
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 15
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 15
- 230000005855 radiation Effects 0.000 description 15
- 230000010410 reperfusion Effects 0.000 description 15
- 230000004614 tumor growth Effects 0.000 description 14
- 230000036961 partial effect Effects 0.000 description 13
- 230000002441 reversible effect Effects 0.000 description 13
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- 108020002663 Aldehyde Dehydrogenase Proteins 0.000 description 10
- 102000005369 Aldehyde Dehydrogenase Human genes 0.000 description 10
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 10
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 10
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 10
- 238000002271 resection Methods 0.000 description 10
- 229960004964 temozolomide Drugs 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 9
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 9
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 102100038081 Signal transducer CD24 Human genes 0.000 description 8
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 230000002440 hepatic effect Effects 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 229940090044 injection Drugs 0.000 description 8
- 230000001394 metastastic effect Effects 0.000 description 8
- 206010061289 metastatic neoplasm Diseases 0.000 description 8
- 230000035945 sensitivity Effects 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 7
- 101800004490 Endothelin-1 Proteins 0.000 description 7
- 102400000686 Endothelin-1 Human genes 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 230000008602 contraction Effects 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 208000003174 Brain Neoplasms Diseases 0.000 description 6
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 6
- 101710113864 Heat shock protein 90 Proteins 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 6
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 6
- 239000008351 acetate buffer Substances 0.000 description 6
- 208000005017 glioblastoma Diseases 0.000 description 6
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 210000005075 mammary gland Anatomy 0.000 description 6
- 230000007959 normoxia Effects 0.000 description 6
- 230000000306 recurrent effect Effects 0.000 description 6
- 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 6
- FLCWJWNCSHIREG-UHFFFAOYSA-N 2-(diethylamino)benzaldehyde Chemical compound CCN(CC)C1=CC=CC=C1C=O FLCWJWNCSHIREG-UHFFFAOYSA-N 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- 230000005778 DNA damage Effects 0.000 description 5
- 231100000277 DNA damage Toxicity 0.000 description 5
- 229930012538 Paclitaxel Natural products 0.000 description 5
- 231100000135 cytotoxicity Toxicity 0.000 description 5
- 230000003013 cytotoxicity Effects 0.000 description 5
- 230000003511 endothelial effect Effects 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 238000010562 histological examination Methods 0.000 description 5
- 230000001976 improved effect Effects 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 238000011580 nude mouse model Methods 0.000 description 5
- 229960001592 paclitaxel Drugs 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 230000000287 tissue oxygenation Effects 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 102000003727 Caveolin 1 Human genes 0.000 description 4
- 108090000026 Caveolin 1 Proteins 0.000 description 4
- 108010028501 Hypoxia-Inducible Factor 1 Proteins 0.000 description 4
- 102000016878 Hypoxia-Inducible Factor 1 Human genes 0.000 description 4
- 241000699660 Mus musculus Species 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 210000005162 left hepatic lobe Anatomy 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 229960001412 pentobarbital Drugs 0.000 description 4
- 230000002980 postoperative effect Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 230000002792 vascular Effects 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 3
- 102000005853 Clathrin Human genes 0.000 description 3
- 108010019874 Clathrin Proteins 0.000 description 3
- 102100022130 High mobility group protein B3 Human genes 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101001045794 Homo sapiens High mobility group protein B3 Proteins 0.000 description 3
- 101000610551 Homo sapiens Prominin-1 Proteins 0.000 description 3
- 238000000134 MTT assay Methods 0.000 description 3
- 231100000002 MTT assay Toxicity 0.000 description 3
- 102100040120 Prominin-1 Human genes 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000033115 angiogenesis Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 230000004087 circulation Effects 0.000 description 3
- 229930193282 clathrin Natural products 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 230000002530 ischemic preconditioning effect Effects 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000000683 nonmetastatic effect Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- 230000001568 sexual effect Effects 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- 206010000830 Acute leukaemia Diseases 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
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 101100257359 Caenorhabditis elegans sox-2 gene Proteins 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 2
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 206010027458 Metastases to lung Diseases 0.000 description 2
- 101100257363 Mus musculus Sox2 gene Proteins 0.000 description 2
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 2
- 206010061309 Neoplasm progression Diseases 0.000 description 2
- 241000391487 Oxylabes Species 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 208000036676 acute undifferentiated leukemia Diseases 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 238000010859 live-cell imaging Methods 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004660 morphological change Effects 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- 210000000441 neoplastic stem cell Anatomy 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 230000001706 oxygenating effect Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 210000002706 plastid Anatomy 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 150000004032 porphyrins Chemical class 0.000 description 2
- 210000003240 portal vein Anatomy 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 238000011808 rodent model Methods 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 230000001235 sensitizing effect Effects 0.000 description 2
- 210000001082 somatic cell Anatomy 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
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 230000005751 tumor progression Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 208000005443 Circulating Neoplastic Cells Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 210000001956 EPC Anatomy 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000998969 Homo sapiens Inositol-3-phosphate synthase 1 Proteins 0.000 description 1
- 101000706678 Homo sapiens Proteasome subunit beta type-1 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 102100036881 Inositol-3-phosphate synthase 1 Human genes 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- 206010023856 Laryngeal squamous cell carcinoma Diseases 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 1
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102100030856 Myoglobin Human genes 0.000 description 1
- 108010062374 Myoglobin Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 239000002033 PVDF binder Substances 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
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 102100031566 Proteasome subunit beta type-1 Human genes 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 208000037323 Rare tumor Diseases 0.000 description 1
- 238000010818 SYBR green PCR Master Mix Methods 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000005497 Thymidylate Synthase Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 208000037280 Trisomy Diseases 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000021375 Xenogenes Species 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 229940105442 cisplatin injection Drugs 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000000235 effect on cancer Effects 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 108010018033 endothelial PAS domain-containing protein 1 Proteins 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 102000034238 globular proteins Human genes 0.000 description 1
- 108091005896 globular proteins Proteins 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 210000002767 hepatic artery Anatomy 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 208000028654 hypopharynx squamous cell carcinoma Diseases 0.000 description 1
- 230000006553 hypoxic activation Effects 0.000 description 1
- 230000006303 immediate early viral mRNA transcription Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 201000005264 laryngeal carcinoma Diseases 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000012976 mRNA stabilization Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000011206 morphological examination Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 208000030266 primary brain neoplasm Diseases 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000001023 pro-angiogenic effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 210000004777 protein coat Anatomy 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000029983 protein stabilization Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 108010054624 red fluorescent protein Proteins 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 102000037983 regulatory factors Human genes 0.000 description 1
- 108091008025 regulatory factors Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 210000001631 vena cava inferior Anatomy 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- UTAZCRNOSWWEFR-ZDUSSCGKSA-N zolmitriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1C[C@H]1COC(=O)N1 UTAZCRNOSWWEFR-ZDUSSCGKSA-N 0.000 description 1
- 229960001360 zolmitriptan Drugs 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/41—Porphyrin- or corrin-ring-containing peptides
- A61K38/42—Haemoglobins; Myoglobins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/38—Silver; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Inorganic Chemistry (AREA)
- Oncology (AREA)
- Pathology (AREA)
- Radiology & Medical Imaging (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261712853P | 2012-10-12 | 2012-10-12 | |
| US13/713,031 US20140106004A1 (en) | 2012-10-12 | 2012-12-13 | Hemoglobin-based oxygen carrier-containing pharmaceutical composition for cancer targeting treatment and prevention of cancer recurrence |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW201414489A true TW201414489A (zh) | 2014-04-16 |
Family
ID=50475529
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW102136951A TW201414489A (zh) | 2012-10-12 | 2013-10-14 | 用於癌症標靶治療及預防癌症復發之含有基於血紅素的氧載體之醫藥組成物 |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US20140106004A1 (enExample) |
| EP (1) | EP2906222A4 (enExample) |
| JP (1) | JP6113850B2 (enExample) |
| KR (1) | KR20150065881A (enExample) |
| CN (1) | CN104717966B (enExample) |
| AP (1) | AP2015008315A0 (enExample) |
| AR (1) | AR093023A1 (enExample) |
| AU (1) | AU2013329121B2 (enExample) |
| BR (1) | BR112015007475A2 (enExample) |
| CA (1) | CA2884521C (enExample) |
| CL (1) | CL2015000897A1 (enExample) |
| EA (1) | EA201500301A1 (enExample) |
| IL (1) | IL237763A (enExample) |
| MA (1) | MA37994A2 (enExample) |
| MX (1) | MX367562B (enExample) |
| PH (1) | PH12015500562B1 (enExample) |
| SG (3) | SG10201608747RA (enExample) |
| TW (1) | TW201414489A (enExample) |
| UY (1) | UY35082A (enExample) |
| WO (1) | WO2014059199A1 (enExample) |
| ZA (1) | ZA201501949B (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY176175A (en) * | 2013-05-13 | 2020-07-24 | Vision Global Holdings Ltd | Pharmaceutical composition comprising modified hemoglobin-based therapeutic agent for cancer targeting treatment and diagnostic imaging |
| CN106536056B (zh) | 2014-06-13 | 2021-07-16 | 儿童医学中心公司 | 分离线粒体的产品和方法 |
| US9814759B2 (en) * | 2014-07-02 | 2017-11-14 | Cheer Global Ltd. | Pharmaceutical composition comprising recombinant hemoglobin protein or subunit-based therapeutic agent for cancer targeting treatment |
| EP4620519A3 (en) | 2015-11-30 | 2025-10-22 | Sana Biotechnology, Inc. | Methods and compositions relating to chondrisomes from blood products |
| EP3402490B1 (en) | 2016-01-15 | 2022-06-01 | The Children's Medical Center Corporation | Therapeutic use of mitochondria and combined mitochondrial agents |
| US20230190947A1 (en) * | 2016-06-21 | 2023-06-22 | Therapure Biopharma Inc. | Hemoglobin-Targeted Drug Delivery For The Treatment of Cancer |
| WO2018195434A1 (en) | 2017-04-21 | 2018-10-25 | Lisanti Michael P | Vitamin c and doxycycline: a synthetic lethal combination therapy for eradicating cancer stem cells (cscs) |
| EP3612177A4 (en) * | 2017-04-21 | 2021-01-13 | Lunella Biotech, Inc. | TARGETING HYPOXIC CARCINOUS STEM CELLS (SCC) USING DOXYCYCLINE: IMPLICATIONS FOR IMPROVING ANTI-ANGIOGENIC THERAPY |
| CA3063717C (en) | 2017-05-19 | 2021-08-24 | Lunella Biotech, Inc. | Antimitoscins: targeted inhibitors of mitochondrial biogenesis for eradicating cancer stem cells |
| WO2018213764A1 (en) | 2017-05-19 | 2018-11-22 | Lunella Biotech, Inc. | Companion diagnostics for mitochondrial inhibitors |
| BR112019026097A2 (pt) | 2017-06-26 | 2020-07-07 | Lunella Biotech, Inc. | mitoketoscins: terapêuticos à base de mitocôndrias com direcionamento no metabolismo da cetona em células cancerígenas |
| JPWO2019124423A1 (ja) * | 2017-12-19 | 2020-10-22 | 国立大学法人 岡山大学 | がんの進行抑制、治療、予防及び／又は再発予防剤 |
| CN111558032B (zh) * | 2020-05-19 | 2023-08-22 | 中国科学院宁波材料技术与工程研究所 | 一种蛋白纳米药物及其制备方法与应用 |
| CN114344263B (zh) * | 2022-02-21 | 2023-08-01 | 杭州普略生物科技有限公司 | 一种用于靶向巨噬细胞增强肿瘤治疗效果的纳米蛋白胶束及其制备方法和应用 |
| KR102793996B1 (ko) | 2022-03-31 | 2025-04-09 | 충남대학교산학협력단 | 저산소증 완화능을 갖는 페길화 헤모글로빈 나노클러스터를 포함하는 항암 화학-광역학 치료용 조성물 |
| WO2025222059A1 (en) * | 2024-04-17 | 2025-10-23 | Prolong Pharmaceuticals Llc | Method of treating cancer using pegylated bovine hemoglobin |
| CN119746044A (zh) * | 2025-03-06 | 2025-04-04 | 润方（北京）生物医药研究院有限公司 | 血红蛋白氧载体在制备抗病毒药物中的应用 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5478806A (en) * | 1989-11-22 | 1995-12-26 | Enzon, Inc. | Enhancement of antitumor therapy with hemoglobin-based conjugates |
| CA2236344A1 (en) * | 1998-04-30 | 1999-10-30 | Hemosol Inc. | Hemoglobin-haptoglobin complexes |
| US20050164915A1 (en) * | 2002-04-01 | 2005-07-28 | Sangart, Inc. | Compositions for oxygen transport comprising a high oxygen affinity modified hemoglobin |
| US20050202559A1 (en) * | 2002-10-29 | 2005-09-15 | Scott Pownall | Cancer treatment by metabolic modulations |
| JP2012515792A (ja) * | 2009-01-23 | 2012-07-12 | キャンサー・リサーチ・テクノロジー・リミテッド | ヘッジホッグ経路阻害剤 |
| SI2440239T1 (en) * | 2009-06-09 | 2018-01-31 | Prolong Pharmaceuticals, LLC | Hemoglobin compositions |
| CN102573853A (zh) * | 2009-07-07 | 2012-07-11 | 诺尔姆奥克西斯公司 | 使用肌醇三焦磷酸减少多药抗性的方法 |
| US8808748B2 (en) * | 2010-04-20 | 2014-08-19 | Vindico NanoBio Technology Inc. | Biodegradable nanoparticles as novel hemoglobin-based oxygen carriers and methods of using the same |
| US7989593B1 (en) * | 2010-05-27 | 2011-08-02 | Bing Lou Wong | Method for the preparation of a high-temperature stable oxygen-carrier-containing pharmaceutical composition and the use thereof |
| US7932356B1 (en) * | 2010-06-23 | 2011-04-26 | Bing Lou Wong | Method for the preparation of a heat stable oxygen carrier-containing pharmaceutical composition |
| US20110319332A1 (en) * | 2010-06-23 | 2011-12-29 | Bing Lou Wong | Treatment methods using a heat stable oxygen carrier-containing pharmaceutical composition |
| US8048856B1 (en) * | 2010-06-23 | 2011-11-01 | Billion King, Ltd. | Treatment methods using a heat stable oxygen carrier-containing pharmaceutical composition |
-
2012
- 2012-12-13 US US13/713,031 patent/US20140106004A1/en not_active Abandoned
-
2013
- 2013-10-11 MA MA37994A patent/MA37994A2/fr unknown
- 2013-10-11 BR BR112015007475A patent/BR112015007475A2/pt not_active IP Right Cessation
- 2013-10-11 WO PCT/US2013/064418 patent/WO2014059199A1/en not_active Ceased
- 2013-10-11 EP EP13844670.3A patent/EP2906222A4/en not_active Ceased
- 2013-10-11 AU AU2013329121A patent/AU2013329121B2/en not_active Ceased
- 2013-10-11 KR KR1020157012185A patent/KR20150065881A/ko not_active Ceased
- 2013-10-11 CN CN201380053346.1A patent/CN104717966B/zh not_active Expired - Fee Related
- 2013-10-11 JP JP2015536905A patent/JP6113850B2/ja not_active Expired - Fee Related
- 2013-10-11 CA CA2884521A patent/CA2884521C/en active Active
- 2013-10-11 SG SG10201608747RA patent/SG10201608747RA/en unknown
- 2013-10-11 SG SG11201502133SA patent/SG11201502133SA/en unknown
- 2013-10-11 AP AP2015008315A patent/AP2015008315A0/xx unknown
- 2013-10-11 EA EA201500301A patent/EA201500301A1/ru unknown
- 2013-10-11 SG SG10201607846PA patent/SG10201607846PA/en unknown
- 2013-10-11 MX MX2015004512A patent/MX367562B/es active IP Right Grant
- 2013-10-14 UY UY35082A patent/UY35082A/es not_active Application Discontinuation
- 2013-10-14 TW TW102136951A patent/TW201414489A/zh unknown
- 2013-10-15 AR ARP130103741A patent/AR093023A1/es unknown
-
2014
- 2014-06-19 US US14/308,725 patent/US9056098B2/en active Active
-
2015
- 2015-03-16 IL IL237763A patent/IL237763A/en active IP Right Grant
- 2015-03-16 PH PH12015500562A patent/PH12015500562B1/en unknown
- 2015-03-20 ZA ZA2015/01949A patent/ZA201501949B/en unknown
- 2015-04-09 CL CL2015000897A patent/CL2015000897A1/es unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW201414489A (zh) | 用於癌症標靶治療及預防癌症復發之含有基於血紅素的氧載體之醫藥組成物 | |
| Grover et al. | Myeloid-derived suppressor cells: a propitious road to clinic | |
| JP2020183406A (ja) | 薬物送達および治療用薬剤の有効性を向上させる方法 | |
| US7795219B2 (en) | Use of an agent that restores tissue perfusion and oxygenation | |
| Pedretti et al. | Combination of temozolomide with immunocytokine F16–IL2 for the treatment of glioblastoma | |
| Wan et al. | Peptide hydrogels loaded with irradiated tumor cell secretions enhance cancer immunotherapy | |
| Ruoslahti | Access granted: iRGD helps silicasome-encased drugs breach the tumor barrier | |
| JPWO2018021200A1 (ja) | Ｒｕｎｘ阻害剤 | |
| Qin et al. | Hybrid cell membranes camouflaged copper-loaded nano-prodrug for tumor angiogenesis inhibition and cell cuproptosis | |
| US12059429B2 (en) | Hornerin: a novel non-VEGF mediated angiogenic protein expressed in both human and mouse angiogenic endothelial cells and human pancreatic cancer cells | |
| Qian et al. | Cell membrane hybrid lipid nanovesicles enhance innate immunity for synergistic immunotherapy by promoting immunogenic cell death and cGAS activation | |
| Xu et al. | Construction and characterization of a truncated tissue factor-coagulation-based composite system for selective thrombosis in tumor blood vessels | |
| CA3162518A1 (en) | Compositions and methods for treating diseases and conditions by depletion of mitochondrial or genomic dna from circulation | |
| JP6489517B2 (ja) | ガン幹細胞に対する分化促進薬及び脳腫瘍治療薬 | |
| TWI882136B (zh) | 類視色素與癌症治療藥之併用療法有效之癌症患者之選擇方法及類視色素與癌症治療藥之併用醫藥 | |
| Xie et al. | SOM230 combined with celecoxib prolongs the survival in nude mice with HepG-2 xenografts | |
| HK1206281B (en) | Hemoglobin-based oxygen carrier-containing pharmaceutical composition for cancer targeting treatment and prevention of cancer recurrence | |
| Zhang et al. | Evaluation of the anti-tumor effect of gambogic acid loaded macrophage membranes nanoparticles combined with radiotherapy and anti-PD-1mAb in the colorectal cancer with liver metastasis model | |
| Luo et al. | Genetically Engineered Biomimetic Nanoparticles for Synergistic Activation of Glioma-Associated Macrophages against Glioblastoma | |
| Li et al. | An albumin-prodrug injectable formulation for synergistic cancer immunotherapy | |
| WO2025242237A1 (zh) | 工程化细胞膜纳米囊泡及其制备方法和应用 | |
| US20180230466A1 (en) | Methods for treating tumors |