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瀹為獙瀹よ祫璁綉

Nature涓ㄤ腑缇庡悎浣滃彂鐜扳€滅檶鐥囦箣鐜嬧€濇不鐤楃殑閲嶈闈剁偣涓庣敓鐗╂爣蹇楃墿

瀹為獙瀹よ祫璁綉鏃堕棿:2019-04-19 鐐瑰嚮: 娆?/span> 鐧惧害鎼滅储

銆愬璇汇€?/strong>姝e鏈爺绌剁殑璧勬繁浣滆€呫€佸闄㈤櫌澹€佸湪鎺㈢储鐧岀棁鏈虹悊鐨勭爺绌朵腑鍙栧緱涓扮鎴愭灉鐨凾ony Hunter鎵€杩帮紝鍦ㄥ叾50澶氬勾鐨勭鐮旂敓娑腑锛岃繖鏄粬棰嗗鐨勬渶鎺ヨ繎涓村簥杞寲搴旂敤鐨勪竴椤圭爺绌讹紱 鑰屼笖鍦ㄧ煭鐭暟骞撮棿瀹屾垚浜嗕粠鏈€鍒濈殑鐩茬瓫鍒癐鏈熶复搴婅瘯楠岀殑寮€灞曪紝浠や粬鏃㈠叴濂嬪張鍏呮弧鏈熷緟銆?鑳拌吅鐧屾槸鎭舵€х▼搴︽渶楂樼殑鑲跨槫涔嬩竴锛屽洜鍏舵渶浣庣殑瀛?.....
TAG鏍囩锛?Nature 鐢熺墿鏍囧織鐗?/a> 涓編鍚堜綔 鐧岀棁涔嬬帇娌荤枟 閲嶈闈剁偣

姝e鏈爺绌剁殑璧勬繁浣滆€呫€佸闄㈤櫌澹€佸湪鎺㈢储鐧岀棁鏈虹悊鐨勭爺绌朵腑鍙栧緱涓扮鎴愭灉鐨凾ony Hunter鎵€杩帮紝鍦ㄥ叾50澶氬勾鐨勭鐮旂敓娑腑锛岃繖鏄粬棰嗗鐨勬渶鎺ヨ繎涓村簥杞寲搴旂敤鐨勪竴椤圭爺绌讹紱鑰屼笖鍦ㄧ煭鐭暟骞撮棿瀹屾垚浜嗕粠鏈€鍒濈殑鐩茬瓫鍒癐鏈熶复搴婅瘯楠岀殑寮€灞曪紝浠や粬鏃㈠叴濂嬪張鍏呮弧鏈熷緟銆?/em>

鑳拌吅鐧屾槸鎭舵€х▼搴︽渶楂樼殑鑲跨槫涔嬩竴锛屽洜鍏舵渶浣庣殑瀛樻椿鐜囧拰鏋佺煭鐨勭敓瀛樻湡鑰岃鍐犱互“鐧岀棁涔嬬帇”銆傝儼鑵虹檶鏃╂湡缂轰箯鐗瑰紓鎬х殑鐥囩姸锛岄€氬父琚‘璇婃椂宸茬粡杩涘叆涓櫄鏈燂紝涓斿ぇ閮ㄥ垎宸插彂鐢熻浆绉绘墿鏁c€傚彟澶栵紝鏅氭湡鑳拌吅鐧屽鍖栫枟鑽墿鏈夊緢寮虹殑鑰愬彈鎬э紝鑰屼笖瀵规斁灏勬不鐤椾笉鏁忔劅锛屾埅姝㈢洰鍓嶈儼鑵虹檶鐨勬不鐤楁晥鏋滈兘闅惧敖浜烘剰銆傚洜姝わ紝寮€鍙戞湁鏁堢殑闈跺悜鎬ц嵂鐗╁拰鐢ㄤ簬鏃╂湡妫€娴嬬殑楂樼伒鏁忓害鐨勭敓鐗╂爣蹇楃墿琚涓烘敾鍏嬭繖绉嶆伓鎬ц偪鐦ょ殑娼滃湪鏈夋晥閫斿緞锛屽苟鎴愪负涓氬唴绉戝瀹跺姫鍔涚殑鏂瑰悜銆?/span>

Nature涓ㄤ腑缇庡悎浣滃彂鐜扳€滅檶鐥囦箣鐜嬧€濇不鐤楃殑閲嶈闈剁偣涓庣敓鐗╂爣蹇楃墿

鍥剧墖寮曡嚜锛?/strong>https://edition.cnn.com

鑳拌吅鐧岀殑涓€澶ф樉钁楃梾鐞嗙壒寰佹槸鍏剁壒娈婄殑鑲跨槫寰幆澧冿紝鍗宠儼鑵虹檶缁嗚優锛坧ancreaticcancer cell, PCC锛?/span>琚瀬澶ч噺鐨勯棿璐ㄧ粏鑳炲強鍏跺垎娉岀殑鑳為棿鍩鸿川鎵€鍖呰9銆傝繖浜涢棿璐ㄧ粏鑳炲舰鎴愬帤鍘氱殑“淇濇姢灞忛殰”锛屾棦淇濇姢鐧岀粏鑳炲厤鍙楀寲鐤楄嵂鐗╁拰鍏嶇柅鐩戞帶鐨勬敾鍑讳粠鑰屼骇鐢熶弗閲嶇殑鑰愯嵂鎬э紝鍚屾椂鍙堟帺鐩栦簡寰堝鐧岀粏鑳炵殑淇″彿鍜岀敓鐞嗗壇鍙嶅簲浠庤€屽ぇ澶у噺寮变簡鍏剁敓鐞嗘€х棁鐘躲€佸鍔犱簡鐤剧梾鐨勬娴嬮毦搴︺€?/span>

 

鑳拌吅鑲跨槫寰幆澧冪殑闂磋川缁嗚優灞備富瑕佺敱鏄熺姸缁嗚優锛坧ancreaticstellate cell锛孭SC锛?/span>缁勬垚锛屽叾鍦ㄦ櫄鏈熻儼鑵鸿偪鐦や腑鐨勫崰姣斿彲楂樿揪90%銆?,2銆?/span>銆?/span>鏄熺姸缁嗚優涓庤儼鑵虹檶缁嗚優涔嬮棿鐨勭浉浜掍綔鐢ㄤ笉浠呬績杩涗簡鐧岀粏鑳炵殑鎭跺寲鍜岃浆绉伙紝鑰屼笖杩樼淮鎸佷簡鍏惰嚜韬殑婵€娲诲拰澧炴畺锛屼粠鑰屼績鎴愪簡鎭舵€ф寰幆锛屽姞鍓т簡鑲跨槫鍙戠敓鍜岃€愯嵂鎬?/strong>銆?,4銆?/span>銆傛澶栵紝鏄熺姸缁嗚優鐨勬縺娲诲浜庤儼鑵虹檶鍙戠敓鐨勬棭鏈?/span>銆?,6銆?/span>锛屾晠鑰屾綔鍦ㄥ湴鍙互涓轰复搴婃娴嬫彁渚涚伒鏁忎笖涓板瘜鐨勮泲鐧藉洜瀛愩€?strong>灏界鏄熺姸缁嗚優涓庣檶缁嗚優闂寸浉浜掍綔鐢ㄧ殑閲嶈鎬у凡琚瘉瀹烇紝浣嗘槸鍏锋湁鏄捐憲鐢熺悊鎬у姛鑳界殑浠嬪杩欎竴鑳為棿閫氳鐨勫垎娉屽洜瀛愬皻鏈鍙戠幇銆?/strong>

 

2019骞?鏈?7鏃ワ紝缇庡浗Salk鐮旂┒鎵€Tony Hunter闄㈠+鍜?strong>鍙插畤鍗氬+銆佷互鍙婂崡鏂圭鎶€澶у鐢扮憺鍐?/strong>鏁欐巿绛夌殑鍚堜綔鍦?strong>Nature涓婂彂琛ㄤ簡棰樹负Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring鐨勭爺绌舵垚鏋滐紝鐮旂┒鑰呬滑鍙戠幇浜嗕粙瀵艰儼鑵虹檶缁嗚優鍜屾槦鐘剁粏鑳炰箣闂翠俊鍙蜂紶瀵肩殑鍏抽敭鍥犲瓙——鐧借鐥呮姂鍒跺洜瀛愶紙Leukemia inhibitory factor, LIF锛夛紝骞剁郴缁熷湴楠岃瘉浜嗗叾浣滀负鑳拌吅鐧屾不鐤楅澏鐐瑰拰鐢熺墿鏍囧織鐗╃殑鍙鎬с€?/span>

Nature涓ㄤ腑缇庡悎浣滃彂鐜扳€滅檶鐥囦箣鐜嬧€濇不鐤楃殑閲嶈闈剁偣涓庣敓鐗╂爣蹇楃墿

 

鐮旂┒鑰呴鍏堝紑鍙戜簡搴旂敤浜庣爺绌惰偪鐦ゅ井鐜涓粏鑳為棿淇″彿杞鐨勯泦鎴愬寲铔嬬櫧璐ㄧ粍瀛﹀垎鏋愮瓥鐣ワ紝閫氳繃鏁村悎绯荤粺鎬х殑纾烽吀鍖栬泲鐧借川缁勫銆佸垎娉岃泲鐧借川缁勫鍜岃泲鐧界浉浜掍綔鐢ㄧ粍瀛︼紝瀵规簮浜庢槦鐘剁粏鑳炵殑鍒嗘硨鍥犲瓙鍙婂叾浣滅敤浜庣檶缁嗚優寮曡捣鐨勮優鍐呬俊鍙疯浆瀵奸€氳矾鐨勫彉鍖栬繘琛屼簡绯荤粺鍦拌В鏋愶紝浠庤€屽彂鐜颁簡杞綍鍥犲瓙STAT3鐨勭7閰稿寲婵€娲绘槸鐧岀粏鑳炲唴鏈€鏄捐憲鐨勫垎瀛愬彉鍖栵紝鑰?/span>鏄熺姸缁嗚優鍒嗘硨鐨凩IF鏄鑷磋繖涓€鍒嗗瓙浜嬩欢鐨勬渶鍏抽敭鏃佸垎娉屽洜瀛愩€侀€氳繃浣滅敤浜庣檶缁嗚優琛ㄩ潰鐨凩IFR-GP130鍙椾綋鑶滆泲鐧藉鍚堢墿鏉ヤ粙瀵兼槦鐘剁粏鑳炲埌鐧岀粏鑳炵殑鍗曞悜鑳為棿淇″彿浼犲锛堜笅鍥撅級銆?/strong>

Nature涓ㄤ腑缇庡悎浣滃彂鐜扳€滅檶鐥囦箣鐜嬧€濇不鐤楃殑閲嶈闈剁偣涓庣敓鐗╂爣蹇楃墿

LIF鍋氫负骞茬粏鑳炲洜瀛愮淮鎸佽儦鑳庡共缁嗚優澶氳兘鎬х殑鍔熻兘涓哄ぇ瀹舵墍鐔熺煡锛屼絾鏄浜庡畠鍦ㄧ檶鐥囦腑鐨勫姛鑳界煡涔嬬敋灏戙€備负浜嗗噯纭湴璇勪及LIF鍦ㄨ儼鑵鸿偪鐦ゅ井鐜涓殑鐢熺悊鍔熸晥锛岀爺绌惰€呭湪鑳拌吅鐧孠PC灏忛紶妯″瀷涓€氳繃閬椾紶瀛︽墜娈电壒寮傛€х殑灏哃IF鐨勫彈浣撹啘铔嬬櫧LIFR浠庣檶缁嗚優涓暡闄や互闃绘柇LIF瀵圭檶缁嗚優鐨勬綔鍦ㄦ晥搴旓紝鍙互鍑忕紦鑳拌吅鑲跨槫鐨勬伓鎬у彂灞曚粠鑰屽欢闀夸簡灏忛紶鐨勫瓨娲绘椂闂达紝骞跺彂鐜?strong>闃绘柇LIFR淇″彿閫氳矾鍙互澧炲己鍖栫枟鑽悏瑗夸粬婊℅em 鐨勭枟鏁?/strong>銆備负浜嗘楠孡IF浣滀负鑽墿浣滅敤闈剁偣鍦ㄨ儼鑵虹檶涓殑鐤楁晥锛岀爺绌惰€呬娇鐢ㄩ拡瀵筁IF鐨勭壒寮傛€ф嫯鎶楁€у崟鍏嬮殕鎶椾綋浣滀负LIF闃绘柇鍓傘€備笌閬椾紶瀛﹁瘯楠岀粨鏋滀竴鑷达紝LIF闃绘柇鍓傚崟鐢ㄥ彲寤堕暱灏忛紶鐨勫瓨娲绘椂闂达紝鑰屼笌鍚夎タ浠栨花鑱斿悎鐢ㄨ嵂鐤楁晥鏇存樉钁?/strong>锛堜笅鍥撅級銆?/span>

Nature涓ㄤ腑缇庡悎浣滃彂鐜扳€滅檶鐥囦箣鐜嬧€濇不鐤楃殑閲嶈闈剁偣涓庣敓鐗╂爣蹇楃墿

 

涓轰簡杩涗竴姝ラ獙璇丩IF闃绘柇鍓傚鏅氭湡鑳拌吅鐧岀殑鐤楁晥锛岀爺绌惰€呭鑳拌吅鐧屽皬榧犳ā鍨嬪厛杩涜浜嗗悏瑗夸粬婊ㄨ仈鍚堢櫧铔嬬櫧绱潐閱囧強椤洪搨鐤楁硶鐨勫己鍖栫枟棰勫鐞嗕互鍘婚櫎鍖栫枟鏁忔劅鍨嬬檶缁嗚優锛屼箣鍚庣殑LIF闃绘柇鍓傛不鐤楄兘澶熸湁鏁堝湴瑙i櫎鍓╀綑鐨勫寲鐤楄€愬彈鎬х檶缁嗚優鐨勮€愯嵂鎬т粠鑰屾樉钁楀湴寤堕暱鑳拌吅鐧屽皬榧犳ā鍨嬬殑瀛樻椿鏈熴€?/span>涓婅堪鐤楁晥鐨勪富瑕佸垎瀛愭満鍒舵槸璋冭妭鐧岀粏鑳炵殑鍒嗗寲鍜屽叿鏈夊己鑰愯嵂鎬х殑鑲跨槫骞茬粏鑳炵殑鐘舵€佽浆鍖栥€?/strong>

鏇翠负閲嶈鐨勬槸锛岄€氳繃閲囩敤澶氫腑蹇?/span>锛堜腑鍥?缇庡浗锛?/span>鍜屽绉嶇被鍨嬫娴嬫墜娈?/span>锛堥澏鍚戞€ц川璋?楂樼伒鏁忓害ELISA锛?/span>鐩哥粨鍚堢殑鏂瑰紡锛岀爺绌惰€呭澶ч噺涓村簥缁勭粐鏍峰搧鐨勫畾閲忓垎鏋愬彂鐜?/span>LIF鍦ㄨ儼鑵鸿偪鐦ょ粍缁囦腑鐗瑰紓鎬ч珮琛ㄨ揪锛堜笅鍥撅級锛屽苟涓斾笌鍏朵粬甯歌瀹炰綋鐦ょ浉姣擫IF鐨勭檶鐗瑰紓鎬ч珮琛ㄨ揪鍏锋湁鏄庢樉鐨勮儼鑵虹檶鐗瑰紓鎬с€?/strong>鐩稿叧鎬у垎鏋愯〃鏄嶭IF鍦ㄨ儼鑵鸿偪鐦ょ粍缁囦腑鐨勮〃杈鹃噺涓庣梾浜虹殑鐥呯悊鐘跺喌锛岀壒鍒槸鍒嗗寲鐘舵€佸強鐢熷瓨鏈燂紝绱у瘑鐩稿叧銆傚悓鏃讹紝鐥呬汉琛€娑蹭腑鐨凩IF鍙樺寲姘村钩涓庤嵂鐞嗗弽搴旂殑鐥呯悊鍒嗘瀽缁撴灉楂樺害涓€鑷达紝璇佹槑鍏朵綔涓鸿儼鑵虹檶鐢熺墿鏍囧織鐗╃殑鍙鎬с€?/span>

Nature涓ㄤ腑缇庡悎浣滃彂鐜扳€滅檶鐥囦箣鐜嬧€濇不鐤楃殑閲嶈闈剁偣涓庣敓鐗╂爣蹇楃墿

鎬讳箣锛岃繖浜涘彂鐜版彮绀轰簡LIF鍦ㄨ儼鑵鸿偪鐦ゅ彂鐢熶腑鐨勯噸瑕佺敓鐗╁鍔熻兘锛屽苟涓旇〃鏄庡叾鎴愪负鏈夋晥鐨勬不鐤楅澏鏍囦互鍙婅偪鐦よ瘖鏂爣蹇楃墿鐨勫厜鏄庡墠鏅€?/strong>鍩轰簬璇ラ」鐮旂┒鎵€寮€鍙戠殑鏁村悎寮忚泲鐧借川缁勫鍒嗘瀽绛栫暐涓烘洿濂藉湴鐞嗚В鑲跨槫寰幆澧冧腑鐨勭粏鑳為棿淇″彿浼犲缃戠粶鎻愪緵浜嗘柊棰栫殑绯荤粺骞冲彴鍜岀爺绌跺伐鍏凤紝涓烘帰瀵昏儼鑵虹檶娌荤枟鍜岃瘖鏂殑鍒嗗瓙闈舵爣鎻愪緵浜嗛噸瑕佸彲闈犵殑绾跨储銆?/span>

Nature涓ㄤ腑缇庡悎浣滃彂鐜扳€滅檶鐥囦箣鐜嬧€濇不鐤楃殑閲嶈闈剁偣涓庣敓鐗╂爣蹇楃墿

鎹倝锛屽熀浜庢湰鐮旂┒鍙戠幇鐨凩IF鍦ㄨ儼鑵虹檶涓殑鍏抽敭鎬т綔鐢紝鍔犳嬁澶orthernBiologics鍏徃灏嗚儼鑵虹檶绾冲叆浜嗕粬浠垰鍒氬紑濮嬬殑宸茬粡FDA鎵瑰噯鐨処鏈熶复搴婅瘯楠岋紝骞跺皢鑳拌吅鐧屼綔涓洪噸鐐归€傜敤鐥呯棁杩涜娴嬭瘯銆?/strong>姝e鏈爺绌剁殑璧勬繁浣滆€呫€佸闄㈤櫌澹€佸湪鎺㈢储鐧岀棁鏈虹悊鐨勭爺绌朵腑鍙栧緱涓扮鎴愭灉鐨凾ony Hunter鎵€杩帮紝鍦ㄥ叾50澶氬勾鐨勭鐮旂敓娑腑锛岃繖鏄粬棰嗗鐨勬渶鎺ヨ繎涓村簥杞寲搴旂敤鐨勪竴椤圭爺绌讹紱鑰屼笖鍦ㄧ煭鐭暟骞撮棿瀹屾垚浜嗕粠鏈€鍒濈殑鐩茬瓫鍒癐鏈熶复搴婅瘯楠岀殑寮€灞曪紝浠や粬鏃㈠叴濂嬪張鍏呮弧鏈熷緟銆?/strong>

Nature涓ㄤ腑缇庡悎浣滃彂鐜扳€滅檶鐥囦箣鐜嬧€濇不鐤楃殑閲嶈闈剁偣涓庣敓鐗╂爣蹇楃墿

“婵€閰朵箣鐜?rdquo;——Tony Hunter銆傚浘鐗囧紩鑷細https://www.salk.edu/scientist/tony-hunter/news/

 

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Nature涓ㄤ腑缇庡悎浣滃彂鐜扳€滅檶鐥囦箣鐜嬧€濇不鐤楃殑閲嶈闈剁偣涓庣敓鐗╂爣蹇楃墿

鍙﹀锛屽幓涓栧凡缁忓皢杩?骞达紝浠や汉鏃犳瘮鎬€蹇电殑Tony  Pawson鐨勫悕瀛椾篃鍑虹幇鍦ㄤ簡璁烘枃缃插悕涔嬩腑锛屽叾璐$尞鏄弬涓庝簡璇鹃鐨勫墠鏈熸瀯鎯炽€?/span>

Nature涓ㄤ腑缇庡悎浣滃彂鐜扳€滅檶鐥囦箣鐜嬧€濇不鐤楃殑閲嶈闈剁偣涓庣敓鐗╂爣蹇楃墿

Tony  Pawson锛?952-2013锛夈€傚浘鐗囧紩鑷細http://www.michaelwosnick.com

Tony  Pawson鍦ㄥ幓涓栦箣鍓嶏紝瀛︽湳鐣屾湁寰堝ぇ鐨勫懠澹板笇鏈涗粬鍜?strong>Tony Hunter鑳藉鎷胯璐濆皵濂栥€傚崕涓鎶€澶у鐨?strong>钖涘畤鏁欐巿鍦?strong>Tony  Pawson鍘讳笘鍚庡啓杩囦竴绡囧崥鏂囥€奣ony Pawson锛氬ぇ甯堢涓栥€嬶紝閲岄潰鎻愬埌锛?ldquo;涓や釜Tony鍦ㄨ繃鍘诲嚑鍗佸勾閲屼竴鐩存槸淇グ锛屽挨鍏舵槸纾烽吀鍖栭鍩熺殑澶╃殗宸ㄦ槦锛屽墠鑰咃紙Hunter锛夊彂鐜伴叒姘ㄩ吀婵€閰?Tyrosine kinase)锛屽悗鑰咃紙Pawson锛夊彂鐜癝H2缁撴瀯鍩熻兘澶熻瘑鍒苟缁撳悎閰皑閰镐綅鐐癸紝涔熷氨鏄痯hospho-binding銆?rdquo;

Nature涓ㄤ腑缇庡悎浣滃彂鐜扳€滅檶鐥囦箣鐜嬧€濇不鐤楃殑閲嶈闈剁偣涓庣敓鐗╂爣蹇楃墿

鍘熸枃閾炬帴锛?/span>

https://www.nature.com/articles/s41586-019-1130-6#article-info

鍒剁増浜猴細瀛愰槼

鍙傝€冩枃鐚?/span>

1.    Chu, G. C., Kimmelman, A. C., Hezel, A. F. & DePinho, R. A.Stromal biology of pancreatic cancer. J.Cell. Biochem. 101,887–907 (2007).

2.    Feig, C. et al. The pancreas cancer microenvironment. Clin. Cancer Res. 18, 4266–4276 (2012).

3.    Omary, M. B., Lugea, A., Lowe, A. W. & Pandol, S. J. Thepancreatic stellate cell: a star on the rise in pancreatic diseases. J. Clin. Invest. 117, 50–59 (2007).

4.    Apte, M. V., Wilson, J. S., Lugea, A. & Pandol, S. J. Astarring role for stellate cells in the pancreatic cancer microenvironment. Gastroenterology 144, 1210–1219 (2013).

5.    Corcoran, R. B. et al. STAT3 plays a critical role in KRAS-inducedpancreatic tumorigenesis. Cancer Res.71, 5020–5029 (2011).

6.    Fukuda, A. et al. Stat3 and MMP7 contribute to pancreatic ductaladenocarcinoma initiation and progression.Cancer Cell 19,441–455 (2011).

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