CA2277865C - Method of inhibiting cancer growth - Google Patents
Method of inhibiting cancer growth Download PDFInfo
- Publication number
- CA2277865C CA2277865C CA002277865A CA2277865A CA2277865C CA 2277865 C CA2277865 C CA 2277865C CA 002277865 A CA002277865 A CA 002277865A CA 2277865 A CA2277865 A CA 2277865A CA 2277865 C CA2277865 C CA 2277865C
- Authority
- CA
- Canada
- Prior art keywords
- cmt
- dimethylamino
- tetracycline
- cancer
- cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 43
- 230000005907 cancer growth Effects 0.000 title claims abstract description 21
- 238000000034 method Methods 0.000 title abstract description 66
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 223
- 239000004098 Tetracycline Substances 0.000 claims abstract description 126
- 235000019364 tetracycline Nutrition 0.000 claims abstract description 125
- 201000011510 cancer Diseases 0.000 claims abstract description 112
- 229960002180 tetracycline Drugs 0.000 claims abstract description 106
- 229930101283 tetracycline Natural products 0.000 claims abstract description 105
- -1 tetracycline compounds Chemical class 0.000 claims abstract description 79
- 206010027476 Metastases Diseases 0.000 claims abstract description 32
- 241000124008 Mammalia Species 0.000 claims abstract description 31
- 210000004072 lung Anatomy 0.000 claims abstract description 29
- 230000009401 metastasis Effects 0.000 claims abstract description 28
- 201000001441 melanoma Diseases 0.000 claims abstract description 20
- NBRQRXRBIHVLGI-OWXODZSWSA-N (4as,5ar,12ar)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=CC=CC(O)=C2C(O)=C(C2=O)[C@@H]1C[C@@H]1[C@@]2(O)C(O)=C(C(=O)N)C(=O)C1 NBRQRXRBIHVLGI-OWXODZSWSA-N 0.000 claims abstract 7
- 210000004027 cell Anatomy 0.000 claims description 191
- 230000000694 effects Effects 0.000 claims description 77
- XCCHQGIGHCRZOS-KBKZQPOHSA-N (4as,5as,6s,12ar)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@@](C)(O)[C@@H](C[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)C3)(O)C3=O)C3=C(O)C2=C1O XCCHQGIGHCRZOS-KBKZQPOHSA-N 0.000 claims description 50
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 35
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 35
- 210000001519 tissue Anatomy 0.000 claims description 33
- 230000014509 gene expression Effects 0.000 claims description 22
- 102000013382 Gelatinases Human genes 0.000 claims description 21
- 108010026132 Gelatinases Proteins 0.000 claims description 21
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 claims description 21
- 230000000477 gelanolytic effect Effects 0.000 claims description 18
- 230000004663 cell proliferation Effects 0.000 claims description 16
- 210000000481 breast Anatomy 0.000 claims description 15
- 231100000433 cytotoxic Toxicity 0.000 claims description 15
- 230000001472 cytotoxic effect Effects 0.000 claims description 15
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 claims description 14
- 102000001776 Matrix metalloproteinase-9 Human genes 0.000 claims description 12
- 210000001072 colon Anatomy 0.000 claims description 12
- 210000002307 prostate Anatomy 0.000 claims description 12
- 210000001550 testis Anatomy 0.000 claims description 12
- 201000009030 Carcinoma Diseases 0.000 claims description 11
- 210000002751 lymph Anatomy 0.000 claims description 8
- 208000009956 adenocarcinoma Diseases 0.000 claims description 7
- 230000000118 anti-neoplastic effect Effects 0.000 claims description 7
- 206010039491 Sarcoma Diseases 0.000 claims description 5
- 230000002147 killing effect Effects 0.000 claims description 5
- 108090000623 proteins and genes Proteins 0.000 claims description 5
- 238000002512 chemotherapy Methods 0.000 claims description 4
- 230000003902 lesion Effects 0.000 claims description 4
- 201000001514 prostate carcinoma Diseases 0.000 claims description 4
- 238000001959 radiotherapy Methods 0.000 claims description 4
- 239000002207 metabolite Substances 0.000 claims description 3
- 238000001356 surgical procedure Methods 0.000 claims description 3
- 239000012472 biological sample Substances 0.000 claims description 2
- 210000000981 epithelium Anatomy 0.000 claims description 2
- BVFDLIAWTKFZQD-JXVDNWKRSA-N cmt-8 Chemical compound O=C1C2=C(O)C=CC=C2C(C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)C[C@@H]1C2O BVFDLIAWTKFZQD-JXVDNWKRSA-N 0.000 claims 6
- 102000000424 Matrix Metalloproteinase 2 Human genes 0.000 claims 2
- 238000011200 topical administration Methods 0.000 claims 1
- 231100000135 cytotoxicity Toxicity 0.000 abstract description 31
- 230000003013 cytotoxicity Effects 0.000 abstract description 29
- 206010060862 Prostate cancer Diseases 0.000 abstract description 21
- 230000012010 growth Effects 0.000 abstract description 13
- 230000035755 proliferation Effects 0.000 abstract description 9
- 206010009944 Colon cancer Diseases 0.000 abstract description 6
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 6
- 206010006187 Breast cancer Diseases 0.000 abstract description 5
- 208000026310 Breast neoplasm Diseases 0.000 abstract description 5
- 208000029742 colonic neoplasm Diseases 0.000 abstract description 4
- 230000001939 inductive effect Effects 0.000 abstract description 4
- BKAYIFDRRZZKNF-VIFPVBQESA-N N-acetylcarnosine Chemical compound CC(=O)NCCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BKAYIFDRRZZKNF-VIFPVBQESA-N 0.000 abstract 1
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 75
- 229960003722 doxycycline Drugs 0.000 description 75
- 150000001875 compounds Chemical class 0.000 description 49
- 150000003522 tetracyclines Chemical class 0.000 description 47
- 210000004881 tumor cell Anatomy 0.000 description 38
- 230000005764 inhibitory process Effects 0.000 description 36
- 241000282414 Homo sapiens Species 0.000 description 31
- 238000000338 in vitro Methods 0.000 description 31
- 238000011282 treatment Methods 0.000 description 30
- 241001465754 Metazoa Species 0.000 description 29
- 241000700159 Rattus Species 0.000 description 24
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 23
- 238000002474 experimental method Methods 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- 239000003814 drug Substances 0.000 description 20
- 229940040944 tetracyclines Drugs 0.000 description 20
- 230000004614 tumor growth Effects 0.000 description 19
- 238000003556 assay Methods 0.000 description 18
- 229940079593 drug Drugs 0.000 description 18
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 17
- 230000000845 anti-microbial effect Effects 0.000 description 15
- 230000007423 decrease Effects 0.000 description 15
- 231100000673 dose–response relationship Toxicity 0.000 description 15
- 239000003636 conditioned culture medium Substances 0.000 description 13
- 238000001727 in vivo Methods 0.000 description 13
- 239000002609 medium Substances 0.000 description 12
- 230000001394 metastastic effect Effects 0.000 description 12
- 206010061289 metastatic neoplasm Diseases 0.000 description 12
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 11
- 239000008273 gelatin Substances 0.000 description 10
- 229920000159 gelatin Polymers 0.000 description 10
- 230000007246 mechanism Effects 0.000 description 10
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 9
- 239000000499 gel Substances 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 8
- 239000002246 antineoplastic agent Substances 0.000 description 8
- 108010010803 Gelatin Proteins 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 235000019322 gelatine Nutrition 0.000 description 7
- 235000011852 gelatine desserts Nutrition 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 229960004023 minocycline Drugs 0.000 description 7
- 208000023958 prostate neoplasm Diseases 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 6
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 6
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 6
- 206010027458 Metastases to lung Diseases 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 description 6
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 6
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 6
- 210000002744 extracellular matrix Anatomy 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 230000009545 invasion Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 239000012679 serum free medium Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- NCQJBPXXRXOIJD-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-naphthalen-2-ylpropanoic acid Chemical compound C1=CC=CC2=CC(C(CC(O)=O)NC(=O)OC(C)(C)C)=CC=C21 NCQJBPXXRXOIJD-UHFFFAOYSA-N 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- 102000008186 Collagen Human genes 0.000 description 5
- 102000029816 Collagenase Human genes 0.000 description 5
- 108060005980 Collagenase Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 108010047956 Nucleosomes Proteins 0.000 description 5
- 238000011579 SCID mouse model Methods 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 5
- 230000001093 anti-cancer Effects 0.000 description 5
- 229940088710 antibiotic agent Drugs 0.000 description 5
- 230000009702 cancer cell proliferation Effects 0.000 description 5
- 230000003833 cell viability Effects 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 229940127089 cytotoxic agent Drugs 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 210000001623 nucleosome Anatomy 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000002062 proliferating effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 230000035899 viability Effects 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000000973 chemotherapeutic effect Effects 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 108010082117 matrigel Proteins 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 210000001672 ovary Anatomy 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 208000003174 Brain Neoplasms Diseases 0.000 description 3
- 101100221122 Caenorhabditis elegans cmt-1 gene Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 108010085895 Laminin Proteins 0.000 description 3
- 238000000134 MTT assay Methods 0.000 description 3
- 231100000002 MTT assay Toxicity 0.000 description 3
- 102000005741 Metalloproteases Human genes 0.000 description 3
- 108010006035 Metalloproteases Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 238000003782 apoptosis assay Methods 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000004709 cell invasion Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 238000003304 gavage Methods 0.000 description 3
- 238000001502 gel electrophoresis Methods 0.000 description 3
- 238000009650 gentamicin protection assay Methods 0.000 description 3
- 230000009036 growth inhibition Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000000099 in vitro assay Methods 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000005522 programmed cell death Effects 0.000 description 3
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 3
- 210000001095 prostate stromal cell Anatomy 0.000 description 3
- 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 3
- 238000011160 research Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000008223 sterile water Substances 0.000 description 3
- 210000002536 stromal cell Anatomy 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000011547 Bouin solution Substances 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 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 2
- 229930182566 Gentamicin Natural products 0.000 description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
- 108010086677 Gonadotropins Proteins 0.000 description 2
- 102000006771 Gonadotropins Human genes 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010061309 Neoplasm progression Diseases 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 108010005246 Tissue Inhibitor of Metalloproteinases Proteins 0.000 description 2
- 102000005876 Tissue Inhibitor of Metalloproteinases Human genes 0.000 description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 230000022534 cell killing Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000035605 chemotaxis Effects 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 238000011613 copenhagen rat Methods 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000010217 densitometric analysis Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229960002518 gentamicin Drugs 0.000 description 2
- 230000000762 glandular Effects 0.000 description 2
- 239000002622 gonadotropin Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 208000024963 hair loss Diseases 0.000 description 2
- 230000003676 hair loss Effects 0.000 description 2
- 230000009610 hypersensitivity Effects 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 206010025482 malaise Diseases 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 231100001221 nontumorigenic Toxicity 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 210000000064 prostate epithelial cell Anatomy 0.000 description 2
- 238000000611 regression analysis Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 238000010186 staining Methods 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
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- 229940072172 tetracycline antibiotic Drugs 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- 230000005751 tumor progression Effects 0.000 description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 2
- 229910000368 zinc sulfate Inorganic materials 0.000 description 2
- 239000011686 zinc sulphate Substances 0.000 description 2
- 235000009529 zinc sulphate Nutrition 0.000 description 2
- 238000007805 zymography Methods 0.000 description 2
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 1
- PPJYSSNKSXAVDB-UHFFFAOYSA-N 3,3',5,5'-tetraiodothyroacetic acid Chemical class IC1=CC(CC(=O)O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 PPJYSSNKSXAVDB-UHFFFAOYSA-N 0.000 description 1
- 102000017304 72kDa type IV collagenases Human genes 0.000 description 1
- 108050005269 72kDa type IV collagenases Proteins 0.000 description 1
- 208000000058 Anaplasia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 208000005443 Circulating Neoplastic Cells Diseases 0.000 description 1
- 101000904177 Clupea pallasii Gonadoliberin-1 Proteins 0.000 description 1
- 102100027995 Collagenase 3 Human genes 0.000 description 1
- 108050005238 Collagenase 3 Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 231100001074 DNA strand break Toxicity 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
- 108010069236 Goserelin Proteins 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
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000990908 Homo sapiens Neutrophil collagenase Proteins 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 239000012741 Laemmli sample buffer Substances 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000008887 Membrane-Associated Matrix Metalloproteinases Human genes 0.000 description 1
- 108010088571 Membrane-Associated Matrix Metalloproteinases Proteins 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 101100056767 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) arp-3 gene Proteins 0.000 description 1
- 102100030411 Neutrophil collagenase Human genes 0.000 description 1
- 101710118230 Neutrophil collagenase Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 208000012868 Overgrowth Diseases 0.000 description 1
- 239000004100 Oxytetracycline 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
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 208000007660 Residual Neoplasm Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 102100030416 Stromelysin-1 Human genes 0.000 description 1
- 101710108790 Stromelysin-1 Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- KIPLYOUQVMMOHB-MXWBXKMOSA-L [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O Chemical compound [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O KIPLYOUQVMMOHB-MXWBXKMOSA-L 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 230000000791 anti-collagenolytic effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 239000007640 basal medium Substances 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000004791 biological behavior Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 230000005880 cancer cell killing Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical class C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 230000003021 clonogenic effect Effects 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000032459 dedifferentiation Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 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 1
- 201000010099 disease Diseases 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000007421 fluorometric assay Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 229960002913 goserelin Drugs 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000000887 hydrating effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000000893 inhibin Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960003538 lonidamine Drugs 0.000 description 1
- WDRYRZXSPDWGEB-UHFFFAOYSA-N lonidamine Chemical compound C12=CC=CC=C2C(C(=O)O)=NN1CC1=CC=C(Cl)C=C1Cl WDRYRZXSPDWGEB-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000003358 metastasis assay Methods 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000022886 mitochondrial translation Effects 0.000 description 1
- 201000010225 mixed cell type cancer Diseases 0.000 description 1
- 208000029638 mixed neoplasm Diseases 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 229960000625 oxytetracycline Drugs 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 108010067415 progelatinase Proteins 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 229940000207 selenious acid Drugs 0.000 description 1
- MCAHWIHFGHIESP-UHFFFAOYSA-N selenous acid Chemical compound O[Se](O)=O MCAHWIHFGHIESP-UHFFFAOYSA-N 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 229940063650 terramycin Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 230000005909 tumor killing Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- 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
- A61K31/65—Tetracyclines
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/783,655 US5837696A (en) | 1997-01-15 | 1997-01-15 | Method of inhibiting cancer growth |
| US08/783,655 | 1997-01-15 | ||
| PCT/US1998/000332 WO1998031224A1 (en) | 1997-01-15 | 1998-01-15 | Method of inhibiting cancer growth |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2277865A1 CA2277865A1 (en) | 1998-07-23 |
| CA2277865C true CA2277865C (en) | 2009-06-02 |
Family
ID=25130005
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002277865A Expired - Fee Related CA2277865C (en) | 1997-01-15 | 1998-01-15 | Method of inhibiting cancer growth |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US5837696A (https=) |
| EP (1) | EP0971585B1 (https=) |
| JP (1) | JP4428727B2 (https=) |
| KR (1) | KR20000070212A (https=) |
| AT (1) | ATE321452T1 (https=) |
| AU (1) | AU729886B2 (https=) |
| CA (1) | CA2277865C (https=) |
| DE (1) | DE69834024T2 (https=) |
| ES (1) | ES2262221T3 (https=) |
| PT (1) | PT971585E (https=) |
| WO (1) | WO1998031224A1 (https=) |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6429204B1 (en) | 1997-01-15 | 2002-08-06 | University Of Miami | Method of inhibiting cancer growth |
| US5837696A (en) * | 1997-01-15 | 1998-11-17 | The Research Foundation Of State University Of New York | Method of inhibiting cancer growth |
| PT1041991E (pt) * | 1997-12-19 | 2008-10-03 | Univ New York | Tetraciclinas não antibacterianas para o tratamento de esclerose múltipla |
| US6277061B1 (en) * | 1998-03-31 | 2001-08-21 | The Research Foundation Of State University Of New York | Method of inhibiting membrane-type matrix metalloproteinase |
| US6015804A (en) * | 1998-09-11 | 2000-01-18 | The Research Foundation Of State University Of New York | Method of using tetracycline compounds to enhance interleukin-10 production |
| US5977091A (en) * | 1998-09-21 | 1999-11-02 | The Research Foundation Of State University Of New York | Method of preventing acute lung injury |
| AU2592600A (en) * | 1998-12-23 | 2000-07-31 | G.D. Searle & Co. | Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
| US6858598B1 (en) | 1998-12-23 | 2005-02-22 | G. D. Searle & Co. | Method of using a matrix metalloproteinase inhibitor and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
| US6833373B1 (en) | 1998-12-23 | 2004-12-21 | G.D. Searle & Co. | Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
| US6984619B1 (en) * | 1999-03-19 | 2006-01-10 | Arch Development Corporation | Method for protection against tumor metastasis formation |
| DE10032256C2 (de) * | 2000-07-03 | 2003-06-05 | Infineon Technologies Ag | Chip-ID-Register-Anordnung |
| AU2002256092C1 (en) * | 2001-04-05 | 2009-10-15 | Collagenex Pharmaceuticals, Inc. | Controlled delivery of tetracycline compounds and tetracycline derivatives |
| EP2329826A1 (en) | 2001-07-13 | 2011-06-08 | Paratek Pharmaceuticals, Inc. | Tetracyclines for the treatment of multiple sclerosis |
| US20060194773A1 (en) * | 2001-07-13 | 2006-08-31 | Paratek Pharmaceuticals, Inc. | Tetracyline compounds having target therapeutic activities |
| RU2300380C2 (ru) * | 2001-10-05 | 2007-06-10 | Тетрадженекс Фармасьютикалс, Инк. | Производные тетрациклина и способы их применения |
| PE20030701A1 (es) * | 2001-12-20 | 2003-08-21 | Schering Corp | Compuestos para el tratamiento de trastornos inflamatorios |
| EP2311799A1 (en) | 2002-01-08 | 2011-04-20 | Paratek Pharmaceuticals, Inc. | 4-dedimethylamino tetracycline compounds |
| JP2005526754A (ja) | 2002-03-08 | 2005-09-08 | パラテック ファーマシューティカルズ インコーポレイテッド | アミノメチル置換されたテトラサイクリン化合物 |
| KR101083498B1 (ko) | 2002-03-21 | 2011-11-16 | 파라테크 파마슈티컬스, 인크. | 치환된 테트라시클린 화합물 |
| US20050153943A1 (en) * | 2002-05-06 | 2005-07-14 | Ashley Robert A. | Methods of simultaneously treating mucositis and fungal infection |
| AU2003245295B2 (en) * | 2002-05-20 | 2008-01-03 | Collagenex Pharmaceuticals, Inc. | Methods of treating allergic reactions |
| CA2492273C (en) | 2002-07-12 | 2013-02-05 | Paratek Pharmaceuticals, Inc. | 3, 10, and 12a substituted tetracycline compounds |
| CA2503446C (en) | 2002-10-24 | 2012-12-18 | Paratek Pharmaceuticals, Inc. | Methods of using substituted tetracycline compounds to modulate rna |
| ES2534827T3 (es) | 2003-04-07 | 2015-04-29 | Supernus Pharmaceuticals, Inc. | Formulaciones de tetraciclinas en dosis única diaria |
| CA2531728A1 (en) | 2003-07-09 | 2005-02-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| JP4738333B2 (ja) | 2003-07-09 | 2011-08-03 | パラテック ファーマシューティカルズ インコーポレイテッド | ９−アミノメチルテトラサイクリン化合物のプロドラッグ |
| CA2553510C (en) * | 2004-01-15 | 2012-09-25 | Paratek Pharmaceuticals, Inc. | Aromatic a-ring derivatives of tetracycline compounds |
| EP2269985A3 (en) | 2004-10-25 | 2011-09-21 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| AU2005299294B2 (en) | 2004-10-25 | 2012-06-07 | Paratek Pharmaceuticals, Inc. | 4-aminotetracyclines and methods of use thereof |
| JP2009502809A (ja) * | 2005-07-21 | 2009-01-29 | パラテック ファーマシューティカルズ インコーポレイテッド | １０−置換テトラサイクリンおよびその使用方法 |
| PT2120963T (pt) | 2006-12-21 | 2018-12-17 | Paratek Pharm Innc | Compostos tetraciclina substituídos para tratamento de distúrbios inflamatórios da pele |
| PL2109602T3 (pl) * | 2006-12-21 | 2014-09-30 | Paratek Pharm Innc | Pochodne tetracyliny do leczenia zakażeń bakteryjnych, wirusowych i pasożytniczych |
| JP2010525069A (ja) * | 2007-04-27 | 2010-07-22 | パラテック ファーマシューティカルズ インコーポレイテッド | アミノアルキルテトラサイクリン化合物の合成方法および精製方法 |
| BRPI0823405A2 (pt) * | 2007-07-06 | 2012-12-25 | Paratek Pharmaceuticals, Inc. | mÉtodos para sintetizar compostos de tetraciclina substituÍda |
| TW202216656A (zh) | 2008-05-19 | 2022-05-01 | 美商Ｐｒｔｋ Ｓｐｖ２公司 | 四環素化合物之甲苯磺酸鹽及同素異形體 |
| PT2323972E (pt) | 2008-08-08 | 2013-10-09 | Tetraphase Pharmaceuticals Inc | Compostos de tetraciclina substituídos com c7-flúor |
| EP2427425B1 (en) | 2009-05-08 | 2017-03-08 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| IN2012DN02502A (https=) | 2009-08-28 | 2015-08-28 | Tetraphase Pharmaceuticals Inc | |
| EP2544692A4 (en) * | 2010-03-10 | 2013-08-07 | Univ Health Network | USE OF TIGECYCLIN FOR THE TREATMENT OF CANCER |
| TWI592390B (zh) | 2010-03-31 | 2017-07-21 | 四相製藥公司 | 聚環狀四環素化合物 |
| BR112015004523B1 (pt) | 2012-08-31 | 2020-08-04 | Tetraphase Pharmaceuticals, Inc | Compostos de tetraciclina, composições farmacêuticas e seus usos |
| JP6513576B2 (ja) | 2013-01-14 | 2019-05-15 | ヘルス クリニックス リミテッド | 抗がん剤および使用 |
| CN110582486B (zh) | 2016-10-19 | 2024-01-12 | 四相制药公司 | 艾若威四环素的结晶形式 |
| US11197872B2 (en) | 2017-04-21 | 2021-12-14 | Lunella Biotech, Inc. | 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 |
| CA3063450A1 (en) | 2017-05-19 | 2018-11-22 | Lunella Biotech, Inc. | Companion diagnostics for mitochondrial inhibitors |
| PH12019502594A1 (en) | 2017-05-19 | 2020-10-26 | Lunella Biotech Inc | Antimitoscins: targeted inhibitors of mitochondrial biogenesis for eradicating cancer stem cells |
| US12570604B2 (en) | 2018-11-09 | 2026-03-10 | Tetraphase Pharmaceuticals, Inc. | Polymorphic forms of a tetracycline compound and uses thereof |
| CN115006411A (zh) * | 2022-07-26 | 2022-09-06 | 中南大学湘雅医院 | 依拉环素类化合物的应用、药物及其制备方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5308839A (en) * | 1989-12-04 | 1994-05-03 | The Research Foundation Of State University Of New York | Composition comprising non-steroidal anti-inflammatory agent tenidap and effectively non-antibacterial tetracycline |
| JP3016587B2 (ja) * | 1989-12-04 | 2000-03-06 | ザ・リサーチ・ファンデーション・オブ・ステート・ユニバーシティ・オブ・ニューヨーク | 非ステロイド抗炎症剤及びテトラサイクリンの配合 |
| US5668122A (en) * | 1993-07-28 | 1997-09-16 | Fife; Rose S. | Method to treat cancer with tetracyclines |
| US5567693A (en) * | 1994-12-13 | 1996-10-22 | American Cyanamid Company | Method for inhibiting angiogenesis, proliferation of endothelial or tumor cells and tumor growth |
| US5563130A (en) * | 1994-12-13 | 1996-10-08 | American Cyanamid Company | Methods for inhibiting angiogenesis, proliferation of endothelial or tumor cells and tumor growth |
| US5574026A (en) * | 1994-12-13 | 1996-11-12 | American Cyanamid Company | Methods for inhibiting angiogenesis proliferation of endothelial or tumor cells and tumor growth |
| US5837696A (en) * | 1997-01-15 | 1998-11-17 | The Research Foundation Of State University Of New York | Method of inhibiting cancer growth |
-
1997
- 1997-01-15 US US08/783,655 patent/US5837696A/en not_active Expired - Lifetime
-
1998
- 1998-01-15 PT PT98902437T patent/PT971585E/pt unknown
- 1998-01-15 WO PCT/US1998/000332 patent/WO1998031224A1/en not_active Ceased
- 1998-01-15 AT AT98902437T patent/ATE321452T1/de active
- 1998-01-15 CA CA002277865A patent/CA2277865C/en not_active Expired - Fee Related
- 1998-01-15 JP JP53443498A patent/JP4428727B2/ja not_active Expired - Fee Related
- 1998-01-15 ES ES98902437T patent/ES2262221T3/es not_active Expired - Lifetime
- 1998-01-15 AU AU59104/98A patent/AU729886B2/en not_active Ceased
- 1998-01-15 KR KR1019997006438A patent/KR20000070212A/ko not_active Ceased
- 1998-01-15 DE DE69834024T patent/DE69834024T2/de not_active Expired - Lifetime
- 1998-01-15 EP EP98902437A patent/EP0971585B1/en not_active Expired - Lifetime
- 1998-01-15 US US09/007,645 patent/US6100248A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| KR20000070212A (ko) | 2000-11-25 |
| AU729886B2 (en) | 2001-02-15 |
| JP2001508794A (ja) | 2001-07-03 |
| WO1998031224A1 (en) | 1998-07-23 |
| US5837696A (en) | 1998-11-17 |
| ES2262221T3 (es) | 2006-11-16 |
| JP4428727B2 (ja) | 2010-03-10 |
| CA2277865A1 (en) | 1998-07-23 |
| DE69834024D1 (de) | 2006-05-18 |
| DE69834024T2 (de) | 2006-12-07 |
| AU5910498A (en) | 1998-08-07 |
| EP0971585B1 (en) | 2006-03-29 |
| PT971585E (pt) | 2006-08-31 |
| ATE321452T1 (de) | 2006-04-15 |
| EP0971585A4 (en) | 2001-01-24 |
| US6100248A (en) | 2000-08-08 |
| EP0971585A1 (en) | 2000-01-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2277865C (en) | Method of inhibiting cancer growth | |
| AU748870B2 (en) | Method of inhibiting membrane-type matrix metalloproteinase | |
| US6429204B1 (en) | Method of inhibiting cancer growth | |
| AU755871B2 (en) | Combination of bisphosphonate and tetracycline | |
| US6713463B2 (en) | Methods and compositions for treating and preventing mucositis | |
| US5308839A (en) | Composition comprising non-steroidal anti-inflammatory agent tenidap and effectively non-antibacterial tetracycline | |
| US5459135A (en) | Composition comprising indomethacin [non-steroidal anti-inflammatory agent] and effectively non-antibacterial tetracycline to reduce bone loss | |
| EP1119362B1 (en) | Use of tetracycline derivatives to enhance interleukin-10 production | |
| Davies et al. | A synthetic matrix metalloproteinase inhibitor decreases tumor burden and prolongs survival of mice bearing human ovarian carcinoma xenografts | |
| US20190091244A1 (en) | Methods of treating acne | |
| Zervos et al. | Matrix Metalloproteinase Inhibition Attenuates Human Pancreatic Cancer Growthin Vitroand Decreases Mortality and Tumorigenesisin Vivo | |
| CA2440472C (en) | Methods of treating acne | |
| MXPA99006554A (en) | Method of inhibiting cancer growth | |
| Seftor et al. | Application of chemically modified tetracyclines (CMTs) in experimental models of cancer and arthritis | |
| Schneider et al. | Tetracyclines inhibit intracellular muscle proteolysis in vitro | |
| NZ522733A (en) | Non-antibacterial tetracycline as anti-fungal agents | |
| MXPA00008902A (en) | Methods and compositions for treating and preventing mucositis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20160115 |