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组织微阵列在生物制药研发中的应用

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„œ˝‰§⁄•¶ˇ˛`˘ˆœ˛˘˘••†Æ                            2005 ˜Œ6 ´     28        3˘        F M ed Sci Sec B io l P rop h D iagn T her, J un. 2005, V o l 28, N o. 3




                                    ( tissue ch ip s) ‡˘Øfl˛¢`—                 ( TM A ) ˚˙‰…‚˜Œ•¢„˘·˜—´……˚ı                    , ¸˚˙‰«˚˚fi
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˛—•¢„‡—                 , »‚“†‰Ł˚˙“`¸‰'˛¨¸                                                    ¡¡¡¡Øfl—˘‹˜˘•‰˚‰“—˚flfl˙—˘‹”˝–ø¶‡˙—
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                                                                                              ¶‡˙—˘‹¶Øflˇ‚ß—¿„›¡¢                                               RNA –£
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……˚ı˜ª            , ¶˘'˛—•¢„‡—˜ˆ‰ł——‡ı                                                        •¢„•‰ˇ¡£
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                   †»˝‹`…                                                                     †Øfl—˜¿„›»¿„                                , ˝¤„ˇ«         ( ˛“˛“
`†»˝‹•¢„‰¶˛…˜†–·¡£                                                                            DAB ) , –‰„ˇ´„†‰Æ„ß¡£
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ˇ‰Æ”ˇ , »ø¡¢                                                                                  ª˚˙      , ¿˝‹˚–»¯˙—˘‹ˇ˚„ˆ˚‚»‚¶˜¿„
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                  †»˝‹¯œ·˛˜˚؉Ƅ߉ł                                                           „ß¡£
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                 „œ˝‰§⁄•¶ˇ˛`˘ˆœ˛˘˘••†Æ                               2005 ˜Œ6 ´           28    3˘        F M ed Sci Sec B io l P rop h D iagn T her, J un. 2005, V o l 28, N o. 3


                                                              [3]
                                    A nderson ¨                      ‰`¸            F ISH       ˆ¡£ »¯                DNA `——¿…†‰‡˙§ˇ˝»ø
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                                    , ˝¤„‚»»–—”‡•¡¢                                                  ¸¯‚ˆ……˚ı˜·`¿ƒˆ
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‰»—¯”¯˙¿            30%¡£                                                                                          ·´ˇ‰†
                                                                                                `—˚‰ł»†‰¨•¨ˇ˜—`ƒ„⁄¡£                                                              , ߈
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IHC ˚flflØfl˜ƒˆ‰Æ„߉ł——`¸–¨‰ˇ                                                 ,      157           ¨ , B ubendo rf ¨                           — ¿ ˙ `— ˇ ' ˚–                    , … † `¸
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4mm ) , ”˝†»˝‹†¿˛»¨¡¶‚ª¡£—§¨ˇ˛“˙»                                                               ¸¿–¸Æˆ‚      ( hep sin ) –·ˆˇˇ¡£ ”‹                                                   700
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•‰•¤Æ‚           TM A ·œ–—˜¿˜—†»·                                  ¡£ ”»•‰                      `·†˙`—ˇ'–Œ–˜                                           TM A —, ˝¤„ˆØfl»fl
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•”˝`–—˝»`·†”„ßfi…˜„ˇ                                                                         ,   ˜‡—'—`·†ˇ„—˜»ø                                                , ¶˘‰ł»†‰¨•¨ˇ˜
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—¿‰Æ„ß˚¨”—¿¶ł•˙‚—¿                                                    ¡£                        ˇº„⁄˝˚˙                TM A ¡£
2¡¡ T A º'˛—•¢
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¶—´…††¡˛`˘˜—»ø             ( ¤¿„''˛                                        ) ‰ł——·¯œ                              •`——†¡§
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•`ƒ¡£         TM A ……˚ı¿··…¿Øfl›˛»•˛˜¸                                                                   ˛“·¸
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„œ˝‰§⁄•¶ˇ˛`˘ˆœ˛˘˘••†Æ                                                 2005 ˜Œ6 ´           28            3˘          F M ed Sci Sec B io l P rop h D iagn T her, J un. 2005, V o l 28, N o. 3


                          , TM A »„¿ˆ—–Œ `†»˝‹‰ł„‰                                                                             ˆ«„¨«ˆ                           TM A •˛            , ¿“•¢`¸»‚߈¶
¶˛—¸ø˘ˆ˜•˛¡£ ˆ·¸•‰ˆ˜—¿˜Øfl—                                                                                                     ««„–Œ…˙˜¶fl¶¤`¿•˛ˇ˝‡                                     , ‚ˆ–Œ…˙˜„»ˇ‚
             ¡
˘‹—”‹`†»˝‹‰¶˛˜•…¶                                                                          …”‹
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         ¡
`˜`·†¸•ˆ˚˜⁄”                                                               ¨¡£¨
                                                                     TM A ¡–                      , R ich ter                  ˆ¸«««„–Œ…˙                   TM A , ˆ DNA —˘‹¤ˆŁ•˛˙‰ł
       [ 16 ]                                                                                                                                                           [ 24 ]
¨               ˚„ ˆ         1842 ˙ `— ˇ ' –Œ – ˘ ‡                                            2317 ª ˜                         , …†˜–·¸fi˘‰
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TM A , †ˆ                         F ISH ”˝ˆØ»fl……˚ı                              , —¿`¸ º'                                      ¡¡¡¡·¸˝          , TM A ˚؉Ƅߔ˝˚˜„†˚˙                                        TM A
˜•˘”˝•…¶ºˇ‚ߢ¸                                                           E ( cyclin E ) fi…˜„                                   ‰Æ„ß•˛–†»¿˜»»•¡£ ¡„—˜˚Ø˚¿“•¢`¸
ˇ , ¨ˇ˛“ˇ‚ߢ¸                                          E ‰¨˘˜˙`—ˇ'—–                                                           »ø –‚æ»˚¿¨…                 ( –¨¨˛¢¨˜                                      excel »
·‰ˇ‚¡£                   Pa rk ¨
                                              [ 17 ]
                                                       —¿`¸‰˙                         27 (CK 27 ) ”˝ CK 2                      A ccess) ˜ TM A ˚„¨…
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                                                                                                                                                                                             , ¨»¶ł , ¿“•¢¿·ƒ
20 –·º–‡ƒ'˜•…¶fi…˜„ˇ                                                                      , ¨ˇ˛“ CK7-                           ·`¿˚˜                     TM A ˇ„˚¿                     , ˚˙˚˚ƒ˛··•¢„
CK20+ ˚˙–‡ƒ'“˘‰´‡†˜—‚–Œ¡£ ¸˘˜                                                                                                  ˜»˙˚˘                , ˇº˜         TM A ˚¿ƒ‚ˆ˚˙–ª˝…ˇæ
—¿»„— E ‚˘‡¯         ( E 2cadherin ) –·º˙`—ˇ                                                                                   ˜·¢·”˝—´»                       , –ª˚Ø—¯ˇ¢”˝Øflª—¯ˇ¢˜
                                                         [ 18 ]
'`·—¡fi…„ˇ                                                      ¡¢   SH P 1 –·º`˝`˜‰ł                                           `·‰ ,          w eb fl˘—¿ˇ˚˝…ˇæ–ª†¡‰œ
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„fi…˜„ˇ—¿                                                   ”˝    CO X 2 ˜–·º¨Øˇ'†¡                                                    »„¤¿¶Øflª¶¤˛»˜»˝…„⁄¨¡£
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¨¸œ·˚–…˜…ıfi…„ˇ                                                                 ¨¡£                                             3¡¡ —¡‰Æ
¡¡¡¡·¸˝                   , TM A »„¿ˆ›•¢`º˘“˘`fi                                                                                ¡¡¡¡–˛˜‰Æ”ˇØfl—˘‹˜ª”˝ˆ˝                                            , ¶˘'˛
…˜˚—•˛¡£ ¨¸ˆ˙˝¤‡£¨ˇ˛“›•¢`”˝“˘`fi                                                                                                —•¢—˜¸ˆ‰ł——`¸‡ı†‰‰                                  , ˘¶¶`                 , ¨˘˚˙
…—¯·«ˇ¸˘—                                         , «˚˙‚ˆ‰Æ´˜ˆ‡—Ł“»‚·                                                          ·˚´'˛—•¢˜¿˘—¨¸–—¸øœ¡£
ø–˜Øfl‰ł——Ø⁄¡£ ›˛»`º¶¶¸˜“˘`¯¶                                                                                                   †˛¿…˛˜ˇ
                                                                                                                               ¡¡ 1 Kononen J , Bubendo rf L , Kallion ien iA ,              et al T issue m icroar2
                                                                                                                                                                                                 .
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                         [ 21 ]
                                                                                                                                         rays fo r h igh 2th roughp u t m o lecu lar p rofiling of tum o r sp eci2
Si on ¨
 m                                ˚„ˆ`¸»“˘`                                      TM A ⁄ˆ          , ERBB 2                               m en s. N atu re M ed, 1998, 4: 8442847.
˜–·                       196 ‚¨Øˇ'›•¢`”˝“˘`fi…—”                                                                               ¡¡ 2      Fejzo M , Slam on D. F rozen tum o r tissue m icroarray techno lo 2
                                                                                                                                         gy fo r analysis of tum o r RNA , DNA , and p ro tein s. Am J
”ˆ˜»´—¡£
                                                                                                                                         Patho l, 2001, 159: 164521650.
2. 3¡¡ TM A ‰Æ„ߘ•˛”˝˚˜„                                                                                                       ¡¡ 3                                                              . m
                                                                                                                                         A ndersen CL , Ho stetter G, Grigo ryan A , et al I p roved
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