JP4685443B2 - 悪性新生物および他の過剰増殖性疾患の治療におけるラクトフェリン - Google Patents
悪性新生物および他の過剰増殖性疾患の治療におけるラクトフェリン Download PDFInfo
- Publication number
- JP4685443B2 JP4685443B2 JP2004506847A JP2004506847A JP4685443B2 JP 4685443 B2 JP4685443 B2 JP 4685443B2 JP 2004506847 A JP2004506847 A JP 2004506847A JP 2004506847 A JP2004506847 A JP 2004506847A JP 4685443 B2 JP4685443 B2 JP 4685443B2
- Authority
- JP
- Japan
- Prior art keywords
- lactoferrin
- tumor
- cancer
- cells
- rhlf
- 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
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 170
- 201000011510 cancer Diseases 0.000 title claims description 37
- 102000010445 Lactoferrin Human genes 0.000 title description 101
- 108010063045 Lactoferrin Proteins 0.000 title description 101
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 title description 101
- 229940078795 lactoferrin Drugs 0.000 title description 101
- 235000021242 lactoferrin Nutrition 0.000 title description 101
- 238000011282 treatment Methods 0.000 title description 57
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 37
- 201000010099 disease Diseases 0.000 title description 31
- 230000003463 hyperproliferative effect Effects 0.000 title description 30
- 101000798114 Homo sapiens Lactotransferrin Proteins 0.000 claims abstract description 34
- 102000050459 human LTF Human genes 0.000 claims abstract description 34
- 229960004316 cisplatin Drugs 0.000 claims description 23
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 18
- 229940079593 drug Drugs 0.000 claims description 17
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 12
- 229960003668 docetaxel Drugs 0.000 claims description 12
- 229940124597 therapeutic agent Drugs 0.000 claims description 12
- 239000002246 antineoplastic agent Substances 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 7
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 6
- 229940123237 Taxane Drugs 0.000 claims description 4
- 229940127089 cytotoxic agent Drugs 0.000 claims description 4
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 229940044683 chemotherapy drug Drugs 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 229910052697 platinum Inorganic materials 0.000 claims description 3
- 239000012830 cancer therapeutic Substances 0.000 claims 13
- 239000008203 oral pharmaceutical composition Substances 0.000 claims 5
- 229940126585 therapeutic drug Drugs 0.000 claims 3
- 238000000034 method Methods 0.000 abstract description 43
- 208000035269 cancer or benign tumor Diseases 0.000 abstract description 7
- 230000012010 growth Effects 0.000 abstract description 6
- 239000000203 mixture Substances 0.000 description 85
- 102000003810 Interleukin-18 Human genes 0.000 description 47
- 108090000171 Interleukin-18 Proteins 0.000 description 47
- 210000004027 cell Anatomy 0.000 description 47
- 241001465754 Metazoa Species 0.000 description 42
- 230000000694 effects Effects 0.000 description 41
- 230000004614 tumor growth Effects 0.000 description 25
- 210000000822 natural killer cell Anatomy 0.000 description 21
- 238000001356 surgical procedure Methods 0.000 description 21
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 20
- 230000002601 intratumoral effect Effects 0.000 description 20
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 19
- 102100037850 Interferon gamma Human genes 0.000 description 19
- 108010074328 Interferon-gamma Proteins 0.000 description 19
- 241000699670 Mus sp. Species 0.000 description 19
- 102000013462 Interleukin-12 Human genes 0.000 description 18
- 108010065805 Interleukin-12 Proteins 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 18
- 238000002591 computed tomography Methods 0.000 description 17
- 210000004881 tumor cell Anatomy 0.000 description 17
- 210000002865 immune cell Anatomy 0.000 description 16
- 210000004698 lymphocyte Anatomy 0.000 description 16
- 238000004519 manufacturing process Methods 0.000 description 16
- 102000000588 Interleukin-2 Human genes 0.000 description 15
- 108010002350 Interleukin-2 Proteins 0.000 description 15
- 230000001093 anti-cancer Effects 0.000 description 15
- 238000001990 intravenous administration Methods 0.000 description 15
- 229940068196 placebo Drugs 0.000 description 15
- 239000000902 placebo Substances 0.000 description 15
- 238000001959 radiotherapy Methods 0.000 description 15
- 210000002966 serum Anatomy 0.000 description 15
- 230000001965 increasing effect Effects 0.000 description 14
- 102000004127 Cytokines Human genes 0.000 description 13
- 108090000695 Cytokines Proteins 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 238000002512 chemotherapy Methods 0.000 description 12
- 238000002648 combination therapy Methods 0.000 description 12
- 210000003491 skin Anatomy 0.000 description 12
- 210000001744 T-lymphocyte Anatomy 0.000 description 11
- 210000000601 blood cell Anatomy 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 102000000589 Interleukin-1 Human genes 0.000 description 10
- 108010002352 Interleukin-1 Proteins 0.000 description 10
- 102000003814 Interleukin-10 Human genes 0.000 description 10
- 108090000174 Interleukin-10 Proteins 0.000 description 10
- 102000004388 Interleukin-4 Human genes 0.000 description 10
- 108090000978 Interleukin-4 Proteins 0.000 description 10
- 108010002616 Interleukin-5 Proteins 0.000 description 10
- 102100039897 Interleukin-5 Human genes 0.000 description 10
- 210000004443 dendritic cell Anatomy 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 210000002381 plasma Anatomy 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 238000009472 formulation Methods 0.000 description 9
- 239000000499 gel Substances 0.000 description 9
- 210000000987 immune system Anatomy 0.000 description 9
- 230000006872 improvement Effects 0.000 description 9
- 206010041823 squamous cell carcinoma Diseases 0.000 description 9
- -1 electroporation Substances 0.000 description 8
- 238000009169 immunotherapy Methods 0.000 description 8
- 230000010412 perfusion Effects 0.000 description 8
- 230000005855 radiation Effects 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 101000798100 Bos taurus Lactotransferrin Proteins 0.000 description 7
- 210000000612 antigen-presenting cell Anatomy 0.000 description 7
- 230000009885 systemic effect Effects 0.000 description 7
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000011319 anticancer therapy Methods 0.000 description 6
- 238000001815 biotherapy Methods 0.000 description 6
- 229940072440 bovine lactoferrin Drugs 0.000 description 6
- 230000002708 enhancing effect Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 210000001035 gastrointestinal tract Anatomy 0.000 description 6
- 230000035800 maturation Effects 0.000 description 6
- 230000005012 migration Effects 0.000 description 6
- 238000013508 migration Methods 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
- 210000000813 small intestine Anatomy 0.000 description 6
- 230000001502 supplementing effect Effects 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 241000283690 Bos taurus Species 0.000 description 5
- 206010008342 Cervix carcinoma Diseases 0.000 description 5
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 5
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 5
- 238000011717 athymic nude mouse Methods 0.000 description 5
- 201000010881 cervical cancer Diseases 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 208000037819 metastatic cancer Diseases 0.000 description 5
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 150000003839 salts Chemical group 0.000 description 5
- 230000004936 stimulating effect Effects 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- 238000011735 C3H mouse Methods 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 4
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 4
- 206010029113 Neovascularisation Diseases 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 206010039491 Sarcoma Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000033115 angiogenesis Effects 0.000 description 4
- 229940124650 anti-cancer therapies Drugs 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 229940117681 interleukin-12 Drugs 0.000 description 4
- 230000000968 intestinal effect Effects 0.000 description 4
- 210000002510 keratinocyte Anatomy 0.000 description 4
- 238000002483 medication Methods 0.000 description 4
- 201000001441 melanoma Diseases 0.000 description 4
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 4
- 206010061289 metastatic neoplasm Diseases 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000002271 resection Methods 0.000 description 4
- 238000009097 single-agent therapy Methods 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000003200 Adenoma Diseases 0.000 description 3
- 206010001233 Adenoma benign Diseases 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 206010061187 Haematopoietic neoplasm Diseases 0.000 description 3
- 206010020843 Hyperthermia Diseases 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000003124 biologic agent Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000012937 correction Methods 0.000 description 3
- 229960003964 deoxycholic acid Drugs 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 201000005787 hematologic cancer Diseases 0.000 description 3
- 230000036031 hyperthermia Effects 0.000 description 3
- 229940121354 immunomodulator Drugs 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012139 lysis buffer Substances 0.000 description 3
- 229960004857 mitomycin Drugs 0.000 description 3
- 229940023041 peptide vaccine Drugs 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000001839 systemic circulation Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229940042129 topical gel Drugs 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 238000012384 transportation and delivery Methods 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- 206010005949 Bone cancer Diseases 0.000 description 2
- 208000018084 Bone neoplasm Diseases 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 208000009458 Carcinoma in Situ Diseases 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 2
- 206010067807 Gingival cancer Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- 206010024612 Lipoma Diseases 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- 206010027406 Mesothelioma Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 description 2
- 208000037538 Myelomonocytic Juvenile Leukemia Diseases 0.000 description 2
- 206010029260 Neuroblastoma Diseases 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 201000000582 Retinoblastoma Diseases 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 description 2
- 206010057644 Testis cancer Diseases 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 206010062129 Tongue neoplasm Diseases 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 206010053648 Vascular occlusion Diseases 0.000 description 2
- 206010047642 Vitiligo Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 238000011394 anticancer treatment Methods 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000011748 cell maturation Effects 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000009096 combination chemotherapy Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 229940029030 dendritic cell vaccine Drugs 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 238000002224 dissection Methods 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 206010016629 fibroma Diseases 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 201000011066 hemangioma Diseases 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 238000001794 hormone therapy Methods 0.000 description 2
- 239000012642 immune effector Substances 0.000 description 2
- 230000003308 immunostimulating effect Effects 0.000 description 2
- 201000004933 in situ carcinoma Diseases 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 210000004347 intestinal mucosa Anatomy 0.000 description 2
- 201000005992 juvenile myelomonocytic leukemia Diseases 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- 201000010260 leiomyoma Diseases 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 210000003622 mature neutrocyte Anatomy 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229960001924 melphalan Drugs 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 230000016379 mucosal immune response Effects 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 230000008481 normal tissue growth Effects 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 229940127084 other anti-cancer agent Drugs 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 230000001855 preneoplastic effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 201000003120 testicular cancer Diseases 0.000 description 2
- 201000006134 tongue cancer Diseases 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 208000021331 vascular occlusion disease Diseases 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010060999 Benign neoplasm Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 101100504320 Caenorhabditis elegans mcp-1 gene Proteins 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000001327 Chemokine CCL5 Human genes 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- OFDNQWIFNXBECV-UHFFFAOYSA-N Dolastatin 10 Natural products CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)CC)C(OC)CC(=O)N1CCCC1C(OC)C(C)C(=O)NC(C=1SC=CN=1)CC1=CC=CC=C1 OFDNQWIFNXBECV-UHFFFAOYSA-N 0.000 description 1
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- JJKOTMDDZAJTGQ-DQSJHHFOSA-N Idoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN2CCCC2)=CC=1)/C1=CC=C(I)C=C1 JJKOTMDDZAJTGQ-DQSJHHFOSA-N 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 208000011200 Kawasaki disease Diseases 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 241000238367 Mya arenaria Species 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 206010031112 Oropharyngeal squamous cell carcinoma Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 108010081690 Pertussis Toxin Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000007541 Preleukemia Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- KSZGVNZSUJHOJA-UHFFFAOYSA-N Zindoxifene Chemical compound CC=1C2=CC(OC(C)=O)=CC=C2N(CC)C=1C1=CC=C(OC(C)=O)C=C1 KSZGVNZSUJHOJA-UHFFFAOYSA-N 0.000 description 1
- IHGLINDYFMDHJG-UHFFFAOYSA-N [2-(4-methoxyphenyl)-3,4-dihydronaphthalen-1-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(OC)=CC=C1C(CCC1=CC=CC=C11)=C1C(=O)C(C=C1)=CC=C1OCCN1CCCC1 IHGLINDYFMDHJG-UHFFFAOYSA-N 0.000 description 1
- OEKMGABCSLYWOP-DHUJRADRSA-N [4-[(2s)-7-(2,2-dimethylpropanoyloxy)-4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2h-chromen-3-yl]phenyl] 2,2-dimethylpropanoate Chemical compound C1=CC([C@H]2C(=C(C3=CC=C(OC(=O)C(C)(C)C)C=C3O2)C)C=2C=CC(OC(=O)C(C)(C)C)=CC=2)=CC=C1OCCN1CCCCC1 OEKMGABCSLYWOP-DHUJRADRSA-N 0.000 description 1
- HEAFLBOWLRRIHV-UHFFFAOYSA-N [Na].[P] Chemical compound [Na].[P] HEAFLBOWLRRIHV-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Chemical compound CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 238000011256 aggressive treatment Methods 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000003181 biological factor Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229960005520 bryostatin Drugs 0.000 description 1
- MJQUEDHRCUIRLF-TVIXENOKSA-N bryostatin 1 Chemical compound C([C@@H]1CC(/[C@@H]([C@@](C(C)(C)/C=C/2)(O)O1)OC(=O)/C=C/C=C/CCC)=C\C(=O)OC)[C@H]([C@@H](C)O)OC(=O)C[C@H](O)C[C@@H](O1)C[C@H](OC(C)=O)C(C)(C)[C@]1(O)C[C@@H]1C\C(=C\C(=O)OC)C[C@H]\2O1 MJQUEDHRCUIRLF-TVIXENOKSA-N 0.000 description 1
- MUIWQCKLQMOUAT-AKUNNTHJSA-N bryostatin 20 Natural products COC(=O)C=C1C[C@@]2(C)C[C@]3(O)O[C@](C)(C[C@@H](O)CC(=O)O[C@](C)(C[C@@]4(C)O[C@](O)(CC5=CC(=O)O[C@]45C)C(C)(C)C=C[C@@](C)(C1)O2)[C@@H](C)O)C[C@H](OC(=O)C(C)(C)C)C3(C)C MUIWQCKLQMOUAT-AKUNNTHJSA-N 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000002281 colonystimulating effect Effects 0.000 description 1
- 235000021277 colostrum Nutrition 0.000 description 1
- 210000003022 colostrum Anatomy 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002681 cryosurgery Methods 0.000 description 1
- 238000011498 curative surgery Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- OFDNQWIFNXBECV-VFSYNPLYSA-N dolastatin 10 Chemical compound CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 OFDNQWIFNXBECV-VFSYNPLYSA-N 0.000 description 1
- 108010045524 dolastatin 10 Proteins 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 229950004203 droloxifene Drugs 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 229960004887 ferric hydroxide Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229960002258 fulvestrant Drugs 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 210000003976 gap junction Anatomy 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960003297 gemtuzumab ozogamicin Drugs 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 150000004688 heptahydrates Chemical class 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229960002163 hydrogen peroxide Drugs 0.000 description 1
- 229950002248 idoxifene Drugs 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- IEECXTSVVFWGSE-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Fe+3] IEECXTSVVFWGSE-UHFFFAOYSA-M 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 108010071397 lactoferrin receptors Proteins 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 238000002430 laser surgery Methods 0.000 description 1
- 230000035777 life prolongation Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- QZUHFMXJZOUZFI-ZQHSETAFSA-N miproxifene phosphate Chemical compound C=1C=C(C(C)C)C=CC=1C(/CC)=C(C=1C=CC(OP(O)(O)=O)=CC=1)\C1=CC=C(OCCN(C)C)C=C1 QZUHFMXJZOUZFI-ZQHSETAFSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229940086322 navelbine Drugs 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 208000022698 oropharynx squamous cell carcinoma Diseases 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 238000011499 palliative surgery Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000011518 platinum-based chemotherapy Methods 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000003405 preventing effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003751 purification from natural source Methods 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000011255 standard chemotherapy Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 238000000015 thermotherapy Methods 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 229950000212 trioxifene Drugs 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 229950006514 zindoxifene Drugs 0.000 description 1
Images
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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/40—Transferrins, e.g. lactoferrins, ovotransferrins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/19—Dairy proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Oncology (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Food Science & Technology (AREA)
- Cardiology (AREA)
- Mycology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、ラクトフェリンの組成物を単独でまたは標準的な抗癌療法と組合せて投与することにより過剰増殖性疾患を治療する方法に関する。ラクトフェリン組成物は、経口投与、静脈内投与、腫瘍内投与、または局所投与することができる。
っていく。
本発明に従って使用されるラクトフェリンは、天然の供給源、例えば、哺乳動物の乳(これに限定されるものではない)から単離および精製することにより得ることができる。ラクトフェリンは、哺乳動物のラクトフェリン、例えばウシまたはヒトのラクトフェリンが好ましい。好ましい態様において、ラクトフェリンは、当該技術においてよく知られかつ使用される遺伝子工学の手法(例えば、遺伝子改変した動物、植物、または真核生物における組換え発現または直接的生産)を用いて組換えにより生産されるヒトラクトフェリン、あるいは化学合成を用いて製造されるヒトラクトフェリンである(米国特許出願第5,571,896、5,571,697および5,571,691号参照。この引用により、これらの内容は本明細書に記載されたものとする)。
本発明によれば、上述した薬学的担体のいずれかにおいて提供されたラクトフェリン組成物を、過剰増殖性疾患の疑いのあるまたは過剰増殖性疾患を有する対象に投与する。当業者は、いくつかの考慮すべき事柄、例えば吸収、代謝、送達の方法、年齢、体重、疾患の重症度、および治療に対する反応に基づいて、対象に投与すべきヒトラクトフェリンの治療上有効な量を決定することができる。
本発明のヒトラクトフェリン組成物の有効性を高めるため、過剰増殖性疾患の治療に有効な他の薬剤、例えば抗癌剤、または手術を、本発明の組成物と組み合わせることが望ましい場合がある。「抗癌」剤(「抗癌」因子)は、対象において、癌に負に作用することができ、例えば、そのような作用は、癌細胞を殺す、癌細胞においてアポトーシスを誘発する、癌細胞の増殖速度を低下させる、転移の出現率または数を減らす、腫瘍のサイズを小さくする、腫瘍の成長を阻害する、腫瘍または癌細胞への血液の供給を減らす、癌細胞または腫瘍に対する免疫応答を促進する、癌の進行を阻止または阻害する、あるいは、癌を有する対象の寿命を延ばすことによるものである。抗癌剤(抗癌因子)は、生物学的薬剤(生物学的作用因子)(生物療法)、化学療法剤、および放射線療法剤(放射線療法因子)を含む。より一般的には、これらの他の組成物は、細胞の増殖を止めるか阻害するのに効果的な組み合わせの量で供給されるだろう。このプロセスは、本発明のヒトラクトフェリン組成物および一つ以上の薬剤または複数の因子を同時に投与することを含みうる。これは、両剤(両因子)を含む単一の組成物または薬理学的製剤を投与することにより、あるいは、異なる二種の組成物または製剤(一方の組成物はヒトラクトフェリン組成物を含み、他方は第二の薬剤(因子)(類)を含む)を同時にまたはその効果が重なるよう十分に近い時期に投与することにより達成することができる。
また、癌の治療法には種々の化学薬品を用いた治療がある。以下に限定されるものではないが、化学療法剤の具体例には、抗生物質の化学療法剤、例えばドキソルビシン、ダウノルビシン、アドリアマイシン、マイトマイシン(ムタマイシンおよび/またはマイトマイシン-Cとしても知られる)、アクチノマイシンD(ダクチノマイシン)、ブレオマイシン、プリコマイシン(Plicomycin)、植物アルカロイド類、例えばタキソール、ビンクリスチン、ビンブラスチン、その他種々の薬剤、例えば白金系薬剤(例えばシスプラチン(CDDP))、エトポシド(VP16)、腫瘍壊死因子、およびアルキル化剤、例えばカルムスチン、メルファラン(アルケラン、L-フェニルアラニンマスタード、フェニルアラニンマスタード、L-PAM、またはL-サルコリシンとしても知られる)(ナイトロジェンマスタードのフェニルアラニン誘導体)、シクロホスファミド、クロラムブシル、ブスルファン(マイレランとしても知られる)、タキサン系薬剤(例えばドセタキセル)およびロムスチンがある。
放射線療法の作用因子およびファクターには、DNA損傷を誘発する放射線および波長があり、例えば、γ線照射、X線、UV照射、マイクロ波、電子射出、放射性同位体などがある。上記形態の放射線を局所的にできた腫瘍部位に照射することにより、治療を行うことができる。これらの因子のすべてが、DNA、DNAの前駆体、DNAの複製および修復、ならびに染色体の構築および維持に広範囲の損傷をもたらしうる。
癌の患者のおよそ60%が、予防的手術、診断用手術またはステージング手術、治療手術および緩和手術を含む、何らかの種類の外科手術をうけることになる。治療手術は、癌の治療であり、他の治療法、例えば、本発明の治療、化学療法、放射線療法、ホルモン療法、遺伝子治療、免疫療法および/またはその他の治療法と組合せて用いることができる。
意図するところによれば、治療上の効果を高めるため、他の生物学的な作用因子を本発明と組合せて用いることができる。以下に限定されるものではないが、それらのさらなる因子には、細胞表面の受容体およびGAP接合のアップレギュレーションに作用する因子、静細胞因子(静細胞剤)および分化因子、細胞接着の阻害剤、過剰増殖性細胞のアポトーシスインデューサーへの感受性を高める因子、またはその他の生物学的因子、さらには温熱療法のような生物療法が含まれる。
免疫療法は、一般に、癌細胞を標的にして破壊するため、免疫エフェクター細胞および分子を使用することによるものである。例えば、免疫エフェクターは、腫瘍細胞の表面にある何らかのマーカーに対して特異的な抗体とすることができる。抗体は、単独で治療のエフェクターとして働くことができ、あるいは、他の細胞を動員して実際に細胞の死滅をもたらすことができる。また、抗体は、薬剤または毒素(化学療法薬、放射性核種、リシンA鎖、コレラ毒素、百日咳毒素など)と接合させることができ、そして、単にターゲティング剤として用いることができる。一方、エフェクターは、腫瘍細胞のターゲットと直接的または間接的に相互作用する表面分子を保持するリンパ球であってもよい。種々のエフェクター細胞には、細胞障害性T細胞およびNK細胞が含まれる。
本発明の好ましい態様を例示するために、以下に実施例を記載する。当業者に明らかなとおり、以下の実施例に開示する技術は、本発明者が見出した本発明の実施に際しうまく機能する技術を表し、従って、その実施の好ましい形態を構成するとみなすことができる。しかし、ここに開示する具体例には数多くの変更を加えることができ、それでもなお本発明の精神および範囲から逸脱することなく、よく似たまたは同類の結果が得られることは、本明細書の開示に照らして、当業者には明らかなことである。
rhLFによる腫瘍増殖の阻害
ヒト扁平上皮細胞癌(O12)を用いた。該細胞を無胸腺ヌードマウスの右側腹に注射した。腫瘍内(49匹、1回あたり0.05μg〜125μgの用量で7回)、静脈内(7匹、125μg/1回の用量)、または経口(7匹、20mg/1回の用量)のいずれかでrhLFを投与した。対照動物はビヒクルのみで処置した。rhLFを対照動物には投与しなかった。定着腫瘍を形成させるべく腫瘍細胞を接種して11日後から、rhLFを1日2回で5日間(静脈内の群)または8日間(その他のすべての群)投与した。
腫瘍の種類に対するrhLFの評価
広範囲にわたる種類の腫瘍細胞を無胸腺ヌードマウスの右側腹に注射する。動物には、rhLF、本来のhLF、またはウシLFのいずれかを経口投与する。対照動物はビヒクルのみで処理する。対照動物にはrhLFを投与しない。定着腫瘍を形成させるべく腫瘍細胞を接種して約11日後から、1、5、7、もしくは14日間または8日間、1日1回または2回、rhLFを投与するか、あるいは、標準的または公開された投薬法で一般に行われるような他の時期にrhLFを投与する。
rhLFおよびbLFの経口投与の効果
組換えヒトラクトフェリンおよびウシラクトフェリンをマウスに経口投与し、そして、小腸におけるIL-18の産生を測定した。
インビボでのNK活性における経口rhLFの効果
Balb/cナイーブマウスにrhLFまたはプラセボを1日1回、3日間、経口投与した(表4参照)。
rhLF経口投与のGM-CSFに対するインビボでの効果
組換えヒトラクトフェリンまたはプラセボをマウスに経口投与し、GM-CSFの小腸における産生を測定した。
hLFの化学療法との組合せ
ネズミ扁平上皮癌細胞株(SCCVII)を、免疫担当C3Hマウスの頸部皮膚を介して口底に注射した(0日目)。腫瘍細胞の移植後5日で(5日目)、頸下部において皮膚の切開を行い、外科的解剖により腫瘍が定着したことを確認した。腫瘍をキャリパスで三次元的に測定した。
化学療法との組合せhLFの用量依存
実施例6に記載するように、ネズミ扁平上皮癌細胞株(SCCVII)を、免疫担当C3Hマウスの頸部皮膚を介して口底に注射した(0日目)。最初の移植後5日目で、腫瘍をベースラインとして測定し、次いで、シスプラチン単独(8日目、i.p.、5mg/kg)またはシスプラチン+3種の用量の経口rhLF(毎日、胃管栄養法により5日目から11/12日目にかけて7〜8日間)のいずれかで処置した。11/12日目で動物をと殺し、そして腫瘍を測定した。図3に示すように、シスプラチン単独を摂取した動物と比較して、rhLFとシスプラチンの両方を摂取した動物では、用量に依存する腫瘍増殖阻害があった。
hLFのドセタキセルとの組合せ
実施例7に記載するように、ネズミ扁平上皮癌細胞株(SCCVII)を、免疫担当C3Hマウスの頸部皮膚を介して口底に注射した(0日目)。最初の移植後5日目で、腫瘍をベースラインとして測定し、次いで、経口プラセボ単独(1日1回、5日目から12日目まで、6匹)、プラセボとドセタキセル(i.v.ボーラス31.3mg/kgドセタキセル、8日目、9匹)、またはドセタキセル+経口rhLF(200mg/kg、胃管栄養法により1日1回、5日目から12日目まで投与、9匹)のいずれかで処置した。14日目に動物をと殺し、そして腫瘍を測定した。プラセボと比較して、ドセタキセル単独は、腫瘍増殖の阻害を引き起こし、そして、rhLFとドセタキセルとの組合せは、さらなる増殖阻害を引き起こした。阻害およびp値(片側検定)を表9に示す。
hLFの放射線療法との組合せ
ネズミ扁平上皮癌細胞株(SCCVII)を、免疫担当C3Hマウスの頸部皮膚を介して口底に注射した(0日目)。腫瘍細胞移植後5日(5日目)で、頸下部において皮膚の切開を行い、外科的解剖により腫瘍が定着したことを確認した。腫瘍をキャリパスで三次元的に測定した。
hLFのヒトにおける経口投与
四カ国(アルゼンチン、ブラジル、チリ、米国)における複数の医療センターで行った二つの異なる研究において、標準的な化学療法が不成功に終わったある範囲の種類にわたる転移性癌のヒト患者に組換えヒトラクトフェリンを経口投与した。rhLFを、1日あたり1.5〜9グラムの用量で2回に分けて14日おきに14のサイクルで投与した。
ヒトにおける経口hLFでの組合せ治療
組換えヒトラクトフェリンをヒト患者に経口投与し、単独でまたは標準的な抗癌投薬法と組合せて腫瘍の増殖を阻害する。
経口rhLFの投与後の免疫刺激
Balb/cナイーブマウスにrhLFまたはプラセボを1日1回、3日間、経口投与した。1日後(4日目)、マウスをと殺し、そして脾臓を採取した。磁気ビーズ細胞選別アッセイ(MACS抗NK-DX5)を用いてNK細胞を分離し、カウントした。次に、乳酸脱水素酵素(LDH)放出試験を用いて、YACターゲットに対するNK活性についてインビトロで細胞を試験した。
静脈内投与の効果
組換えラクトフェリン、ウシラクトフェリンおよび天然のラクトフェリンを、動物、好ましくはラットに、静脈内投与し、そして、IL-18、IL-1、IL-2、IL-4、IL-5、IL-10、IL-12およびIFN-ガンマの血漿、血清および血液内細胞における産生を測定する。
静脈内rhLFの他の薬剤との組合せ化学療法
試験すべき腫瘍細胞を、無胸腺ヌードマウスの右側腹に注射する。動物にrhLFを単独でまたは他の抗癌投薬法と組合わせて、実施例13のように静脈内投与する。対照動物をビヒクルのみで処置する。対照動物にはrhLFを投与しない。実施例13に記載した試験において最適と判断される投薬計画を用いてrhLFを投与する。標準的または公知の投薬法を用いて抗癌治療を行う。定着腫瘍を形成させるべく腫瘍細胞を接種してから約11日後に治療を開始するか、あるいは、標準的または公知の投薬法で一般に行われるような他の時期に治療を開始する。
hLFのヒトにおける静脈内投与
腫瘍増殖を阻害するため、組換えラクトフェリンを患者に静脈内投与する。
静脈内hLFによる組合せ治療
組換えラクトフェリンを患者に静脈内投与し、単独でまたは標準的な抗癌投薬法と組合せて腫瘍の増殖を阻害する。
腫瘍内rhLFの活性
O12ヒト口腔咽頭扁平上皮細胞癌の腫瘍細胞を無胸腺ヌードマウスの右側腹に注射した。組換えヒトラクトフェリンおよびビヒクル対照を腫瘍内注射により投与した。各動物には、異なる濃度のrhLFを50μLで投与した。該50μLは、異なる方向および角度(ほぼS/N/E/W)からの約12.5μLの4回の注射に分け、該用量が腫瘍のいたるところに確実に一様に分配(ファンニング)されるようにした。
腫瘍内rhLF後の免疫刺激
正常なC3H/HeJマウスに、実施例17記載の方法により、二種類のマウス腫瘍のうちのいずれかを移植した。使用した腫瘍はSCCVIIおよびRIFマウス腫瘍細胞株であった。マウスにおいて腫瘍を定着させた後、1用量あたり250または500μgのrhLFまたはビヒクル対照物を、毎日、4日間、腫瘍内に注射した。最後の腫瘍内注射の後24時間で動物をと殺し、その血液をリンパ球の集団について調べた。循環リンパ球の数は、プラセボ処置対照動物に対し34%〜56%増加した(表14)。
hLFの他の薬剤との組合せ化学療法
試験すべき腫瘍細胞を、無胸腺ヌードマウスの右側腹に注射する。動物にrhLFを単独でまたは他の抗癌投薬法と組合わせて、実施例1または実施例17記載のように腫瘍内投与する。対照動物をビヒクルのみで処置する。対照動物にはrhLFを投与しない。標準的または公知の投薬法を用いて抗癌治療を行う。定着腫瘍を形成させるべく腫瘍細胞を接種してから約11日後に治療を開始するか、あるいは、標準的または公知の投薬法で一般に行われるような他の時期に治療を開始する。
hLFの腫瘍内投与
腫瘍増殖を阻害するため、組換えラクトフェリンを患者に腫瘍内投与する。
腫瘍内hLFによる組合せ治療
組換えラクトフェリンを患者に腫瘍内投与し、単独でまたは標準的な抗癌投薬法と組合せて腫瘍の増殖を阻害する。
ヒトにおけるhLFの局所投与
腫瘍増殖を阻害するため、組換えラクトフェリンをゲル製剤で患者に投与する。
局所hLFによる組合せ治療
組換えラクトフェリンをゲル製剤で患者に投与し、単独でまたは標準的な抗癌投薬法と組合せて腫瘍の増殖を阻害する。
本明細書に記載するすべての特許および刊行物は、本発明に関し、当業者の技術水準を示すものである。すべての特許および刊行物は、引用することによって、その内容が具体的かつ個々に本明細書に記載されたものとする。
米国特許第5,629,001号
Bezault J 他, Cancer Res. 1994, 54(9):2310-2.
Broxmeyer HE. Blood. 1983; 61:982-993.
Damiens E, 他, Biochim Biophys Acta. 1998, 1402(3):277-87.
Dhennin-Duthille I, 他, J Cell Biochem. 2000, 79(4):583-93.
Erlandsson, Cancer Genet. Cytogenet, 104:1-18, 1998.
Gahr M, 他, J Leukocyte Biol. 1991;49: 427-33.
Gertig および Hunter, Semin. Cancer Biol., 8(4):285-298, 1997.
Horowitz DA, 他, J Immunol. 1984; 132: 2370-4.
Iigo M, 他, Clin Exp Metastasis. 1999, 17(1):35-40.
Kolmel, J. Neurooncol., 38:121-125, 1998.
Kuhara T, 他, Nutr Cancer. 2000, 38(2):192-9.
Magi-Galluzzi 他, Anal. Quant. Cytol. Histol., 20:343-350, 1998.
Mangray および King, Front Biosci., 3:D1148-1160, 1998,
Masuda C, 他 Jpn J Cancer Res. 2000, 91(6):582-8.
Mayer, Radiat Oncol Investig. 6:281-8, 1998.
Mumby および Walter, Cell Regul, 2:589-598, 1991.
Natoli 他, Biochem. Pharmacol., 56(8):915-920, 1998.
Ohara, Acta Oncol. 37:471-4, 1998.
Shau H, 他, J Leukocyte Biol. 1992;51:343-9.
Solyanik 他, Cell Prolif., 28:263-278, 1995.
Spik G, 他, Adv Exp Med Biol 1994;357:13-9.
Stokke 他, Cell Prolif., 30(5):197-218, 1997.
Tanaka T, 他, Jpn J Cancer Res. 2000, 91(l):25-33.
Tsuda H, 他, Biofactors. 2000;12(l-4):83-8.
Ushida Y, 他, Jpn J Cancer Res: 1999, 90(3):262-7.
Wang WP, 他, Jpn J Cancer Res. 2000, 91(10):1022-7.
Yoo YC, 他, Adv Exp Med Biol. 1998, 443:285-91.
Yoo YC, 他, Jpn J Cancer Res. 1997, 88(2):184-90.
本発明およびその利点を詳細に説明してきたが、勿論、添付の特許請求の範囲に規定する本発明の精神および範囲から逸脱することなく、さまざまな変更、置換、および改変を施すことができる。さらに、本願の範囲は、本明細書に記載した特定の態様のプロセス、装置、製品、組成物、手段、方法および工程に限定されるものではない。本発明の開示から当業者には明らかなように、本明細書に記載した対応する態様と実質的に同じ機能を果たすか、または実質的に同じ結果をもたらす、既存のまたは将来開発されるプロセス、装置、製品、組成物、手段、方法または工程を、本発明に従って用いることができる。従って、そのようなプロセス、装置、製品、組成物、手段、方法または工程もまた、添付の特許請求の範囲に包含するものとする。
Claims (10)
- 固形癌としての肺癌を治療する為の癌治療薬であって、ヒトラクトフェリンを該癌治療薬の有効成分として含有する経口医薬組成物を含む癌治療薬。
- 前記ヒトラクトフェリンが、前記経口医薬組成物において、薬学的に許容される担体中に分散されている、請求項1記載の癌治療薬。
- 該ヒトラクトフェリンが組換えヒトラクトフェリンである、請求項1または2記載の癌治療薬。
- 前記ヒトラクトフェリンを該癌治療薬の有効成分として含有する経口医薬組成物に、さらに化学療法用薬剤を組合せてなる、請求項1から3までのいずれかに記載の癌治療薬。
- 前記化学療法用薬剤が、白金系の薬剤を含む、請求項4記載の癌治療薬。
- 前記白金系の薬剤がシスプラチンである、請求項5記載の癌治療薬。
- 前記ヒトラクトフェリンを該癌治療薬の有効成分として含有する経口医薬組成物の投与が、シスプラチン投与前あるいはシスプラチン投与と同時に行われる、請求項6記載の癌治療薬。
- 前記化学療法用薬剤が、タキサン系の薬剤を含む、4から7までのいずれかに記載の治療薬。
- 前記タキサン系の薬剤が、ドセタキセルである、請求項8記載の癌治療薬。
- 前記ヒトラクトフェリンを該癌治療薬の有効成分として含有する経口医薬組成物の投与が、ドセタキセル投与前あるいはドセタキセル投与と同時に行われる、請求項9記載の癌治療薬。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US37944202P | 2002-05-10 | 2002-05-10 | |
US37944102P | 2002-05-10 | 2002-05-10 | |
US37947402P | 2002-05-10 | 2002-05-10 | |
PCT/US2003/014789 WO2003099323A1 (en) | 2002-05-10 | 2003-05-09 | Lactoferrin in the treatment of malignant neoplasms and other hyperproliferative diseases |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010274944A Division JP5156084B2 (ja) | 2002-05-10 | 2010-12-09 | 定着固形癌の治療におけるラクトフェリン |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2005533029A JP2005533029A (ja) | 2005-11-04 |
JP2005533029A5 JP2005533029A5 (ja) | 2006-02-16 |
JP4685443B2 true JP4685443B2 (ja) | 2011-05-18 |
Family
ID=29424524
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004506847A Expired - Fee Related JP4685443B2 (ja) | 2002-05-10 | 2003-05-09 | 悪性新生物および他の過剰増殖性疾患の治療におけるラクトフェリン |
JP2010274944A Expired - Fee Related JP5156084B2 (ja) | 2002-05-10 | 2010-12-09 | 定着固形癌の治療におけるラクトフェリン |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010274944A Expired - Fee Related JP5156084B2 (ja) | 2002-05-10 | 2010-12-09 | 定着固形癌の治療におけるラクトフェリン |
Country Status (12)
Country | Link |
---|---|
US (5) | US7901879B2 (ja) |
EP (2) | EP2286827A1 (ja) |
JP (2) | JP4685443B2 (ja) |
CN (2) | CN100467059C (ja) |
AT (1) | ATE519499T1 (ja) |
AU (2) | AU2003273182B8 (ja) |
CA (1) | CA2484656A1 (ja) |
CY (1) | CY1111999T1 (ja) |
DK (1) | DK1507554T3 (ja) |
HK (2) | HK1080722A1 (ja) |
PT (1) | PT1507554E (ja) |
WO (2) | WO2003094952A1 (ja) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6399570B1 (en) | 1999-02-05 | 2002-06-04 | Agennix, Inc. | Antimicrobial/endotoxin neutralizing polypeptide |
ATE519499T1 (de) * | 2002-05-10 | 2011-08-15 | Agennix Inc | Lactoferrin bei der behandlung maligner neoplasien und anderer hyperproliferativer erkrankungen |
AU2003233583A1 (en) * | 2002-05-24 | 2003-12-12 | Agennix Incorporated | Oral lactoferrin in the treatment of respiratory disorders |
DK2298338T3 (da) * | 2002-09-16 | 2012-09-24 | Agennix Inc | Lactoferrin-sammensætninger og fremgangsmåder til behandling af hudsår |
EP1581243A4 (en) * | 2002-12-06 | 2008-01-02 | Agennix Inc | ORAL LACTOFERRINE FOR THE TREATMENT OF SEPSIES |
AU2003296447A1 (en) * | 2002-12-10 | 2004-06-30 | Agennix Incorporated | Lactoferrin as an agent in the prevention of organ transplant rejection and graft-versus-host-disease |
AU2003293500A1 (en) * | 2002-12-12 | 2004-07-09 | Agennix Incorporated | Lactoferrin in the reduction of pain |
JP2007524654A (ja) * | 2003-06-06 | 2007-08-30 | エイジェニックス インコーポレイテッド | 癌ワクチン中のアジュバントとしてのラクトフェリン |
WO2005018542A2 (en) * | 2003-07-10 | 2005-03-03 | Agennix Incorporated | Use of lactoferrin in prophylaxis against infection and/or inflammation in immunosuppressed subjects |
GB0413954D0 (en) * | 2004-06-22 | 2004-07-28 | Altunkaya Ali | Compositions for topical treatment |
WO2006047744A2 (en) * | 2004-10-26 | 2006-05-04 | Agennix Incorporated | Compositions of lactoferrin related peptides and uses thereof |
WO2006054908A1 (en) * | 2004-11-19 | 2006-05-26 | Fonterra Corporate Research And Development Limited | Methods of immune or haematological enhancement, inhibiting tumour formation or growth, and treating or preventing cancer |
WO2007022537A2 (en) * | 2005-08-19 | 2007-02-22 | Agennix Incorporated | Use of lactoferrin as a chemokine and a chemotactic modulator |
WO2007145520A1 (en) * | 2006-06-14 | 2007-12-21 | N.V. Nutricia | Anti-inflammatory composition comprising glycine and lactoferrin and the use thereof |
BRPI0919847A2 (pt) * | 2008-09-19 | 2015-12-15 | Nestec Sa | suporte nutricional do sistema imunológico durante o tratamento anticâncer |
US9115211B2 (en) * | 2009-01-28 | 2015-08-25 | Jean-Paul Perraudin | Method for production of lactoferrin |
US10307167B2 (en) | 2012-12-14 | 2019-06-04 | Corquest Medical, Inc. | Assembly and method for left atrial appendage occlusion |
US10314594B2 (en) | 2012-12-14 | 2019-06-11 | Corquest Medical, Inc. | Assembly and method for left atrial appendage occlusion |
US10813630B2 (en) | 2011-08-09 | 2020-10-27 | Corquest Medical, Inc. | Closure system for atrial wall |
US20140142689A1 (en) | 2012-11-21 | 2014-05-22 | Didier De Canniere | Device and method of treating heart valve malfunction |
JP2015067560A (ja) * | 2013-09-27 | 2015-04-13 | 国立大学法人広島大学 | ラクトフェリンを含有する癌転移抑制剤 |
US9566443B2 (en) | 2013-11-26 | 2017-02-14 | Corquest Medical, Inc. | System for treating heart valve malfunction including mitral regurgitation |
WO2015089316A1 (en) * | 2013-12-12 | 2015-06-18 | Cornell University | Methods for preventing and treating oral cancers |
US10842626B2 (en) | 2014-12-09 | 2020-11-24 | Didier De Canniere | Intracardiac device to correct mitral regurgitation |
CN106174462A (zh) * | 2016-04-17 | 2016-12-07 | 马鞍山市志诚科技有限公司 | 一种防治血管瘤的营养配方纳米颗粒及制备加工方法 |
WO2018079701A1 (ja) * | 2016-10-28 | 2018-05-03 | 株式会社Nrlファーマ | ラクトフェリン活性を有するタンパク質を含む、抗ガン治療補助剤 |
CN111544579A (zh) * | 2020-03-13 | 2020-08-18 | 中国农业科学院北京畜牧兽医研究所 | 一种抗癌症的药物组合物 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6351337A (ja) * | 1986-08-22 | 1988-03-04 | Snow Brand Milk Prod Co Ltd | 抗腫瘍剤 |
JPH05186368A (ja) * | 1992-01-08 | 1993-07-27 | Santen Pharmaceut Co Ltd | 抗リウマチ剤 |
JPH07233064A (ja) * | 1992-08-03 | 1995-09-05 | Bristol Myers Squibb Co | タキソールを有効成分とする制癌剤 |
JPH09194388A (ja) * | 1996-01-22 | 1997-07-29 | Morinaga Milk Ind Co Ltd | 血管新生病治療剤 |
JP2000229881A (ja) * | 1999-02-10 | 2000-08-22 | Morinaga Milk Ind Co Ltd | 癌疾患の予後改善剤 |
JP2001504447A (ja) * | 1996-08-12 | 2001-04-03 | エイプラス サイエンス インベスト アーベー | ラクトフェリンおよび/またはラクトフェリシンでの、感染、炎症および/または腫瘍の処置および予防 |
JP2002519332A (ja) * | 1998-06-26 | 2002-07-02 | エヌ・ヴェー・ニュートリシア | 微生物によって引き起こされる表面感染症の治療または予防に使用するための医薬調製物 |
Family Cites Families (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4977137B1 (en) * | 1987-06-03 | 1994-06-28 | Baylor College Medicine | Lactoferrin as a dietary ingredient promoting the growth of the gastrointestinal tract |
US5766939A (en) * | 1989-05-05 | 1998-06-16 | Baylor College Of Medicine | Production of recombinant lactoferrin and lactoferrin polypeptides using CDNA sequences in various organisms |
US5571691A (en) | 1989-05-05 | 1996-11-05 | Baylor College Of Medicine | Production of recombinant lactoferrin and lactoferrin polypeptides using CDNA sequences in various organisms |
US5571697A (en) * | 1989-05-05 | 1996-11-05 | Baylor College Of Medicine Texas Medical Center | Expression of processed recombinant lactoferrin and lactoferrin polypeptide fragments from a fusion product in Aspergillus |
IL94183A (en) * | 1989-05-05 | 2003-09-17 | Baylor College Medicine | cDNA SEQUENCE CODING FOR HUMAN LACTOFERRIN PROTEIN OR PORTION THEREOF AND LACTOFERRIN PROTEIN PRODUCED FROM SAID SEQUENCE |
US6100054A (en) * | 1989-05-05 | 2000-08-08 | Baylor College Of Medicine | Production for recombinant lactoferrin and lactoferrin polypeptides using DNA sequences in various organisms |
US5849881A (en) * | 1989-05-05 | 1998-12-15 | Baylor College Medicine | Production of recombinant lactoferrin and lactoferrin polypeptides using cDNA sequences in various organisms |
US5198419A (en) * | 1989-12-08 | 1993-03-30 | Immuno Japan Inc. | Formulated medicines for enhancing the efficacy of beta-lactam antibiotics in prophylaxis and treatment against infectious disease due to pathogenic bacteria |
AU664561B2 (en) | 1991-06-21 | 1995-11-23 | University Of Cincinnati, The | Orally administrable therapeutic proteins and method of making |
ZA932568B (en) * | 1992-04-24 | 1993-11-12 | Baylor College Midecine A Non | Production of recombinant human lactoferrin |
US5679807A (en) * | 1995-01-30 | 1997-10-21 | Hauser, Inc. | Preparation of taxol and docetaxel through primary amines |
JPH08217693A (ja) * | 1995-02-17 | 1996-08-27 | Yoshihisa Naito | 新規医薬組成物 |
JP3496387B2 (ja) | 1996-01-23 | 2004-02-09 | 花王株式会社 | 毛髪化粧料 |
US6111081A (en) * | 1996-05-31 | 2000-08-29 | Baylor College Of Medicine | Lactoferrin variants and uses thereof |
EP1017407A2 (en) * | 1997-02-03 | 2000-07-12 | Pharming Intellectual Property BV | Useful properties of human lactoferrin and variants thereof |
ES2245028T3 (es) | 1997-04-10 | 2005-12-16 | Agennix, Inc. | Uso de lactoferrina en el tratamiento de trastornos inducidos por alergenos. |
GB9818938D0 (en) * | 1998-08-28 | 1998-10-21 | Alpharma As | Bioactive peptides |
US6399570B1 (en) * | 1999-02-05 | 2002-06-04 | Agennix, Inc. | Antimicrobial/endotoxin neutralizing polypeptide |
RU2165769C1 (ru) | 2000-07-13 | 2001-04-27 | Якубовская Раиса Ивановна | Антибактериальный, антиоксидантный, иммуномодулирующий и антиканцерогенный препарат и способ его применения |
US20030096736A1 (en) * | 2001-05-09 | 2003-05-22 | Kruzel Marian L. | Lactoferrin for age related disorders in humans |
ATE519499T1 (de) * | 2002-05-10 | 2011-08-15 | Agennix Inc | Lactoferrin bei der behandlung maligner neoplasien und anderer hyperproliferativer erkrankungen |
AU2003233583A1 (en) * | 2002-05-24 | 2003-12-12 | Agennix Incorporated | Oral lactoferrin in the treatment of respiratory disorders |
DK2298338T3 (da) * | 2002-09-16 | 2012-09-24 | Agennix Inc | Lactoferrin-sammensætninger og fremgangsmåder til behandling af hudsår |
JP2007524654A (ja) * | 2003-06-06 | 2007-08-30 | エイジェニックス インコーポレイテッド | 癌ワクチン中のアジュバントとしてのラクトフェリン |
WO2005018542A2 (en) * | 2003-07-10 | 2005-03-03 | Agennix Incorporated | Use of lactoferrin in prophylaxis against infection and/or inflammation in immunosuppressed subjects |
WO2006054908A1 (en) | 2004-11-19 | 2006-05-26 | Fonterra Corporate Research And Development Limited | Methods of immune or haematological enhancement, inhibiting tumour formation or growth, and treating or preventing cancer |
JP2007233064A (ja) | 2006-03-01 | 2007-09-13 | Bitsign:Kk | 表示システム及び表示器 |
-
2003
- 2003-05-09 AT AT03755357T patent/ATE519499T1/de active
- 2003-05-09 CN CNB038163853A patent/CN100467059C/zh not_active Expired - Fee Related
- 2003-05-09 US US10/434,769 patent/US7901879B2/en not_active Expired - Fee Related
- 2003-05-09 WO PCT/US2003/014584 patent/WO2003094952A1/en not_active Application Discontinuation
- 2003-05-09 DK DK03755357.5T patent/DK1507554T3/da active
- 2003-05-09 US US10/435,319 patent/US20040082504A1/en not_active Abandoned
- 2003-05-09 AU AU2003273182A patent/AU2003273182B8/en not_active Ceased
- 2003-05-09 CN CNB038163918A patent/CN100467060C/zh not_active Expired - Fee Related
- 2003-05-09 AU AU2003239393A patent/AU2003239393A1/en not_active Abandoned
- 2003-05-09 EP EP10010751A patent/EP2286827A1/en not_active Withdrawn
- 2003-05-09 EP EP03755357A patent/EP1507554B1/en not_active Expired - Lifetime
- 2003-05-09 CA CA002484656A patent/CA2484656A1/en not_active Abandoned
- 2003-05-09 PT PT03755357T patent/PT1507554E/pt unknown
- 2003-05-09 JP JP2004506847A patent/JP4685443B2/ja not_active Expired - Fee Related
- 2003-05-09 WO PCT/US2003/014789 patent/WO2003099323A1/en active Application Filing
-
2006
- 2006-01-13 HK HK06100605.1A patent/HK1080722A1/xx not_active IP Right Cessation
- 2006-03-14 HK HK06103271.8A patent/HK1083203A1/xx not_active IP Right Cessation
-
2009
- 2009-09-17 US US12/561,429 patent/US20100137208A1/en not_active Abandoned
-
2010
- 2010-12-09 US US12/964,327 patent/US8242079B2/en not_active Expired - Fee Related
- 2010-12-09 JP JP2010274944A patent/JP5156084B2/ja not_active Expired - Fee Related
-
2011
- 2011-11-03 CY CY20111101064T patent/CY1111999T1/el unknown
-
2012
- 2012-07-11 US US13/546,208 patent/US20120276126A1/en not_active Abandoned
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6351337A (ja) * | 1986-08-22 | 1988-03-04 | Snow Brand Milk Prod Co Ltd | 抗腫瘍剤 |
JPH05186368A (ja) * | 1992-01-08 | 1993-07-27 | Santen Pharmaceut Co Ltd | 抗リウマチ剤 |
JPH07233064A (ja) * | 1992-08-03 | 1995-09-05 | Bristol Myers Squibb Co | タキソールを有効成分とする制癌剤 |
JPH09194388A (ja) * | 1996-01-22 | 1997-07-29 | Morinaga Milk Ind Co Ltd | 血管新生病治療剤 |
JP2001504447A (ja) * | 1996-08-12 | 2001-04-03 | エイプラス サイエンス インベスト アーベー | ラクトフェリンおよび/またはラクトフェリシンでの、感染、炎症および/または腫瘍の処置および予防 |
JP2002519332A (ja) * | 1998-06-26 | 2002-07-02 | エヌ・ヴェー・ニュートリシア | 微生物によって引き起こされる表面感染症の治療または予防に使用するための医薬調製物 |
JP2000229881A (ja) * | 1999-02-10 | 2000-08-22 | Morinaga Milk Ind Co Ltd | 癌疾患の予後改善剤 |
Also Published As
Publication number | Publication date |
---|---|
US7901879B2 (en) | 2011-03-08 |
CA2484656A1 (en) | 2003-12-04 |
JP2005533029A (ja) | 2005-11-04 |
US20040009895A1 (en) | 2004-01-15 |
EP2286827A1 (en) | 2011-02-23 |
HK1083203A1 (en) | 2006-06-30 |
JP5156084B2 (ja) | 2013-03-06 |
AU2003273182B8 (en) | 2009-05-07 |
US20100137208A1 (en) | 2010-06-03 |
PT1507554E (pt) | 2011-11-21 |
AU2003273182A1 (en) | 2003-12-12 |
CN1668326A (zh) | 2005-09-14 |
WO2003099323A1 (en) | 2003-12-04 |
ATE519499T1 (de) | 2011-08-15 |
WO2003094952A1 (en) | 2003-11-20 |
CN100467059C (zh) | 2009-03-11 |
JP2011079858A (ja) | 2011-04-21 |
AU2003273182B2 (en) | 2009-04-23 |
CY1111999T1 (el) | 2015-11-04 |
EP1507554A1 (en) | 2005-02-23 |
EP1507554A4 (en) | 2007-05-09 |
US20120276126A1 (en) | 2012-11-01 |
US20110076295A1 (en) | 2011-03-31 |
CN1668325A (zh) | 2005-09-14 |
DK1507554T3 (da) | 2011-11-21 |
EP1507554B1 (en) | 2011-08-10 |
US8242079B2 (en) | 2012-08-14 |
US20040082504A1 (en) | 2004-04-29 |
AU2003239393A1 (en) | 2003-11-11 |
CN100467060C (zh) | 2009-03-11 |
HK1080722A1 (en) | 2006-05-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5156084B2 (ja) | 定着固形癌の治療におけるラクトフェリン | |
US20110110983A1 (en) | Lactoferrin as an adjuvant in cancer vaccines | |
TW201427681A (zh) | 用空間構象改變的重組干擾素治療腫瘤的方法 | |
EP0942741B1 (en) | Lectin compositions and uses thereof | |
WO2010111807A1 (zh) | 一种多糖脂质体、其制备方法及用途 | |
TWI725947B (zh) | 巴豆酯組成物及用於治療或減少血球細胞減少期間之用途 | |
KR102115468B1 (ko) | 마이코박테리움 파라고르도네의 항암 면역치료법 용도 | |
ES2368214T3 (es) | Lactoferrina en el tratamiento de neoplasmas malignos y de otras enfermedades hiperproliferativas. | |
JP2023544310A (ja) | プロバイオティクス成分の使用及びプロバイオティクス成分を含む医薬組成物 | |
TW202023568A (zh) | 用於治療癌症之組合療法 | |
Yogeswaran et al. | AN OVERVIEW OF CURCUMIN AS ADJUVANT IN CANCER VACCINES | |
Bowen | Prevention and treatment of regimen-related mucosal toxicity | |
MXPA98010846A (es) | Composiciones de lecitina y usos de las mismas |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20051222 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20051222 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20081127 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20081127 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090129 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090427 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090508 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090728 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20090729 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100810 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20101209 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20110117 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20110201 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20110210 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140218 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |