{"id":4846,"date":"2023-01-30T20:52:10","date_gmt":"2023-01-30T12:52:10","guid":{"rendered":"http:\/\/dh.oncolab.cn\/index.php\/2023\/01\/30\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac17%e7%ab%a0%ef%bc%9aido-tdo%e7%9a%84%e6%8a%91%e5%88%b6%e5%9c%a8%e7%99%8c%e7%97%87%e6%b2%bb%e7%96%97%e4%b8%ad%e7%9a%84%e5%ba%94%e7%94%a8-2\/"},"modified":"2023-01-30T20:52:10","modified_gmt":"2023-01-30T12:52:10","slug":"%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac17%e7%ab%a0%ef%bc%9aido-tdo%e7%9a%84%e6%8a%91%e5%88%b6%e5%9c%a8%e7%99%8c%e7%97%87%e6%b2%bb%e7%96%97%e4%b8%ad%e7%9a%84%e5%ba%94%e7%94%a8-2","status":"publish","type":"post","link":"http:\/\/dh.oncolab.cn\/index.php\/2023\/01\/30\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac17%e7%ab%a0%ef%bc%9aido-tdo%e7%9a%84%e6%8a%91%e5%88%b6%e5%9c%a8%e7%99%8c%e7%97%87%e6%b2%bb%e7%96%97%e4%b8%ad%e7%9a%84%e5%ba%94%e7%94%a8-2\/","title":{"rendered":"\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c17\u7ae0\uff1aIDO\/TDO\u7684\u6291\u5236\u5728\u764c\u75c7\u6cbb\u7597\u4e2d\u7684\u5e94\u7528\uff08\u4e0b\uff09"},"content":{"rendered":"
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\u4e0a\u671f\u5185\u5bb9\uff1a\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c17\u7ae0\uff1aIDO\/TDO\u7684\u6291\u5236\u5728\u764c\u75c7\u6cbb\u7597\u4e2d\u7684\u5e94\u7528\uff08\u4e0a\uff09<\/span><\/a><\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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17.6 \u708e\u75c7\u4e2d\u7684\u8272\u6c28\u9178\u53cc\u52a0\u6c27\u9176(TDO): \u514d\u75ab\u9003\u9038\u3001\u5931\u5de2\u51cb\u4ea1\u62b5\u6297\u548c\u8f6c\u79fb<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5728\u809d\u810f\u4e2d\u8868\u8fbe\u7684TDO\u8d1f\u8d23\u7ef4\u6301\u8840\u6db2\u4e2d\u8272\u6c28\u9178\u6c34\u5e73\u7684\u52a8\u6001\u5e73\u8861\u3002\u4e0eIDO1\u7c7b\u4f3c\uff0c\u4e00\u4e9b\u80bf\u7624\u4ee5\u8fc7\u5ea6\u8868\u8fbeTDO\u7684\u65b9\u5f0f\u8fdb\u884c\u514d\u75ab\u9003\u907f\u3002<\/p>\n

\u56e0\u6b64\uff0c\u4eba\u4eec\u5bf9TDO\u7684\u5c0f\u5206\u5b50\u6291\u5236\u5242\u8d8a\u6765\u8d8a\u611f\u5174\u8da3\uff0c\u5c06\u5176\u4f5c\u4e3a\u4e00\u79cd\u5e76\u884c\u7684\u514d\u75ab\u8c03\u8282\u7b56\u7565\u6765\u6d88\u9664\u80bf\u7624\uff0c\u6700\u8fd1\u8be5\u9886\u57df\u7684\u5148\u884c\u8005\u5df2\u8be6\u7ec6\u5730\u56de\u987e\u4e86\u5176\u57fa\u672c\u539f\u7406\u3002<\/p>\n

\u6700\u521d\u572820\u4e16\u7eaa90\u5e74\u4ee3\u5f00\u53d1\u7684\u751f\u7269\u6d3b\u6027\u94c5\u7ed3\u678468OC91\u5df2\u88ab\u7528\u4e8e\u5c0f\u9f20\u7814\u7a76\uff0c\u5e76\u4e14\u6709\u62a5\u9053\u79f0\uff0c\u4f18\u5316\u4ea7\u751f\u7684\u6548\u529b\u66f4\u5f3a\uff0c\u836f\u7406\u7279\u5f81\u66f4\u597d\u7684\u5316\u5408\u7269\u4e5f\u5df2\u7ecf\u7814\u53d1\u51fa\u6765\u3002<\/p>\n

\u5c0f\u9f20\u4f53\u5185TDO\u7f16\u7801\u57fa\u56e0TDO2\u7684\u7f3a\u5931\u5bfc\u81f4\u8840\u6db2\u4e2dL-\u8272\u6c28\u9178\u6d53\u5ea6\u5347\u9ad8\uff0c\u4e00\u4e9b\u795e\u7ecf\u7cfb\u7edf\u6539\u53d8\u53ef\u80fd\u4e0e\u8fd9\u4e9b\u5c0f\u9f20\u8840\/\u8111\u4e2d5-\u7f9f\u8272\u80fa\u6c34\u5e73\u7684\u534f\u540c\u5347\u9ad8\u6709\u5173\u3002\u6709\u8da3\u7684\u662f\uff0c\u7528TDO2\u6291\u5236\u5242680C91\u6cbb\u7597\u7684\u5c0f\u9f20\uff0c\u5bf9\u5185\u6bd2\u7d20\u8bf1\u5bfc\u7684\u4f11\u514b\u7684\u654f\u611f\u5ea6\u660e\u663e\u5347\u9ad8\uff0cTDO2\u2212\/\u2212\u5c0f\u9f20\u4e5f\u5177\u6709\u7c7b\u4f3c\u7684\u73b0\u8c61\uff0c\u8fd9\u610f\u5473\u7740TDO\u53c2\u4e0e\u4e86\u708e\u75c7\u8fc7\u7a0b\u3002<\/p>\n

\u7136\u800c\uff0c\u5c3d\u7ba1\u4e0eIDO1\u6216IDO2\u7c7b\u4f3c\uff0c\u4f46TDO\u4f3c\u4e4e\u8d4b\u4e88\u7684\u708e\u75c7\u7279\u5f81\u5b58\u5728\u5dee\u5f02\uff0c\u5c3d\u7ba1\u8fd9\u4e9b\u9176\u5728\u8272\u6c28\u9178\u5206\u89e3\u4ee3\u8c22\u4e2d\u53d1\u6325\u7740\u5171\u540c\u4f5c\u7528\u3002\u867d\u7136\u9176\u5b66\u5dee\u5f02\u53ef\u80fd\u6709\u52a9\u4e8e\u89e3\u91ca\u8fd9\u4e9b\u4e0d\u540c\u7684\u4f5c\u7528\uff0c\u4f46\u5b83\u4eec\u4f3c\u4e4e\u4e5f\u53cd\u6620\u4e86\u72ac\u5c3f\u6c28\u9178\u53ca\u5176\u4ee3\u8c22\u7269\u4ea7\u751f\u7684\u5c40\u90e8\u533a\u57df\u63a7\u5236\u6216\u72ac\u5c3f\u6c28\u9178\u6548\u5e94\u673a\u5236(AhR\u3001\u72ac\u5c3f\u6c28\u9178\u9014\u5f84\u5206\u89e3\u4ee3\u8c22\u9176\u7b49)\u7684\u76f8\u5bf9\u53ef\u7528\u6027\u6216\u6548\u7387\u7684\u5dee\u5f02\u3002<\/p>\n

\u5173\u4e8eTDO\uff0c\u867d\u7136\u6709\u901a\u8fc7\u9009\u62e9\u6027\u751f\u7269\u6d3b\u6027\u6291\u5236\u5242\u5728\u4e34\u5e8a\u524d\u9636\u6bb5\u7684\u8bc1\u636e\u8868\u660e\u5b83\u5728\u80bf\u7624\u514d\u75ab\u9003\u9038\u4e2d\u7684\u4f5c\u7528\uff0c\u4f46\u76ee\u524d\u5728\u5c0f\u9f20\u8eab\u4e0a\u8fd8\u6ca1\u6709\u9057\u4f20\u8bc1\u636e\uff0c\u4e5f\u6ca1\u6709\u5173\u4e8eTDO\u5728\u80bf\u7624\u7ec6\u80de\u6216\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u8868\u8fbe\u7684\u6027\u8d28\u6216\u7a0b\u5ea6\u7684\u4e86\u89e3\u3002<\/p>\n

\u6b64\u5916\uff0c\u5982\u5728\u6587\u7ae0\u5176\u4ed6\u90e8\u5206\u8ba8\u8bba\u7684\u90a3\u6837\uff0cTDO\u6291\u5236\u5242\u5f15\u8d77\u4e86\u4e0eIDO1\u6291\u5236\u5242\u4e0d\u540c\u7684\u5b89\u5168\u6027\u95ee\u9898\uff0c\u5305\u62ec\u5728\u809d\u810f\u548c\u4e2d\u67a2\u795e\u7ecf\u7cfb\u7edf\u4e2d\u3002\u5c3d\u7ba1\u5982\u6b64\uff0cTDO\u6291\u5236\u5242\u4ee5\u53caIDO\/TDO\u7ec4\u5408\u6291\u5236\u5242\u7684\u5f00\u53d1\u4ecd\u5728\u7ee7\u7eed\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u8fd1\u671f\u6709\u8bc1\u636e\u8868\u660e\uff0cTDO\u53c2\u4e0e\u4e86IDO1\u7b49\u4e0e\u764c\u75c7\u76f8\u5173\u7684\u708e\u6027\u8fc7\u7a0b\u3002\u5177\u4f53\u5730\u8bf4\uff0c\u764c\u7ec6\u80de\u4e2dTDO\u7684\u4e0a\u8c03\u5df2\u88ab\u53d1\u73b0\u5bf9\u80bf\u7624\u7ec6\u80de\u7684\u5b58\u6d3b\u548c\u8f6c\u79fb\u80fd\u529b\u6709\u4fc3\u8fdb\u4f5c\u7528\uff0c\u800c\u4e0d\u4ec5\u4ec5\u662f\u5b83\u5728\u514d\u75ab\u9003\u9038\u4e2d\u7684\u4f5c\u7528\u3002<\/p>\n

\u5bf9\u5931\u5de2\u51cb\u4ea1\u7684\u62b5\u6297\u662f\u80bf\u7624\u8f6c\u79fb\u8fc7\u7a0b\u4e2d\u7684\u5173\u952e\u6b65\u9aa4\uff0c\u5b83\u662f\u4e00\u79cd\u7531\u7ec6\u80de\u9ecf\u9644\u5265\u593a\u89e6\u53d1\u7684\u7ec6\u80de\u51cb\u4ea1\u3002\u5728\u4e00\u9879\u5bf9\u4fb5\u88ad\u6027\u201c\u4e09\u9634\u6027\u201d\u4e73\u817a\u764c(TNBC)\u7684\u5f00\u521b\u6027\u7814\u7a76\u4e2d\uff0cD\u2019Amato\u548c\u4ed6\u7684\u540c\u4e8b\u5c55\u793a\u4e86\u5f3a\u5236\u60ac\u6d6e\u57f9\u517b\u4e2dTDO\u7684\u4e0a\u8c03\u662f\u5982\u4f55\u5728TNBC\u7ec6\u80de\u7684\u5931\u5de2\u62b5\u6297\u548c\u8f6c\u79fb\u80fd\u529b\u4e2d\u53d1\u6325\u91cd\u8981\u4f5c\u7528\u7684\u3002<\/p>\n

\u4e0e\u5176\u5728\u514d\u75ab\u9003\u9038\u4e2d\u7684\u4f5c\u7528\u76f8\u4f3c\uff0c\u7531TDO\u4e0a\u8c03\u5f15\u8d77\u7684\u72ac\u5c3f\u6c28\u9178\u8bf1\u5bfc\u8db3\u4ee5\u6fc0\u6d3bAhR\u4fe1\u53f7\u901a\u8def\uff0c\u800c\u5bf9TDO\u6216AhR\u7684\u836f\u7406\u6291\u5236\u6216\u9057\u4f20\u8870\u51cf\u5747\u8db3\u4ee5\u6062\u590d\u5931\u5de2\u7ec6\u80de\u7684\u654f\u611f\u6027\u5e76\u964d\u4f4eTNBC\u7ec6\u80de\u7684\u4fb5\u88ad\u6027\u3002\u652f\u6301\u8fd9\u4e9b\u89c2\u5bdf\u7ed3\u679c\u7684\u8bc1\u636e\u662f\uff0c\u7528TDO\u6291\u5236\u5242680C91\u6cbb\u7597\u7684\u8377\u7624\u5c0f\u9f20\u80ba\u8f6c\u79fb\u51cf\u5c11\u3002<\/p>\n

\u6700\u540e\uff0cTDO\u5728\u4e34\u5e8aTNBC\u6807\u672c\u4e2d\u7684\u9ad8\u8868\u8fbe\u4e0e\u75be\u75c5\u5206\u7ea7\u589e\u52a0\u3001\u96cc\u6fc0\u7d20\u53d7\u4f53\u9634\u6027\u72b6\u6001\u548c\u603b\u751f\u5b58\u671f\u7f29\u77ed\u6709\u5173\u3002\u8fd9\u4e9b\u53d1\u73b0\u63d0\u4f9b\u4e86\u8fd9\u6837\u4e00\u4e2a\u6982\u5ff5\uff0c\u5373TDO\u7684\u4f5c\u7528\u7c7b\u4f3c\u4e8eIDO1\uff0c\u5728\u764c\u75c7\u4e2d\u9a71\u52a8\u81f4\u75c5\u6027\u708e\u75c7\u8fc7\u7a0b\uff0c\u5176\u8303\u56f4\u8d85\u51fa\u4e86\u5b83\u4eec\u5bf9\u5b9e\u73b0\u9002\u5e94\u6027\u514d\u75ab\u8010\u53d7\u7684\u8d21\u732e\u3002<\/p>\n

Fig. 17.3<\/span>\u603b\u7ed3\u4e86IDO\/TDO\u6291\u5236\u5242\u901a\u8fc7\u5f71\u54cd\u708e\u75c7\u8fc7\u7a0b\u548c\u9002\u5e94\u6027\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u6765\u5f71\u54cd\u514d\u75ab\u68c0\u67e5\u70b9\u6cbb\u7597\u548c\u5316\u7597\u7684\u4e00\u4e9b\u60c5\u51b5\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Fig. 17.3<\/span> IDO\/TDO\u6291\u5236\u5242\u5229\u7528\u514d\u75ab\u68c0\u67e5\u70b9\u6cbb\u7597\u548c\u5316\u7597\u3002IDO\/TDO\u6291\u5236\u5242\u4e0d\u4ec5\u5728\u8054\u5408\u6cbb\u7597\u65b9\u6848\u4e2d\u6709\u6548\uff0c\u4f5c\u4e3a\u514d\u75ab\u8c03\u8282\u5242\u7f13\u89e3\u514d\u75ab\u9003\u9038\u548c\u4fc3\u8fdb\u9002\u5e94\u6027\u514d\u75ab\u53cd\u5e94\uff0c\u800c\u4e14\u8fd8\u53ef\u4ee5\u6d88\u9664\u6216\u91cd\u65b0\u7f16\u7a0b\u708e\u75c7\u8fc7\u7a0b\uff0c\u5f71\u54cd\u5316\u7597\u548c\u514d\u75ab\u68c0\u67e5\u70b9\u6cbb\u7597\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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17.7\u4e3b\u8981\u4e34\u5e8a\u7528\u836f\uff1a\u5432\u54da\u83ab\u5fb7\u3001GDC-0919\u548c\u827e\u5361\u54da\u53f8\u4ed6<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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17.7.1  \u5432\u54da\u83ab\u5fb7<\/p>\n<\/section>\n

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\u6211\u4eec\u66fe\u5728\u522b\u5904\u53d1\u8868\u8fc7\u8be6\u7ec6\u7684\u5173\u4e8e\u4e34\u5e8a\u524d\u7814\u7a76\u7684\u8ba8\u8bba\uff0c\u5e76\u57fa\u4e8e\u7406\u8bba\u57fa\u7840\u5bf9\u8fd9\u79cd\u7b80\u5355\u7684D-\u8272\u6c28\u9178\u76841-\u7532\u57fa\u884d\u751f\u7269\u8fdb\u884c\u4e34\u5e8a\u8bc4\u4f30\u3002\u5230\u76ee\u524d\u4e3a\u6b62\uff0c\u4e34\u5e8a\u524d\u6587\u732e\u4e2d\u7814\u7a76IDO\u6700\u5e38\u7528\u7684\u5206\u5b50\u63a2\u9488\u662f1-\u7532\u57fa-\u8272\u6c28\u9178\u7684D\uff0cL\u5916\u6d88\u65cb\u6df7\u5408\u7269(1MT)\u3002L-1MT\u662fIDO\u7684\u5f31\u5e95\u7269\u800c\u4e0d\u662f\u771f\u6b63\u7684\u6291\u5236\u5242\uff1bD-1MT\u65e2\u4e0d\u662fIDO\u7684\u5e95\u7269\uff0c\u4e5f\u4e0d\u662fIDO\u7684\u6291\u5236\u5242\uff0c\u5c3d\u7ba1\u5728\u591a\u79cd\u6a21\u578b\u7cfb\u7edf\u4e2d\uff0c\u5b83\u8868\u73b0\u51fa\u76f8\u5bf9\u66f4\u5f3a\u7684\u6297\u80bf\u7624\u7279\u6027\uff0c\u8fd9\u4e0eIDO\u4ecb\u5bfc\u7684\u4eba\u6811\u7a81\u7ec6\u80de\u8272\u6c28\u9178\u5206\u89e3\u4ee3\u8c22\u7684\u6291\u5236\u76f8\u5173\u3002\u6240\u4ee5\u5b83\u4e5f\u4e0d\u662f\u9009\u62e9\u6027\u63a2\u9488\u3002<\/p>\n

\u5432\u54da\u83ab\u5fb7\u662f\u7b2c\u4e00\u4e2a\u8fdb\u5165I\u671f\u8bd5\u9a8c\u7684\u5316\u5408\u7269\uff0c\u5728\u591a\u6b21II\u671f\u8bd5\u9a8c\u4e2d\u53d1\u73b0\u5f53\u5b83\u4f5c\u4e3a\u5355\u4e00\u836f\u7269\u6216\u4e0e\u5316\u7597\u8054\u5408\u4f7f\u7528\u65f6\u5177\u6709\u826f\u597d\u7684\u8010\u53d7\u6027\uff0c\u4e14\u8be5\u7814\u7a76\u5bf9\u6bcf\u59291200\u6beb\u514b\u7684\u5242\u91cf\u8fdb\u884c\u4e86\u8bc4\u4f30\u3002<\/p>\n

\u5728\u8fd9\u9879\u5de5\u4f5c\u4e2d\uff0c\u6709\u4e09\u4e2a\u503c\u5f97\u5173\u6ce8\u7684\u8bd5\u9a8c\u96c6\uff0c\u8054\u5408\u5e94\u7528Taxotere(\u5316\u7597\u8054\u5408)\u7684\u4e73\u817a\u764c\u60a3\u8005\uff0c\u8054\u5408\u5e94\u7528\u6811\u7a81\u72b6\u7ec6\u80de\u75ab\u82d7siPuleucel-T(\u75ab\u82d7\u8054\u5408)\u7684\u524d\u5217\u817a\u764c\u60a3\u8005\uff0c\u4ee5\u53ca\u8054\u5408\u6297PD1(\u514d\u75ab\u68c0\u67e5\u70b9\u8054\u5408)\u7684\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u867d\u7136\u5c1a\u672a\u786e\u5b9a\u5432\u54da\u83ab\u5fb7\u786e\u5207\u7684\u4f5c\u7528\u673a\u5236\uff0c\u4f46\u7ec6\u80de\u5b9e\u9a8c\u53ef\u53cd\u6620\uff0cmTORC1\u901a\u8def\u5c06\u4e34\u5e8a\u76f8\u5173\u7684\u7eb3\u6469\u5c14\u6d53\u5ea6\u7684\u5432\u54da\u83ab\u5fb7\u8f6c\u53d8\u4e3al-\u8272\u6c28\u9178\u7684\u6a21\u62df\u7269\u3002\u56e0\u6b64\uff0c\u5432\u54da\u83ab\u5fb7\u53ef\u80fd\u90e8\u5206\u51cf\u8f7bIDO-\/TDO-\u4ecb\u5bfc\u7684\u8272\u6c28\u9178\u5265\u593a\u5bf9T\u7ec6\u80de\u6297\u80bf\u7624\u6d3b\u6027\uff08\u9700\u8981mTOR\u4fe1\u53f7\uff09\u7684\u6291\u5236\u3002\u6df1\u5165\u7814\u7a76\u540e\u53d1\u73b0\u4e86\u5432\u54da\u83ab\u5fb7\u8fd9\u79cd\u7b80\u5355\u7684D-\u8272\u6c28\u9178\u884d\u751f\u7269\u7684\u786e\u5207\u7684\u4f5c\u7528\u673a\u5236\uff0c\u5b83\u7684\u4f4e\u6bd2\u6027\u4ecd\u7136\u662f\u5176\u4e34\u5e8a\u5f00\u53d1\u4e2d\u5438\u5f15\u4eba\u7684\u7279\u5f81\uff0c\u4e5f\u4fc3\u8fdb\u4e86IDO1\u548cIDO\/TDO\u9176\u6291\u5236\u5242\u7684\u7814\u7a76\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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17.7.2 GDC-0919<\/p>\n<\/section>\n

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\u57282005\u5e74\u4e4b\u524d\uff0c\u51e0\u4e4e\u6ca1\u6709\u52a8\u529b\u5f00\u53d1IDO1\u8fd9\u79cd\u4e0d\u8d77\u773c\u7684\u8272\u6c28\u9178\u5206\u89e3\u4ee3\u8c22\u9176\u7684\u6291\u5236\u5242\u3002\u8fd9\u79cd\u60c5\u51b5\u5728\u5f97\u5230IDO1\u5728\u764c\u75c7\u4e2d\u7684\u4f5c\u7528\u4ee5\u53caIDO1\u6291\u5236\u5242\u4e0e\u5316\u7597\u8054\u5408\u4f5c\u7528\u6548\u679c\u7684\u4e34\u5e8a\u524d\u8bc1\u636e\u65f6\u53d1\u751f\u4e86\u6539\u53d8\u3002<\/p>\n

\u57282005\u5e74\uff0c\u552f\u4e00\u5177\u6709\u751f\u7269\u6d3b\u6027\u7684IDO\u6291\u5236\u5242\u662f1-\u7532\u57fa-D, L-\u8272\u6c28\u9178(1-MT)\uff0c\u5176Ki<\/sub><\/em>\u636e\u62a5\u9053\u662f34 \u03bcM\u30021989\u5e74Sono\u548cCady\u5c064-\u82ef\u57fa\u54aa\u5511(4-PI)\u786e\u5b9a\u4e3aIDO1\u7684\u5f31\u975e\u7ade\u4e89\u6027\u6291\u5236\u5242\uff0c\u5b83\u662f\u5f53\u65f6\u4e3a\u6570\u4e0d\u591a\u7684\u88ab\u62a5\u9053\u7684IDO\u6291\u5236\u5242\u4e4b\u4e00\u3002\u6709\u8da3\u7684\u662f\uff0c\u5c3d\u7ba1\u5728\u5149\u8c31\u7814\u7a76\u4e2d4-PI\u663e\u793a\u975e\u7ade\u4e89\u6027\u6291\u5236\uff0c\u4f46Sono\u548cCady\u8ba4\u4e3a4-PI\u5b9e\u9645\u4e0a\u662f\u4e0e\u6d3b\u6027\u90e8\u4f4d\u7684\u8840\u7ea2\u7d20\u94c1\u7ed3\u5408\u7684\u3002\u968f\u540e\uff0c\u7b2c\u4e00\u4e2a\u88ab\u62a5\u9053\u7684IDO\u7684\u6676\u4f53\u7ed3\u6784\u901a\u8fc7\u663e\u793a4-PI\u4e0e\u8840\u7ea2\u7d20\u94c1\u7ed3\u5408\u8bc1\u5b9e\u4e86\u8fd9\u4e00\u53d1\u73b0(Fig. 17.4a<\/span>)\u3002\u8fd9\u4e00\u53d1\u73b0\u4ee5\u53ca\u4e30\u5bcc\u7684\u6676\u4f53\u7ed3\u6784\u4fe1\u606f\u4fc3\u4f7fMalachowski\u548c\u4ed6\u7684\u540c\u4e8b\u4eec\u5f00\u59cb\u4e86\u7b2c\u4e00\u6b21\u57fa\u4e8e\u7ed3\u6784\u7684\u836f\u7269\u8bbe\u8ba1\u7814\u7a76\uff0c\u4ed6\u4eec\u8fdb\u884c\u7684\u5173\u4e8e\u82ef\u5e76\u54aa\u5511\u7cfb\u5217\u7684\u5f00\u521b\u6027\u5de5\u4f5c\uff0c\u4fc3\u4f7f\u4e86\u540e\u6765\u7684\u4e34\u5e8a\u5148\u5bfc\u836f\u7269GDC-0919\u7684\u8bde\u751f\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Fig. 17.4<\/span> \u82ef\u57fa\u54aa\u5511\u7c7b\u836f\u7269\u690d\u6839\u4e8eGDC-0919\u5f00\u53d1\u3002(a)4-PI\u4e0eIDO1\u7684\u8840\u7ea2\u7d20\u94c1\u7ed3\u5408\u3002C129\u4f4d\u4e8e4-PI\u82ef\u73af\u7684\u4e0a\u65b9\uff0c\u800cS167\u4f4d\u4e8e\u7ed3\u5408\u90e8\u4f4d\u7684\u540e\u9762\u3002\u7f13\u51b2\u5206\u5b50CHES(\u9ec4\u8272)\u5728IDO\u6676\u4f53\u7ed3\u6784\u7684\u6d3b\u6027\u4e2d\u5fc3\u7684\u5165\u53e3\u5904\u7ed3\u5408\u3002\u7531Delano Science LLC\u5f00\u53d1\u3001\u652f\u6301\u548c\u7ef4\u62a4\u7684\u5f00\u6e90\u5206\u5b50\u56fe\u5f62\u7cfb\u7edfPYMOL1.0[http:\/\/wwwpymol.org]\u751f\u6210\u56fe\u5f62\u3002http:\/\/www.delanoscientific.com.(b) 4-\u82ef\u57fa\u54aa\u5511\u7ed3\u6784\u7684\u73af\u7f16\u53f7\u3002(c)N-3-\u82c4\u57fa\u53d6\u4ee34-PI\u7684\u7ed3\u6784\u548cNLG-919\u7684\u6839\u7ed3\u6784\u3002(d)\u4e24\u4e2a\u53ef\u80fd\u76844-PI\u68382\u2018-OH\u53d6\u4ee3\u7684\u76ca\u5904\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Malachowski\u548c\u4ed6\u7684\u540c\u4e8b\u5728\u65e9\u671f\u7684\u57fa\u7840\u6027\u5de5\u4f5c\u4e2d\u63a2\u7d22\u4e864-PI\u7684\u7c7b\u4f3c\u7269\uff0c\u901a\u8fc7\u4fee\u6539\u7ed3\u6784\u4ee5\u63a2\u7d22IDO1\u7684\u6d3b\u6027\u90e8\u4f4d\uff0c\u4e3b\u8981\u5229\u7528\u4e86IDO\u6d3b\u6027\u90e8\u4f4d\u5185\u7684\u4e09\u79cd\u7ed3\u5408\u4f5c\u7528\uff1a(1)\u4f5c\u7528\u4e8e\u8840\u7ea2\u7d207-\u4e19\u9178\u4fee\u9970\u7684\u6d3b\u6027\u90e8\u4f4d\u5165\u53e3\u533a\uff0c(2)\u4f5c\u7528\u4e8e\u6d3b\u6027\u90e8\u4f4d\u7684\u5185\u90e8\uff0c\u7279\u522b\u662f\u4e0eC129\u548cS167\u7684\u76f8\u4e92\u4f5c\u7528\uff0c(3)\u4f5c\u7528\u4e8e\u8840\u7ea2\u7d20\u94c1\u7ed3\u5408\u57fa\u56e2\u3002<\/p>\n

\u901a\u8fc7\u6d3b\u6027\u4e2d\u5fc3\u5165\u53e3\u5904\u7684\u76f8\u4e92\u4f5c\u7528\u589e\u5f3a\u4e864-PI\u7ed3\u6784\u7684IDO\u6291\u5236\u4f5c\u7528\uff0c\u8be5\u4f5c\u7528\u96c6\u4e2d\u5728\u54aa\u5511\u73af\u7684N-1\u3001C-2\u548cN-3\u4f4d(Fig. 17.4b<\/span>)\u3002\u8fd9\u4e09\u4e2a\u4f4d\u7f6e\u90fd\u88ab\u53d6\u4ee3\u4ee5\u589e\u52a0\u5360\u636e\u6d3b\u6027\u4e2d\u5fc3\u5165\u53e3\u7684\u57fa\u56e2\u3002\u57284-PI\u4e0eIDO\u7684\u6676\u4f53\u7ed3\u6784\u4e2d\uff0c\u8be5\u533a\u57df\u542b\u6709N-\u73af\u5df1\u57fa-2-\u6c28\u57fa\u4e59\u78fa\u9178(CHS)\u7f13\u51b2\u5206\u5b50\uff0c\u5176\u70f7\u57fa\u90e8\u5206\u4e0eF163\u548cF226\u5f62\u6210\u758f\u6c34\u76f8\u4e92\u4f5c\u7528\u3002\u6b64\u5916\uff0cCHES\u5206\u5b50\u7684\u6c28\u57fa\u4e0e\u8840\u7ea2\u7d207-\u4e19\u9178\u5f62\u6210\u79bb\u5b50\u5bf9\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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N-1\u53d6\u4ee3\u76844-PI\u884d\u751f\u7269\u5b8c\u5168\u6ca1\u6709\u6291\u5236\u6d3b\u6027\u5e76\u4e0d\u4ee4\u4eba\u60ca\u8bb6\uff0c\u5b83\u8bc1\u5b9e\u4e86N-1\u6c2e\u4e0e\u8840\u7ea2\u7d20\u94c1\u7684\u7ed3\u5408\uff0c\u66f4\u91cd\u8981\u7684\u662f\uff0c\u8bc1\u660e\u4e86\u54aa\u5511\u7684N-3\u6c2e\u4e0d\u80fd\u53d6\u4ee3\u7ed3\u5408\u5728\u8840\u7ea2\u7d20\u94c1\u4e0a\u3002\u7136\u800c\uff0c\u610f\u5916\u5730\u53d1\u73b0N-3\u82c4\u57fa\u53d6\u4ee3\u7684\u884d\u751f\u7269(Fig. 17.4c1<\/span>)\u4e0e4-PI\u5927\u81f4\u7b49\u4ef7\uff0c\u4ece\u800c\u8bc1\u660e\u54aa\u5511\u73af\u662f\u53ef\u4ee5\u53d6\u4ee3\u7684\u3002N-3-\u82c4\u57fa\u53d6\u4ee3\u5316\u5408\u7269\u786e\u5b9a\u4e86\u6b63\u786e\u7684\u54aa\u5511\u73af\u4f4d\u7f6e\u53ca\u7a7a\u95f4\u5bb9\u5dee\uff0c\u53ef\u80fd\u5360\u636e\u4e86\u6d3b\u6027\u4e2d\u5fc3\u5165\u53e3\uff0c\u5176\u4e2dCHS\u7f13\u51b2\u5206\u5b50\u4f4d\u4e8eIDO-4-PI\u6676\u4f53\u7ed3\u6784\u4e2d\u3002\u8fd9\u4e00\u53d1\u73b0\u4e0e\u6cb9\u83dc\u7d20\u884d\u751f\u7269\u6291\u5236IDO1\u7684\u7814\u7a76\u4e2d\u5f00\u53d1\u7684\u836f\u6548\u56e2\u662f\u4e00\u81f4\u7684\uff0c\u5373\u5728\u4e24\u4e2a\u5927\u7684\u82b3\u9999\u65cf\u6216\u78b3\u6c22\u5316\u5408\u7269\u7ed3\u6784\u7684\u4e24\u4fa7\u662f\u4e00\u4e2a\u8840\u7ea2\u7d20\u94c1\u7ed3\u5408\u57fa\u56e2\u3002NewLink Genetics Inc.\u968f\u540e\u5728\u4e34\u5e8a\u5019\u9009\u836f\u7269NLG-919(Fig. 17.4c<\/span>)\u7684\u9aa8\u5e72\u7ed3\u6784\u65b9\u9762\u7684\u5f00\u53d1\u5de5\u4f5c\u4e5f\u8bc1\u660e\u8fd9\u662f\u5177\u6709\u5148\u89c1\u4e4b\u660e\u7684\uff0c\u5728\u6388\u6743\u7ed9Genentech\/Roche\u540e\u5c06\u5176\u91cd\u547d\u540d\u4e3aGDC-0919\u3002\u5982\u56fe\u6240\u793a\uff0cNLG-919\u4e3b\u5e72\u4ece\u76f8\u540c\u7684N-3\u4f4d\u7f6e\u5ef6\u4f38\u5230IDO1\u7684\u6d3b\u6027\u4e2d\u5fc3\u5165\u53e3\u5904\uff0c\u4f4d\u4e8e\u76f8\u4f3c\u7684\u78b3\u6c22\u5316\u5408\u7269\u90e8\u5206\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u901a\u8fc7\u5206\u67904-PI\u4e0eIDO1\u7ed3\u5408\u7684\u6676\u4f53\u7ed3\u6784\uff0c\u53ef\u4ee5\u8bc1\u660eS167\u548cC129\u4f4d\u4e8e\u6d3b\u6027\u4e2d\u5fc3\u5185\u90e8\u76844-PI\u7684\u82ef\u73af\u9644\u8fd1\u3002\u5bf9\u82ef\u73af\u4e0e\u6c27\u3001\u786b\u548c\u6c1f\u7684\u90bb\u4f4d\u3001\u95f4\u4f4d\u548c\u5bf9\u4f4d\u53d6\u4ee3\u8fdb\u884c\u4e86\u7cfb\u7edf\u7684\u8bc4\u4f30\uff0c\u4ee5\u786e\u5b9a\u662f\u5426\u53ef\u4ee5\u5229\u7528\u7279\u5b9a\u7684\u86cb\u767d\u8d28-\u914d\u4f53\u76f8\u4e92\u4f5c\u7528\u30022\u2018-\u7f9f\u57fa(\u90bb\u4f4d\u53d6\u4ee3)\u4fee\u9970\u6548\u679c\u6700\u597d\uff0c\u6548\u4ef7\u6bd44-PI\u63d0\u9ad8\u4e8610\u500d(Fig. 17.4d<\/span>)\u3002\u8fd9\u79cd\u6548\u4ef7\u7684\u63d0\u9ad8\u6709\u4e24\u79cd\u53ef\u80fd\u6027\uff1a\u4e0es167\u5206\u5b50\u95f4\u6c22\u952e\u6216\u4e0eN-3\u5206\u5b50\u5185\u6c22\u952e\u9501\u5b9a\u7684\u82ef\u73af\u548c\u54aa\u5511\u73af\u8fd8\u5408\u6210\u4e862\u2018\uff0c6\u2019-\u4e8c\u7f9f\u57fa\u82ef\u57fa\u884d\u751f\u7269\uff0c\u5b83\u63d0\u4f9b\u4e86s167\u6216N-3-\u54aa\u5511\u7684\u4e24\u4e2a\u65cb\u8f6c\u4f53\u4e2d\u7684\u7f9f\u57fa\uff0c\u5e76\u4e14\u5b83\u4e0e2\u2018-\u7f9f\u57fa\u884d\u751f\u7269\u5927\u81f4\u76f8\u7b49\uff0c\u8868\u660e\u4e86\u8fd9\u4e24\u4e2a\u7f9f\u57fa\u6ca1\u6709\u989d\u5916\u7684\u4f5c\u7528\u3002\u968f\u540e\uff0cNewLink Genetics\u5f15\u5165\u4e86\u4e00\u79cd\u5c06\u6c22\u952e\u590d\u5236\u5230N-3\u54aa\u5511\u4e0a\u7684\u78b3\u6c22\u6865\uff0c\u5373\u5c06\u82ef\u548c\u54aa\u5511\u73af\u7684\u6784\u8c61\u9501\u5b9a\u5728\u4e00\u4e2a\u5e73\u9762\u4e0a\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Malachowski\u548c\u4ed6\u7684\u540c\u4e8b\u8fd8\u5bf9\u8840\u7ea2\u7d20\u94c1\u7ed3\u5408\u54aa\u5511\u73af\u7684\u4fee\u9970\u7684\u5173\u952e\u53ca\u5176\u5bf9IDO1\u6291\u5236\u7684\u5f71\u54cd\u8fdb\u884c\u4e86\u63a2\u7d22\u3002\u4e3a\u4e86\u63a2\u8ba8\u6742\u73af\u4e0e\u8840\u7ea2\u7d20\u94c1\u7684\u7ed3\u5408\u4f5c\u7528\uff0c\u7528\u53d6\u4ee3\u82b3\u73af\u53d6\u4ee3\u4e864-PI\u7684\u54aa\u5511\u3002\u8fd9\u4e9b\u53d8\u5316\u5bfc\u81f4\u4e86\u5316\u5408\u7269\u4e0e4-PI\u76f8\u6bd4\u6548\u529b\u8f83\u5f31\u3002\u4f8b\u5982\uff0c\u5421\u5576\u3001\u567b\u5511\u3001\u5421\u5511\u548c\u544b\u5583\u90fd\u6ca1\u6709\u8868\u73b0\u51fa\u4efb\u4f55\u6291\u5236\u4f5c\u7528\u3002\u4f17\u6240\u5468\u77e5\u54aa\u5511\u662f\u4e00\u79cd\u94c1\u914d\u4f53\uff0c\u4f8b\u5982\u7ec4\u6c28\u9178\uff0c\u636e\u63a8\u6d4b\uff0c\u567b\u5511\u3001\u5421\u5511\u548c\u544b\u5583\u90fd\u4e0d\u80fd\u4ee5\u4e0e\u5176\u76f8\u540c\u7684\u4eb2\u548c\u529b\u7ed3\u5408\u5230\u8840\u7ea2\u7d20\u94c1\u4e0a\u30024-PI\u7684\u82ef\u57fa\u53ef\u66ff\u6362\u4e3a\u567b\u5429\u57fa\uff0c\u5c3d\u7ba1\u6d3b\u6027\u635f\u5931\u4e86\u5927\u7ea6\u4e94\u500d\u3002\u53ea\u6709\u5f53\u82ef\u73af\u4e0a\u7684\u7f9f\u57fa\u8fd4\u56de\u65f6\uff0c\u6d3b\u6027\u624d\u80fd\u6062\u590d\u6216\u6bd44-PI\u7565\u6709\u63d0\u9ad8\u3002\u5982\u524d\u6240\u8ff0\uff0c\u8fd9\u4e0e\u7f9f\u57fa\u4e0e\u5421\u5511\u6c2e\u5f62\u6210\u5206\u5b50\u5185\u6c22\u952e\u5e76\u5c06\u4e24\u4e2a\u73af\u9501\u5b9a\u5728\u540c\u4e00\u5e73\u9762\u4e0a\u662f\u4e00\u81f4\u7684\u3002\u867d\u7136\u8fd9\u4e9b\u7814\u7a76\u8868\u660e\u54aa\u5511\u57fa\u56e2\u5728\u4e0e\u94c1\u7ed3\u5408\u5f3a\u5ea6\u548c\u5f62\u72b6\u4e92\u8865\u6027\u65b9\u9762\u90fd\u662f\u6700\u4f18\u7684\uff0c\u4f46\u968f\u540e\u7684\u7814\u7a76\u8868\u660e\u4e09\u5511\u7c7b\u5316\u5408\u7269\u4e5f\u5177\u6709\u76f8\u5173\u7684\u6d3b\u6027\u3002\u603b\u4f53\u800c\u8a00\uff0c\u65e9\u671f\u7814\u7a76\u53d1\u73b0\u4e86\u5173\u4e8e\u82ef\u5e76\u54aa\u5511\u7cfb\u5217\u7684\u4e09\u9879\u5173\u952e\u53d1\u73b0\uff0c\u4fc3\u8fdb\u4e86NLG-919\/GDC0919\u7684\u5f00\u53d1\uff1a\uff081\uff09N-3\u53d6\u4ee3\u662f\u5141\u8bb8\u7684\uff0c\u6d3b\u6027\u4e2d\u5fc3\u5b58\u5728\u8f83\u5927\u7684\u7a7a\u95f4\u6765\u5bb9\u7eb3\u8be5\u4f4d\u7f6e\u7684\u78b3\u6c22\u5316\u5408\u7269\u90e8\u5206\uff1b(2)\u5f15\u5165\u90bb\u4f4d\u7f9f\u57fa\u662f\u6709\u5229\u7684\uff1b(3)\u54aa\u5511\u73af\u4e0e\u8840\u7ea2\u7d20\u94c1\u7684\u7ed3\u5408\u6548\u679c\u6700\u597d\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u4e34\u5e8a\u524d\u7814\u7a76\u8868\u660e\uff0cGDC-0919\u5728\u7ec6\u80de\u68c0\u6d4b\u4e2d\u4f5c\u4e3aIDO1\u6291\u5236\u5242\uff0cEC50=75 nM\uff0c\u5bf9TDO\u7684\u9009\u62e9\u6027\u4e3a10-20\u500d\u3002GDC-0919\u662f\u4e00\u79cd\u53e3\u670d\u751f\u7269\u5229\u7528\u5ea6\u836f\u7269\uff0c\u5177\u6709\u826f\u597d\u7684\u836f\u4ee3\u52a8\u529b\u5b66\u548c\u6bd2\u6027\u3002\u53e3\u670d\u7ed9\u836f\u53ef\u4f7f\u5c0f\u9f20\u8840\u6d46\u4e2d\u72ac\u5c3f\u6c28\u9178\u6c34\u5e73\u964d\u4f4e\u7ea650%\u3002\u5728\u4ebaIDO1+\u7684\u6811\u7a81\u72b6\u7ec6\u80de\u7684\u540c\u79cd\u5f02\u4f53\u6df7\u5408\u6dcb\u5df4\u7ec6\u80de\u53cd\u5e94\u4e2d\uff0cGDC-0919\u963b\u65ad\u4e86IDO1\u8bf1\u5bfc\u7684T\u7ec6\u80de\u6291\u5236\u5e76\u5728\u4f53\u5916\u6062\u590d\u4e86T\u7ec6\u80de\u53cd\u5e94\u3002\u5728B16\u9ed1\u8272\u7d20\u7624\u5c0f\u9f20\u6a21\u578b\u4e2d\uff0c\u8054\u5408\u5e94\u7528\u4e86GDC-0919\u4e0ePMEL-1 T\u7ec6\u80de\u548cgp100\u591a\u80bd\u75ab\u82d7\uff0c\u5728\u63a5\u79cd\u540e\u76844\u5929\u5185\uff0c\u80bf\u7624\u4f53\u79ef\u76f8\u5bf9\u51cf\u5c11\u4e8695%\u3002\u6b64\u5916\uff0c\u5728EMT6\u540c\u57fa\u56e0\u6a21\u578b\u4e2d\uff0c\u5c06GDC-0919\u4e0e\u6297PD-L1\u6297\u4f53\u76f8\u7ed3\u5408\u53ef\u63d0\u9ad8\u76f8\u5bf9\u6297\u80bf\u7624\u6548\u679c\u3002\u8054\u5408\u5e94\u7528\u5bfc\u81f4CD8+<\/sup>T\/Treg\u6bd4\u503c\u5347\u9ad8\u4ee5\u53ca\u8840\u6d46\u5e72\u6270\u7d20-\u03b3\u6c34\u5e73\u5347\u9ad8\u3002GDC-0919\u8fd8\u80fd\u6fc0\u6d3b\u7624\u5185\u5de8\u566c\u7ec6\u80de\u548c\u6811\u7a81\u72b6\u7ec6\u80de\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5230\u76ee\u524d\u4e3a\u6b62\uff0c\u5728\u4e34\u5e8a\u4e0aGDC-0919\u7684\u5355\u4e00\u7597\u6cd5\u5df2\u7528\u4e8e\u590d\u53d1\/\u665a\u671f\u5b9e\u4f53\u7624\u60a3\u8005\u8eab\u4e0a\uff0c\u5e76\u62a5\u544a\u4e861a\u671f\u8bd5\u9a8c\u7684\u5b89\u5168\u6027\u3001\u836f\u4ee3\u52a8\u529b\u5b66\u548c\u836f\u6548\u5b66\u7ed3\u679c\u3002\u603b\u4f53\u800c\u8a00\uff0cGDC-0919\u572821\/28\u5929\u7684\u5468\u671f\u4e2d\u8840\u6d46\u542b\u91cf\u9ad8\u8fbe800\u6beb\u514b\u300217\u4f8b\u60a3\u8005\u4e2d\u67097\u4f8b\u75c5\u60c5\u7a33\u5b9a\u3002GDC-0919\u7684\u8840\u6d46\u542b\u91cf\u4ece50 mg\u589e\u52a0\u5230800 mg\uff0c\u8840\u6d46\u72ac\u5c3f\u6c28\u9178\u6c34\u5e73\u5728\u7ed9\u836f\u540e4h\u77ed\u6682\u4e0b\u964d~30%\uff0c\u4e0e\u9884\u6d4b\u7684\u836f\u7269\u534a\u8870\u671f\u4e00\u81f4\u3002\u636e\u62a5\u9053\uff0cGDC-0919\u7684\u5b89\u5168\u6027\u3001\u836f\u52a8\u5b66\u548c\u836f\u6548\u5b66\u6b63\u5728\u901a\u8fc7\u8fde\u7eed\u7ed9\u836f\u8ba1\u5212(BID\uff0c28\/28\u5929)\u8fdb\u884c\u8bc4\u4f30\u3002GDC-0919\u4e0e\u6297PD-L1\u6297\u4f53\u963f\u7279\u5511\u73e0\u5355\u6297(NCT0271846)\u7684\u8054\u5408\u4f7f\u7528\u4ecd\u5728\u7814\u7a76\u4e2d\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n

17.7.3 \u827e\u5361\u54da\u53f8\u4ed6 (INCB024360) <\/p>\n<\/section>\n

\n
\n
\n

\u827e\u5361\u54da\u53f8\u4ed6\u7684\u5f00\u53d1\u4ee3\u53f7\u4e3aINCB24360\uff0c\u662f\u8d70\u5728\u4e34\u5e8a\u5f00\u53d1\u65b9\u9762\u524d\u6cbf\u7684Incyte\u516c\u53f8\u9996\u521b\u7684\u7f9f\u80fa\u7cfb\u5217IDO1\u9009\u62e9\u6027\u6291\u5236\u5242\u7684\u4e3b\u8981\u4e34\u5e8a\u836f\u7269\u3002\u9886\u5bfc\u8be5\u9879\u76ee\u7684Incyte\u56e2\u961f\u5728\u6700\u8fd1\u53d1\u8868\u7684\u5173\u4e8e\u5176\u9274\u5b9a\u548c\u7ed3\u6784\u7684\u6587\u7ae0\u4e2d\u4ecb\u7ecd\u4e86\u827e\u5361\u54da\u53f8\u4ed6\u5f00\u53d1\u4e2d\u63a2\u7d22\u7684\u7ec6\u8282\u3002\u827e\u5361\u54da\u53f8\u4ed6\u5728\u4e34\u5e8a\u524d\u7814\u7a76\u57fa\u4e8e\u7ec6\u80de\u7684\u5206\u6790\u4e2d\u9009\u62e9\u6027\u5730\u6291\u5236\u4ebaIDO1\u7684\u8272\u6c28\u9178\u5206\u89e3\u4ee3\u8c22\u6d3b\u6027(IC50=10 nM)\uff0c\u5bf9IDO2\u548cTDO2\u51e0\u4e4e\u6ca1\u6709\u6d3b\u6027\u3002\u5728\u4eba\u540c\u79cd\u5f02\u4f53\u6dcb\u5df4\u7ec6\u80de\u4e0e\u6811\u7a81\u72b6\u7ec6\u80de\u6216\u80bf\u7624\u7ec6\u80de\u5171\u57f9\u517b\u65f6\uff0c\u827e\u5361\u54da\u53f8\u4ed6\u53ef\u4fc3\u8fdb\u6548\u5e94T\u7ec6\u80de\u548cNK\u7ec6\u80de\u7684\u751f\u957f\uff0c\u51cf\u5c11\u539f\u59cbT\u7ec6\u80de\u5411Tregs\u7684\u8f6c\u5316\uff0c\u5e76\u589e\u52a0CD86 \u9ad8\u8868\u8fbe\u6811\u7a81\u72b6\u7ec6\u80de\u7684\u6570\u91cf\u3002\u4e0e\u8fd9\u4e9b\u6548\u5e94\u4e00\u81f4\u7684\u662f\uff0c\u540c\u57fa\u56e0\u8377\u7624\u5c0f\u9f20\u5728\u7ed9\u836f\u540e\uff0c\u8840\u6d46\u548c\u80bf\u7624\u4e2d\u7684\u72ac\u5c3f\u6c28\u9178\u6c34\u5e73\u5747\u88ab\u6291\u5236\u4e86~90%\uff0c\u514d\u75ab\u529f\u80fd\u6b63\u5e38\u4e14\u4e0d\u4f4e\u4e0b\u7684\u5c0f\u9f20\u7684\u80bf\u7624\u751f\u957f\u53d7\u963b\uff0c\u8fd9\u8bc1\u5b9e\u4e86\u836f\u7269\u7597\u6548\u4f9d\u8d56\u4e8e\u529f\u80fd\u514d\u75ab\u3002\u6b64\u5916\uff0c\u5728B16\u9ed1\u8272\u7d20\u7624\u6a21\u578b\u4e2d\uff0c\u7814\u7a76\u53d1\u73b0\u827e\u5361\u54da\u53f8\u4ed6\u53ef\u4ee5\u589e\u5f3a\u6297CTLA4\u6216\u6297PDL1\u6297\u4f53\u7684\u6297\u80bf\u7624\u6548\u679c\uff0c\u5176\u4e2dIL-2\u7684\u4ea7\u751f\u548cCD8+T\u7ec6\u80de\u7684\u589e\u6b96\u8868\u660e\uff0c\u8054\u5408\u6bd4\u5355\u72ec\u4f7f\u7528\u8fd9\u4e24\u79cd\u836f\u7269\u5177\u6709\u66f4\u660e\u663e\u7684\u6548\u679c\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u827e\u5361\u54da\u53f8\u4ed6\u7684\u4e34\u5e8a\u8bc4\u4ef7\u4ee5\u4eba\u7c7b\u9996\u4e2aI\u671f\u7814\u7a76\u5f00\u59cb\uff0c\u7814\u7a76\u5176\u5b89\u5168\u6027\u3001\u6700\u5927\u8010\u53d7\u91cf\u3001\u836f\u4ee3\u52a8\u529b\u5b66\u3001\u836f\u6548\u5b66\u548c\u6297\u80bf\u7624\u6d3b\u6027\u3002\u5728\u8fd9\u9879\u7814\u7a76\u4e2d\uff0c\u827e\u5361\u54da\u53f8\u4ed6\u603b\u4f53\u8010\u53d7\u6027\u826f\u597d\uff0c\u53ef\u4ee5\u6709\u6548\u5730\u4f7f\u8840\u6d46\u72ac\u5c3f\u6c28\u9178\u6c34\u5e73\u6b63\u5e38\u5316\uff0c\u5e76\u5728>100 mg Bid\u7684\u5242\u91cf\u4e0b\u5bf9IDO1\u6d3b\u6027\u6709\u6700\u5927\u6291\u5236\u4f5c\u7528\u3002\u867d\u7136\u6ca1\u6709\u68c0\u6d4b\u5230\u5ba2\u89c2\u53cd\u5e94\uff0c\u4f46\u572852\u4f8b\u60a3\u8005\u4e2d\u67097\u4f8b\u89c2\u5bdf\u5230\u75be\u75c5\u7a33\u5b9a\u65f6\u95f4\u6301\u7eed\u226516\u5468\u7684\u3002\u5728\u665a\u671f\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\u8fdb\u884c\u4e86\u4e00\u9879\u8054\u5408\u5e94\u7528\u827e\u5361\u54da\u53f8\u4ed6\u548c\u6613\u666e\u5229\u59c6\u739b\u7684\u7814\u7a76\u3002\u752825\u6beb\u514b\u548c50\u6beb\u514b\u5242\u91cf\u7684\u827e\u5361\u54da\u53f8\u4ed6\u90fd\u666e\u904d\u8010\u53d7\u6027\u826f\u597d\u3002\u503c\u5f97\u6ce8\u610f\u7684\u662f\uff0c\u6839\u636e\u514d\u75ab\u76f8\u5173\u53cd\u5e94\u6807\u51c6(IRRC)\uff0c31%\u7684ORR\u5305\u62ec3\/32\u4f8b\u5b8c\u5168\u5e94\u7b54\u7684\u60a3\u8005\u3002\u5728\u6ca1\u6709\u63a7\u5236\u7684\u60c5\u51b5\u4e0b\uff0cIRRC\u5bf9\u6ca1\u6709\u63a5\u53d7\u8fc7\u514d\u75ab\u6cbb\u7597\u7684\u60a3\u8005\u7684\u4e2d\u4f4dPFS\u4e3a8.2\u4e2a\u6708\u3002\u4e0e\u4e4b\u524d\u62a5\u9053\u7684\u6613\u666e\u5229\u59c6\u739b\u76f8\u6bd4\uff0c\u7597\u6548\u7ec8\u70b9\u66f4\u6709\u5229\uff0c\u540e\u8005\u663e\u793a11%\u7684ORR\uff0c\u4e2d\u4f4dPFS\u4e3a2.86\u4e2a\u6708\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u827e\u5361\u54da\u53f8\u4ed6\u76ee\u524d\u6b63\u572814\u79cd\u80bf\u7624\u7c7b\u578b\u4e2d\u8fdb\u884c\u7814\u7a76\uff0c\u4e0e\u6297PD-1\u6297\u4f53(\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u6216\u5e15\u535a\u5229\u73e0\u5355\u6297)\u6216\u6297PD-L1\u6297\u4f53(\u963f\u66ff\u5229\u73e0\u5355\u6297\u548c\u5ea6\u4f10\u5229\u5c24\u5355\u6297)\u8054\u5408\u4f7f\u7528\u3002\u65e9\u671f\u7684\u5e15\u535a\u5229\u73e0\u5355\u6297\u8054\u5408\u7528\u836f\u6570\u636e\u8868\u660e\uff0c\u8be5\u8054\u5408\u7528\u836f\u8010\u53d7\u6027\u826f\u597d\uff0c\u5177\u6709\u826f\u597d\u7684\u4e34\u5e8a\u6d3b\u6027\u3002\u572819\u4f8b\u6cbb\u7597\u521d\u671f\u7684\u665a\u671f\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\uff0c4\u4f8b\u5b8c\u5168\u7f13\u89e3\uff0c7\u4f8b\u90e8\u5206\u7f13\u89e3\uff0c3\u4f8b\u75be\u75c5\u7a33\u5b9a\uff0c\u5ba2\u89c2\u7f13\u89e3\u7387\u4e3a58%\uff0c\u75be\u75c5\u63a7\u5236\u7387\u4e3a74%\uff0c\u5728\u6240\u6709\u5242\u91cf\u961f\u5217\u4e2d\u6709\u6548\u7387\u226550mgBid\uff0c\u9776\u75c5\u53d8\u90e8\u4f4d\u5305\u62ec\u809d\u3001\u80ba\u548c\u6dcb\u5df4\u7ed3\u3002\u5728\u4ecb\u7ecd\u65f6\u62a5\u544a\u7684\u6240\u6709\u7b54\u590d\u90fd\u5df2\u5f97\u5230\u786e\u8ba4\u5e76\u5728\u8fdb\u884c\u4e2d\uff0c\u5c1a\u672a\u8fbe\u5230\u4e2d\u671f\u65b9\u6848\u7684\u6267\u884c\u60c5\u51b5\u3002\u5728\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\uff0c\u8fd9\u4e9b\u7ed3\u679c\u4f18\u4e8e\u5e15\u535a\u5229\u73e0\u5355\u6297\u6cbb\u7597\u6216\u7eb3\u6b66\u5229\u5c24\u5355\u6297- \u6613\u666e\u5229\u59c6\u739b\u8054\u5408\u6cbb\u7597\u3002\u5728\u827e\u5361\u54da\u53f8\u4ed6-\u5e15\u535a\u5229\u73e0\u5355\u6297\u8054\u5408\u7814\u7a76\u4e2d\uff0c\u89c2\u5bdf\u5230\u4e86\u4ee5\u4e0b\u60a3\u8005\u7684\u53cd\u5e94\uff1a\u66fe\u7ecf\u6cbb\u7597\u8fc7\u7684\u665a\u671f\u9ed1\u8272\u7d20\u7624\u60a3\u8005(n=3\uff1b1CR\uff0c1SD)\uff1b\u975e\u5c0f\u7ec6\u80de\u80ba\u764c(n=12\uff1b5PR\uff0c2SD)\u3001\u80be\u764c(n=11\uff1b3PR\uff0c5SD)\u3001\u5b50\u5bab\u5185\u819c\u817a\u764c(n=7\uff1b1CR\uff0c1PR)\u3001TCC(n=5\uff1b3PR)\u3001TNBC(n=3\uff1b2SD)\u548cSCCHN(n=2\uff1b1PR\uff0c1SD)\u3002\u57fa\u4e8e\u8fd9\u4e9b\u7ed3\u679c\uff0c2016\u5e746\u6708\u542f\u52a8\u4e86\u4e00\u9879\u7b2c\u4e09\u9636\u6bb5\u968f\u673a\u3001\u53cc\u76f2\u3001\u5b89\u6170\u5242\u5bf9\u7167\u7814\u7a76\uff0c\u8c03\u67e5\u5e15\u535a\u5229\u73e0\u5355\u6297\u4e0e\u827e\u5361\u54da\u53f8\u4ed6\u6216\u5b89\u6170\u5242\u8054\u5408\u6cbb\u7597\u665a\u671f\u6216\u8f6c\u79fb\u6027\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u7684\u4e00\u7ebf\u6cbb\u7597\u6548\u679c(ECHO-301[NCT02752074])\u3002\u9884\u8ba1\u5c06\u4e8e2017\u5e74\u5f00\u59cb\u5bf9\u80ba\u764c\u3001\u80be\u764c\u3001\u5934\u9888\u90e8\u764c\u548c\u8180\u80f1\u764c\u7684\u5176\u4ed6\u7814\u7a76\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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17.8 \u5176\u4ed6IDO\/TDO\u6291\u5236\u5242\u4e34\u5e8a\u5019\u9009\u836f\u7269<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u636e\u62a5\u9053\uff0c\u66f4\u591a\u7684IDO1\u6291\u5236\u5316\u5408\u7269\u6b63\u5728\u8fdb\u5165\u4e34\u5e8a\u6d4b\u8bd5\u3002PF-06840003\u662f\u4e00\u79cd\u8272\u6c28\u9178\u975e\u7ade\u4e89\u6027\u3001\u975e\u8840\u7ea2\u7d20\u7ed3\u5408\u7684IDO1\u6291\u5236\u5242\uff0c\u7531iTeos SA\u6388\u6743\u8f89\u745e\u7528\u4e8e\u4e34\u5e8a\u5f00\u53d1(Wyths\u7b49\u4eba\uff0cSITC2016\uff0cPost253)\u3002\u8fd9\u79cd\u5316\u5408\u7269\u88ab\u9884\u6d4b\u5177\u6709\u826f\u597d\u7684\u4eba\u7c7bPK\u7279\u6027\uff0c\u5b83\u534a\u8870\u671f\u76f8\u5bf9\u8f83\u957f\uff0c\u53ef\u80fd\u5141\u8bb8\u6bcf\u5929\u5355\u6b21\u7ed9\u836f\uff0c\u5e76\u4e14\u4e2d\u67a2\u795e\u7ecf\u7cfb\u7edf\u7684\u7a7f\u900f\u7279\u6027\u53ef\u4f7f\u5176\u6709\u6548\u5730\u5230\u8fbe\u8111\u8f6c\u79fb\u7624\u3002\u5728\u4e34\u5e8a\u524d\u7814\u7a76\u4e2d\uff0cPF-06840003\u589e\u5f3a\u4e86\u6297PD1\/PDL1\u8f74\u963b\u65ad\u7684\u6297\u80bf\u7624\u6548\u679c\u30022016\u5e74\u542f\u52a8\u4e86\u4e00\u9879\u9996\u6b21\u9488\u5bf9\u6076\u6027\u80f6\u8d28\u7624\u7684\u4f4f\u9662\u7814\u7a76(NCT02764151)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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BMS-986205\u662fFlexus Inc.\u6388\u6743Bristol-Myers Squibb\u8fdb\u884c\u4e34\u5e8a\u5f00\u53d1\u7684\u4e00\u79cdIDO1\u6291\u5236\u5242\u3002\u636e\u62a5\u9053\uff0c\u4e0e\u827e\u5361\u54da\u53f8\u4ed6\u548cGDC-0919\u76f8\u6bd4\uff0c\u8be5\u5316\u5408\u7269\u5177\u6709\u66f4\u597d\u7684\u6548\u529b\u548c\u836f\u4ee3\u52a8\u529b\u5b66\uff0c\u5e76\u4e8e2015\u5e74\u8fdb\u5165\u5b9e\u4f53\u80bf\u76241\u671f\u7814\u7a76\uff0c\u8fdb\u884c\u4e86\u5355\u4e00\u7597\u6cd5\u7814\u7a76\u548c\u4e0e\u7eb3\u6b66\u5229\u5c24\u5355\u6297(NCT02658890)\u8054\u5408\u4f7f\u7528\u7814\u7a76\u3002\u5230\u76ee\u524d\u4e3a\u6b62\uff0c\u5176\u4ed6\u51e0\u79cdIDO1\u6291\u5236\u5242\u4ecd\u5904\u4e8e\u4e34\u5e8a\u524d\u5f00\u53d1\u7684\u665a\u671f\u9636\u6bb5\uff0c\u62a5\u9053\u7684\u4fe1\u606f\u5f88\u5c11\u3002Fig. 17.5<\/span>\u5217\u51fa\u4e86\u4e0a\u8ff0\u6240\u6709\u5316\u5408\u7269\u7684\u4fe1\u606f\u6458\u8981\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Fig 17.5<\/span> \u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u7684IDO1\u6291\u5236\u5242\u4fe1\u606f<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u672c\u6587\u7531Oncolab\u5fae\u4fe1\u516c\u4f17\u53f7\u7ffb\u8bd1\u6574\u7406\u81eaOncoimmunology: A Practical Guide for Cancer Immunotherapy\uff0c\u4ec5\u7528\u4e8e\u5b66\u4e60\u4ea4\u6d41\u4f7f\u7528\uff0c\u5982\u9700\u8d2d\u4e70\u539f\u7248\u4e66\u7c4d\u53ef\u70b9\u51fb\u9605\u8bfb\u539f\u6587\u8d2d\u4e70\u3002<\/span><\/p>\n


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\u2014 THE  END \u2014<\/span><\/p>\n


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\u6765\u6e90 | Oncoimmunology: A Practical Guide <\/span><\/section>\n
for Cancer Immunotherapy<\/span><\/section>\n
\u4f5c\u8005 | George C. Prendergast, William J. Malachowski, Arpita Mondal, Peggy Scherle, and Alexander J. Muller<\/span><\/section>\n
\u7ffb\u8bd1 |  \u949f\u96ea\u83b9 \u9648\u6653\u610f \u6e29\u946b \u90d1\u68a6\u6021<\/span><\/section>\n
\u7f16\u8f91\u6392\u7248 | \u9648\u6653\u610f<\/span><\/span><\/section>\n
\u521d\u5ba1 | \u5218\u7389\u5a07 \u4f55\u4e3d\u5a1c<\/span><\/section>\n
\u7ec8\u5ba1 | \u8096\u5efa\u52c7 \u738b\u5764<\/span><\/section>\n
\uff08\u8f6c\u8f7d\u8bf7\u4fdd\u7559\u6b64\u90e8\u5206\u5185\u5bb9\uff09<\/span><\/strong><\/section>\n


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\u2589  OncoLab\u5b9e\u9a8c\u5ba4\u7f51\u7ad9<\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u7f51\u7ad9\u81ea\u5e26\u68c0\u7d22\u529f\u80fd\uff0c\u53ef\u4ee5\u6839\u636e\u5173\u952e\u8bcd\u8fdb\u884c\u68c0\u7d22<\/span>\uff0c\u5e76\u4e14\u53ef\u4ee5\u6839\u636e\u65e5\u671f\u53ca\u5185\u5bb9\u5206\u7c7b<\/span>\u8fdb\u884c\u67e5\u770b ,\u5927\u5bb6\u53ef\u4ee5\u6536\u85cf\u65b9\u4fbf\u5728\u7535\u8111\u4e0a\u67e5\u770b\u3002<\/p>\n

\u7f51\u5740\u662f\uff1aoncolab.cn<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u2589  OncoLab\u5b66\u672f\u5bfc\u822a<\/strong><\/strong><\/p>\n

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\u6b64\u5916\uff0c\u68b3\u7406\u4e86\u4e00\u4e0b\u8fd9\u51e0\u5e74\u6512\u7684\u6536\u85cf\u5939\uff0c\u505a\u4e86\u4e00\u4e2a\u5bfc\u822a\u7f51\u9875\uff0c\u5305\u542b\u5e38\u7528\u7f51\u7ad9<\/span>\u3001\u6587\u732e\u9605\u8bfb<\/span>\u3001\u8bd5\u5242\u8ba2\u8d2d<\/span>\u3001\u57fa\u91d1\u76f8\u5173<\/span>\u3001\u5b9e\u7528\u5de5\u5177<\/span>\u3001\u5e38\u7528\u6570\u636e\u5e93<\/span>\u7b49\u5206\u7c7b\u5185\u5bb9\uff0c\u5e76\u4e14\u6574\u5408\u4e86<\/span>\u767e\u5ea6\u3001\u8c37\u6b4c\u3001\u5fc5\u5e94<\/span>\u4e09\u5927\u641c\u7d22\u5f15\u64ce\u5230\u68c0\u7d22\u5de5\u5177\u4e2d\uff0c\u6b22\u8fce\u6536\u85cf\u6216\u8bbe\u7f6e\u4e3a\u4e3b\u9875\u4f7f\u7528~<\/span><\/p>\n

\u7f51\u5740\u662f\uff1adh.<\/strong><\/span>oncolab.cn<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u2589  OncoLab\u77e5\u8bc6\u661f\u7403<\/strong><\/strong><\/strong><\/strong><\/p>\n<\/section>\n

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OncoLab\u77e5\u8bc6\u661f\u7403\u4e5f\u5df2\u5f00\u901a\uff0c\u5728\u5b66\u4e60\u672c\u516c\u4f17\u53f7\u5185\u5bb9\u7684\u8fc7\u7a0b\u4e2d\u5982\u679c\u6709\u4ec0\u4e48\u9700\u8981\u8ba8\u8bba\u4ea4\u6d41\u7684\u5730\u65b9\u53ef\u4ee5\u5728\u661f\u7403\u53d1\u8868\u7559\u8a00\uff0c\u4e5f\u53ef\u4ee5\u5206\u4eab\u4e00\u4e0b\u81ea\u5df1\u7684\u5b66\u4e60\u5fc3\u5f97\u4f53\u4f1a\uff0c\u5176\u4ed6\u5c0f\u4f19\u4f34\u770b\u5230\u4e86\u53ef\u4ee5\u79ef\u6781\u7559\u8a00\u56de\u590d\uff0c\u6211\u4e5f\u4f1a\u79ef\u6781\u53c2\u4e0e\u5176\u4e2d\uff0c\u5e76\u65f6\u5e38\u653e\u4e00\u4e9b\u5b66\u4e60\u8d44\u6599\u5728\u4e0a\u9762\uff0c\u5e0c\u671b\u5927\u5bb6\u80fd\u591f\u5728\u79ef\u6781\u4ea4\u6d41\u4e92\u5e2e\u4e92\u52a9\u4e2d\u5171\u540c\u8fdb\u6b65~<\/p>\n

\u8be5\u661f\u7403\u7528\u4e8eOncoLab\u516c\u4f17\u53f7\u8bfb\u8005\u4ea4\u6d41\u5b66\u4e60\u4f7f\u7528\uff0c\u6c38\u4e45\u514d\u8d39<\/span>\u3002<\/span><\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u70b9\u4eae\u8d5e\u4e0e\u5728\u770b <\/span><\/section>\n
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\u672c\u7bc7\u6587\u7ae0\u6765\u6e90\u4e8e\u5fae\u4fe1\u516c\u4f17\u53f7:OncoLab<\/p>\n<\/blockquote>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

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