CN113929764B - 一种乳腺叶状肿瘤分子标志物cd146及其应用 - Google Patents
一种乳腺叶状肿瘤分子标志物cd146及其应用 Download PDFInfo
- Publication number
- CN113929764B CN113929764B CN202111200916.8A CN202111200916A CN113929764B CN 113929764 B CN113929764 B CN 113929764B CN 202111200916 A CN202111200916 A CN 202111200916A CN 113929764 B CN113929764 B CN 113929764B
- Authority
- CN
- China
- Prior art keywords
- tumor
- breast
- leu
- glu
- val
- 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.)
- Active
Links
- 101000623903 Homo sapiens Cell surface glycoprotein MUC18 Proteins 0.000 title claims abstract description 137
- 102100023126 Cell surface glycoprotein MUC18 Human genes 0.000 title claims abstract description 121
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 105
- 210000000481 breast Anatomy 0.000 title claims abstract description 91
- 239000003147 molecular marker Substances 0.000 title abstract description 23
- 230000003211 malignant effect Effects 0.000 claims abstract description 59
- 239000003814 drug Substances 0.000 claims abstract description 24
- 210000005075 mammary gland Anatomy 0.000 claims abstract description 9
- 108020004459 Small interfering RNA Proteins 0.000 claims description 4
- 230000000692 anti-sense effect Effects 0.000 claims 3
- 210000004881 tumor cell Anatomy 0.000 abstract description 60
- 230000014509 gene expression Effects 0.000 abstract description 55
- 238000013508 migration Methods 0.000 abstract description 12
- 230000002401 inhibitory effect Effects 0.000 abstract description 10
- 230000005012 migration Effects 0.000 abstract description 10
- 230000012010 growth Effects 0.000 abstract description 6
- 238000004393 prognosis Methods 0.000 abstract description 6
- 238000004458 analytical method Methods 0.000 abstract description 5
- 230000001105 regulatory effect Effects 0.000 abstract description 5
- 238000003745 diagnosis Methods 0.000 abstract description 3
- 238000003748 differential diagnosis Methods 0.000 abstract description 3
- 230000001404 mediated effect Effects 0.000 abstract description 3
- 210000001519 tissue Anatomy 0.000 description 36
- 210000004027 cell Anatomy 0.000 description 34
- 230000000694 effects Effects 0.000 description 21
- 238000003197 gene knockdown Methods 0.000 description 21
- 238000002474 experimental method Methods 0.000 description 19
- 208000026310 Breast neoplasm Diseases 0.000 description 14
- 108010035532 Collagen Proteins 0.000 description 13
- 102000008186 Collagen Human genes 0.000 description 13
- 229920001436 collagen Polymers 0.000 description 13
- 239000002609 medium Substances 0.000 description 13
- 206010027476 Metastases Diseases 0.000 description 12
- 230000009401 metastasis Effects 0.000 description 12
- 206010006187 Breast cancer Diseases 0.000 description 11
- 230000002018 overexpression Effects 0.000 description 9
- 230000007730 Akt signaling Effects 0.000 description 8
- 102100027043 Discoidin, CUB and LCCL domain-containing protein 2 Human genes 0.000 description 8
- 101000911787 Homo sapiens Discoidin, CUB and LCCL domain-containing protein 2 Proteins 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 230000004663 cell proliferation Effects 0.000 description 8
- 108010009298 lysylglutamic acid Proteins 0.000 description 8
- 230000004709 cell invasion Effects 0.000 description 7
- 230000012292 cell migration Effects 0.000 description 7
- 230000035755 proliferation Effects 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 241000745988 Phyllostachys Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 230000018109 developmental process Effects 0.000 description 6
- 238000005755 formation reaction Methods 0.000 description 6
- 230000009545 invasion Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 108010062796 arginyllysine Proteins 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 201000001441 melanoma Diseases 0.000 description 5
- 230000001575 pathological effect Effects 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- YUZPQIQWXLRFBW-ACZMJKKPSA-N Cys-Glu-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O YUZPQIQWXLRFBW-ACZMJKKPSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- DXVOKNVIKORTHQ-GUBZILKMSA-N Glu-Pro-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O DXVOKNVIKORTHQ-GUBZILKMSA-N 0.000 description 4
- PPGBXYKMUMHFBF-KATARQTJSA-N Leu-Ser-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PPGBXYKMUMHFBF-KATARQTJSA-N 0.000 description 4
- YPLVCBKEPJPBDQ-MELADBBJSA-N Lys-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N YPLVCBKEPJPBDQ-MELADBBJSA-N 0.000 description 4
- NXEYSLRNNPWCRN-SRVKXCTJSA-N Pro-Glu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NXEYSLRNNPWCRN-SRVKXCTJSA-N 0.000 description 4
- XJDMUQCLVSCRSJ-VZFHVOOUSA-N Ser-Thr-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O XJDMUQCLVSCRSJ-VZFHVOOUSA-N 0.000 description 4
- LYERIXUFCYVFFX-GVXVVHGQSA-N Val-Leu-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N LYERIXUFCYVFFX-GVXVVHGQSA-N 0.000 description 4
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 4
- 108010013835 arginine glutamate Proteins 0.000 description 4
- 230000003021 clonogenic effect Effects 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- 108010087823 glycyltyrosine Proteins 0.000 description 4
- 108010037850 glycylvaline Proteins 0.000 description 4
- 210000002570 interstitial cell Anatomy 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 230000005305 organ development Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 206010001233 Adenoma benign Diseases 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 208000007659 Fibroadenoma Diseases 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 3
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 3
- 229940079156 Proteasome inhibitor Drugs 0.000 description 3
- NQQMWWVVGIXUOX-SVSWQMSJSA-N Thr-Ser-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O NQQMWWVVGIXUOX-SVSWQMSJSA-N 0.000 description 3
- 201000003149 breast fibroadenoma Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 108010082117 matrigel Proteins 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000003207 proteasome inhibitor Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- KIUYPHAMDKDICO-WHFBIAKZSA-N Ala-Asp-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KIUYPHAMDKDICO-WHFBIAKZSA-N 0.000 description 2
- VGPWRRFOPXVGOH-BYPYZUCNSA-N Ala-Gly-Gly Chemical compound C[C@H](N)C(=O)NCC(=O)NCC(O)=O VGPWRRFOPXVGOH-BYPYZUCNSA-N 0.000 description 2
- QCTFKEJEIMPOLW-JURCDPSOSA-N Ala-Ile-Phe Chemical compound C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 QCTFKEJEIMPOLW-JURCDPSOSA-N 0.000 description 2
- IORKCNUBHNIMKY-CIUDSAMLSA-N Ala-Pro-Glu Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O IORKCNUBHNIMKY-CIUDSAMLSA-N 0.000 description 2
- NONSEUUPKITYQT-BQBZGAKWSA-N Arg-Asn-Gly Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)NCC(=O)O)N)CN=C(N)N NONSEUUPKITYQT-BQBZGAKWSA-N 0.000 description 2
- JUWQNWXEGDYCIE-YUMQZZPRSA-N Arg-Gln-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O JUWQNWXEGDYCIE-YUMQZZPRSA-N 0.000 description 2
- HPKSHFSEXICTLI-CIUDSAMLSA-N Arg-Glu-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O HPKSHFSEXICTLI-CIUDSAMLSA-N 0.000 description 2
- AQPVUEJJARLJHB-BQBZGAKWSA-N Arg-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N AQPVUEJJARLJHB-BQBZGAKWSA-N 0.000 description 2
- ZATRYQNPUHGXCU-DTWKUNHWSA-N Arg-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CCCN=C(N)N)N)C(=O)O ZATRYQNPUHGXCU-DTWKUNHWSA-N 0.000 description 2
- NMRHDSAOIURTNT-RWMBFGLXSA-N Arg-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N NMRHDSAOIURTNT-RWMBFGLXSA-N 0.000 description 2
- VRTWYUYCJGNFES-CIUDSAMLSA-N Arg-Ser-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O VRTWYUYCJGNFES-CIUDSAMLSA-N 0.000 description 2
- JEPNYDRDYNSFIU-QXEWZRGKSA-N Asn-Arg-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(N)=O)C(O)=O JEPNYDRDYNSFIU-QXEWZRGKSA-N 0.000 description 2
- UGXVKHRDGLYFKR-CIUDSAMLSA-N Asn-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(N)=O UGXVKHRDGLYFKR-CIUDSAMLSA-N 0.000 description 2
- DDPXDCKYWDGZAL-BQBZGAKWSA-N Asn-Gly-Arg Chemical compound NC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N DDPXDCKYWDGZAL-BQBZGAKWSA-N 0.000 description 2
- DJIMLSXHXKWADV-CIUDSAMLSA-N Asn-Leu-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(N)=O DJIMLSXHXKWADV-CIUDSAMLSA-N 0.000 description 2
- PBFXCUOEGVJTMV-QXEWZRGKSA-N Asn-Met-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(O)=O PBFXCUOEGVJTMV-QXEWZRGKSA-N 0.000 description 2
- VCJCPARXDBEGNE-GUBZILKMSA-N Asn-Pro-Pro Chemical compound NC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 VCJCPARXDBEGNE-GUBZILKMSA-N 0.000 description 2
- UGXYFDQFLVCDFC-CIUDSAMLSA-N Asn-Ser-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O UGXYFDQFLVCDFC-CIUDSAMLSA-N 0.000 description 2
- MJIJBEYEHBKTIM-BYULHYEWSA-N Asn-Val-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N MJIJBEYEHBKTIM-BYULHYEWSA-N 0.000 description 2
- VTYQAQFKMQTKQD-ACZMJKKPSA-N Asp-Ala-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O VTYQAQFKMQTKQD-ACZMJKKPSA-N 0.000 description 2
- XYBJLTKSGFBLCS-QXEWZRGKSA-N Asp-Arg-Val Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CC(O)=O XYBJLTKSGFBLCS-QXEWZRGKSA-N 0.000 description 2
- GWTLRDMPMJCNMH-WHFBIAKZSA-N Asp-Asn-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O GWTLRDMPMJCNMH-WHFBIAKZSA-N 0.000 description 2
- BKXPJCBEHWFSTF-ACZMJKKPSA-N Asp-Gln-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O BKXPJCBEHWFSTF-ACZMJKKPSA-N 0.000 description 2
- IJHUZMGJRGNXIW-CIUDSAMLSA-N Asp-Glu-Arg Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IJHUZMGJRGNXIW-CIUDSAMLSA-N 0.000 description 2
- PAYPSKIBMDHZPI-CIUDSAMLSA-N Asp-Leu-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O PAYPSKIBMDHZPI-CIUDSAMLSA-N 0.000 description 2
- DWOGMPWRQQWPPF-GUBZILKMSA-N Asp-Leu-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O DWOGMPWRQQWPPF-GUBZILKMSA-N 0.000 description 2
- XXAMCEGRCZQGEM-ZLUOBGJFSA-N Asp-Ser-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O XXAMCEGRCZQGEM-ZLUOBGJFSA-N 0.000 description 2
- CXEFNHOVIIDHFU-IHPCNDPISA-N Asp-Trp-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](CC(=O)O)N CXEFNHOVIIDHFU-IHPCNDPISA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- UKVGHFORADMBEN-GUBZILKMSA-N Cys-Arg-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UKVGHFORADMBEN-GUBZILKMSA-N 0.000 description 2
- BMHBJCVEXUBGFI-BIIVOSGPSA-N Cys-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)[C@H](CS)N)C(=O)O BMHBJCVEXUBGFI-BIIVOSGPSA-N 0.000 description 2
- KEBJBKIASQVRJS-WDSKDSINSA-N Cys-Gln-Gly Chemical compound C(CC(=O)N)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CS)N KEBJBKIASQVRJS-WDSKDSINSA-N 0.000 description 2
- AZDQAZRURQMSQD-XPUUQOCRSA-N Cys-Val-Gly Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O AZDQAZRURQMSQD-XPUUQOCRSA-N 0.000 description 2
- PRBLYKYHAJEABA-SRVKXCTJSA-N Gln-Arg-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O PRBLYKYHAJEABA-SRVKXCTJSA-N 0.000 description 2
- KCJJFESQRXGTGC-BQBZGAKWSA-N Gln-Glu-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O KCJJFESQRXGTGC-BQBZGAKWSA-N 0.000 description 2
- FGYPOQPQTUNESW-IUCAKERBSA-N Gln-Gly-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)N)N FGYPOQPQTUNESW-IUCAKERBSA-N 0.000 description 2
- HWEINOMSWQSJDC-SRVKXCTJSA-N Gln-Leu-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O HWEINOMSWQSJDC-SRVKXCTJSA-N 0.000 description 2
- FNAJNWPDTIXYJN-CIUDSAMLSA-N Gln-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCC(N)=O FNAJNWPDTIXYJN-CIUDSAMLSA-N 0.000 description 2
- LGWNISYVKDNJRP-FXQIFTODSA-N Gln-Ser-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O LGWNISYVKDNJRP-FXQIFTODSA-N 0.000 description 2
- SXFPZRRVWSUYII-KBIXCLLPSA-N Gln-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N SXFPZRRVWSUYII-KBIXCLLPSA-N 0.000 description 2
- LKDIBBOKUAASNP-FXQIFTODSA-N Glu-Ala-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LKDIBBOKUAASNP-FXQIFTODSA-N 0.000 description 2
- HJIFPJUEOGZWRI-GUBZILKMSA-N Glu-Asp-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)N HJIFPJUEOGZWRI-GUBZILKMSA-N 0.000 description 2
- BUZMZDDKFCSKOT-CIUDSAMLSA-N Glu-Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O BUZMZDDKFCSKOT-CIUDSAMLSA-N 0.000 description 2
- LGYZYFFDELZWRS-DCAQKATOSA-N Glu-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O LGYZYFFDELZWRS-DCAQKATOSA-N 0.000 description 2
- QIQABBIDHGQXGA-ZPFDUUQYSA-N Glu-Ile-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O QIQABBIDHGQXGA-ZPFDUUQYSA-N 0.000 description 2
- SUIAHERNFYRBDZ-GVXVVHGQSA-N Glu-Lys-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O SUIAHERNFYRBDZ-GVXVVHGQSA-N 0.000 description 2
- CBOVGULVQSVMPT-CIUDSAMLSA-N Glu-Pro-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O CBOVGULVQSVMPT-CIUDSAMLSA-N 0.000 description 2
- CQAHWYDHKUWYIX-YUMQZZPRSA-N Glu-Pro-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O CQAHWYDHKUWYIX-YUMQZZPRSA-N 0.000 description 2
- NNQDRRUXFJYCCJ-NHCYSSNCSA-N Glu-Pro-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O NNQDRRUXFJYCCJ-NHCYSSNCSA-N 0.000 description 2
- WIKMTDVSCUJIPJ-CIUDSAMLSA-N Glu-Ser-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N WIKMTDVSCUJIPJ-CIUDSAMLSA-N 0.000 description 2
- GPSHCSTUYOQPAI-JHEQGTHGSA-N Glu-Thr-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O GPSHCSTUYOQPAI-JHEQGTHGSA-N 0.000 description 2
- NTHIHAUEXVTXQG-KKUMJFAQSA-N Glu-Tyr-Arg Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O NTHIHAUEXVTXQG-KKUMJFAQSA-N 0.000 description 2
- RXJFSLQVMGYQEL-IHRRRGAJSA-N Glu-Tyr-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(O)=O)CC1=CC=C(O)C=C1 RXJFSLQVMGYQEL-IHRRRGAJSA-N 0.000 description 2
- KIEICAOUSNYOLM-NRPADANISA-N Glu-Val-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O KIEICAOUSNYOLM-NRPADANISA-N 0.000 description 2
- HQTDNEZTGZUWSY-XVKPBYJWSA-N Glu-Val-Gly Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)CCC(O)=O)C(=O)NCC(O)=O HQTDNEZTGZUWSY-XVKPBYJWSA-N 0.000 description 2
- KKBWDNZXYLGJEY-UHFFFAOYSA-N Gly-Arg-Pro Natural products NCC(=O)NC(CCNC(=N)N)C(=O)N1CCCC1C(=O)O KKBWDNZXYLGJEY-UHFFFAOYSA-N 0.000 description 2
- JVWPPCWUDRJGAE-YUMQZZPRSA-N Gly-Asn-Leu Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JVWPPCWUDRJGAE-YUMQZZPRSA-N 0.000 description 2
- GNPVTZJUUBPZKW-WDSKDSINSA-N Gly-Gln-Ser Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O GNPVTZJUUBPZKW-WDSKDSINSA-N 0.000 description 2
- NNCSJUBVFBDDLC-YUMQZZPRSA-N Gly-Leu-Ser Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O NNCSJUBVFBDDLC-YUMQZZPRSA-N 0.000 description 2
- BXICSAQLIHFDDL-YUMQZZPRSA-N Gly-Lys-Asn Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O BXICSAQLIHFDDL-YUMQZZPRSA-N 0.000 description 2
- YHYDTTUSJXGTQK-UWVGGRQHSA-N Gly-Met-Leu Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](CC(C)C)C(O)=O YHYDTTUSJXGTQK-UWVGGRQHSA-N 0.000 description 2
- OOCFXNOVSLSHAB-IUCAKERBSA-N Gly-Pro-Pro Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OOCFXNOVSLSHAB-IUCAKERBSA-N 0.000 description 2
- FFJQHWKSGAWSTJ-BFHQHQDPSA-N Gly-Thr-Ala Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O FFJQHWKSGAWSTJ-BFHQHQDPSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- WJGSTIMGSIWHJX-HVTMNAMFSA-N His-Ile-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N WJGSTIMGSIWHJX-HVTMNAMFSA-N 0.000 description 2
- YYOCMTFVGKDNQP-IHRRRGAJSA-N His-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N YYOCMTFVGKDNQP-IHRRRGAJSA-N 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- DVRDRICMWUSCBN-UKJIMTQDSA-N Ile-Gln-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)O)N DVRDRICMWUSCBN-UKJIMTQDSA-N 0.000 description 2
- XLXPYSDGMXTTNQ-DKIMLUQUSA-N Ile-Phe-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(O)=O XLXPYSDGMXTTNQ-DKIMLUQUSA-N 0.000 description 2
- XLXPYSDGMXTTNQ-UHFFFAOYSA-N Ile-Phe-Leu Natural products CCC(C)C(N)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=CC=C1 XLXPYSDGMXTTNQ-UHFFFAOYSA-N 0.000 description 2
- KCTIFOCXAIUQQK-QXEWZRGKSA-N Ile-Pro-Gly Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O KCTIFOCXAIUQQK-QXEWZRGKSA-N 0.000 description 2
- MLSUZXHSNRBDCI-CYDGBPFRSA-N Ile-Pro-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)O)N MLSUZXHSNRBDCI-CYDGBPFRSA-N 0.000 description 2
- MITYXXNZSZLHGG-OBAATPRFSA-N Ile-Trp-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)N MITYXXNZSZLHGG-OBAATPRFSA-N 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 2
- FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 2
- LZDNBBYBDGBADK-UHFFFAOYSA-N L-valyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C(C)C)C(O)=O)=CNC2=C1 LZDNBBYBDGBADK-UHFFFAOYSA-N 0.000 description 2
- 241000880493 Leptailurus serval Species 0.000 description 2
- HASRFYOMVPJRPU-SRVKXCTJSA-N Leu-Arg-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HASRFYOMVPJRPU-SRVKXCTJSA-N 0.000 description 2
- IGUOAYLTQJLPPD-DCAQKATOSA-N Leu-Asn-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IGUOAYLTQJLPPD-DCAQKATOSA-N 0.000 description 2
- WXHFZJFZWNCDNB-KKUMJFAQSA-N Leu-Asn-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WXHFZJFZWNCDNB-KKUMJFAQSA-N 0.000 description 2
- TWQIYNGNYNJUFM-NHCYSSNCSA-N Leu-Asn-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O TWQIYNGNYNJUFM-NHCYSSNCSA-N 0.000 description 2
- ZFNLIDNJUWNIJL-WDCWCFNPSA-N Leu-Glu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZFNLIDNJUWNIJL-WDCWCFNPSA-N 0.000 description 2
- YWYQSLOTVIRCFE-SRVKXCTJSA-N Leu-His-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(O)=O YWYQSLOTVIRCFE-SRVKXCTJSA-N 0.000 description 2
- LXKNSJLSGPNHSK-KKUMJFAQSA-N Leu-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N LXKNSJLSGPNHSK-KKUMJFAQSA-N 0.000 description 2
- JLWZLIQRYCTYBD-IHRRRGAJSA-N Leu-Lys-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JLWZLIQRYCTYBD-IHRRRGAJSA-N 0.000 description 2
- KLSUAWUZBMAZCL-RHYQMDGZSA-N Leu-Thr-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(O)=O KLSUAWUZBMAZCL-RHYQMDGZSA-N 0.000 description 2
- GZRABTMNWJXFMH-UVOCVTCTSA-N Leu-Thr-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZRABTMNWJXFMH-UVOCVTCTSA-N 0.000 description 2
- XZNJZXJZBMBGGS-NHCYSSNCSA-N Leu-Val-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O XZNJZXJZBMBGGS-NHCYSSNCSA-N 0.000 description 2
- YQFZRHYZLARWDY-IHRRRGAJSA-N Leu-Val-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN YQFZRHYZLARWDY-IHRRRGAJSA-N 0.000 description 2
- QESXLSQLQHHTIX-RHYQMDGZSA-N Leu-Val-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QESXLSQLQHHTIX-RHYQMDGZSA-N 0.000 description 2
- JCFYLFOCALSNLQ-GUBZILKMSA-N Lys-Ala-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O JCFYLFOCALSNLQ-GUBZILKMSA-N 0.000 description 2
- FUKDBQGFSJUXGX-RWMBFGLXSA-N Lys-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)N)C(=O)O FUKDBQGFSJUXGX-RWMBFGLXSA-N 0.000 description 2
- YFGWNAROEYWGNL-GUBZILKMSA-N Lys-Gln-Asn Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O YFGWNAROEYWGNL-GUBZILKMSA-N 0.000 description 2
- DRCILAJNUJKAHC-SRVKXCTJSA-N Lys-Glu-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O DRCILAJNUJKAHC-SRVKXCTJSA-N 0.000 description 2
- GCMWRRQAKQXDED-IUCAKERBSA-N Lys-Glu-Gly Chemical compound [NH3+]CCCC[C@H]([NH3+])C(=O)N[C@@H](CCC([O-])=O)C(=O)NCC([O-])=O GCMWRRQAKQXDED-IUCAKERBSA-N 0.000 description 2
- KZOHPCYVORJBLG-AVGNSLFASA-N Lys-Glu-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)N KZOHPCYVORJBLG-AVGNSLFASA-N 0.000 description 2
- YUAXTFMFMOIMAM-QWRGUYRKSA-N Lys-Lys-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O YUAXTFMFMOIMAM-QWRGUYRKSA-N 0.000 description 2
- XBAJINCXDBTJRH-WDSOQIARSA-N Lys-Val-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CCCCN)N XBAJINCXDBTJRH-WDSOQIARSA-N 0.000 description 2
- WYEXWKAWMNJKPN-UBHSHLNASA-N Met-Ala-Phe Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCSC)N WYEXWKAWMNJKPN-UBHSHLNASA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 2
- 108010047562 NGR peptide Proteins 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- LJUUGSWZPQOJKD-JYJNAYRXSA-N Phe-Arg-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)Cc1ccccc1)C(O)=O LJUUGSWZPQOJKD-JYJNAYRXSA-N 0.000 description 2
- RLUMIJXNHJVUCO-JBACZVJFSA-N Phe-Gln-Trp Chemical compound C([C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CC=CC=C1 RLUMIJXNHJVUCO-JBACZVJFSA-N 0.000 description 2
- KDYPMIZMXDECSU-JYJNAYRXSA-N Phe-Leu-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 KDYPMIZMXDECSU-JYJNAYRXSA-N 0.000 description 2
- KNYPNEYICHHLQL-ACRUOGEOSA-N Phe-Leu-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 KNYPNEYICHHLQL-ACRUOGEOSA-N 0.000 description 2
- CVAUVSOFHJKCHN-BZSNNMDCSA-N Phe-Tyr-Cys Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(O)=O)C1=CC=CC=C1 CVAUVSOFHJKCHN-BZSNNMDCSA-N 0.000 description 2
- VXCHGLYSIOOZIS-GUBZILKMSA-N Pro-Ala-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 VXCHGLYSIOOZIS-GUBZILKMSA-N 0.000 description 2
- ICTZKEXYDDZZFP-SRVKXCTJSA-N Pro-Arg-Pro Chemical compound N([C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(O)=O)C(=O)[C@@H]1CCCN1 ICTZKEXYDDZZFP-SRVKXCTJSA-N 0.000 description 2
- LSIWVWRUTKPXDS-DCAQKATOSA-N Pro-Gln-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O LSIWVWRUTKPXDS-DCAQKATOSA-N 0.000 description 2
- UAYHMOIGIQZLFR-NHCYSSNCSA-N Pro-Gln-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O UAYHMOIGIQZLFR-NHCYSSNCSA-N 0.000 description 2
- PULPZRAHVFBVTO-DCAQKATOSA-N Pro-Glu-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PULPZRAHVFBVTO-DCAQKATOSA-N 0.000 description 2
- XQHGISDMVBTGAL-ULQDDVLXSA-N Pro-His-Phe Chemical compound C([C@@H](C(=O)[O-])NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1[NH2+]CCC1)C1=CC=CC=C1 XQHGISDMVBTGAL-ULQDDVLXSA-N 0.000 description 2
- FXGIMYRVJJEIIM-UWVGGRQHSA-N Pro-Leu-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 FXGIMYRVJJEIIM-UWVGGRQHSA-N 0.000 description 2
- MRYUJHGPZQNOAD-IHRRRGAJSA-N Pro-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@@H]1CCCN1 MRYUJHGPZQNOAD-IHRRRGAJSA-N 0.000 description 2
- KWMZPPWYBVZIER-XGEHTFHBSA-N Pro-Ser-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KWMZPPWYBVZIER-XGEHTFHBSA-N 0.000 description 2
- VDHGTOHMHHQSKG-JYJNAYRXSA-N Pro-Val-Phe Chemical compound CC(C)[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](Cc1ccccc1)C(O)=O VDHGTOHMHHQSKG-JYJNAYRXSA-N 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- HQTKVSCNCDLXSX-BQBZGAKWSA-N Ser-Arg-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O HQTKVSCNCDLXSX-BQBZGAKWSA-N 0.000 description 2
- KJMOINFQVCCSDX-XKBZYTNZSA-N Ser-Gln-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KJMOINFQVCCSDX-XKBZYTNZSA-N 0.000 description 2
- YQQKYAZABFEYAF-FXQIFTODSA-N Ser-Glu-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O YQQKYAZABFEYAF-FXQIFTODSA-N 0.000 description 2
- UFKPDBLKLOBMRH-XHNCKOQMSA-N Ser-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)N)C(=O)O UFKPDBLKLOBMRH-XHNCKOQMSA-N 0.000 description 2
- AEGUWTFAQQWVLC-BQBZGAKWSA-N Ser-Gly-Arg Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O AEGUWTFAQQWVLC-BQBZGAKWSA-N 0.000 description 2
- BPMRXBZYPGYPJN-WHFBIAKZSA-N Ser-Gly-Asn Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O BPMRXBZYPGYPJN-WHFBIAKZSA-N 0.000 description 2
- IXCHOHLPHNGFTJ-YUMQZZPRSA-N Ser-Gly-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N IXCHOHLPHNGFTJ-YUMQZZPRSA-N 0.000 description 2
- GZFAWAQTEYDKII-YUMQZZPRSA-N Ser-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO GZFAWAQTEYDKII-YUMQZZPRSA-N 0.000 description 2
- WSTIOCFMWXNOCX-YUMQZZPRSA-N Ser-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N WSTIOCFMWXNOCX-YUMQZZPRSA-N 0.000 description 2
- ZUDXUJSYCCNZQJ-DCAQKATOSA-N Ser-His-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CO)N ZUDXUJSYCCNZQJ-DCAQKATOSA-N 0.000 description 2
- UIPXCLNLUUAMJU-JBDRJPRFSA-N Ser-Ile-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O UIPXCLNLUUAMJU-JBDRJPRFSA-N 0.000 description 2
- GJFYFGOEWLDQGW-GUBZILKMSA-N Ser-Leu-Gln Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CO)N GJFYFGOEWLDQGW-GUBZILKMSA-N 0.000 description 2
- VMLONWHIORGALA-SRVKXCTJSA-N Ser-Leu-Leu Chemical compound CC(C)C[C@@H](C([O-])=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]([NH3+])CO VMLONWHIORGALA-SRVKXCTJSA-N 0.000 description 2
- QPPYAWVLAVXISR-DCAQKATOSA-N Ser-Pro-His Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CO)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O QPPYAWVLAVXISR-DCAQKATOSA-N 0.000 description 2
- FZXOPYUEQGDGMS-ACZMJKKPSA-N Ser-Ser-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O FZXOPYUEQGDGMS-ACZMJKKPSA-N 0.000 description 2
- BMKNXTJLHFIAAH-CIUDSAMLSA-N Ser-Ser-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O BMKNXTJLHFIAAH-CIUDSAMLSA-N 0.000 description 2
- SNXUIBACCONSOH-BWBBJGPYSA-N Ser-Thr-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CO)C(O)=O SNXUIBACCONSOH-BWBBJGPYSA-N 0.000 description 2
- DWYAUVCQDTZIJI-VZFHVOOUSA-N Thr-Ala-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DWYAUVCQDTZIJI-VZFHVOOUSA-N 0.000 description 2
- CAGTXGDOIFXLPC-KZVJFYERSA-N Thr-Arg-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CCCN=C(N)N CAGTXGDOIFXLPC-KZVJFYERSA-N 0.000 description 2
- RKDFEMGVMMYYNG-WDCWCFNPSA-N Thr-Gln-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O RKDFEMGVMMYYNG-WDCWCFNPSA-N 0.000 description 2
- DKDHTRVDOUZZTP-IFFSRLJSSA-N Thr-Gln-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)[C@@H](C)O)C(O)=O DKDHTRVDOUZZTP-IFFSRLJSSA-N 0.000 description 2
- FHDLKMFZKRUQCE-HJGDQZAQSA-N Thr-Glu-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FHDLKMFZKRUQCE-HJGDQZAQSA-N 0.000 description 2
- FQPDRTDDEZXCEC-SVSWQMSJSA-N Thr-Ile-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O FQPDRTDDEZXCEC-SVSWQMSJSA-N 0.000 description 2
- BVOVIGCHYNFJBZ-JXUBOQSCSA-N Thr-Leu-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O BVOVIGCHYNFJBZ-JXUBOQSCSA-N 0.000 description 2
- FLPZMPOZGYPBEN-PPCPHDFISA-N Thr-Leu-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FLPZMPOZGYPBEN-PPCPHDFISA-N 0.000 description 2
- VRUFCJZQDACGLH-UVOCVTCTSA-N Thr-Leu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VRUFCJZQDACGLH-UVOCVTCTSA-N 0.000 description 2
- QFEYTTHKPSOFLV-OSUNSFLBSA-N Thr-Met-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H]([C@@H](C)O)N QFEYTTHKPSOFLV-OSUNSFLBSA-N 0.000 description 2
- LKJCABTUFGTPPY-HJGDQZAQSA-N Thr-Pro-Gln Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O LKJCABTUFGTPPY-HJGDQZAQSA-N 0.000 description 2
- AAZOYLQUEQRUMZ-GSSVUCPTSA-N Thr-Thr-Asn Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(N)=O AAZOYLQUEQRUMZ-GSSVUCPTSA-N 0.000 description 2
- UQCNIMDPYICBTR-KYNKHSRBSA-N Thr-Thr-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O UQCNIMDPYICBTR-KYNKHSRBSA-N 0.000 description 2
- VPRHDRKAPYZMHL-SZMVWBNQSA-N Trp-Leu-Glu Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CNC2=C1 VPRHDRKAPYZMHL-SZMVWBNQSA-N 0.000 description 2
- SEFNTZYRPGBDCY-IHRRRGAJSA-N Tyr-Arg-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)O)N)O SEFNTZYRPGBDCY-IHRRRGAJSA-N 0.000 description 2
- IWRMTNJCCMEBEX-AVGNSLFASA-N Tyr-Glu-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N)O IWRMTNJCCMEBEX-AVGNSLFASA-N 0.000 description 2
- SOEGLGLDSUHWTI-STECZYCISA-N Tyr-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=C(O)C=C1 SOEGLGLDSUHWTI-STECZYCISA-N 0.000 description 2
- XGZBEGGGAUQBMB-KJEVXHAQSA-N Tyr-Pro-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC2=CC=C(C=C2)O)N)O XGZBEGGGAUQBMB-KJEVXHAQSA-N 0.000 description 2
- PWKMJDQXKCENMF-MEYUZBJRSA-N Tyr-Thr-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O PWKMJDQXKCENMF-MEYUZBJRSA-N 0.000 description 2
- ASQFIHTXXMFENG-XPUUQOCRSA-N Val-Ala-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O ASQFIHTXXMFENG-XPUUQOCRSA-N 0.000 description 2
- AZSHAZJLOZQYAY-FXQIFTODSA-N Val-Ala-Ser Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O AZSHAZJLOZQYAY-FXQIFTODSA-N 0.000 description 2
- DBOXBUDEAJVKRE-LSJOCFKGSA-N Val-Asn-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)O)N DBOXBUDEAJVKRE-LSJOCFKGSA-N 0.000 description 2
- AHHJARQXFFGOKF-NRPADANISA-N Val-Glu-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N AHHJARQXFFGOKF-NRPADANISA-N 0.000 description 2
- OQWNEUXPKHIEJO-NRPADANISA-N Val-Glu-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)O)N OQWNEUXPKHIEJO-NRPADANISA-N 0.000 description 2
- UEHRGZCNLSWGHK-DLOVCJGASA-N Val-Glu-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O UEHRGZCNLSWGHK-DLOVCJGASA-N 0.000 description 2
- CHWRZUGUMAMTFC-IHRRRGAJSA-N Val-His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CNC=N1 CHWRZUGUMAMTFC-IHRRRGAJSA-N 0.000 description 2
- HGJRMXOWUWVUOA-GVXVVHGQSA-N Val-Leu-Gln Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N HGJRMXOWUWVUOA-GVXVVHGQSA-N 0.000 description 2
- WDIWOIRFNMLNKO-ULQDDVLXSA-N Val-Leu-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WDIWOIRFNMLNKO-ULQDDVLXSA-N 0.000 description 2
- IJGPOONOTBNTFS-GVXVVHGQSA-N Val-Lys-Glu Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O IJGPOONOTBNTFS-GVXVVHGQSA-N 0.000 description 2
- SJRUJQFQVLMZFW-WPRPVWTQSA-N Val-Pro-Gly Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O SJRUJQFQVLMZFW-WPRPVWTQSA-N 0.000 description 2
- SSYBNWFXCFNRFN-GUBZILKMSA-N Val-Pro-Ser Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O SSYBNWFXCFNRFN-GUBZILKMSA-N 0.000 description 2
- HTONZBWRYUKUKC-RCWTZXSCSA-N Val-Thr-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O HTONZBWRYUKUKC-RCWTZXSCSA-N 0.000 description 2
- RLVTVHSDKHBFQP-ULQDDVLXSA-N Val-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CC=C(O)C=C1 RLVTVHSDKHBFQP-ULQDDVLXSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 2
- 108010005233 alanylglutamic acid Proteins 0.000 description 2
- 108010008355 arginyl-glutamine Proteins 0.000 description 2
- 108010052670 arginyl-glutamyl-glutamic acid Proteins 0.000 description 2
- 108010091092 arginyl-glycyl-proline Proteins 0.000 description 2
- 108010093581 aspartyl-proline Proteins 0.000 description 2
- 230000004791 biological behavior Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000004737 colorimetric analysis Methods 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000010201 enrichment analysis Methods 0.000 description 2
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 108010078144 glutaminyl-glycine Proteins 0.000 description 2
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 2
- 108010008237 glutamyl-valyl-glycine Proteins 0.000 description 2
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 2
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 2
- 108010050475 glycyl-leucyl-tyrosine Proteins 0.000 description 2
- 108010010147 glycylglutamine Proteins 0.000 description 2
- 108010050848 glycylleucine Proteins 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 108010018006 histidylserine Proteins 0.000 description 2
- 238000011532 immunohistochemical staining Methods 0.000 description 2
- 108010053037 kyotorphin Proteins 0.000 description 2
- 108010034529 leucyl-lysine Proteins 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 108010003700 lysyl aspartic acid Proteins 0.000 description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 210000002220 organoid Anatomy 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 210000004738 parenchymal cell Anatomy 0.000 description 2
- 238000010827 pathological analysis Methods 0.000 description 2
- 108010051242 phenylalanylserine Proteins 0.000 description 2
- 108700042769 prolyl-leucyl-glycine Proteins 0.000 description 2
- 108010077112 prolyl-proline Proteins 0.000 description 2
- 108010004914 prolylarginine Proteins 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 108010005652 splenotritin Proteins 0.000 description 2
- 210000002536 stromal cell Anatomy 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 108010061238 threonyl-glycine Proteins 0.000 description 2
- 108010080629 tryptophan-leucine Proteins 0.000 description 2
- 108010015666 tryptophyl-leucyl-glutamic acid Proteins 0.000 description 2
- 108010051110 tyrosyl-lysine Proteins 0.000 description 2
- IBIDRSSEHFLGSD-UHFFFAOYSA-N valinyl-arginine Natural products CC(C)C(N)C(=O)NC(C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-UHFFFAOYSA-N 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 239000012224 working solution Substances 0.000 description 2
- PJOHVEQSYPOERL-SHEAVXILSA-N (e)-n-[(4r,4as,7ar,12br)-3-(cyclopropylmethyl)-9-hydroxy-7-oxo-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-4a-yl]-3-(4-methylphenyl)prop-2-enamide Chemical compound C1=CC(C)=CC=C1\C=C\C(=O)N[C@]1(CCC(=O)[C@@H]2O3)[C@H]4CC5=CC=C(O)C3=C5[C@]12CCN4CC1CC1 PJOHVEQSYPOERL-SHEAVXILSA-N 0.000 description 1
- APRZHQXAAWPYHS-UHFFFAOYSA-N 4-[5-[3-(carboxymethoxy)phenyl]-3-(4,5-dimethyl-1,3-thiazol-2-yl)tetrazol-3-ium-2-yl]benzenesulfonate Chemical compound S1C(C)=C(C)N=C1[N+]1=NC(C=2C=C(OCC(O)=O)C=CC=2)=NN1C1=CC=C(S([O-])(=O)=O)C=C1 APRZHQXAAWPYHS-UHFFFAOYSA-N 0.000 description 1
- GKWFMNNNYZHJHV-SRVKXCTJSA-N Asp-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC(O)=O GKWFMNNNYZHJHV-SRVKXCTJSA-N 0.000 description 1
- 238000001353 Chip-sequencing Methods 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 208000007842 Fibroepithelial Neoplasms Diseases 0.000 description 1
- KDXKFBSNIJYNNR-YVNDNENWSA-N Gln-Glu-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KDXKFBSNIJYNNR-YVNDNENWSA-N 0.000 description 1
- PXAFHUATEHLECW-GUBZILKMSA-N Gln-Glu-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N PXAFHUATEHLECW-GUBZILKMSA-N 0.000 description 1
- MFJAPSYJQJCQDN-BQBZGAKWSA-N Gln-Gly-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O MFJAPSYJQJCQDN-BQBZGAKWSA-N 0.000 description 1
- SMLDOQHTOAAFJQ-WDSKDSINSA-N Gln-Gly-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CO)C(O)=O SMLDOQHTOAAFJQ-WDSKDSINSA-N 0.000 description 1
- CVPXINNKRTZBMO-CIUDSAMLSA-N Glu-Arg-Asn Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)CN=C(N)N CVPXINNKRTZBMO-CIUDSAMLSA-N 0.000 description 1
- VSRCAOIHMGCIJK-SRVKXCTJSA-N Glu-Leu-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O VSRCAOIHMGCIJK-SRVKXCTJSA-N 0.000 description 1
- SJJHXJDSNQJMMW-SRVKXCTJSA-N Glu-Lys-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O SJJHXJDSNQJMMW-SRVKXCTJSA-N 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- WXJKFRMKJORORD-DCAQKATOSA-N Lys-Arg-Ala Chemical compound NC(=N)NCCC[C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CCCCN WXJKFRMKJORORD-DCAQKATOSA-N 0.000 description 1
- QYOXSYXPHUHOJR-GUBZILKMSA-N Lys-Asn-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QYOXSYXPHUHOJR-GUBZILKMSA-N 0.000 description 1
- MYAPQOBHGWJZOM-UWVGGRQHSA-N Met-Gly-Leu Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(C)C MYAPQOBHGWJZOM-UWVGGRQHSA-N 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- FRKBNXCFJBPJOL-GUBZILKMSA-N Pro-Glu-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O FRKBNXCFJBPJOL-GUBZILKMSA-N 0.000 description 1
- ULIWFCCJIOEHMU-BQBZGAKWSA-N Pro-Gly-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 ULIWFCCJIOEHMU-BQBZGAKWSA-N 0.000 description 1
- GOMUXSCOIWIJFP-GUBZILKMSA-N Pro-Ser-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GOMUXSCOIWIJFP-GUBZILKMSA-N 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 101150023114 RNA1 gene Proteins 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- MUARUIBTKQJKFY-WHFBIAKZSA-N Ser-Gly-Asp Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O MUARUIBTKQJKFY-WHFBIAKZSA-N 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- NCXVJIQMWSGRHY-KXNHARMFSA-N Thr-Leu-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O NCXVJIQMWSGRHY-KXNHARMFSA-N 0.000 description 1
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 1
- 206010064390 Tumour invasion Diseases 0.000 description 1
- 108091005906 Type I transmembrane proteins Proteins 0.000 description 1
- JAKHAONCJJZVHT-DCAQKATOSA-N Val-Lys-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)O)N JAKHAONCJJZVHT-DCAQKATOSA-N 0.000 description 1
- NLNCNKIVJPEFBC-DLOVCJGASA-N Val-Val-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O NLNCNKIVJPEFBC-DLOVCJGASA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 108010069020 alanyl-prolyl-glycine Proteins 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000002001 anti-metastasis Effects 0.000 description 1
- 229940125644 antibody drug Drugs 0.000 description 1
- 108010092854 aspartyllysine Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000009274 differential gene expression Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000005206 flow analysis Methods 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000001046 green dye Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 1
- 108010057821 leucylproline Proteins 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001617 migratory effect Effects 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 229940125645 monoclonal antibody drug Drugs 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000013188 needle biopsy Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 238000013414 tumor xenograft model Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- 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
- A61P15/14—Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57415—Specifically defined cancers of breast
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Food Science & Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Physics & Mathematics (AREA)
- Genetics & Genomics (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
Abstract
本发明公开了一种乳腺叶状肿瘤分子标志物CD146及其应用，涉及肿瘤分子生物学技术领域。本发明提供的乳腺叶状肿瘤分子标志物CD146包括具有与SEQ ID NO.1所示序列同源性为80％以上的CD146基因或具有与SEQ ID NO.2或SEQ ID NO.3所示序列同源性为80％以上的CD146蛋白。通过对叶状肿瘤CD146表达水平的检测，可辅助乳腺叶状肿瘤的鉴别诊断，分级及预后预测分析。针对CD146靶点，通过抑制性抗体或小分子药物等对CD146表达水平或其介导的信号通路进行调控，可有效抑制乳腺叶状肿瘤细胞的生长、迁移及恶性进展，为乳腺叶状肿瘤的诊断与治疗提供一种新途径。
Description
技术领域
本发明涉及肿瘤分子生物学技术领域，具体涉及一种乳腺叶状肿瘤分子标志物CD146及其应用。
背景技术
乳腺叶状肿瘤(Phyllodes tumor,PT)是一种罕见的纤维上皮性肿瘤，其发生率在乳腺肿瘤中不足1％。世界卫生组织(World Health Organization，WHO)根据叶状肿瘤的组织学特性包括***数目，***异型性，间质过度增生以及肿瘤边界特征等将叶状肿瘤划分为良性、交界性及恶性[2]。目前，影像学检查：乳腺超声和钼靶的准确性有限。术前穿刺活检，由于肿瘤不同部位异质性的存在，很难进行准确的组织学分级。所以，目前诊断的金标准仍是术后病理组织学检查。然而，叶状肿瘤从良性到恶性呈现出一种形态学的连续性。目前，病理诊断变量的截断值仍未达到有效共识。因此，叶状肿瘤的病理诊断分类相对缺乏客观性。现有的分子标记物在诊断以及预测肿瘤生物学行为方面的价值也有限。叶状肿瘤易复发，交界性及恶性叶状肿瘤还会发生血行转移。化疗和放疗对叶状肿瘤的治疗效果均不确切，能够降低其复发、转移几率的治疗方法只有扩大的手术切除，但即使是扩大的手术切除，恶性叶状肿瘤的局部复发率仍高达28～67％不等，转移率高达21～30％，发生远处转移的病例中，死亡率高达88％。
CD146(MCAM)，属于免疫球蛋白超家族，为细胞表面I型跨膜蛋白，于1987由Johnson团队首次从黑色素瘤中发现并克隆，因而也称为黑色素瘤粘附分子(Mel-CAM)。其主要表达于新生血管内皮，促进血管新生。同时在部分正常和恶性肿瘤组织中高表达，如黑色素瘤、三阴性乳腺癌、骨肉瘤等。CD146在黑色素瘤中的高表达促进黑色素瘤的生长和转移。在乳腺癌中，CD146参与上皮间质转化(EMT)过程，具有促进肿瘤侵袭转移的作用。在骨肉瘤中，CD146的表达促进肿瘤的发展和转移。此外，还有报道显示CD146也表达于间充质干细胞上，参与间充质干细胞的分化、迁移等。
不同于发病率较高的乳腺癌，目前针对乳腺叶状肿瘤发生发展及机制的研究甚少，尚缺乏特异性的标志物，相关诊断试剂及相应药物的开发则更少。寻找乳腺叶状肿瘤的分子标志物，对这类肿瘤的临床诊断和精准治疗尤为重要。
发明内容
本发明的目的在于克服现有技术的不足，提供一种乳腺叶状肿瘤分子标志物CD146及其应用。
为实现上述目的，本发明采取的技术方案为：一种乳腺叶状肿瘤分子标志物CD146，所述乳腺叶状肿瘤分子标志物CD146包括具有与SEQ ID NO.1所示序列同源性80％以上的CD146基因或具有与SEQ ID NO.2或SEQ ID NO.3所示序列同源性80％以上的CD146蛋白。
本发明还提供一种用于乳腺叶状肿瘤诊断的引物组，所述引物组是基于上述的乳腺叶状肿瘤分子标志物CD146设计的引物。
作为本发明所述的用于乳腺叶状肿瘤诊断的引物组的优选实施方式，所述引物组包括引物CD146-F和引物CD146-R；所述引物CD146-F的核苷酸序列如SEQ ID NO.4所示；所述引物CD146-R的核苷酸序列如SEQ ID NO.5所示。
本发明还提供所述乳腺叶状肿瘤分子标志物CD146作为分子标记物在制备用于诊断乳腺叶状肿瘤的试剂中的应用。
本申请发明人经过大量的实验研究发现，CD146在不同组织学分级的乳腺叶状肿瘤中的表达规律：在乳腺叶状肿瘤癌旁组织及良性乳腺叶状肿瘤组织***上低表达，在交界性叶状肿瘤***上中等表达，而在恶性叶状肿瘤组织中高表达。在恶性乳腺叶状肿瘤组织中，70％以上的间质肿瘤细胞为CD146阳性，而在良性组织中，CD146阳性的***占比不到25％。此外，在纤维腺瘤实质细胞上CD146表达水平更低。因此，通过对CD146表达水平的病理检测，可以辅助乳腺叶状肿瘤的鉴别诊断、分类及预后，CD146作为分子标记物可应用于制备用于诊断乳腺叶状肿瘤的试剂。
作为本发明所述的乳腺叶状肿瘤分子标志物CD146作为分子标记物在制备用于诊断乳腺叶状肿瘤的试剂中的应用的优选实施方式，所述试剂包括免疫组织化学病理检测、分子生物学方法、基因芯片或蛋白芯片检测乳腺叶状肿瘤分子标志物CD146的表达水平以诊断乳腺叶状肿瘤的试剂。
本发明还提供所述乳腺叶状肿瘤分子标志物CD146作为分子标记物在制备用于诊断乳腺叶状肿瘤、乳腺叶状肿瘤疗效监测或乳腺叶状肿瘤预后评估的试剂盒中的应用。
作为本发明所述乳腺叶状肿瘤分子标志物CD146作为分子标记物在制备用于诊断乳腺叶状肿瘤、乳腺叶状肿瘤疗效监测或乳腺叶状肿瘤预后评估的试剂盒中的应用的优选实施方式，所述试剂盒包括上述的引物组和用于组织水平CD146蛋白检测的抗体。
本发明还提供所述乳腺叶状肿瘤分子标志物CD146在制备治疗乳腺叶状肿瘤的药物中的应用。
本申请发明人经大量的研究发现，针对CD146靶点，通过抑制性抗体或小分子药物等对CD146表达水平或其介导的信号通路进行调控，可有效抑制乳腺叶状肿瘤细胞的生长、迁移及恶性进展，为乳腺叶状肿瘤的治疗提供新思路和新方法。
作为本发明所述乳腺叶状肿瘤分子标志物CD146在制备治疗乳腺叶状肿瘤的药物中的应用的优选实施方式，所述药物包括抑制乳腺叶状肿瘤细胞增殖的药物、抑制乳腺叶状肿瘤侵袭和转移的药物、抑制CD146 mRNA表达的药物、抑制CD146蛋白表达的药物、抑制CD146蛋白活性的药物或抑制CD146信号转导的药物。
作为所述乳腺叶状肿瘤分子标志物CD146在制备治疗乳腺叶状肿瘤的药物中的应用的优选实施方式，所述药物包括核酸药物、抗体药物、小分子化学药物或细胞治疗药物；所述抗体药物包括单克隆抗体药物或抗体偶联药物。
本发明的有益效果：本发明提供了CD146作为乳腺叶状肿瘤的分子标志物，其表达与叶状肿瘤的生长、转移等恶性进展密切相关，通过对叶状肿瘤CD146表达水平的检测，可辅助乳腺叶状肿瘤的鉴别诊断，分级及预后预测分析。针对CD146靶点，通过抑制性抗体或小分子药物等对CD146表达水平或其介导的信号通路进行调控，可有效抑制乳腺叶状肿瘤细胞的生长、迁移及恶性进展，为乳腺叶状肿瘤的靶向治疗提供新思路和新方法。
附图说明
图1：A：CD146在乳腺叶状肿瘤细胞及组织中的表达水平结果；B：良性、交界性及恶性乳腺叶状肿瘤标本中CD146 mRNA表达水平结果；C：良性及恶性乳腺叶状肿瘤标本中CD146蛋白表达水平情况；D：良性及恶性乳腺叶状肿瘤细胞系表面CD146表达水平流式分析图。
图2：A：敲低CD146基因的恶性乳腺叶状肿瘤细胞中CD146 mRNA表达水平结果；B：敲低CD146基因的恶性乳腺叶状肿瘤细胞增殖情况；C：敲低CD146基因的恶性乳腺叶状肿瘤细胞克隆形成情况；D：敲低CD146基因的恶性乳腺叶状肿瘤细胞迁移及侵袭情况；E：敲低CD146基因的恶性乳腺叶状肿瘤细胞胶原收缩情况。
图3：A：过表达CD146的良性乳腺叶状肿瘤细胞内CD146 mRNA表达水平结果；B：过表达CD146良性乳腺叶状肿瘤细胞增殖情况；C：过表达CD146良性乳腺叶状肿瘤细胞克隆形成情况；D：过表达CD146良性乳腺叶状肿瘤细胞迁移及侵袭情况；E：过表达CD146良性乳腺叶状肿瘤细胞胶原收缩情况。
图4：A：CD146特异性抗体对恶性乳腺叶状肿瘤细胞增殖的影响；B：CD146特异性抗体对恶性乳腺叶状肿瘤细胞迁移及侵袭的影响；C：CD146特异性抗体对乳腺叶状肿瘤细胞类器官形成的影响。
图5：A：CD146特异性抗体对乳腺叶状肿瘤PDX模型肿瘤生长的影响；B：CD146特异性抗体对乳腺叶状肿瘤PDX模型肿瘤体积的影响。
图6：A：乳腺叶状肿瘤细胞内CD146相关信号通路富集分析结果；B：细胞系过表达或敲低CD146对PI3K/AKT信号通路水平的影响；C：CD146抗体注射组PDX模型肿瘤组织磷酸化AKT水平结果；D：CD146敲低及过表达对恶性乳腺叶状肿瘤细胞系DCBLD2水平及AKT信号的影响；E：蛋白酶体抑制剂MG132处理对CD146敲低细胞DCBLD2水平的影响。
具体实施方式
以下通过实施例形式的具体实施方式，对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
实施例1乳腺叶状肿瘤组织及细胞水平CD146表达谱分析
1、本实施例采用CD146的特异性抗体，进行免疫组织化学染色，评估纤维腺瘤、乳腺叶状肿瘤组织中CD146蛋白水平。
(1)实验方法：实验所采用病理切片均来自于73例临床确诊乳腺叶状肿瘤病例。按以下步骤进行石蜡包埋组织免疫组化染色：60℃烘烤处理，预热二甲苯脱蜡两次，每次5min；脱蜡后的切片经100％-95％-80％-70％-50％乙醇梯度及蒸馏水水化，每个梯度放置5min；0.01M(pH6.0)柠檬酸缓冲液高压热修复10min，自然冷却后PBS洗三次，每次5min；0.3％过氧化氢溶液处理30min，消除内源性过氧化物酶活性；PBS洗三次，每次5min；10％羊血清37℃封闭1h；滴加羊血清稀释一抗工作液(AA4)，4℃孵育过夜，PBS清洗；加入生物素标记二抗工作液，37℃孵育20min，PBS清洗三次；加入辣根过氧化物酶标记链霉亲和素，37℃孵育20min，PBS清洗三次；滴加DAB显色液，室温避光显色2min，PBS洗去多余显色液；苏木素复染，蒸馏水清洗；50％-70％-80％-90％-100％-100％乙醇梯度逐级脱水，每个梯度5min；中性树脂封片，于显微成像***拍片。
(2)实验结果如图1A所示。由图1A可知，CD146在乳腺叶状肿瘤癌旁组织及良性乳腺叶状肿瘤组织***上低表达，在交界性叶状肿瘤***上中等表达，而在恶性叶状肿瘤组织中高表达。在恶性乳腺叶状肿瘤组织中，70％以上的间质肿瘤细胞为CD146阳性，而在良性组织中，CD146阳性的***占比不到25％。此外，在纤维腺瘤实质细胞上CD146表达水平更低。由此可知叶状肿瘤组织***上CD146蛋白或mRNA表达水平与叶状肿瘤的恶性程度呈正相关。
2、采用荧光定量PCR检测不同类型乳腺叶状肿瘤组织标本中CD146 mRNA表达水平
(1)实验方法：a.分别选取3例良性叶状肿瘤组织标本、1例交界性叶状肿瘤标本及8例恶性叶状肿瘤组织。b.提取肿瘤组织总mRNA：将肿瘤组织研碎，加入Trizol裂解液，反复吹打或振荡以裂解细胞，室温放置5min，按每1ml Trizol裂解液加入0.2ml氯仿，用力振荡15s，室温静置2～3min后，于4℃，12000×g离心15min，取上层水相至新EP管中，加入等体积异丙醇沉淀RNA；于4℃，12000×g离心10min；加入75％乙醇清洗，于4℃，7500×g离心15min，弃上清；室温下超静台内晾干RNA沉淀，溶解于适量RNase-free水中，测定RNA浓度及纯度。c.反转录合成cDNA：反转录合成cDNA：在PCR管中加入模板RNA 1μg，4μl反转录酶SuperScript II mix(含Buffer、dNTP、HiScript II逆转录酶、RNA酶、Random primers/Oligo dT)，补充RNase-free水至20μl，65℃反应5min，于冰上放置5min后加入8μl 5×Buffer及2μl 0.1MDTT，混匀后补加ddH2O至40μl，50℃反应15min，85℃反应15s，4℃保存。d.实时定量PCR扩增：将模板cDNA稀释3倍并混匀备用。每个实验组设置3个平行管。反应体系为cDNA 1μl，SYBR green染料5μl，正向引物0.3μl，反向引物0.3μl，ddH2O 3.4μl，离心混匀。95℃反应5min，95℃反应30s，55℃～60℃反应30s，共40个循环。e.以GAPDH作为内参分析检测基因的相对转录水平。引物序列如下：GAPDH-Forward:5’-ATCACCATCTTCCAGGAGCGA-3’；GAPDH-Reverse:5’-CCTTCTCCATGGTGG TGAAGAC-3’。定量分析mRNA相对表达水平。统计数据根据三次重复实验结果计算平均值，显著性差异由T-检验来判断，以P<0.05定义为有统计学差异。
(2)实验结果如图1B所示。由图1B可知，良性叶状肿瘤组织中CD146mRNA表达水平低，交界性肿瘤组织表达水平较良性高，而恶性叶状肿瘤组织中CD146 mRNA表达水平至少为交界性肿瘤组织的2倍。
3、蛋白免疫印迹(Western blot)实验检测不同类型叶状肿瘤组织中CD146蛋白表达水平。
(1)实验方法：经SDS-PAGE电泳、转膜、封闭之后，采用CD146特异性抗体(AA98)作为一抗孵育，进一步采用辣根过氧化物酶标二抗孵育之后进行凝胶成像分析。
(2)实验结果如图1C所示。由图1C可知，6例恶性叶状肿瘤组织中CD146蛋白表达量较高，而在3例良性叶状肿瘤组织中CD146蛋白不表达或低表达。
4、流式细胞术检测叶状肿瘤组织分离得到原代细胞株表面标志物。
(1)实验方法：收集良性及恶性乳腺叶状肿瘤细胞，孵育PE标记抗CD146抗体及同型对照，采用流式细胞仪检测。
(2)实验结果如图1D所示。由图1D的表达量直方图可知，恶性叶状肿瘤细胞系表面CD146表达显著高于良性肿瘤细胞系。
实施例2
本实施例对临床病乳腺叶状肿瘤CD146表达水平与临床病理指标情况相关性进行分析。
(1)实验方法：以实施例1中的确诊为乳腺叶状肿瘤的203名患者为实验对象，统计203名患者的性别、肿瘤级别、肿瘤大小、局部复发情况、转移情况、核***像和***增生情况。
(2)分析结果如表1所示。
表1
结果显示，CD146高表达(SI≥4)与叶状肿瘤恶性分级有显著相关性(P<0.001)；此外，CD146高表达(SI≥4)的病人局部复发率显著高于CD146低表达组(SI<4)(P<0.01)；出现转移的情况中CD146高表达病人多于CD146低表达病人(P＝0.0811)。可见，CD146高表达与乳腺叶状肿瘤病理分级及预后情况密切相关。
实施例3敲低CD146基因对恶性乳腺叶状肿瘤细胞增殖、克隆形成、迁移、侵袭及胶原收缩能力的影响
1、敲低CD146基因对恶性乳腺叶状肿瘤细胞增殖、克隆形成的影响
(1)实验方法：采用Lipo3000瞬时转染siRNA(siRNA1:sense:CCA GCU CCGCGUCUACAA AdTdT,antisense:UUU GUA GAC GCG GAG CUG GdTdT；siRNA2:sense:GGGAGAGAAAUACAUCGAUTT,antisense:AUCGAUGUAUUUCUCUCCCTG；siRNA3:sense:GGAACUACUGGUGAACUAUTT；antisense:AUAGUUCACCAGUAGUUCCTG)至恶性乳腺叶状肿瘤细胞系中，敲低CD146表达(如图2A所示)；接种敲低CD146表达及未进行基因敲低的对照组细胞，采用MTS比色法，测试不同时间点(1～4天)细胞存活率，绘制细胞增殖曲线。接种敲低CD146表达及未进行基因敲低的对照组细胞至60mm中皿的完全培养基中，每皿200个细胞，培养14天后，计数克隆形成数量。
(2)实验结果如图2B和图2C所示。
2、敲低CD146基因对恶性乳腺叶状肿瘤细胞迁移和侵袭能力的影响
(1)实验方法：将敲低CD146基因表达及未进行基因敲低的对照组细胞以2*104/孔的密度接种于Transwell板(Costar)上层小室无血清培养基中或预铺Matrigel薄层上层培养室中，下层为含10％胎牛血清的完全培养基，每组设置三个重复孔；37℃培养箱分别培养8小时或24小时后，小心擦去膜上层细胞，利用结晶紫对下室细胞进行染色，显微镜下计数发生迁移或侵袭的细胞数目。
(2)实验结果如图2D所示。
3、敲低CD146基因对恶性乳腺叶状肿瘤细胞胶原收缩能力的影响
(1)实验方法：用含乙酸和NaOH的DMEM培养基稀释Ⅰ型鼠尾胶原，叶状肿瘤细胞悬液与稀释后的鼠尾胶原1:1混合后，接种到24孔板中，加入含血清的培养基4小时后，换上无血清DMEM培养基孵育过夜，使胶与孔壁分离，8小时后观察、测量收缩后的直径。
(2)实验结果如图2E所示。
由图2可知，敲低CD146基因使恶性乳腺叶状肿瘤细胞的增殖能力降低；敲低CD146基因使恶性乳腺叶状肿瘤细胞克隆形成能力显著降低；敲低CD146基因的恶性乳腺叶状肿瘤细胞的迁移及侵袭能力显著下降；敲低CD146基因使恶性乳腺叶状肿瘤细胞胶原收缩能力显著降低。CD146高表达于恶性乳腺叶状肿瘤细胞上，发挥促进细胞生长、迁移、侵袭及胶原收缩的功能，提示CD146可作为恶性乳腺叶状肿瘤的分子标志物，促进乳腺叶状肿瘤恶性进展。
实施例4过表达CD146对良性叶状肿瘤细胞增殖、克隆形成、迁移、侵袭及胶原收缩能力的影响
1、过表达CD146对良性乳腺叶状肿瘤细胞增殖的影响
(1)实验方法：接种原代良性叶状肿瘤细胞至6孔板中，采用传染试剂Viafect转染CD146过表达质粒(1.5μg/孔)，转染4～6小时后更换正常完全培养基，收集细胞提取RNA样品，检测CD146过表达水平(如图3A所示)。接种过表达CD146及未进行处理的对照组细胞，采用MTS比色法，测试不同时间点(1～4天)细胞存活率，绘制细胞增殖曲线。接种过表达CD146及未进行处理的对照组细胞至60mm中皿的完全培养基中，每皿200个细胞，培养14天后，计数克隆形成数量。
(2)实验结果如图3B和图3C所示。
2、过表达CD146对恶性乳腺叶状肿瘤细胞迁移和侵袭能力的影响
(1)实验方法：将过表达CD146及未进行处理的对照组细胞以2*104/孔的密度接种于Transwell板(Costar)上层小室无血清培养基中或预铺Matrigel薄层上层培养室中，下层为含10％胎牛血清的完全培养基，每组设置三个重复孔；37℃培养箱分别培养8小时或24小时后，小心擦去膜上层细胞，利用结晶紫对下室细胞进行染色，显微镜下计数发生迁移或侵袭的细胞数目。
(2)实验结果如图3D所示。
3、过表达CD146对恶性乳腺叶状肿瘤细胞胶原收缩能力的影响
(1)实验方法：用含乙酸和NaOH的DMEM培养基稀释Ⅰ型鼠尾胶原，叶状肿瘤细胞悬液与稀释后的鼠尾胶原1:1混合后，接种到24孔板中，加入含血清的培养基4小时后，换上无血清DMEM培养基孵育过夜，使胶与孔壁分离，8小时后观察、测量收缩后的直径。
(2)实验结果如图3E所示。
由图3可知，在过表达CD146的乳腺叶状肿瘤细胞株中，观察到细胞的增殖，克隆形成、迁移、侵袭及胶原收缩能力显著增强，表现出与恶性叶状肿瘤细胞类似的生物学行为。
实施例5CD146特异性抗体抑制恶性叶状肿瘤细胞增殖、迁移、侵袭及类器官形成
1、CD146特异性抗体抑制恶性叶状肿瘤细胞增殖实验
(1)实验方法：接种恶性乳腺叶状肿瘤细胞至96孔板，同时加入CD146抗体mAA98(150μg/ml)或同型对照mIgG及PBS，培养至24、48、72、96小时，采用MTS试剂检测细胞活力，绘制细胞增殖曲线。
(2)实验结果如图4A所示。由图4A可知，相对于PBS及IgG对照组，CD146抗体显著抑制恶性乳腺肿瘤细胞的生长，提示CD146可作为乳腺叶状肿瘤潜在的药物新靶点。
2、CD146特异性抗体抑制恶性叶状肿瘤细胞迁移和侵袭
(1)实验方法：将恶性叶状肿瘤细胞以2*104/孔的密度接种于Transwell板(Costar)上层小室无血清培养基中或预铺Matrigel薄层上层培养室中，下层为含10％胎牛血清的完全培养基，接种细胞的同时加入CD146抗体mAA98孵育，以加入mIgG或PBS的恶性叶状肿瘤细胞作为对照，37℃培养箱培养8小时或24小时后，统计分析细胞迁移及侵袭数量。
(2)实验结果如图4B所示。由图4B可知，CD146抗体能够显著抑制乳腺叶状肿瘤细胞的迁移及侵袭，提示可利用靶向CD146的治疗性抗体进行乳腺叶状肿瘤抗转移新药的研制。
3、CD146特异性抗体抑制恶性叶状肿瘤细胞类器官形成
(1)实验方法：从临床标本中分离原代乳腺叶状肿瘤细胞，进行类器官培养，在微孔板中同时加入CD146抗体mAA98(150μg/ml)进行孵育培养，以加入mIgG或PBS作为对照，分别在0、7、14、21、28及38天于显微镜下观察孔板中类器官形成情况。
(2)实验结果如图4C所示。由图4C可知，CD146抗体AA98对原代叶状肿瘤细胞类器官形成具有显著的抑制作用。
实施例6CD146特异性抗体抑制人恶性叶状肿瘤异种移植模型(PDX)肿瘤生长
(1)实验方法：构建乳腺叶状肿瘤PDX模型：取恶性乳腺叶状肿瘤组织，将其剪成直径约1mm组织块，在距离小鼠左前肢腋窝部皮下***脂肪垫约2cm处做3mm切口，套管针通过皮下隧道将3-4个小组织块送至皮下脂肪垫。待肿瘤生长至100m3左右时，对荷瘤小鼠进行随机分组，每组6只，分别腹腔注射CD146抗体(mAA98、chAA98)及对照试剂(PBS、mIgG、hIgG)，注射剂量为250μg/只，每周注射两次，连续注射5次。每周持续监测肿瘤大小，根据公式V＝1/2(L×W2)计算移植瘤平均体积。待肿瘤体积达到直径1.5cm时停止注射，并绘制肿瘤生长变化曲线。
(2)实验结果如图5A和图5B所示。由图5A和图5B可知，与对照组(PBS、mIgG或hIgG组)相比，CD146抗体注射组肿瘤生长明显被抑制。
实施例7CD146通过激活下游PI3K-Akt信号通路促进乳腺叶状肿瘤恶性进展
(1)实验方法：a.采用良性乳腺叶状肿瘤细胞株及相应CD146过表达细胞，恶性乳腺叶状肿瘤细胞株及CD146敲低表达细胞，进行mRNA表达谱芯片测序及差异基因表达、信号通路富集分析；b.采用western blot验证PI3K-Akt信号通路下游相关信号蛋白的表达变化；c.对实施例5的小鼠PDX肿瘤组织进行western blot检测；d.恶性乳腺叶状肿瘤细胞系CD146敲低及过表达后DCBLD2及AKT信号变化；e.蛋白酶体抑制剂MG132处理(4h)对CD146敲低细胞中DCBLD2水平的影响。
(2)实验结果如图6所示。由图6A可知，PI3K-Akt信号通路及细胞因子相互作用通路均涉及较多的基因表达水平改变；由图6B可知，相对于良性乳腺叶状肿瘤细胞，在CD146过表达或恶性乳腺叶状肿瘤细胞中，磷酸化Akt(p-Akt)表达显著上调，p-Akt上调表明Akt信号通路激活，Akt信号通路的活化与肿瘤的发生、发展与转移密切相关；由图6C可知，对照组相比(PBS、mIgG或hIgG组)，CD146抗体(mAA98、chAA98)注射组肿瘤组织磷酸化Akt(p-Akt)表达显著下调；由图6D可知，由图6D可知，敲低CD146抗体显著下调DCBLD2表达及p-Akt水平，恢复CD146表达可上调DCBLD2表达及p-Akt水平；由图6E可知，使用蛋白酶体抑制剂MG132处理CD146敲低细胞系可抑制DCBLD2水平的下调，表明CD146可抑制DCBLD2的蛋白降解，从而激活下游AKT信号通路。
最后应当说明的是，以上实施例仅用以说明本发明的技术方案而非对本发明保护范围的限制，尽管参照较佳实施例对本发明作了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的实质和范围。
SEQUENCE LISTING
<110> 中山大学孙逸仙纪念医院、中国科学院生物物理研究所
<120> 一种乳腺叶状肿瘤分子标志物CD146及其应用
<130> 2021.09.30
<160> 5
<170> PatentIn version 3.3
<210> 1
<211> 1941
<212> DNA
<213> 人工序列
<400> 1
atggggcttc ccaggctggt ctgcgccttc ttgctcgccg cctgctgctg ctgtcctcgc 60
gtcgcgggtg tgcccggaga ggctgagcag cctgcgcctg agctggtgga ggtggaagtg 120
ggcagcacag cccttctgaa gtgcggcctc tcccagtccc aaggcaacct cagccatgtc 180
gactggtttt ctgtccacaa ggagaagcgg acgctcatct tccgtgtgcg ccagggccag 240
ggccagagcg aacctgggga gtacgagcag cggctcagcc tccaggacag aggggctact 300
ctggccctga ctcaagtcac cccccaagac gagcgcatct tcttgtgcca gggcaagcgc 360
cctcggtccc aggagtaccg catccagctc cgcgtctaca aagctccgga ggagccaaac 420
atccaggtca accccctggg catccctgtg aacagtaagg agcctgagga ggtcgctacc 480
tgtgtaggga ggaacgggta ccccattcct caagtcatct ggtacaagaa tggccggcct 540
ctgaaggagg agaagaaccg ggtccacatt cagtcgtccc agactgtgga gtcgagtggt 600
ttgtacacct tgcagagtat tctgaaggca cagctggtta aagaagacaa agatgcccag 660
ttttactgtg agctcaacta ccggctgccc agtgggaacc acatgaagga gtccagggaa 720
gtcaccgtcc ctgttttcta cccgacagaa aaagtgtggc tggaagtgga gcccgtggga 780
atgctgaagg aaggggaccg cgtggaaatc aggtgtttgg ctgatggcaa ccctccacca 840
cacttcagca tcagcaagca gaaccccagc accagggagg cagaggaaga gacaaccaac 900
gacaacgggg tcctggtgct ggagcctgcc cggaaggaac acagtgggcg ctatgaatgt 960
cagggcctgg acttggacac catgatatcg ctgctgagtg aaccacagga actactggtg 1020
aactatgtgt ctgacgtccg agtgagtccc gcagcccctg agagacagga aggcagcagc 1080
ctcaccctga cctgtgaggc agagagtagc caggacctcg agttccagtg gctgagagaa 1140
gagacaggcc aggtgctgga aagggggcct gtgcttcagt tgcatgacct gaaacgggag 1200
gcaggaggcg gctatcgctg cgtggcgtct gtgcccagca tacccggcct gaaccgcaca 1260
cagctggtca acgtggccat ttttggcccc ccttggatgg cattcaagga gaggaaggtg 1320
tgggtgaaag agaatatggt gttgaatctg tcttgtgaag cgtcagggca cccccggccc 1380
accatctcct ggaacgtcaa cggcacggca agtgaacaag accaagatcc acagcgagtc 1440
ctgagcaccc tgaatgtcct cgtgaccccg gagctgttgg agacaggtgt tgaatgcacg 1500
gcctccaacg acctgggcaa aaacaccagc atcctcttcc tggagctggt caatttaacc 1560
accctcacac cagactccaa cacaaccact ggcctcagca cttccactgc cagtcctcat 1620
accagagcca acagcacctc cacagagaga aagctgccgg agccggagag ccggggcgtg 1680
gtcatcgtgg ctgtgattgt gtgcatcctg gtcctggcgg tgctgggcgc tgtcctctat 1740
ttcctctata agaagggcaa gctgccgtgc aggcgctcag ggaagcagga gatcacgcta 1800
cccccgtctc gtaagagcga acttgtagtt gaagttaagt cagataagct cccagaagag 1860
atgggcctcc tgcagggcag cagcggtgac aagagggctc cgggagacca gggagagaaa 1920
tacatcgatc tgaggcatta g 1941
<210> 2
<211> 646
<212> PRT
<213> 人工序列
<400> 2
Met Gly Leu Pro Arg Leu Val Cys Ala Phe Leu Leu Ala Ala Cys Cys
1 5 10 15
Cys Cys Pro Arg Val Ala Gly Val Pro Gly Glu Ala Glu Gln Pro Ala
20 25 30
Pro Glu Leu Val Glu Val Glu Val Gly Ser Thr Ala Leu Leu Lys Cys
35 40 45
Gly Leu Ser Gln Ser Gln Gly Asn Leu Ser His Val Asp Trp Phe Ser
50 55 60
Val His Lys Glu Leu Arg Thr Leu Ile Phe Arg Val Arg Gln Gly Gln
65 70 75 80
Gly Gln Ser Glu Pro Gly Glu Tyr Glu Gln Arg Leu Ser Leu Gln Asp
85 90 95
Arg Gly Ala Thr Leu Ala Leu Thr Gln Val Thr Pro Gln Asp Glu Arg
100 105 110
Ile Phe Leu Cys Gln Gly Lys Arg Pro Arg Ser Gln Glu Tyr Arg Ile
115 120 125
Gln Leu Arg Val Tyr Lys Ala Pro Glu Glu Pro Asn Ile Gln Val Asn
130 135 140
Pro Leu Gly Ile Pro Val Asn Ser Lys Glu Pro Glu Glu Val Ala Thr
145 150 155 160
Cys Val Gly Arg Asn Gly Tyr Pro Ile Pro Gln Val Ile Trp Tyr Lys
165 170 175
Asn Gly Arg Pro Leu Lys Glu Glu Lys Asn Arg Val His Ile Gln Ser
180 185 190
Ser Gln Thr Val Glu Ser Ser Gly Leu Tyr Thr Leu Gln Ser Ile Leu
195 200 205
Lys Ala Gln Leu Val Lys Glu Asp Lys Asp Ala Gln Phe Tyr Cys Glu
210 215 220
Leu Asn Tyr Arg Leu Pro Ser Gly Asn His Met Lys Glu Ser Arg Glu
225 230 235 240
Val Thr Val Pro Val Phe Tyr Pro Thr Glu Lys Val Trp Leu Glu Val
245 250 255
Glu Pro Val Gly Met Leu Lys Glu Gly Asp Arg Val Glu Ile Arg Cys
260 265 270
Leu Ala Asp Gly Asn Pro Pro Pro His Phe Ser Ile Ser Lys Gln Asn
275 280 285
Pro Ser Thr Arg Glu Ala Glu Glu Glu Thr Thr Asn Asp Asn Gly Val
290 295 300
Leu Val Leu Glu Pro Ala Arg Lys Glu His Ser Gly Arg Tyr Glu Cys
305 310 315 320
Gln Gly Leu Asp Leu Asp Thr Met Ile Ser Leu Leu Ser Glu Pro Gln
325 330 335
Glu Leu Leu Val Asn Tyr Val Ser Asp Val Arg Val Ser Pro Ala Ala
340 345 350
Pro Glu Arg Gln Glu Gly Ser Ser Leu Thr Leu Thr Cys Glu Ala Glu
355 360 365
Ser Ser Gln Asp Leu Glu Phe Gln Trp Leu Arg Glu Glu Thr Gly Gln
370 375 380
Val Leu Glu Arg Gly Pro Val Leu Gln Leu His Asp Leu Lys Arg Glu
385 390 395 400
Ala Gly Gly Gly Tyr Arg Cys Val Ala Ser Val Pro Ser Ile Pro Gly
405 410 415
Leu Asn Arg Thr Gln Leu Val Asn Val Ala Ile Phe Gly Pro Pro Trp
420 425 430
Met Ala Phe Lys Glu Arg Lys Val Trp Val Lys Glu Asn Met Val Leu
435 440 445
Asn Leu Ser Cys Glu Ala Ser Gly His Pro Arg Pro Thr Ile Ser Trp
450 455 460
Asn Val Asn Gly Thr Ala Ser Glu Gln Asp Gln Asp Pro Gln Arg Val
465 470 475 480
Leu Ser Thr Leu Asn Val Leu Val Thr Pro Glu Leu Leu Glu Thr Gly
485 490 495
Val Glu Cys Thr Ala Ser Asn Asp Leu Gly Lys Asn Thr Ser Ile Leu
500 505 510
Phe Leu Glu Leu Val Asn Leu Thr Thr Leu Thr Pro Asp Ser Asn Thr
515 520 525
Thr Thr Gly Leu Ser Thr Ser Thr Ala Ser Pro His Thr Arg Ala Asn
530 535 540
Ser Thr Ser Thr Glu Arg Lys Leu Pro Glu Pro Glu Ser Arg Gly Val
545 550 555 560
Val Ile Val Ala Val Ile Val Cys Ile Leu Val Leu Ala Val Leu Gly
565 570 575
Ala Val Leu Tyr Phe Leu Tyr Lys Lys Gly Lys Leu Pro Cys Arg Arg
580 585 590
Ser Gly Lys Gln Glu Ile Thr Leu Pro Pro Ser Arg Lys Asn Glu Leu
595 600 605
Val Val Glu Val Lys Ser Asp Lys Leu Pro Glu Glu Met Gly Leu Leu
610 615 620
Gln Gly Ser Ser Gly Asp Lys Arg Ala Pro Gly Asp Gln Gly Glu Lys
625 630 635 640
Tyr Ile Asp Leu Arg His
645
<210> 3
<211> 604
<212> PRT
<213> 人工序列
<400> 3
Met Gly Leu Pro Arg Leu Val Cys Ala Phe Leu Leu Ala Ala Cys Cys
1 5 10 15
Cys Cys Pro Arg Val Ala Gly Val Pro Gly Glu Ala Glu Gln Pro Ala
20 25 30
Pro Glu Leu Val Glu Val Glu Val Gly Ser Thr Ala Leu Leu Lys Cys
35 40 45
Gly Leu Ser Gln Ser Gln Gly Asn Leu Ser His Val Asp Trp Phe Ser
50 55 60
Val His Lys Glu Lys Arg Thr Leu Ile Phe Arg Val Arg Gln Gly Gln
65 70 75 80
Gly Gln Ser Glu Pro Gly Glu Tyr Glu Gln Arg Leu Ser Leu Gln Asp
85 90 95
Arg Gly Ala Thr Leu Ala Leu Thr Gln Val Thr Pro Gln Asp Glu Arg
100 105 110
Ile Phe Leu Cys Gln Gly Lys Arg Pro Arg Ser Gln Glu Tyr Arg Ile
115 120 125
Gln Leu Arg Val Tyr Lys Ala Pro Glu Glu Pro Asn Ile Gln Val Asn
130 135 140
Pro Leu Gly Ile Pro Val Asn Ser Lys Glu Pro Glu Glu Val Ala Thr
145 150 155 160
Cys Val Gly Arg Asn Gly Tyr Pro Ile Pro Gln Val Ile Trp Tyr Lys
165 170 175
Asn Gly Arg Pro Leu Lys Glu Glu Lys Asn Arg Val His Ile Gln Ser
180 185 190
Ser Gln Thr Val Glu Ser Ser Gly Leu Tyr Thr Leu Gln Ser Ile Leu
195 200 205
Lys Ala Gln Leu Val Lys Glu Asp Lys Asp Ala Gln Phe Tyr Cys Glu
210 215 220
Leu Asn Tyr Arg Leu Pro Ser Gly Asn His Met Lys Glu Ser Arg Glu
225 230 235 240
Val Thr Val Pro Val Phe Tyr Pro Thr Glu Lys Val Trp Leu Glu Val
245 250 255
Glu Pro Val Gly Met Leu Lys Glu Gly Asp Arg Val Glu Ile Arg Cys
260 265 270
Leu Ala Asp Gly Asn Pro Pro Pro His Phe Ser Ile Ser Lys Gln Asn
275 280 285
Pro Ser Thr Arg Glu Ala Glu Glu Glu Thr Thr Asn Asp Asn Gly Val
290 295 300
Leu Val Leu Glu Pro Ala Arg Lys Glu His Ser Gly Arg Tyr Glu Cys
305 310 315 320
Gln Gly Leu Asp Leu Asp Thr Met Ile Ser Leu Leu Ser Glu Pro Gln
325 330 335
Glu Leu Leu Val Asn Tyr Val Ser Asp Val Arg Val Ser Pro Ala Ala
340 345 350
Pro Glu Arg Gln Glu Gly Ser Ser Leu Thr Leu Thr Cys Glu Ala Glu
355 360 365
Ser Ser Gln Asp Leu Glu Phe Gln Trp Leu Arg Glu Glu Thr Gly Gln
370 375 380
Val Leu Glu Arg Gly Pro Val Leu Gln Leu His Asp Leu Lys Arg Glu
385 390 395 400
Ala Gly Gly Gly Tyr Arg Cys Val Ala Ser Val Pro Ser Ile Pro Gly
405 410 415
Leu Asn Arg Thr Gln Leu Val Asn Val Ala Ile Phe Gly Pro Pro Trp
420 425 430
Met Ala Phe Lys Glu Arg Lys Val Trp Val Lys Glu Asn Met Val Leu
435 440 445
Asn Leu Ser Cys Glu Ala Ser Gly His Pro Arg Pro Thr Ile Ser Trp
450 455 460
Asn Val Asn Gly Thr Ala Ser Glu Gln Asp Gln Asp Pro Gln Arg Val
465 470 475 480
Leu Ser Thr Leu Asn Val Leu Val Thr Pro Glu Leu Leu Glu Thr Gly
485 490 495
Val Glu Cys Thr Ala Ser Asn Asp Leu Gly Lys Asn Thr Ser Ile Leu
500 505 510
Phe Leu Glu Leu Val Asn Leu Thr Thr Leu Thr Pro Asp Ser Asn Thr
515 520 525
Thr Thr Gly Leu Ser Thr Ser Thr Ala Ser Pro His Thr Arg Ala Asn
530 535 540
Ser Thr Ser Thr Glu Arg Lys Leu Pro Glu Pro Glu Ser Arg Gly Val
545 550 555 560
Val Ile Val Ala Val Ile Val Cys Ile Leu Val Leu Ala Val Leu Gly
565 570 575
Ala Val Leu Tyr Phe Leu Tyr Lys Lys Gly Lys Leu Pro Cys Arg Arg
580 585 590
Ser Gly Lys Gln Glu Met Glu Arg Asn Thr Ser Ile
595 600
<210> 4
<211> 20
<212> DNA
<213> 人工序列
<400> 4
gctgcccagt gggaaccaca 20
<210> 5
<211> 23
<212> DNA
<213> 人工序列
<400> 5
atcatggtgt ccaagttcca ggc 23
Claims (2)
1.敲低CD146基因的siRNA在制备治疗恶性乳腺叶状肿瘤的药物中的应用；所述siRNA为siRNA1: sense: CCA GCU CCG CGUCUACAA AdTdT, antisense: UUU GUA GAC GCG GAGCUG GdTdT、siRNA2:sense:GGGAGAGAAAUACAUCGAUTT,antisense:AUCGAUGUAUUUCUCUCCCTG或siRNA3:sense:GGAACUACUGGUGAACUAUTT;antisense:AUAGUUCACCAGUAGUUCCTG。
2.CD146特异性抗体在制备治疗恶性乳腺叶状肿瘤的药物中的应用；所述CD146特异性抗体为mAA98。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111200916.8A CN113929764B (zh) | 2021-10-15 | 2021-10-15 | 一种乳腺叶状肿瘤分子标志物cd146及其应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111200916.8A CN113929764B (zh) | 2021-10-15 | 2021-10-15 | 一种乳腺叶状肿瘤分子标志物cd146及其应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113929764A CN113929764A (zh) | 2022-01-14 |
| CN113929764B true CN113929764B (zh) | 2023-12-29 |
Family
ID=79279604
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111200916.8A Active CN113929764B (zh) | 2021-10-15 | 2021-10-15 | 一种乳腺叶状肿瘤分子标志物cd146及其应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113929764B (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116083567A (zh) * | 2022-09-08 | 2023-05-09 | 中山大学孙逸仙纪念医院 | 一种乳腺叶状肿瘤的诊断试剂及其应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103157109A (zh) * | 2011-12-12 | 2013-06-19 | 中国科学院生物物理研究所 | Cd146及其抗体诊断和治疗三阴性乳腺癌的应用 |
| CN103399144A (zh) * | 2008-02-25 | 2013-11-20 | 雀巢产品技术援助有限公司 | 用抗体阵列选择乳腺癌治疗药物 |
| CN110967489A (zh) * | 2018-09-28 | 2020-04-07 | 中国科学院生物物理研究所 | 可溶性cd146作为血脑屏障损伤标志物在中枢神经***疾病中的应用 |
-
2021
- 2021-10-15 CN CN202111200916.8A patent/CN113929764B/zh active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103399144A (zh) * | 2008-02-25 | 2013-11-20 | 雀巢产品技术援助有限公司 | 用抗体阵列选择乳腺癌治疗药物 |
| CN103157109A (zh) * | 2011-12-12 | 2013-06-19 | 中国科学院生物物理研究所 | Cd146及其抗体诊断和治疗三阴性乳腺癌的应用 |
| CN107929732A (zh) * | 2011-12-12 | 2018-04-20 | 中国科学院生物物理研究所 | Cd146及其抗体诊断和治疗三阴性乳腺癌的应用 |
| CN110967489A (zh) * | 2018-09-28 | 2020-04-07 | 中国科学院生物物理研究所 | 可溶性cd146作为血脑屏障损伤标志物在中枢神经***疾病中的应用 |
Non-Patent Citations (2)
| Title |
|---|
| Kinga A. Kocemba-Pilarczyk等.The relationship between expression of VIMENTIN and CD146 genes in breast cancer.Bio-Algorithms and Med-Systems.2021,第第17卷卷(第第1期期),全文. * |
| 樊静等."CD105和CD146在乳腺组织中的表达".海南医学院学报.2011,第第17卷卷(第第12期期),参见摘要，第1620页左栏第1段-右栏第3段. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113929764A (zh) | 2022-01-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Bellone et al. | Overexpression of epithelial cell adhesion molecule in primary, metastatic, and recurrent/chemotherapy-resistant epithelial ovarian cancer: implications for epithelial cell adhesion molecule-specific immunotherapy | |
| CN109797151A (zh) | Circ-CDH1抑制剂的应用 | |
| CN106834486B (zh) | 骨肉瘤分子诊疗标志物及其应用 | |
| CN112501299A (zh) | 一种用于预测肝癌复发和转移的方法及应用 | |
| Li et al. | Loss of periplakin expression is associated with the tumorigenesis of colorectal carcinoma | |
| CN108203732B (zh) | Trim24在胶质瘤诊断中的应用 | |
| CN113929764B (zh) | 一种乳腺叶状肿瘤分子标志物cd146及其应用 | |
| Wu et al. | Expression and significance of c-kit and epithelial-mesenchymal transition (EMT) molecules in thymic epithelial tumors (TETs) | |
| Tian et al. | LncRNA LINC00974 downregulates miR-122 to upregulate RhoA in oral squamous cell carcinoma | |
| CN111040032B (zh) | 双向调节素在制备细胞衰老及肿瘤的诊断或调控制剂中的应用 | |
| KR102157895B1 (ko) | 대장암 환자의 항암제 치료 반응성 예측용 마커 | |
| CN103103264B (zh) | Smoc2基因在制备检测或治疗子宫内膜癌和卵巢癌药物中的应用 | |
| CN116287249A (zh) | 一种肝细胞癌诊断和预后标志物及其应用 | |
| CN114561470A (zh) | 三阴性乳腺癌分子标志物及其应用 | |
| Ye et al. | HER2 and VEGF expression in breast cancer and their correlations | |
| KR101612356B1 (ko) | Hoxb5의 유방암 진단 및 치료 용도 | |
| CN103525941A (zh) | Cthrc1基因在制备检测/治疗***药物中的应用 | |
| US20080096210A1 (en) | Cancer suppressing agent | |
| CN113699240B (zh) | Nrk在肺癌治疗和预后诊断中的医药用途 | |
| CN111593124B (zh) | Ugt3a2基因及其编码的蛋白在上消化道肿瘤辅助诊断中的应用 | |
| WO2024050860A1 (zh) | 一种乳腺叶状肿瘤的诊断试剂及其应用 | |
| JP7250307B2 (ja) | 子宮癌の発症、転移又は再発の予測方法 | |
| CN108410986B (zh) | Cdh6促进骨肉瘤生长和转移 | |
| Zheng et al. | Tumor-associated fibroblasts promote the migration and invasion of Hepatocellular carcinoma cells by regulating THY-1 | |
| KR20160029053A (ko) | Hoxb5의 유방암 진단 및 치료 용도 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |