                         ˿µϣ20060407գ

06.04.07, ӡż߻ǡƦӡ
06.04.07, ͬӡƦĩ
06.04.07, ӢȻ鹹ı½
06.04.07, ˾Ҫκȫҽ
06.04.07, ̫ƽˡκȫԺʿ¼Ŀǰ۵ܺۡ
06.04.07, нκȫлһĵĿ
06.04.07, һҽһԱκȫ2000ǰĿоѴƮƮ
06.04.07, NOһԱκȫ2000ǰĿоѴƮƮиС
06.04.07, ֮ޡκڵľ̻һԱ
06.04.07, 齣ӡ˴𸴡һԱ
06.04.07, ĴˡһԱκȫ2000ǰĿоѴƮƮ
06.04.07, ҪѧҪ̣뻪һԱȶ
06.04.07, ʯѧģһκNature Medicineһĵ
06.04.07, zhenzhouϷбı
06.04.07, βͷڡзۡԼһ㿴
06.04.07, ڡ˿ѯ޹˾˿У԰Ļ޹˾
06.04.07, Ф߱ƼϽȨ״
06.04.07, ԬΰʱΪΡʱΡ۷⽨

˿(www.xys.org)(xys.dxiong.com)(xys.3322.org)(xys.xlogit.com)

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ҪⱾ⣬޴бԭ


ӣٶʿǡƦӡ 

ӳ˾Ӧ廪¼

/ 
    ĩ2006.4.6.



1967ڸء1990йƼѧϵҵ
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ܣٵ˲֪Լûܼʱǲ
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һԼҲ֤˫ͬķλá

ַҺܾܺЦ

ܣʲôоѧ٣

ӣҵĴٲһʼͼƻõģŻһչġ1998
оһڵԼȤд
֮ǡϵġ2000꣬ںܶ౨ֽˣϿ̫
ĿƼĸ䡢ţѧ棬˻ɡ
ͨߵĽҴӴſʼ뵽ѧٷ档
ʼǹעЩӹعƭˡ

ܣִ˲ƣѧٵĶʲô

ӣҲûִ˲ƣ2001Ҿ˵һġֵ
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ӣǸȽִŵˣԼĶλҲǸ
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ֻҪ¶ʵҲν

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ӣѧǷǷ⣬߱ദ壬ѧ
ð٣Ҹ˺ûжԹҶ²ˡ

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ӣû֤ϵֻǷ񡣡ӡҸʱ
Լȡı ۡڹҲСۣӡǼ
ҴˡӸʱҾͼȰѧҲѧϣԼܼʻѧ
ѧҶСĴг˷ˡ

(XYS20060407)

˿(www.xys.org)(xys.dxiong.com)(xys.3322.org)(xys.xlogit.com)

Ʀĩ

ߣͬ

֮У̯ȥһݿзӷ̸¼ġĩ

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תһ룬ʵҲûʲôóԾģ޷Ϊһʱ䣬
Ӵٺò׼˵Чý屨ܸߣҲƵƵڵ
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棬ݱֽûٶһ֣ԺҲ
Ȥζ£ΪʲϧһѵĻûʲôƦ

(XYS20060407)

˿(www.xys.org)(xys.dxiong.com)(xys.3322.org)(xys.xlogit.com)

鹹ı½

ӢȻ2006.4.6

ʲô˼أ밴ɯʿǡŷҶе̨ʣ
廪ѧҽѧԺԺύһ֮˸ְ
һƪ"H. Liu"ڡͨѧ־ϵġϸ£УϤ
ŦԼɽҽѧԺоԱд֮˹

Уȥʮһ´ӷ֪ġλλʥǸ
ﻯѧѧߴһеվйѧٵĴš˵ڵ
һٱ֮󣬶廪վϵ˵顣ҷе
Ļ߲ڣˣ˵

Уڵ֮Խ͡

룩

Nature 440, 728-729 (6 April 2006) | doi:10.1038/440728a

Fantasy reference list leads to the sack

What's in a name? Hui Liu, assistant dean of the medical school at 
Tsinghua University in Beijing, got his job after submitting a resume 
that cited, among other things, a paper by "H. Liu" in the Journal of 
General Virology. He lost his job last month when the university 
learned that the paper was written by Hong Liu, a researcher at Mount 
Sinai School of Medicine in New York.

The school was told of the problem last November by Shi-min Fang, 
a San Diego-based biochemist whose home page is a popular place to 
post rumours of scientific fraud. Following up an anonymous tip-off, 
Fang says he investigated Liu's resume, which had been posted on 
Tsinghua's website. "I found that several papers were either 
non-existent or belonged to somebody else," Fang says.

The university's investigation led to Hui's dismissal.

(XYS20060407)

˿(www.xys.org)(xys.dxiong.com)(xys.3322.org)(xys.xlogit.com)

Ҫκȫҽ

˾

κȫ2000꣭2003乲˶ƪ,ûʱϸͳ,
ԭѾᵽƪ,ֿ7ƪ⿯ϵ.ţ
һͳǲȫġ

1.A gene therapy for cancer based on the angiogenesis inhibitor, 
vasostatin, Gene Therapy (2002) 9, 1207C1213

2.Immunotherapy of tumors with vaccine based on quail homologous 
vascular endothelial growth factor receptor,BLOOD, 2003 _ 102, 5 

3.Immunogene therapy of tumors with vaccine based on Xenopus 
homologous vascular endothelial growth factor as a model antigen, PNAS 
September 25, 2001 u vol. 98 u no. 20 u 11545C11550

4.Inhibition of Tumor Growth with a Vaccine Based on Xenogeneic 
Homologous Fibroblast Growth Factor Receptor-1 in Mice, THE JOURNAL OF 
BIOLOGICAL CHEMISTRY Vol. 278, No. 24, Issue of June 13, pp. 21831C
21836, 2003


5.Immunogene Therapy of Tumors with Vaccine Based on Xenogeneic 
Epidermal Growth Factor Receptor1, Journal of Immunology, 2003, 170: 
3162C3170.

6.Immunogene therapy of tumors with a vaccine based on the 
ligand-binding domain of chicken homologous integrin beta3. Immunol 
Invest. 2002 31:51-69

7.Active immunogene therapy of cancer with vaccine on the basis of 
chicken homologous matrix metalloproteinase-2, cancer res 65,600,2003.

һʵĳɼ,ʵǲ.ϸЩ
Ժ,ҵ.˵еļ.

κʵƷǳ,ǳ,,κnature medicineһƪ
д,õͶ
HUVEC,HUV-EC-Cs,HDMVECs,GEN-T,SVEC4-10,T/GHAVSMCsBϸ,PBSһ8,
ע10^2-10^7ϸС.5ϸ꽨ģ,Ѫ
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һֻСʧܵ,ܹپ͵7200ֻ.ƪ,κ
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һƪImmunotherapy of tumors with vaccine based on quail 
homologousvascular endothelial growth factor receptor, ʹVEGFR-2
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ͬоо,ʹqVEGFRΪ磬 mVEGFR, Alum PBSΪգע
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飬800ֻټʵ飬֪Ҳǧֻ
ƪǾͲϸˡ

һκʵ鶼ǳڹ۲ʵ飬Cancer Resᵽ
ĶӰ죬ôһֱ۲쵽Ȼnature 
medicineһҲͬļBlood Уᵽ۲14£
ܴСûܵӰ죬PNASУҲǹ۲14
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˵ֻҲκôĲҵô
ȻҸйһĻڵλʱṩ
Ķ

ʹһɵǣκĶֻʾ˹۲50ҵĽ
ͼʾ50ʱСδȫʧЩ˵
Ը֪ǣЩƺʹսǿе
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ͷ. 

(XYS20060407)

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κȫԺʿ¼Ŀǰ۵ۣܺ2006.4.6 22:00

ߣ̫ƽ

ȻκǴ2000nature medicineϵģô
ԴĽм򵥵Ľ÷пΣ۵ʱԻؿ

κȫNature Medicineimmunotherapy of the tumors with xenogeneic 
endothelial cells as a vaccinenature medicine 2000, 6(10): 1160
1166½

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1.

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ƣbiw4ӦñȽȷ4ܡʹӻ˻
ʧҴʱҲ϶Գͼ2
Сĸ֯δָӦ

3.Ƥϸȷ

ΪȷܻƣòͬHUVECsSVEC4-10ߺδС
򵰰ƤϸϸʵࡢСţ
Ƥϸͼ3ϸá

ʵСĹת򵰰׿Чͼ4
Ƥϸ򵰰׺ٹתƾûãͼ4Щ
ƤHUVECsСѪȾɫԣSVEC4-10СѪ
ȾɫȴΪԡδ

HUVECsСѪ΢ѪȾɫҲԣδСѪ
ͼ5aѿ֯ͼ5b֯ͼ5cȾɫͬ

黯⵽HUVECsС֯Ƥϸ򵰰׳
ͼ5dûСδߺͷС
֯Ƥûгδ

3.Ѫɵ

ֲⶨߺ΢Ѫܶȵı仯ͼ5eƺ
ʱܶȽͣͼ5eù̵ʵѪƺѪܳȡʱ
Ѫֱڶ飩687281ֱͬHUVECs
ߵСвⶨҲõƽ

4.CD4+T ϸڿеĹ

δʾTϸ÷Ӧͬʱע俹CD4Ŀ弰
ҲûбáԿCD8NKIgGӰ쿹ܣͼ6a
ڵ4ߺ7ѪߵףձȽIgG1IgG2aIgG2b
ӣIgMIgAӡCD4+ TϸСƤϸͼ6b

5.ܵĽ淴Ӧض
ƤϸȡʵѪһwestern blotʱжԴͼ
7ab220kD130kDVEGFRIIav integrinСơELISA
δҲ֤ʵ˵㡣˺СVEGFRIIav integrinͬԴԷֱ
8289Ȼϳ42һԶУȻѪýELISAעС
ⶨ߻ԡ3Խ1
СѪпãСĶߵСѪ
޿á

6.

мָ߿ܲͬϵͳĿá
δƽϸBܰͽϸҲá

ΪCD8+TϸڿãȴCD4+Tϸá

淴Ӧӵıλ

4޷֪Ѫطӹдһо

Ĳûϸ

һƪл־ֺɫϸյС󿹶Ժɫ
߷Ӧ20013µ232ڣ118121Ϊģۼڼ
С㣬׸

һƪȽҪImmunogene therapy of tumors with vaccine 
based on Xenopus homologous vascular endothelial growth factor as a 
model antigen.Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11545-50.
ϻNature Medicine·ݣЩͬ

ڴ˴¼жҪӿ͹ϽУ˫ϵĿΪ֤
Ĳ֣ͣϵۻһЩԽǿҲױ
ĲϡôǿľģҾȻӦôӷصĿʼһ
Щ¿߳ʧ٣ȷʵڵĻΣ
ǰӻ

Ŀǰ˫ѾûкͽĻȡͶע
һʶѵͬͬǷǳģҪ
֤ݣ֤ϡʶϼȥ񶨶Էǲ԰ģ
ҶԺĸоطصʱ̣xjĻ
κܰأתžŵȥˡ [w38 ]ܷNobel
ǵǿȥ²⣬κܷ񰾹ؾͱ֤˵
κ飬Ϊ֪ĵƾʲô϶Ѿŭ
ȻǰҲй¼ܵսĲǲͬģҲûǰλӲ
ظ漰Ŀ弫ΪشҸ˾õе
λ¡ţ˵ʱΨһֵҵǵµѧֻû侮
ʯκԾܻáͷμѧһˡ
ο֮еֻţΪǴһЩ©ģĿǰ
Ӧǳϵģʹ˰ݣҲֵóϣЩΪԱ
˵ĿǰƿѧԺҲûпܡκԺʿһҪ
Ӧǰ̲𺦹Եһ׼ְ
һҵ꣬ȫ׼һƴףλҵ꣬
Ǽҳ㷹һκѺ

ʽǰԼ£ȲܰĳĳȨй
жǷǣΪ¼⼰˶ԣһǴ¡Ժʿ
һ֤ݡרҵʿЩרҵԼԦ֣̽
¼ȨʥNatureScienceı༭רҵˮ׼;ҵ
ʧβҪĳĳۡʵ顢鼮ʱʱˣ
ҪעǴ£ҲԴµ彫Ƚνչ׳ΪЩ
δؽʱĿ顣һʵ˵ÿѧʵеĿ͹
˵֤˵˵ǵһʱµ֤ʵ˵

ԹͶκԺʿ¼֤ݵǿΪ˳չ

ÿ۵Ľṹգʡݡط͡Ĵ
[ ]ڸЩֵԴֻ˿ڵ£ֻ
ʽһdajiaµweiyuquan*ļ֣ԺΪw*⼸ƪ
ӵ£Ϊf**Ĵ˿վԭļһ¡
Ҫʱ»עԴʵԴµʽҪ
ʱ޸ġֱȡ˾κʻشڹڼж
ʶͬ˵Ĺ۵ֶ

һNature Medicineص

1
Уκʹϸ꣬LewisΰFM3A 鰩ȣ
һģһȫصһ𣬶20ԺͬС
ǲ˼ġ

ݣ

طͣ

ߣҿͼһȫMeth A ϸͼMeth AH22
MA782/5SϸLewisΰֻͼBֻͼһͼߡ
֪Ƿ⣿黯ͬ˾ڵĽ飬ӦרҵĲѧ
ҰѰѹء[w17]



˵㻹ǱȽȷģȻ˾⣬ǵˮƽġ

2

ĴСֱʾ֪βġ

ݣ

ΪϸСƤº󣬳ε,ֻǱ
ԲεĺͲεģһ㶼,ʹǰĹʽм,ѵ
κԺʿõϸСǺͨĴһ᳤ֵ
Ρ

Nature Medicine (NM) ֱǲһ
ͼĴʵںʶһ󣬶Բԡһ
εģҼĴ󲿷״ǲģȡǸߣ
[w28]

Nature Medicineеͼ2Ҳи⡣ͼУκԺʿ
ֱʾĴС˾ڹ˵ģκУĴС
ֱʾҲ֪βġΪϸСƤ
󣬳εģֻǱԲεĺͲεģһ㶼
ߣʹǰĹʽм㣬ѵκԺʿõϸС
ͨĴһ᳤ֵΡκԺʿ˵
ֱʾСǿԵģҲô˱˵ƪΪ
κԺʿûβ⡣ҶκԺʿԺУ
ҲֱʾСȫʾˡҵ
ǣκԺʿƪУβģ״Σֱ
гж̣κԺʿõľǳǶ̾ǧǶԶó
ʵö̾[f2]

طͣ

κԺʿѴǲȡĲֱֱⷨ3ֱȡƽ
ֵ[f3]



ҪNMΪֱʵ
ǽΣַӦöԡǲΣWHOй涨
ȻͨⶨֱҲԣܴͬ󣬲ָ
۲ֵļ¼ܴﵽľȷʵָô
ҪؼҪ˵ǷϡܵʱûͳһĹ涨Բܿ
󡣲κNMûи巽ǲ׵ģڷʹñȽϻҵʱ
ڡ

3

κУͼ2ʾƤϸԺСã
7ʼע磬4ܣӻˡȻ
ͼ2ʾֺԼ14켴ߺԼ7Ѿ
ʼˣôأ 

ݣ

˭֪ԿԭķӦҪʱģʹǲ߷ӦҲ
Ҫһܵʱ䣬ԷӦǿǲĿԭο
һ缲ôߵһνء

NMУʵоʵǶ
established tumorơͼУϸ7ʼģ
ʱûestablishⲻìκδãҲֻ
˵Ԥãá[w28]

طͣ

nature medicineеͼ2л־ͼ2ʱıǲһ
ģnature medicineеͼ2ʱָDays after tumor 
injectionͼʾмѾ˵ˡ벻Ҫ߻Ϊһ[f2]



NMе˫ûֺ˾Ϊ
ֺԼ14켴ߺԼ7Ѿʼˡ˼顣Ϊʱ
7첻Ϊestablished tumorǰҪظʵԻ
𡣺ͨòͬ֡Ƽʱ䣨1234ܻ
ࣩʵ鲢۲ߡ

NMͼ2ͼα˻һЩ뷨Ӧòʵ漰
ͨ߸ָ꣬ԱȱµĽϾͼ2
ĸ߻ЩӽġκҲͬӦʱΪ1
˵NMл־Ϊ1ܴʼתۡ
ʱӦǿʼãӦüһʱſʼתۣ
γһߵӳ󣬳һʼȫ1Ҳ
ãôʼӦ1ܻ磩Ǳ˵ڡ

4

ͼ5ʾ黯֯΢Ѫļ(5-e)ͼ
ȷֺ14212835Ĺ۲ڵ14ʱʵ
Ѫܼû𣬵21Ѫܲſʼ٣28Ժ٣
ͼ2ĽԵì𣬼ȻΪѪ
ܵƵĽôͼ5вδ14ҵ֯Ѫܼ٣ͼ2
ʾһʱѾӻνءͼ5Уͼ5
c֯Ƭе΢ѪܲƤϸĿǣͼ5-e У
GEN-TϸߵСȻ֯еѪܷӦôΪʲôֲ
֯ѪƤӦء

ݣκ˻Ͳ֪һ40Massuge
ֶСѪ彨ģ͵ʵ飬Ҳ˾ͬһƪ
ΪƤϸԤͨ߶ڲ˿
VEGFR2 alphaVintegrinõģСǡǡԵı
ԭôѪΪʲôС΢ѪܷӦأ

IntegrinVEGFR֯ѧֲϵ칹ΪʲôǵĿֻʶ
Ѫܺ޸֯Ѫܣʶ֯΢ѪܣFig.5
⵹κԺʿµľˣҲΪѧϵش֣
ͬͬԴͬĶͬһĲͬ֯ȴͬˣ˷ѽ⣡
زѧѧ߼Ը<0.000000000000001%[w36]

΢Ѫܶ (MVD) ۲ͷ˶֪󲿷Ѫܶ
ǲ״ֻƤϸԹǻFig5a ˹йǻģ
ѪӦ 10%ͼȾɫԵĶǹĹǻ 
˵߷ӦëϸѪܡ͵СѪƤϸ԰Ӧ
ӽƤϸFig5c ֯Ƥϸȫԣ治⡣
ѵ˿߶ѡĳ͵СѪܵƤϸ˿
΢ʹǣ˴ʾԵѪӦѪ 1/10 (󲿷
Ƥϸ)ȫ𣬶Ӧ̫Ӱ졣[w54]

طͣ

ΪʲôȾ黯˶ֻ֪ͬ
黯ȾɫžжԱȵ壬Ҳǽձ֯оƬ
ض׵ıĳ֮һܽ׼ȷرȽоڲͬ걾֮
Բ졣΢ѪӦIntegrinVEGFRԵʱ
ͨúʵĿϡͶȣֻȾɫѪܶȾɫѪܣ
Ӷʾ֯еױˮƽĲ졣ģ
ʼѪģ͵йأձԵĽۡ[w42]



ΪʲôͬIntegrinVEGFRӣȾɫȴͬʵ
ϡͶ¶ڲͬˮƽԭȾɫʾ졣Ǻ
ģͬʱҲ͸¶һʵ鴦ļɡNMߵı쾿Σ
дظʵ顣Ӧȷκû˵Ⱦɫ
ģͨƪκҲֻΪӡܡҪɫ
ѡȾɫӦǸ࿹ԭ߳Ӧ֡ô
ôԣСѪ࿹ľͲѪ
֯㹻ķӦҪͬظʵ鲢黯ش

⻹Ǹ⣬κȻΪСѪɼйأ
֮һ˾ָ⻹Ǻܼġͼ5eͼ2ȷʵìܣѵһ
ãƺ1ܣ߳ѪѪûм
٣ѼСڵĸӦѸٰκҪ
͡ɲصСظʵ顣Ͻ޷ŷ

5

κķƵ֧ͬǲͬû֧֣κ
ĴϵɡҲķѧɣ

ݣ

ȻӦҲҪӦĿ, ϸҲһӦ, 
ӦĿô˵κĵĺġϸƷκ
ELISA⵽򵰰ǴӺζ㲻ڰﵹæ
ѧʶҵȣϸºѡε֪Щϸ
עСܱأвǽ̵˱кܶ൰ˮ
Ê𣿱˵ø߸£ڻкֿܶɽϸĤ֬ˮÊ
[w27]

κڴ˾ʱ˴(Scappaticci, F.A. et al, 2003, 
Polyclonal antibodies to xenogeneic endothelial cells induce apoptosis 
and block support of tumor growth in mice. Vaccine, 21:2667-2677)֧
ϸƷһԭı֪ɶ¡Stanfordѧ
ŶԴһ㡣һõƤϸӲĶ
¡۲ϵĿãνġϸƷ
ȷ˵俹ԷƤϸн淴Ӧκ죻
Western Blot޷ȷκοԭףж״100kDa
ԣκԺʿҪʲôܵõʲôסڴֻǼм
˵κԺʿһص˵¶ѡ[w27]

еĹͻƲ˵ģ̫תҪһ
ϸϸľжֿԭĽṹȻܶопԭ
Ӷܲ壬ҲǶԴ󲿷ֿԭǾ󲿷ֿԭҪģ
ѧûйɿѭˣҽҲûа취ˡ

طͣ

κȫڻش˾кĽһ㣬һ
νѧԭһʵ飬ǲѧġ˾ᵽѧ
ԭָһԭһӦѾƫκȫʵݡӦ
óϲеϸɷֶпԭԣпԭ߻пԭǿ֣
ӦҲҪӦĿ壬ϸҲһӦ𣬵Ӧ
ﲢ漰ѧԭǷʱ⡣[w19]

лл˾ʦ2001232ص ֺɫϸյ
С󿹶Ժɫ߷Ӧ ļоֺɫϸ
յԺɫ߷Ӧһԭѵõλоߵ֧
֤ʵʹôӺɫϸзĵַӡϸԴַ
ӻϸյԺɫĿ߷ӦGold, JS., 
et al, The Journal of Immunology, 2003; 170: 5188-5194; Hawkins, WG., 
et al, J Surg Res. 2002; 102: 137-43; Roberts, WK., et al, Blood, 2002; 
99: 3748-3755; Scappaticci, FA., et al. Vaccine, 2003; 2667C2677; 
Sioud, M., et al. Eur J Immunol 2003; 33: 38-45ȣ[עȻ
лµģۻһµģһڴˣ]

кܶ๫磨вѯڶģ͵ף
ضģԤЧȷʵôãҿСĸ
״̬ءϵٴĽȴԤƵ̫ԶЧСҲ˵
ߵĸԡʵϣڸֿƵĶʵУСֲ
ԷȫƲʲô𾪵ĳɹܴﵽЧıѾ
вѯֿƵףٴûбˡ
[w42]



Ҳǰ;ȾСڵۡκĹ۵죨֣
ϸӦʵãΪϸߡҺ߶롣
㲢û⴦رֶΣϸʹáȷ
ΪȫκʵĿԺýۣҪ۵
˼ָõʵݵʵԡµı޷κ
ܵɣЩֻ֧ǲģȫġ

6

κеӡκʹõƤϸСߣƤ
ϸл־еĺɫϸһĵףΪʲô
СԼֵײ壬ѡԵķӦ

ݣ

ѧĻԭκοԭע;ĸ
֮󣬻ϵͳ֮ӦǰƤϸкüǧֿԭ
˵ƤϸעСԺС󲻿ֻеļֻʮֲӦȻ
κȫȴóѧһԭȫͬĽ

ϸĤ׳ȫϸѪӡֻȼ
ʮ˸е֡⣬֯ϸ϶еһҪ֯Կԭ
MHC-I࿹ԭƤϸΪְԭϸMHC-II࿹ԭ
MHC-III࿹ԭоֲ֯ųⷴӦʱֵģֲųⷴӦ
ҲӦӦʹֲͬ֯ϸע䣬ֻҪ
֮MHC-III࿹ԭϣͻǿҵӦ𣬲϶
MHC-III࿹ԭĿ壬˵֮䣬˵ƤϸעС
Ӧò࿹塣ͼ7aֻܼһǷ
СԼ30KDһ220KDκȫΪVEGFRII
رMHCԭص[w10]

֯ԿԭĶԺ͸ͬһͬ
֮ѧϲķӣȻҲǲ֮ͬԭԲķ
µ֪ʶĹ۵㣬ͬó֤ݣһͬ
ԴԶԶﲻԭԲ졣ѧһʵл
ͣףϸӦMLR䱾ʾǲ֮ͬMHCӵĲֱ
ԷϵͳȻϸߡͬMHCԭټڶͬ
Դ嵰ףˣƤϸСĿֹֻʶʮֵ
?ǧĵͬԴ칹ֻԵʾintegrinVEGF
ûʾintegrinӵͬԴ칹гǿԭ԰
ϵwesternǺܲȷʵġ[w36]

طͣ

˾ʦᵽMHCּĿԭշּġǿ߷
Ӧ֪ͣȣÿԭӦͬĿԭǿҵͬ
߷ӦųⷴӦĻδȫȻMHCԭܲ룬
֤˵MHCǡּĿԭ շּġǿ߷
Ӧ, ֿԭҲܲ߷ӦRossini, A., et al. 
Physiological Reviews, 1999; 79: 99-129; Fox, A., et al. The Journal 
of Immunology, 2001; 166: 2133-2140ȣڱҲûж
߷ӦֿԭмǿǺֿԭҪĹЩҲ
ĿǰڽеĹǳʵѪɸѡϸcDNAĿ⣬
߷Ӧ漰ַӣаMHCӡ ʵ, ʹ
MHCӺɫϸзĵֿԭ100hysonase
ַӻϸҲյԵĿ (Gold, JS., et al, 
The Journal of Immunology, 2003; 170: 5188-5194; Hawkins, WG., et al, 
J Surg Res. 2002; 102: 137-43; Roberts, WK., et al, Blood, 2002; 99: 
3748-3755; Scappaticci, FA., et al. Vaccine, 2003; 2667C2677; Sioud, 
M., et al. Eur J Immunol 2003; 33: 38-45)දģУ
ϸߺյĲδѪ岡Ӧ
Roberts, WK., et al, Blood, 2002; 99: 3748-3755; Scappaticci, FA., 
et al. Vaccine, 2003; 2667C2677; Sioud, M., et al. Eur J Immunol 2003; 
33: 38-45ȣԴȾ(Ҳֳɷ)ڶģͼ
ߣҲɲԵĿ壬ҲδѪ岡ĸı䡣⣬
ʱ뿹ҲδԵѪ岡Ӧյڿ
岢һᷢѪ岡ӦоĶ
ûвı䡣

ۺʵءȣӦǷǳӵģԺܶ
޷͡˾ڽѧԭָġ¡ѡ
ۡȷʵкܶȱݣ磺ĿǰõϸͲ磬ֱ
עڣӦͱЧڼ롰󣬲ſյЧ
Ӧ𡣶ͲôǿܻĿԭ
ͬ¡ѡ޷ΪʲôӡˣһֱŬ
µͣģʽʶΣźŵȡУӦû
СһƤϸпԭӦ𣨾ǼҲ
⵽пԭӦ𣩡ʵأÿַԵ
ƣʹСѲӦ𣬵ҲֻܼҪ[w17]

һֻᵽ˿ԭ⣬WBʾСѪʶĿԭ
Եģ߿ѪŨȣеᱻȾɫҲ
˵ѸַȵĿӦĿԭһӦòֹʮô򵥡
integrinVEGF(VEGFR)ӦǿֻظʵĽ˵
ܲԳΪѧԵĽ͡ڴоѾ֤IntegrinVEGFR
֮ͬ֯䣬Լ֮ͬ䣬ȷʵڱˮƽ
ϵ졣Intergrinָһճӣɲͬalphabetaǻ
ͬɣͬ֯ٵϸƤϸıIntergrinalpha
betaǻ죬Ѿ֤һЩIntergrin alpha v, beta3
ԽʶѪܣʶѪܣ1999Ѿ׼
Intergrin alpha v, beta3Դٴ顣VEGFRҲֶ֣
һָֻӦκᵽVEGFR2VEGFR2ڲڵķֲҲ
ͱ֤нϺõ֯Եģһ߱1999Ϳʼз
俹ҩVEGFR2ǶϿIMC-1C11Ŀǰٴ
ЧԣIntegrinVEGFRоֻ֤ʵǰ˵Ľ̸
ʲôش֡[w42]



Ҫͬ족ּ͡족⣬
κʹ˵Ĺ۵㵹ǶԵġͬǿҷӦƶϵּǿҷӦ
ǲȫȷģµԽܣٿһ¡صӡ
ĽҾô⣬ʵˮƽͻ⣬򲻻ô
һҪظ

7

߸western blottingΪֵף220KD
VEGFRII͵130KD alphaV integrin߷ӦҪԭףȻ
ͼ7ʾĵУ130KDֻһ෴30KDλȴ
һʮԵ

ݣ

˵VEGFRIIڰˮƽ82%ͬģ˵ǵͬԴ
൱ˣVEGFRIIһӦԭӦòǿ
Ӧ𣬵ͼ7aVEGFRIIȴһ[w10]

κڴ˾ʱᵽ30kDaĵײڽнһо˵
ôҷСôҪĵ͸üˣ˵
һȫµĿеءôȥˣôҪĵ׾ӰˡҲ
κԺʿѶԡϸƷȤˣ[w27]

طͣ

ΪʲôӦǿ30kDaףƲҲһע⵽ǿ
ӦҲȥԡǶ֪ʱֻԼΪȷĶ
ʱ޷ȷ͵󣨰30kDaףԺԼ
Ҳܶ࣬ͬʱҲҲɸЩϸԵȥٻ
˷ǵõȵдġ⣬ǿҲһӦ
ȣѡʱһ㲻ǵǿȷбꡣѡһЩ
֪ܵģ֪EGFRչأ˵һ⡣һ
㣬ÿ˾һ»򿴿Щ־¶⡣ǿ
ǣӦǷǳӵģǶһƪֵ
ȫҲоֱܻᷢEGFRIntegrinҪķӣ
Ĳìܡ[w17]



ӡѡڿǶ෽غģܻҲķ
κͲӡûٵǰ£ǸҪѡ
⣬漰¡NatureScienceºCellȫҪͬǰ
עĲּ֧Ӧüֵһ֧ǿȾ㹻NM
Ҫһ㡣Դ˲ܹڿκ

ӦýһǲףκҲû
ûиELISAݣֻӹ֤һֺ֤Ҳ
κ´ӵһؼ裬µNMĹؼء
ǣǿһԾûбʵELISAͼк鷳
Ǳ˴ʵĵطҪκʲôף
ó֤ݡ

8

Ϊ֤ȷʵܲalphaV integrinãϳalphaV 
integrinϸļĶΣ֮߶ֵõԤĽ
һ֤ƤϸСԤļ˵
ַһĴintegrinǵλɵ壬
ĽϽγһĹԱλκɸѡĶβ
alphaV integrinĽϣʹҲ֮ϣ
ء

ݣ

ָκȫϳɵĦV integrinVأϸƬΣ
330-364ƬΣֻ֮һ᲻ͬ1˵Ƭζ
˵ûԭԣ˿壬ƬеVӰᣩΪƬ
еS˿ᣩԭȴǿ࣬ߺ壬ȡúõ
Чͼ7cǺɵġΪѧۣĳƬοԭλе
һᱻûɴİ就û
ԭλԭԲкܴı仯ң330-364Ƭһ
仯ЧڦV integrin 545-579Ƭ8仯
Ч8одİYҰᣩûȥ1
ͼ7cҲ˸еֵġ[w10]

 integrin˵˾Ӧαɷ֣1
alpha-v ĿǰΪֹֻ뵽꿹壬Ϊλ
ʶ壬Դ integrin alpha-v beta-x߷Եõ2ձ
Ϊϳĵõ岻ʶintegrinӣ̸ƣֵκԺʿ
Ȼ֪ integrinpeptides֮Чepitope over 
lappingĽܣдЧƱǰ;
[w11]

˵ͼ7c⻹1һ˵ᵽļpeptide
㹻߷ӦӦ򵰰ףǾalpha-v interin 
(330-364)ԣȫĻѧѧʶڴƬУ
С֮Ψһǵ24λİᡣ˵˿ᣬС򡰱ᣬ
˿򡰱֮𲻴ôϸ΢Ĳ34peptide
ǲܲ仯ģڿռ乹ҲԵĲͬ (÷ģ
֤peptidesǻص)Ȼˣͼ7c˵alpha-v 
interin (330-364)С򵰰ôĿ
أͬΨһĽ;ͼ7cҲαģ˲²⣬ҲκԺʿƬ
˿ᵱĳÊĻء[w15]

ȣ֪ǱÊ彵Ϊ8-11ᡱʲôÊ
أֽĸλ㣿ڵ׻PEPTIDEÊĵǺǿ
ģҪ⿴KRΪˮλ㣬ΪȫTRYPSINء
Σ˿һڻѧλ㡱ǲܸ߱
 alpha-V-integrin-H(330-364)ĵ353˿ʲôĻѧβ
ôĲأữ׻ữˣˣҲӰ
ṹͿռ乹ΰɡʲôףô˵ʲôף
Ê߻أΪʲôֲSTأ㲻ѧ
һ±˵Ļѧ[w27]

BϸTϸԿԭʶǲͬģBϸʶĿԭλǲҪӹ
Ϊĵġ

׷2000nature medicineλpropeller domainǶ
˵integrinϸöϿaccessibleİΪ2-3⼸
лӦ3-DṹڽģһṹԶĲлͬγɱλκ
һؽpeptideͲintegrinԿ塣[w47]

طͣ

εķûпǵԭڵļӹ̣ԭȱ
APCϸø彵Ϊ8-11ĶģIIHCMϣһ
߹̡ӻѧϷһĲ죬
alpha-V-integrin-H(330-364)alpha-V-integrin-M(330-364) û̫
ѧԵĲ졣ϸڵḴӵö࣬˭Ҳ֪һ
ĲǷıøλ㣬Ƿ׵໥÷˸ı䣬˿
һڻѧλ㣬򡰱Ͳˡûѧ
ѧڻʱ[w19]



ҲܲһҪ漰άṹǱȽϸӵĵ׷ӽṹ֪
ʶȴκԷ׽úȷάṹ
ǵ壩ԵģôΪһԶģ⡣Ȼ
νĿԭʵݣʹðɣνġ߶̬ԡ
ԶԶġ3ܷӦӦ𾿾ǿû
ԿҪ֤֯Ծʹ˻ɡнṹ
רҿԿһ3ĵĿռṹǷԣǷȷľλ
ȵȡӷһӽṹˮƽѹNM༭ۻҡ
ϿǵģԽɡҪظʵشҾе⣬κ
ô˼·ǲ֪ӼʶĻɻո˵󰡡

9

ͼ7aʲôŨȵĽַܳpatternκϷݶ
[w12]

ݣ

markerõĴHigh-Range Rainbow Molecular Weight Markersм
ٱ6630齺жϷΪʲôףȻһǹ
Ҳֻκʵˡ[w12]

־صһͼ7̸7a˵7cͼ7aУ׷ıʾ
22097.446 21.5kDa֮伸ǵȾġδ˵õǺ
ŨȺͺֽʲҼӲ²⡣ʲôŨȵĽʹ4-12%
4-20%ݶȽֻҪܹ׵ӾļԱӦ֪ǲܵġԭ
ܼ򵥣õŨȽĻ21.5kDaĵӦܵײĩˣ֮
øŨȽĻ220kDaĵ׻ԭλδδ׷ֿ
ݶȽĻֱ׼ҲֵܳȾλơôΨһĽ
;ͼ7aαģ[w15]

׵ΪʲôҪ220kDa׼޳κв˵220kDaĵ״
VEGFR-2˵ڡδܿ£ʲôWesternѽ㲻
ڰﵹæ[w27]

طͣ

SDS-PAGEܵľ͵ʷĶɷȡ
22097.44521.5ĵֱΪ0.430.500.600.75ǵ
δܿһŽλʼ10%ȵĵȷ㣬ˣ
Ϊ220ıǲơԽĲļǻȾ, ֽ֧ĶԸͼ
αĽۡ[w19]



ͼ˵ٺǺܺʣֻǴŵȾ࣬ͼ
ǳףֻǵӾܵòôƯ֮ͼҿر쳣
κóʱĵƬһ㶼ǻᱣģ֪NMյʱǷҪ
κṩƬ

10

Ҳ˵öĵĿԭԵ⣬ĿԭƱKLHBSA
ֱ߶ܲ߷Ӧ𣿶ĵעֱϸֵκϵ
һǡŵˡ[w12]

ݣ

طͣ



Ƿѧ⣬ķڷκ̫ʡҸ˸ое㲻
̫СֻظʵشȷʵЧ⵹ҲǱĵһ󿴵㡣

11

κڱĲõһ⿹Ƥϸʵ飨Fig.3
һ£ЧŨȳҲng/ml𣩡ⴿһ߳
ʵ顣[w36]

ݣ

ѧĻ۸ǣЧӦ֣ϸ鵼ϸ
(ADCC)Ͳ鵼ϸCDCκھȻⳣ(
̥ţѪҪģûв)ʵһܣһɱ
ϸ޲壩ɱ˵ɱϸͲ壬ֻdata not shown!
κõЩintegrinVEGF꣬ӵĿ廹ǿԭ
׺ʹģǳͷβļʵ飡[w36]

طͣ

ڿѪԿĺ޷׼ȷش𣬵ԼĶʵ
Ѿ۲쵽õ׿ԭߣѪ壨ãELISAЧ۴ﵽ1
109ηʱͨԿ庬0.2-0.6mg/ml֮䣨ԭ׺Ͳ
ʣʲôngˮƽ[w42]



жϣط֤Ҫһ㡣ظʵӦòѡ

12

һ㲻κԺʿڶʱڴ˴ض򵰰ס
[w15]

ݣ

Ȼвδ͵ʵȣⲢˡ
ʵ裬һ򵰰ףСʡвδ
˵ֻ˸Χ(10-300mg/kg)ȸһΣϸÿ
ܡ˸Сעÿִ򵰰׹7Ρÿ
ʮֻСÿֻСӦ25ңÿԼ250ˡ300mg/kgĻ
ÿעҪ75mgĴ򵰰סע7Σظʵ100%ɹ
㣬ܹ525mgĴ򵰰סȻСǿ߷Ӧпܲ
򵰰(5-10mg/mlȫѪ)ҪءһÿֻСռ
1-1.5ȫѪԵĴ򵰰׵ĺӦ΢ˮƽ˵
κԺʿʹϼʮš񹤡ԼҹزͣСעߣѪ
׵ȵȣһҲӦһСõκԺʿ
ĲרŽһ򵰰Ҳ޿ܡ[w15]

ε֪κȫõȻȫѪgamma-򵰰סκп
ûôȻͬʱԲ˵һǴȫѪgamma-
ǲҪ׺Ͳģһ㴿ԵIgM׺֬κ
CM affi-gel Blue ûôߵ׵Ľϲ
Nature/Medicineġ[w27]

طͣ

ĵĴǰѪ򵰰׺ߵ׻Ϊһ̸κȫõ
ȻȫѪgamma-򵰰ף京ĵΪ5-10 mg/mlѪ壬Ϊ
3-13 mg/mlѪ塣޼㣬ÿ10ֻСҪ525mg50-100ֻСͿ
Ҫ޼㣬Сƽ20(СƷַ࣬زϴ
κδ֪СϵСƽ20˼Ӧ϶ƷϵС)ע
10 mg/kg 㣬ÿ10ֻСҪ14 mg1-2ֻСͿҪ󡣷ǳ
ĿС񹤵ĲҪ[w19]



κȷʵû˵Ҫ򵰰ףĶԭģԭ׺
ҲֻҪõ򵰰ףȥһЩĵףҪԵ򵰰ף
ôҪ˵ԲĴȻõӦЩԵ
ףʹûй

Сڣ

Ŀǰг12⣬3 11㶼д֤ʵκûй
С飨ãظʵ飬3Ӧ㹻۵ĽҪ
ڣ1.κ߷ݡ2.ߵĲϳ3.ͼ2ͼ5e
ìܡ4. western blotting׵⡣5.Ŀԭƺ
ԺԭԡӦ˵κĵľ֣ǴӺ߷Ӧˮ
ƽṹˮƽμԾ漰κЩҪûи
ȷЩҪ֧δǺܶˮƽ¶ڵģ
ʱǣ⡣ڼȻѾܵɣκӦ
ЩҪͣϻֱӵĽܻͣͣ
ϼԷܣиžͽսƽȴСظ
ʵ顣κģͲ»Ҳûвȡжؼ
ϣԷѧֶν£Ϊһȷı֤ʵκڹ
ѧ󣬷֮ʹݲƽϢ̬ҲǶѧһƻ
ϣκ˼ϣпԺйز˼

л־ֺɫϸյСԺɫ߷Ӧ
ص

1漰ʵݽϼڷʴУ˴׸

ͼ2⣨NMPNASGTCRCTµһ
ڴ˻ܣ



κеͼ2κ˵ƿʼߣô
Ͳýˣƿʼʱλϣ10
ףʱֱ2ףֻ1סô,
ģʣκȥвءĶܷ񳤳
޷϶ôܿʼأôܽзء

1Nature еͼ2˵ǲǾСѧѧα˵Ǹ
ǣΪֵͼ2adһError barԽ
ˮƽᡣⲻǿǲ˵пʹΪֵˡ
Ҳ2л־ͼ2ǾһԣԽ
Error barҲԽ󡣸ͼʵ߼Natureͼ2ĸ߶
ȻͼĶȴError barȴͻȻС
̫ҼٶError barָƽĹ۲еʱ
Error barҲĲ췶ΧΪл
־ͼ2һĽͣԵ㿪ʼٶȷ
仯ԭٶȱԭСٶȼӿ죬Ψˣ
ʹô˺СӶԳɹʵError 
barͻȻСôΪʲôٶȱԭСٶȼ
أһܵĽǶһֵӽֵʱ㲻
()ĻǷƲ⣬ڵ25֮
ƽúܡ[w35]

СģͶʵٴ˶֪һֻҲ֪
СģٴܴٴչΪʵȣ
ѪܷǳḻʵԲѪ(״С
û)һڲͻҺȻܴٽѪ
ɵ᳤ôһЩǣκڵƤϸ߾Ȼ
3mmֱֱ3mmʵõųѪ𣿣Fig1ֱʾ
СǲҲŰŴˣƤϸ߲ԿȻ
󲻳fig4Ŀ廹⡣ʵ󲻽⣡
[w36]

ط

ͼ2ṩϣ˾ʦᵽ ϸֺ
6~7Ժ󡱣 ϸƺ6~7Ժͼ2˵
ȷƺʱϸֵʱ䡣 ʱо
ֿЧӦҲ˾ʦᵽĳ߷ӦԼһǺϵġ⣬
ɷֽڿԼǿҵķϸgd-Tϸϸ
ӡصȣYi, S., et al. The Journal of Immunology, 2003; 
170: 2750-2758;  Rossini, A., et al. Physiological Reviews, 1999; 79: 
99-129; Fox, A., et al. The Journal of Immunology, 2001; 166: 
2133-2140 ȣCTLԼ֮ǰǷЩҲ
˽ڿҲֵýһо⡣ڱƣܣǰ
󣵣ϾδһֻСڼԭһǲ
Ʒǻƣÿ2ƣ7ÿܾƣм䲻
ϣϸ˵ǽֵϸԽ٣510^4
˾ʦᵽӦ510^5ͬƱֺɫϸ
нϳ־õĿЧӦʵϣбB16ɫ
50ϲ80%~100%С80%~100%Сȫ
ˣ޲״̬ (Linardakis, E., et al. Cancer Research,2002; 62: 
5495-5504; van Elsas, A., et al. J. Exp. Med., 1999; 190: 355-366; 
Kaplan, JM., et al. The Journal of Immunol., 1999;163: 699-707)
ĵСֻδˡ[w14]

ڼ˱׼Ϊֵܺ⣬SDʱ
9ֻ1cm1ֻ10cmµľֵSDҲǸֵ
һ̶ȷӳһΧͨС
3mm޷׼ȷֱʱֱкĲο壬
Сʱڲ߿ֱ򳤶̾ʱɽץֶ
ơɽֵСֱҲСᷢϴı
CV󣩡һ¶ģȷʵѲ²Ϊ
Ǳڣڣƽ̨ڻܶදģĳʱڿ
ĳΧ֮Գ󣬲ɳںɴ˴61
ϡͣΧģйأҲܿ϶
ɴɡ[w42]



ڴ˵࣬κҲԸʹ˲䷳ĸͣٽ͡ʵ
ĵĶκ岻NM£ָسΣκα˷˱ī
ִ̽⣿Ҫֱ˼̣Ҿκбؾᣬ۵ɡ

ͼıʶȷʵҲȷҵָ壬ǿ
ͨжϵõᵽָֺ֡ɫϸ綼Ϊ
ע䡱µ2ҳ½СڿɱȽϵʱ(ֺ924 d)
ͬʱȽԭͼȷϸֺҾκһҪΪǡ
ʱ䡱ǣǽֺô03mmʱڣҪʵһ
Ҫʱ䣩ӦصͼûеصֻΪǡ
ʱ䡱ܡԲ

ʵûԲΪζһƿʼãͺκͬ
ġʼӦʱҪ1ܡìܡҺNMеͼ2нֺ014
߼صìܡȻκҲͼĵλһҪֱ
ʾ⣨֪κԸԸܣҲϣ
˵ʵģ

κԴ˵ĽǿȫڶԿá
ҲκǰΪҲӻ
޷Բ

ιʽ϶ӡˢΪ4/3**r^3תΪֱ
dʾǣ/6*d^3Բǣ/6*abcΪΣb
cͱʾΪ/6*a*b^2/6Խ1/2ԹʽͱΪ1/2
*a*b^2

۵ĿǰΪֹͬǡƺʱ䡱ʽǣ1/2*a*b^2
κͱµ2ҳ½СڿɱȽϵʱ(ֺ9
24 d)ıǴģԭȹʽӡˢ

ʹ֮ͬ޷Ǻϡͬͬһƪ
Ƶߣͬͬڲͬȴ
ܴߡ[f3]

ڡ50%Сܵơ⣬Ҿᷨ
ȱֵ֧ģ̫ɻδƵǷУûж
ʱжǷƵȡ

ڱ׼صⲻҪͼαжûаС
ݵľʵгִȫпܵģóͳԭ
һŶۡ

Сһ£Ŀǰκڴ˻Ҫͣ1.Ϊߴӿʼû
ϡ2.ɫٶΪγ3. ͬͬһƪг
Ƶߣͬͬڲͬȴ˲
ߡ

ԱκӦԴĸͲ˶ɱָ٣ֱ
ϵıȻظʵǿҪġ

2

ȱһ鲻κƵĻģƵĿհ׶ա

ݣ

ɫһΪʲô飬омǷϿѧԭ
⣬ǼѧαѧԽʯκӦ֪ġ

طͣ



ʵ⣬ԿɴСٵûֱϵ

3

ʵǶԽе鶯Ҳδܽƽй۲죬۲30ң
ʵ۲50촦

ݣ

طͣ



ͬڴҪ⣬еʵ鶼ϸѭƱ׼ֻҪ
ݼ¼ʵ֧۵»ǿԱͨġ

4

ڽжʵͶСļ¼Ϊ<500mm^3>500mm^3
δκξͳѧ(p<0.05)ûб׼ͱ׼
ݣܼpֵ

ݣ

ʹǡл־ĵͼҲбʡĶ
ͼ˵СѸٳ,24 ʱƽ> 500 mm^3 ;
ʵ,50ʱƽ< 500 mm^3 (ͼ2) , 50 %С
ܵơô50СδܵƵǷ
ͼϣͼϣ50ӦΪ500mm^3
ƵĻδܵƵģȻʱѾûжԱȣ24ʱ
ȫжûܵƣ[f2]

طͣ



ԭt飬֪μģûмֱĿġҲܴ
ǰ漸ʱֱ㣬һp<0.05Ժ߲󣬾϶
۳Ҳڿ⣬޷ѧ¹ҹ

5

ͼ3ʾȻɱ˻ڵĽزʵ
CTL϶ֱ34.024.113.9%ͼ3ʾԶԶһ֣ʵ
֮,˵ȱѵ

ݣ

طͣ



ûбϸһӦÿȷɱ˻Եֵ
ڶİٷֱȣ˰ٷֱȷǱ˰ٷֱȡ

С

ʲࣨѾ⵱˾ԴĵĲ⣬ΪκѾش˾Ҳû
׷ʣҾЩ⻹ֵüۣҪľ1ȴǶ
κɰܵ⣬޷رܣһֱ֮Զûȷۡ
ظʵ֤ԭĵĴͲ֮Ķ࣬ڱֵ
мֻΪдߣֱƽ
ӹԷʵʵԡ

κݷ˾ʹ˾¸ǳ̲

1

һ5ܣÿӳɶɵҵİ칫ҿһ
Ҫһ¡ÿһζд

ݣ

κȫ,ר˳ĵ⣬
ûбҪ˷ʱ,ȥ⡣Ȼ˵,ҾͲò˵䡣
ǿƵͬ־ǿģοҶ֪һˣر⡣κ
˵ζı䲻ʵ

κﵽأֵǮҲ֪ܼǵõģв˿ã
ȣȳ޹޹⣬ĴݲˣĴ±Ʒȣÿζ
Щ˵ҵȷ̫ءҪȻڶΪʲôҪ
һ5060Ԫ±ء

κҪʲôֻԼ.ûк۹ѧ
⣬Ҳû۹е⡣˵ҳƪ.
Ҳûκҵʵȥιۡ

طͣ

κڶΰݷ˾ڵ£᲻Ǹʱڣ2003Ժ
ʿѡ꣩йأϣκǱϢ˵̬ȲġҶ
󲿷ֵԺʿڱϺطҪиԺʿףһǵѧ
ԭ򣩡[w17]

ȷȥݷù˾ҼǵӦȥľҽ˳˾
˰ݷá2003꣬ڽӵ˾ɵźҷǵо
кܶ⡣ΪһԱҶᣬϣԼڿ
뷨۵㱻⣬ɹ˷˽ҵ˶֪رϲ
̽һЩѧ⣬Լ뷨оչ˷ˣͨ
Ľõ˾˽ǵĹоݣ˽
ҵĵԼʵϸԼ֮ѧϵĲ
Ҫ⡣

Ҹ˾ʲô񡱣˵Цǲò壬ȥ
·ϣںһɶСزܹ100ԪǮ˾Ϊһ
Ҳҵʦĺѣй֮飬СزҲǶԳ
𾴣ܲܿȥ

˾ѾκУ˿,,ȳ,޹,
޹,Ĵݲ,Ĵ,±,ƷǺǣʵЩζ
ˣȻСѧ뿪磬ζûģ±ԣĶ
ԣЩֵǮĴȥпȻѼǮһͿ֪
Ҫ񣬿Ҳ̫ƲйõķչˣЩ
ƽģԳҶò֮֡˵ƾĹ
˾[w42]



κȥ˾ֻǶԿĸƵʲͬѾȽ
˫̸ݸִһʡʵǸʱڼʹǳϸƵʰݷҲ
ûʲô쳣ԣһԼѧǰ;شӰ˵ȻӦ
ӣ˭ԸΪ¹һĶƽ£ԽԽ
ͬκΪҲû̫񡣶Ĺ۹˾׾
˾ҲԼ̫ߡκ̬Ϊ쳣˾һҪκϸ
ƵʾҪó֤ݣʹʵΣֻ⡣

Ҫ̸ݣκ˵⣬ǿд衣˾Ϊ
ûѧۣǿ·ҶʵĲ²κͺͿ
߼Уһֱ⡣˾˵ʲôôҪ
⵱ȻǰݷõĿģﻹнͨ鰡!κ˵ùڵ
˾Ҳ˵ùءȻ˾ʾ֤ݡ

Ȿ˵˾NMǷѾ˱ܲ׼Ľ׶Ρ
һƪ˹۵㣬ѧߡѧԲǿ
ߣ»ᱻܣûпԭĲýһۡҲϣ
˾ܾʹ˶˵䡣֪ûѹNatureӦ
Ҳʮء

2

ֻҪҽ³أԸ100ԪĿоѡ

ݣ

طͣ

˾Ľм䣬̸ĿԱȱٿ
оѡԴҲιʵңҿĿȷȽϲ
˾Ľ̸зһоˣҺͬ鵱ʱĿ
ҲΪʲô̸ȱоʲôĿģҿǲ
һǽǺǲѧһЩƣЩо
ԱܽиõĻͬһЩĿ100ϵĿ
ҵĽԺܸˡ



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ݣ

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5

⣬Աҵѣʶ(ҲԺʿ)
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ţҪnature medicineE-mailǩ𷢱ͬʱУһλ
ܿе쵼ͨУһλڸ˵ͷ˴кҲҪ
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ݣ

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ҵʱ˾˵¼ģNaturemedicineҪ֤ѧ
İܻnaturemedicineѧѲǺҪҵκ
һЩٶ˾Ƿ̰ҽκֶͨ
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طͣ

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ݣ

2000Nature MedicineϵķͼıԺʿȥˣʱ
ڲ˽ҷ⣬һǻѡĲѩһڶ
µ⣬ʵѧ˵ʵǲɹģڵܴ
ǺκԺʿԲٵˣµĵһߣ˵ǣ
ˮƽһ

طͣ



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ܶסѹվ֪ûվҲڻѡǣ̫㣬
Ҳ׵롣

2

κߣһ2.5Ͷ[w9]

ݣμ[w9]ȫġ

طͣ



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Чرغãشһһ

ݣ

طͣ



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֪2002 κȫαֻ֤ǲͿġImmunogene 
therapy of tumors with a vaccine based on the ligand-binding domain of 
chicken homologous integrin beta3. Immunol Invest. 2002 31:51-69.

ݣ

Ǻκȫ֪integrinǼѪֶ֮һԿ
ƵĹ²򵥣߲Ŀûѧܵģintegrin
ģintegrinࡣڴǷintegrinĸЧ¡
壬Ϊֱ߻ܼѪ

طͣ



漰ʵԭԵ⣬ԭϿܣáҲӦ
ظʵش

5

κ2000ǰ㹻ľ˵Щʵ[w55]

ݣ

[w55]ȫ

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ߣһҽ

1.κԺʿ굽׺ûϳɹЩģ鵱ʱйƱ˵Ӧú
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һ

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ģȴصΪˣMITHarvardû
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4.˳һ£ЩҽԺɱƶøͶôκԺʿΪ׵Ļо
ϣüĳɹʲôӦõٴĻٴǰʲôκ
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ҲٴҽѧԺԺڸ㲻֪Ƶ"ѧо"
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⣬ƮƮһɣκԺʿͷûvEGFR 
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˻κʱľѲ, Щʵ鹤 

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ˣ˵500ˣٶԻҽԺ˵Ҳ㲻ϡ֡Ʈ
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ҪѧҪ̣뻪һԱȶ



ѧоĿС˵Ȼ̽˵Ҫ
ٵļ⣬츣ࡣڿѧоɼ
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ѧģһκNature Medicineһĵ

ʯ

λѣ˶ǰһЩ˵͹۵Щȫ⡣
ҲһЩҸ˵Ĺ۵㣬ܻ߷ԵҶͨԡ

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ĿһˣΪ֮ߣȻ÷ɷ[xxv]Щ
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ȫʷʶδܿ͸Щͽ̰ıԡ

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527գͬĹݡѧõȣʦͽķš[xxvi]
ûճɣǵв£ѧͽɢһա[xxvii]ǵ
ִĻ̬ѱ¶š⣬֮ѧС
ߣԲڽߣȭ˼ָ֮ΪϸӵҴ̡[xxviii]
ѧˣֻʱңǦһֽ֧һţ;ŷѳ
ҵ£𢳼ʹ֮»ԺϸʡӼ䣬
̸;αϵ£˵ۣתţ
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Ǹ֮ãϵǰ뷽ߡűͽջˡ[xxx]ǰš¥޴
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ǺŵʥСָ屻ӵñضǣеıջ٣е
͵䱾ӽ˳[xxxii]

ִĺǶءż֧˷ָ
ϵжˣ塣ݵʱļأһأ
շٽ١ߣָΪȫҽԾʮˡɱì
£ѣӤδߣɱ֮п޸[xxxiii]

ʵЩʷо¼ѧ߶֪ġΨһĽǣ
ڸʷʵǿʶ

ļʷʵڶѻƬս롰۷⽨

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Աܻѡú÷ʡҳѵΪṩ䣬
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кܶżȻԣӶΪǵѡṩ˹Ŀռ䣬ԱȻǡ
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ѻƬսԺѻƬóû̫ܵ谭ʮУ̫ƽ
սķѺܴ󣬼ѣȲѻƬȡ1857괺죬
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ѻƬ˰ѣΪһʱȨ֮ƣ಻ʾš
Ϊһʵ׼ѻƬ˰Ҳ־ѻƬʽ
[xxxiv]18581013վеġ˰̸УѻƬó׺Ϸ
йûбʾԡ[xxxv]

ڶѻƬ˰Ӣ1858꡶ͨ³ƺԼ˰򡷣1860
׼ӶʹѻƬóʽϷѻƬܵӲ󡣡1840
1894ѻƬڣ˽ڣԼ388򵣡[xxxvi]ƽÿԼ򵣣
ʮʮûдﵽƽʮ3ﵽǧ
ʮֽǧൣ[xxxvii]

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1854 10ӢʮҪȷ޸ġͨ˰򡷲
׼ѻƬһĿǱóей
⽻˫ĲġЩҪ̸СǣΪ⽻
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򱬷Ҳ۴ѡһǹݷǣڶǽ
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2ݷ

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1842 ꡶ϾԼʼʮĹݷǣ
һټìܣֱӵȼսԭ򡣡˵ʵйٷӢѹ
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֮Ϊϵڴˡ[xxxviii]Ҳ˵ӢĲģ
ݳǣά⽨ʶ̬͹Ϻ޹
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ˣȫڷ⽨ͳ߲½еġ1849 귴Ϊ
֪֮ҲΥΥĴͳԼѭ
ԼȻܶƺ͹㶫ѲҶ衳˫ɣ졢Ҷ
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͢ķ͡[xxxix]

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Ĺ̫ˡ

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ռ꣬㶫Ѳعͬռ˽йһȨ
صǣǻʦϣռʹǩ¸ġԼ

Ҫ⽨ӦЩ⽨ͳ߼ʶ̬Ĺªʵ߶ߡ

3¼ȫһ

ǿ1859 625磬Ӣ̨ͻȻ
ؾ˼ػսһҹӢʮֻӢʿ
464ˣ14 ˣӢ˾ҲˣòǱߡӢ
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ǩġԼǲƽԼЩӦǴģ˭ȿڣ
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˹ҰΣȦҪڣԼжĿġ

Ϊʲ1859 꽻׼֦¾ʦռԲ԰գǩ
ġԼʷѧоѾʾʲۡۡ¹ع
ص⣬˿ЦõķʹפڱԼ
̸йУ̷ʵָʾһϧھѿսΪ˷
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ıЩҪļ һطٱܸеʮ־桭峯֮
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ʵۡ׵ݹ飡[xli]

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İЩ˵ǡۡӿ͹ЧŪߣ

4¼ûΥ

д˵ΪΥȣڴ
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ճȵķѧԭΪʲ۲߷أ

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ҪԼͽڷ¹١ǳ⡣

ٿʱйذɡ1854ꡰ4£ʿֱر
11£ϱѺա[xlii]ԼĹ涨ûκ
Ҳû𺦹档Ͳö˵ˡ

ʹĽѵ

ߵһƪ£һ粨޷ǽйѧĻ״һӰ
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19 20йڹûʵĿںбĴͳ
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(2)ΪйδӦŬάѧɡ

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ѵ۸ݡѾʵִĹңɡѧɵõϣЩ
Ҫִ֣ǷܶĿĹңЩߣΪѧ
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˴η粨һ̸Ӧǵľ裺ѡūӰʷѧñ
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ʲôūһ֮ԣӵĸŷ磬Ҳ
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ʷʵϸӦÿǼ١νӰ䡱Ǵɫʵ
ʷ޹ء»ЩΪ



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[ix] ԭƽ顢Ž<ȭҼ>ϴԿһ108ҳ
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[xxvii] ӹ¼Ӽ¡248ҳ

[xxviii] <ȭ˱Ҽ>ϴԿڶ10ҳ

[xxix] ԭƽ飺<ȭӼ>ϴԿһ289ҳ

[xxx] ھ<Ӵ¼>Ӽ¡82ҳ

[xxxi] ϡʹݱΧǡ32ҳ

[xxxii] Īѭ173174ҳ

[xxxiii] ϣʥ<ӹ>ϴԿһ14ҳ

[xxxiv] 񣺡Ǩ203206ҳϺ2000
档

[xxxv] ʿл۹ϵʷһ624ҳ

[xxxvi] ƽйñǨ149ҳϺ1992档

[xxxvii] ֣񣺡йĶó׺͹ҵչ1840194820ҳ
ѧԺ1984档

[xxxviii] ͢ķżǡ145ҳл1985걱档

[xxxix] ͬϣ167ҳ

[xl] 塷268ҳ´1983곤ɳ档

[xli] éӡ190198ҳϺ1995档

[xlii] 񣺡й̱ʷ371ҳϺ2003档

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