簡(jiǎn)介：中文中文77007700字出處出處SATARUPAS,RAFALK,SATISHD,ETALROLEOFHEXOKINASE1INTHESURVIVALOFHIV1INFECTEDMACROPHAGESJCELLCYCLE,2015,JAN200EPUBAHEADOFPRINT7980989己糖激酶己糖激酶11在被HIV1HIV1感染的巨噬細(xì)胞的生存過程中的作用感染的巨噬細(xì)胞的生存過程中的作用SATARUPASEN，RAFALKAMINISKI，SATISHDESHMANE，DIANNELANGFORD，KAMELKHALILI，SHOHREHAMINI，ANDPRASUNKDATTA關(guān)鍵詞關(guān)鍵詞細(xì)胞凋亡，葡萄糖代謝，己糖激酶，HIV1，巨噬細(xì)胞，線粒體縮略語縮略語HK1，HEXOKINASE1（己糖激酶1）；VPR，VIRALPROTEINR（病毒蛋白R(shí)）；CTZ，CLOTRIMAZOLE（克霉唑）；G6P，GLUCOSE6PHOSPHATE（葡萄糖6磷酸）；G6PD，GLUCOSE6PHOSPHATEDEHYDROGENASE（葡萄糖6磷酸脫氫酶）；OMM，OUTERMITOCHONDRIALMEMBRANE（線粒體外膜）；VDAC，VOLTAGEDEPENDENTANIONCHANNEL（電壓依賴性陰離子通道）；COXIV，CYTOCHROMECOXIDASESUBUNITIV（細(xì)胞色素C氧化酶亞基IV），CART，COMBINATIONANTIRETROVIRALTHERAPY（抗逆轉(zhuǎn)錄病毒聯(lián)合療法）；MCSF，MACROPHAGECOLONYSTIMULATINGFACTOR（巨噬細(xì)胞菌落刺激因子）病毒已經(jīng)有多種方式來保護(hù)被感染的細(xì)胞免于凋亡。被HIV1感染的巨噬細(xì)胞壽命長(zhǎng)，并且被當(dāng)做是儲(chǔ)存HIV1的容器。細(xì)胞存活還是死亡的一個(gè)重要的決定性因素是葡萄糖代謝。我們推測(cè)，HIV1保護(hù)被感染的細(xì)胞免于凋亡，從某種程度上是通過調(diào)節(jié)宿主的糖酵解途徑更準(zhǔn)確地說是調(diào)節(jié)己糖激酶1（一種將葡萄糖轉(zhuǎn)化為葡萄糖6磷酸的酶）來實(shí)現(xiàn)的。因此，我們分別分析了在HIV1接種的外周血單核細(xì)胞和長(zhǎng)期接種HIV1的單核細(xì)胞系U1中己糖激酶1的調(diào)節(jié)。結(jié)果表明，HIV1誘導(dǎo)己糖激酶1的表達(dá)量顯著增強(qiáng)。令人驚奇的是，己糖激酶的酶活性在被感染的外周血單核細(xì)胞和PMA分化的U1細(xì)胞系中被顯著抑制。有趣的是，我們觀察了在PMA誘導(dǎo)的U1細(xì)胞和HIV1依附的蛋白病毒蛋白R(shí)轉(zhuǎn)換的巨噬細(xì)胞U937中與線粒體結(jié)合的己糖激酶1的增長(zhǎng)水平。使用藥劑將U1細(xì)胞系線粒體中的己糖激酶1解離出來，此過程中克霉唑誘導(dǎo)線粒體膜去極化和細(xì)胞凋亡蛋白酶3和7介導(dǎo)細(xì)胞凋亡。從病毒蛋白R(shí)轉(zhuǎn)化的U937細(xì)胞線粒體中解離己糖激酶1同樣會(huì)增強(qiáng)細(xì)胞凋亡蛋白酶3和7的活性。這些觀察結(jié)果表明，己糖激酶1在HIV1感染的巨噬細(xì)胞中不參與代謝，而是結(jié)合到線粒體上從而維持其完整性。這些結(jié)果表明，靶向己糖激酶1與線粒體的相互作用從而持續(xù)誘導(dǎo)受到感染的巨噬細(xì)胞凋亡可能會(huì)被證明對(duì)凈化成為HIV儲(chǔ)存容器的巨噬細(xì)胞有好處。介紹介紹單核細(xì)胞和巨噬細(xì)胞在先天性免疫防御中起重要作用。但是在HIV1感染的情況下，巨噬細(xì)胞可以加快病毒從體表傳播到大腦等末梢器官。許多研究已經(jīng)證明，HIV1感染的單核細(xì)胞和巨噬細(xì)胞是相對(duì)耐凋亡的。因此，這些生存能力強(qiáng)的被感染細(xì)胞可以在大腦中作為HIV1持續(xù)存在的儲(chǔ)存容器，也可以促使病人中樞神經(jīng)系統(tǒng)的炎癥接受抗逆轉(zhuǎn)錄病毒聯(lián)合治療。了解被HIV1感染的巨噬細(xì)胞抵抗凋亡的機(jī)制對(duì)于這些病毒儲(chǔ)存容器的靶向治療是很重要的。被感染的巨噬細(xì)胞的對(duì)凋亡抗性可能是源于HIV1和宿主葡萄糖代謝之間的相互作用。事實(shí)上，早期研究表明，VPR基因可以調(diào)節(jié)巨噬細(xì)胞的糖酵解途徑。葡萄糖代謝的第一步是在己糖激酶的作用下葡萄糖轉(zhuǎn)化為葡萄糖6磷酸。在哺乳動(dòng)物細(xì)胞中有4種同類型的己糖激酶HK1，HK2，HK3，HK4。在這些同型的己糖激酶中，HK1和HK2可以結(jié)合線粒體。線粒體結(jié)合的己糖激酶在維持線粒體外膜完整性上起了重要作用。研究表明，己糖激酶結(jié)合于電壓依賴性陰離子通道抑制了膜間蛋白收到凋亡信號(hào)刺激而釋放，并抑制了凋亡。當(dāng)前時(shí)代，作為病毒容器的巨噬細(xì)胞，其生命力較頑強(qiáng)的持久性對(duì)于規(guī)劃用抗逆轉(zhuǎn)錄病毒聯(lián)合療法根除HIV1的策略而言是一個(gè)重要的挑戰(zhàn)。此外，闡明HIV1介導(dǎo)的葡萄糖代謝途徑阻截機(jī)制將會(huì)使我們對(duì)設(shè)計(jì)清除潛伏的HIV1病毒的治療策略有了更深刻的認(rèn)識(shí)。在這項(xiàng)研究中，我們發(fā)現(xiàn)了HIV1誘導(dǎo)單核細(xì)胞和巨噬細(xì)胞中己糖激酶1的表達(dá)。但是，HIV1的表達(dá)抑制了己糖激酶的活性卻促使己糖激酶與線粒體結(jié)合以維持線粒體外膜的完整性。研究還發(fā)現(xiàn)，在巨噬細(xì)胞U937細(xì)胞中VPR基因的過度表達(dá)增強(qiáng)了線粒體與己糖激酶1的結(jié)合能力。在HIV1感染的巨噬細(xì)胞中分離線粒體上的己糖激酶1和克霉唑會(huì)降低線粒體膜的電勢(shì)，以及誘導(dǎo)凋亡蛋白酶3和7介導(dǎo)的細(xì)胞凋亡。類似地，在病毒蛋白R(shí)另加一組二甲基亞砜作對(duì)照，10小時(shí)后測(cè)定胞質(zhì)和線粒體中的己糖激酶1蛋白水平。這項(xiàng)分析證明了己糖激酶1在胞質(zhì)中（圖3A3A、B）和線粒體中（圖3C3C、D）的含量比受到克霉唑劑量依賴性的調(diào)節(jié)。特別地，25ΜMOL/L克霉唑顯著地增加了胞質(zhì)中的己糖激酶水平（圖3A3A、B）并且伴隨著線粒體中己糖激酶水平下降（圖3C3C、D）。在接下來的實(shí)驗(yàn)中，我們使用了25ΜMOL/L克霉唑。為了測(cè)定在線粒體中用25ΜMOL/L克霉唑改變己糖激酶的亞細(xì)胞定位帶來的影響，我們使用膜滲透性染料JC1測(cè)量了線粒體膜電位變化（ΔΨ）。在對(duì)照、PMA處理、PMA外加25ΜMOL/L克霉唑處理的U1細(xì)胞中極化細(xì)胞（紅色熒光）的百分比分別為7239±16、7398±28和3171±13，去極化細(xì)胞（綠色熒光）的百分比分別為2683±12、2128±35和6805±10（圖3E3E）。這些數(shù)據(jù)表明，25ΜMOL/L克霉唑改變了PMA處理的U1細(xì)胞的線粒體膜電位。線粒體膜電位的變化是細(xì)胞凋亡早期的一個(gè)顯著特點(diǎn)。因此我們測(cè)定了PMA處理的和PMA外加25ΜMOL/L克霉唑處理的U1細(xì)胞存活水平細(xì)胞事先用熒光激活細(xì)胞分選術(shù)和碘化丙啶（PI）染色處理過?？嗣惯蚺cPMA處理的凋亡率是單獨(dú)用PMA處理的3倍（圖4A4A）。半胱天冬酶家族成員細(xì)胞凋亡蛋白酶3和7在哺乳動(dòng)物細(xì)胞凋亡中起著關(guān)鍵的作用。因此，我們使用凋亡蛋白酶血清球蛋白3/7鑒定法判斷克霉唑誘導(dǎo)U1細(xì)胞隨著己糖激酶1與線粒體分離而凋亡凋亡蛋白酶血清球蛋白3/7鑒定法利用激活發(fā)光的凋亡蛋白酶3/7作為測(cè)量凋亡蛋白酶活性的底物。結(jié)果表明，同對(duì)照組相比，克霉唑處理的細(xì)胞，其凋亡蛋白酶3/7活性增加了23倍（圖4B4B）。HIV1HIV1的病毒蛋白的病毒蛋白R(shí)基因在調(diào)節(jié)己糖激酶基因在調(diào)節(jié)己糖激酶11轉(zhuǎn)移中的作用轉(zhuǎn)移中的作用在觀察到HIV1感染的巨噬細(xì)胞的線粒體中己糖激酶1含量增加之后，我們提出如下問題是不是病毒蛋白VPR調(diào)節(jié)了己糖激酶1的亞細(xì)胞定位轉(zhuǎn)移。最近，使用穩(wěn)定同位素標(biāo)記（SILAC）蛋白質(zhì)組學(xué)分析，我們證明了HIV1的病毒蛋白R(shí)誘導(dǎo)了巨噬細(xì)胞中己糖激酶1的表達(dá)。此外，研究表明，病毒蛋白R(shí)對(duì)于HIV1感染的巨噬細(xì)胞而言是必需的，因?yàn)樵谌狈Σ《镜鞍識(shí)的巨噬細(xì)胞中病毒的復(fù)制效率降低。我們測(cè)定了VPR基因過度表達(dá)對(duì)于U937巨噬細(xì)胞中細(xì)胞質(zhì)和線粒體組分的己糖激酶1含量的影響。線粒體和細(xì)胞質(zhì)餾分的純度通過細(xì)胞色素C氧化酶亞基IV代表線粒體、微管蛋白代表細(xì)胞質(zhì)來確定。我們首先測(cè)定了U937細(xì)胞中VPR基因的表達(dá)量（轉(zhuǎn)換成ADVPR基因），然后定量測(cè)定這些細(xì)胞中己糖激酶的總活性。這些研究表明，VPR基因在轉(zhuǎn)入ADVPR基因的巨噬細(xì)胞中過度表達(dá)（圖5A5A）抑制了全部細(xì)胞的溶胞產(chǎn)物中己糖激酶的總活性（圖5B5B）。有趣的是，同單獨(dú)導(dǎo)入腺病毒的U937細(xì)胞相比，ADVPR顯著增加了線粒體組分中的己糖激酶含量（圖5C5C、D）并且顯著減少了細(xì)胞質(zhì)組分中的含量（圖5C5C、E）。這些發(fā)現(xiàn)證明，VPR確實(shí)調(diào)節(jié)了己糖激酶1從細(xì)胞質(zhì)到線粒體的轉(zhuǎn)移。為了顯示VPR介導(dǎo)己糖激酶1轉(zhuǎn)移至線粒體的重要性，我們使用克霉唑?qū)?dǎo)入VPR的U937細(xì)胞的線粒體和己糖激酶1分離，然后測(cè)定細(xì)胞凋亡蛋白酶3和7的活性。結(jié)果顯示同對(duì)照組（導(dǎo)入VPR的U937細(xì)胞）相比，使用25ΜMOL/L克霉唑處理后細(xì)胞凋亡蛋白酶3和7的活性增加了22倍（圖5F5F）?？偠灾?，這些發(fā)現(xiàn)闡明了VPR介導(dǎo)線粒體和己糖激酶1結(jié)合在維持線粒體完整上的重要性，因?yàn)樵谵D(zhuǎn)入VPR的細(xì)胞中用克霉唑?qū)⒕€粒體與己糖激酶1解離會(huì)誘導(dǎo)激活細(xì)胞凋亡蛋白酶3和7。討論討論同未被感染的單核細(xì)胞相比，持續(xù)受到感染的原單核細(xì)胞對(duì)于凋亡刺激并不敏感。HIV1感染的巨噬細(xì)胞比HIV1感染的其他細(xì)胞對(duì)凋亡有更強(qiáng)抗性，更有能力被當(dāng)作病毒儲(chǔ)藏庫(kù)。此外，病毒從這些潛在儲(chǔ)藏庫(kù)中傳播可以促進(jìn)病毒感染那些易受感染的靶細(xì)胞。HIV1感染的巨噬細(xì)胞抵抗凋亡的機(jī)制目前還不是很清楚。但是有推測(cè)認(rèn)為巨噬細(xì)胞可能因?yàn)榉只蛘唛g接因?yàn)镠IV感染又或者是因?yàn)楸磉_(dá)了特殊的病毒蛋白如TAT和NEF激發(fā)了固有抵抗凋亡的方式。迄今為止的研究表明，細(xì)胞中的HIV1誘導(dǎo)巨噬細(xì)胞菌落刺激因子表達(dá)促進(jìn)了抗凋亡蛋白如MCL1和BFL1的表達(dá)。研究還表明，活化HIV1感染的細(xì)胞的壓力誘導(dǎo)PI3K/AKT細(xì)胞存活途徑也會(huì)保護(hù)巨噬細(xì)胞免于凋亡。我們推測(cè)降低細(xì)胞凋亡蛋白酶3的活性可能是持續(xù)受到HIV1感染的細(xì)胞抵抗凋亡的一種機(jī)制。最近我們證明了HIV

簡(jiǎn)介：1中文中文2740字出處出處WANGXJ,YUANSL,XIAOL,ETALTHEEXPRESSIONOFCSRCGENEINTHECARCINOGENESISPROCESSOFHUMANCARDIAADENOCARCINOMAJWORLDJOURNALOFGASTROENTEROLOGY,1999,56488491人賁門癌癌變進(jìn)程中人賁門癌癌變進(jìn)程中CSRC基因的表達(dá)基因的表達(dá)關(guān)鍵詞CSRC基因表達(dá)產(chǎn)物PP60CSRC；腫瘤轉(zhuǎn)移；摘要目的探討CSRC基因在人賁門癌（CA）癌變進(jìn)程中的活性，表達(dá)和作用。方法對(duì)56例CA，34例正常，36例癌旁上皮和20例CA的轉(zhuǎn)移淋巴結(jié)用特異的單克隆抗體MAB327，免疫組化法檢測(cè)PP60CSRC和CSRC基因的表達(dá)。結(jié)果PP60CSRC的陽(yáng)性率在正常上皮，增生上皮，CA和轉(zhuǎn)移淋巴結(jié)中分別為29410/34,94434/36,71440/56和60012/20。而且，各陽(yáng)性率間有顯著的統(tǒng)計(jì)學(xué)差異P＜001。CA和增生上皮中的PP60CSRC的表達(dá)水平顯著高于正常上皮P＜001＝。PP60CSRC的陽(yáng)性率在乳頭狀，管狀，低分化和粘膜腺癌中分別為7506/8,81818/22,50010/20和10006/6，管狀和粘膜腺癌中顯著高于乳頭狀和低分化腺癌（P005）。結(jié)論CSRC基因的活性和表達(dá)與人CA的發(fā)生和發(fā)展相關(guān)；PP60CSRC蛋白數(shù)量在發(fā)癌過程中增加；PP60CSRC的表達(dá)與淋巴結(jié)轉(zhuǎn)移相關(guān)。介紹目前遠(yuǎn)端胃癌的發(fā)病率逐年下降，而賁門癌的發(fā)病率卻在穩(wěn)定增加。CA的生物學(xué)和流行病學(xué)特征于遠(yuǎn)端胃癌明顯不同，且原因不明［13］。PP60CSRC是CSRC基因的產(chǎn)物，具有酪氨酸激酶活性。CSRC基因表達(dá)的增加在乳腺癌［4］，食管癌［5］，胃癌［6］和結(jié)腸癌［7］中都有報(bào)道。CSRC基因活性和表達(dá)可能與一些腫瘤的發(fā)生發(fā)展有關(guān)。我們先前的研究表明CSRC基因的活性和表達(dá)與食管鱗癌的分化和發(fā)展有關(guān)［8］。因此我們相信在賁門癌中也有相似的變化。材料和方法標(biāo)本的收集和處理所有的56例CA標(biāo)本均來自腫瘤中心的手術(shù)后CS患者。所有的標(biāo)本均經(jīng)固定化程序，甲醛固定，石蠟包埋，至少兩套4ΜM6ΜM厚的石蠟切片。一個(gè)用HE染色，一個(gè)做免疫組化。試劑單克隆抗體MAB327小鼠IGG由日本大學(xué)分子病理系提供，抗生蛋白鏈菌素免疫組化試劑盒ZYMEDUSA從FUZHOUMAXIMBIOTECH公司購(gòu)買。PP60CSRC蛋白的免疫組化分析PP60CSRC蛋白用LSAB方法的免疫組化分析。組織切片在梯度乙醇中脫蠟脫水后，用胰蛋白酶消化。用3H2O2阻滯內(nèi)源性過氧化物酶的活性，用正常血清處理后，切片在稀釋為1∶100的MAB327中孵育，4℃過夜。在室溫下，生物素化的第二抗體20分鐘，抗生蛋白鏈菌素30分鐘。再用含有0005H2O2的002的3,3四鹽酸二氨基聯(lián)苯胺染色。再用蘇木精復(fù)染。組織病理學(xué)檢查CA和有關(guān)的損傷的組織病理學(xué)診斷，以及CA的組織學(xué)類型均由2名有經(jīng)驗(yàn)的病理醫(yī)生根據(jù)一定的標(biāo)準(zhǔn)做出［8］。PP60CSRC免疫組化染色的定性和定量分析PP60CSRC的免疫染色按照已知的標(biāo)準(zhǔn)分析［5］。CA中PP60CSRC陽(yáng)性細(xì)胞的百分率按以下標(biāo)準(zhǔn)分級(jí)陰性,＜25,2550,＞50。PP60CSRC陽(yáng)性細(xì)胞表性和細(xì)胞膜的染色強(qiáng)度與陰性對(duì)照陰性,弱,中度和強(qiáng)。結(jié)果組織病理學(xué)檢查在56例CA標(biāo)本中，包括乳頭狀8/56，管狀22/56，低分化3多正常細(xì)胞中均可發(fā)現(xiàn)PP60CSRC的表達(dá)。在細(xì)胞增生，分化和轉(zhuǎn)化的調(diào)控中起重要的作用［4］。目前的研究顯示PP60CSRC蛋白數(shù)量和激酶活性的增加與一些人類腫瘤的發(fā)身發(fā)展相關(guān)，而且活性和表達(dá)增加是腫瘤發(fā)生的一個(gè)因素［48］。本研究中，PP60CSRC蛋白在CA，乳頭狀，管狀，低分化和粘液腺癌中的表達(dá)分別為71440/56,94434/36和29410/34，在CA和增生上皮中PP60CSRC的陽(yáng)性率比在正常上皮中高（P001）。JANKOWISKIETAL分析了15例食管腺癌和15例BARRETT′S食管上皮中CSRC基因產(chǎn)物表達(dá)，陽(yáng)性率為203/15，提示CSRC基因的表達(dá)于食管腺癌的發(fā)展相關(guān)。因此，本研究的結(jié)果顯示CSRC基因的活性和表達(dá)可能與CA的發(fā)生發(fā)展相關(guān)。但是，在增生上皮中PP60CSRC的高表達(dá)可能與老年大鼠的腺上皮細(xì)胞的增生相關(guān)［9］。在一些癌旁正常上皮PP60CSRC的低表達(dá)可能是由于在正常上皮中PP60CSRC的表達(dá)與癌的發(fā)生相關(guān)［58］。另一方面，也說明CSRC基因的活性和表達(dá)可能使CA發(fā)癌過程中的一個(gè)早期事件。盡管CSRC基因的活性和表達(dá)與一些人類腫瘤的發(fā)生相關(guān)。用生化方法測(cè)定PP60CSRC的激酶活性和蛋白數(shù)量的結(jié)果因方法而不同。大部分的研究報(bào)道，PP60CSRC的激酶活性在癌細(xì)胞株和胃癌，腸癌，肺癌和腎癌的組織中有增加。但是與腫瘤相比，正常組織中無PP60CSRC蛋白數(shù)量的不同。PP60CSRC的激酶活性的增加無法用CSRC基因編碼的蛋白表達(dá)的增加而解釋［6,10］。本研究中，PP60CSRC蛋白用特異的單克隆抗體MAB327檢測(cè)，在CA和增生上皮中PP60CSRC的高表達(dá)分別為357和778，在癌旁的一些正常上皮中有PP60CSRC的低表達(dá)，兩者表達(dá)的不同有顯著的統(tǒng)計(jì)學(xué)意義（P001）。本研究的結(jié)果提示PP60CSRC蛋白數(shù)量在CA中增加。關(guān)于CSRC基因表達(dá)產(chǎn)物，PP60CSRC和癌細(xì)胞分化之間的關(guān)系，有不同的意見［6,8,9,11］。FANNINGETAL［1］報(bào)道了在高分化膀胱癌中有CSRC基因的高水平表達(dá)，提出PP60CSRC蛋白和激酶活性與泌尿道和ⅠⅡ期膀胱癌上皮細(xì)胞的分化相關(guān)。TAKEKURAETAL［6］PP60CSRC激酶活性在高分化和低分化胃癌中未發(fā)現(xiàn)不同。本研究中，不同組織類型的CA中PP60CSRC陽(yáng)性率也不同。在粘液腺癌中陽(yáng)性率為1000,6/6，在管狀腺癌中為818,18/22，比乳頭狀750,6/8和低分化500,10/20要高，這種不同有顯著性差異（P005）。在粘液和管狀腺癌中高水平的表達(dá)分別為10006/6和63614/18，在乳頭和低分化腺癌中只有低表達(dá)，這種不同也有顯著的差異（P001）。這些結(jié)果提示，PP60CSRC表達(dá)水平與CA的分化和組織學(xué)類型相關(guān)，在粘液和管狀腺癌中的PP60CSRC高表達(dá)可能與它們的高分化和其他的生物學(xué)行為相關(guān)。帶有激酶活性增加的PP60CSRC表達(dá)與結(jié)腸癌轉(zhuǎn)移的關(guān)系也有報(bào)道［12,13］。但是用免疫組化染色檢測(cè)轉(zhuǎn)移淋巴結(jié)中PP60CSRC蛋白暫無報(bào)導(dǎo)。TALAMONTIETAL［12］發(fā)現(xiàn)PP60CSRC激酶活性在原發(fā)和多發(fā)癌中也有增加。TERMUHLENETAL［13］報(bào)道了在結(jié)腸癌干轉(zhuǎn)移中也有PP60CSRC激酶活性的增加。本研究中，檢測(cè)CA的轉(zhuǎn)移淋巴結(jié)中的PP60CSRC蛋白，陽(yáng)性率為60012/20，PP60CSRC表達(dá)水平與相同的原發(fā)腺癌相同。本研究的結(jié)果顯示，PP60CSRC表達(dá)與CA的淋巴結(jié)轉(zhuǎn)移相關(guān)。

簡(jiǎn)介：中文中文3150字出處出處YINGD,XUY,LINGD,ETALDOWNREGULATIONOFMIR141INGASTRICCANCERANDITSINVOLVEMENTINCELLGROWTHJJOURNALOFGASTROENTEROLOGY,2009,446556561MIR141MIR141在胃癌和它相關(guān)細(xì)胞生長(zhǎng)中的下調(diào)在胃癌和它相關(guān)細(xì)胞生長(zhǎng)中的下調(diào)摘要摘要目的人類小RNA141（MIR141）是MIR200家族的成員之一，已經(jīng)被報(bào)道和多種人類惡性腫瘤相關(guān)。然而，它與胃癌發(fā)生機(jī)理是否相關(guān)仍然未知。因此，我們檢測(cè)了MIR141在胃癌組織中的表達(dá)和MIR141的過表達(dá)對(duì)于癌細(xì)胞增殖的影響。方法MIR141的表達(dá)水平在35組胃癌組織和癌旁組織以及5中胃癌細(xì)胞系中用實(shí)時(shí)定量PCR分別檢測(cè)。轉(zhuǎn)染MIRNA前體的MGC803細(xì)胞的生長(zhǎng)通過MTT分析方法被檢測(cè)到。結(jié)果與對(duì)照的癌旁組織相比MIR141在80的初期胃癌組織中明顯下調(diào)。在人類胃癌細(xì)胞系MGC803,HGC27,SGC7901和BGC823中，同樣發(fā)現(xiàn)MIR141的表達(dá)大量減少。MIR141和它前體的過表達(dá)能夠明顯的抑制胃癌細(xì)胞的增殖。結(jié)論這些結(jié)果都暗示了，MIR141可能通過抑制細(xì)胞的增殖與胃癌的發(fā)展密切相關(guān)。關(guān)鍵詞關(guān)鍵詞MIR141，胃癌，MGC803細(xì)胞，細(xì)胞增殖引言引言MICRORNASMIRNAS，是新近在動(dòng)物和植物中發(fā)現(xiàn)的一類新的內(nèi)源性，非編碼的單鏈RNA。他們觸發(fā)翻譯的阻滯和/或MRNA的降解，大多數(shù)通過互補(bǔ)的結(jié)合靶MRNA的3’非翻譯區(qū)。研究表明MIRNAS能夠廣泛調(diào)節(jié)生物進(jìn)程，如細(xì)胞增殖，分化，凋亡。越來越多的證據(jù)表明，通過調(diào)節(jié)MIRNAS的表達(dá)可能在人類癌癥的病理機(jī)制中起到多種多樣的作用。一些MIRNAS已經(jīng)被證實(shí)有致癌或抑癌活性。高通量技術(shù)已經(jīng)被用于檢測(cè)在良性腫瘤和惡性腫瘤樣本中MIRNAS的差異表達(dá)，同時(shí)，在人類多種腫瘤中一些MIRNAS失控也被發(fā)現(xiàn)，包括肺癌，乳腺癌，肝癌，食道癌和前列腺癌。在這些

簡(jiǎn)介：中文中文2500字出處出處ZAMBONA,MANDRUZZATOS,PARENTIA,ETALMAGE,BAGE,ANDGAGE,GENEEXPRESSIONINPATIENTSWITHESOPHAGEALSQUAMOUSCELLCARCINOMAANDADENOCARCINOMAOFTHEGASTRICCARDIAJCANCER,2001,911018828食管癌和賁門癌患者中食管癌和賁門癌患者中MAGE,MAGE,BAGEBAGE和GAGEGAGE基因的表達(dá)基因的表達(dá)關(guān)鍵詞關(guān)鍵詞食管癌；腫瘤抗原；MAGE,BAGE，GAGE摘要摘要方法從24例食管癌ESCC和24例賁門癌CAC患者中得到的手術(shù)標(biāo)本用RTPCR檢測(cè)基因表達(dá)。這些患者均未經(jīng)化療和放療，生存時(shí)間都在4年以上。結(jié)果由16例ESCC67和9例CAC375樣本中有至少一種基因的表達(dá)。兩個(gè)組織類型中的MAGE基因表達(dá)無顯著性差異，但MAGE4基因在ESCC中的表達(dá)要多于CAC。BAGE和GAGE在每個(gè)樣本中表達(dá)得都相當(dāng)少，與至少一個(gè)MAGE基因表達(dá)相關(guān)。結(jié)論從整體上以及從ESCC和CAC上來說，這些基因的表達(dá)與預(yù)后因素，如腫瘤程度，淋巴結(jié)或病期之間均無顯著的聯(lián)系。但是，BAGE和GAGE的表達(dá)與較差的預(yù)后顯著相關(guān)，而MAGE基因表達(dá)與較好的預(yù)后顯著相關(guān)。正文正文近些年，許多的人腫瘤抗原用自體的細(xì)胞毒淋巴細(xì)胞CTLS被確定。1即所謂的T細(xì)胞確定腫瘤抗原其中一個(gè)重要的類別包括正常的基因產(chǎn)物，其在大多數(shù)人體組織中并不表達(dá)，除了男性胚系細(xì)胞和胎盤，且在許多不同的腫瘤中起作用由MAGE,BAGE，GAGE基因家族編碼的抗原多肽也是這種腫瘤抗原的一部分。25雖然其最初是在黑色素瘤中被發(fā)現(xiàn)，但是也在許多實(shí)體瘤中也有表達(dá)，如肺，乳腺，膀胱，頭頸，食管和胃等2。因?yàn)樗鼈儗?duì)腫瘤有較強(qiáng)的特異性，所以對(duì)腫瘤的免疫治療有很大的幫助。食管癌主要有兩個(gè)組織類型鱗狀細(xì)胞癌ESCC和腺癌CAC?，F(xiàn)在對(duì)無轉(zhuǎn)移的食管癌患者的治療方法主要是單純手術(shù)切除或結(jié)合放療化療。但是，術(shù)后的整體預(yù)后不好，5年生存率為2035。67高轉(zhuǎn)移復(fù)發(fā)提示，在病程早期已有了少量細(xì)胞的擴(kuò)散。因此，積極的免疫治療可能是其他方法之外的有效幫助。已有報(bào)道ESCC中有MAGE1,MAGE2,MAGE3和MAGE4的高表達(dá)。8還未見到關(guān)于CAC患者中腫瘤抗原表達(dá)的研究。我們研究了MAGE1,MAGE2,MAGE3和MAGE4，MAGE6，BAGE，GAGE基因在ESCC和CAC患者中的表達(dá)，基因表達(dá)和公認(rèn)的預(yù)后因素的關(guān)系，如腫瘤的病理分期PT，淋巴結(jié)分期PN，病程PSTAGE和長(zhǎng)期生存率。材料和方法材料和方法患者和材料的收集24例食管鱗癌和24例遠(yuǎn)端食管或賁門癌患者的腫瘤標(biāo)本從意大利PADOVA大學(xué)病理庫(kù)中獲得。所有的患者在手術(shù)切除前均未經(jīng)放化療。這些患者的臨床病理數(shù)據(jù)見表1腫瘤的分級(jí)和分期根據(jù)國(guó)際抗癌聯(lián)盟UICC第四版TNM分類。經(jīng)R0切除后的患者均為手術(shù)后輔助治療，包括化療和放療。而經(jīng)不完全腫瘤切除術(shù)的四個(gè)患者接受了術(shù)后輔助治療。所有的患者均接受隨訪，兩個(gè)患者死于術(shù)后并發(fā)癥，故排除在生存分析之外。所有的手術(shù)標(biāo)本均經(jīng)規(guī)范的組織學(xué)分析，切除后立即經(jīng)液氮冷凍，在放入80度保存直到進(jìn)行RNA分析。有五個(gè)患者還取了正常的食管粘膜作為對(duì)照。表124例食管鱗癌和遠(yuǎn)端食管或賁門癌患者的臨床病理數(shù)據(jù)食管鱗癌N24賁門癌N24合計(jì)N48因的表達(dá)。圖1顯示了8例CAC樣本中MAGEBAGEGAGE基因的表達(dá)。表2顯示了MAGE基因在ESCC和CAC中的表達(dá)非常相似，除了MAGE4在ESCC中的表達(dá)顯著增多58比25,P0019。有兩個(gè)ESCC8,，而無CAC表達(dá)BAGEP0149。四個(gè)ESCC17和三個(gè)CAC13有GAGE表達(dá)（P0683）。在正常組織中無任何基因的表達(dá)。表2MAGE1,MAGE2,MAGE3和MAGE4，MAGE6，BAGE，GAGE基因表達(dá)的比例組織類型MAGE1MAGE2MAGE3MAGE4MAGE6BAGEGAGEESCC13384258A21817CAC17333825A17013合計(jì)1535404219415我們探討了MAGEBAGEGAGE基因的表達(dá)之間的聯(lián)系。從整體上以及從ESCC和CAC上來說，這些基因的表達(dá)與預(yù)后因素，如腫瘤程度，淋巴結(jié)或病期之間均無顯著的聯(lián)系。MAGEBAGEGAGE基因的表達(dá)呈現(xiàn)出集簇表達(dá)，可能是由于大部分損傷無其他基因的表達(dá)4848患者中有23或者有3個(gè)或多個(gè)基因的共表達(dá)3548患者中有17TABLE3。表3每個(gè)患者M(jìn)AGE1,MAGE2,MAGE3和MAGE4，MAGE6，BAGE，GAGE基因表達(dá)的數(shù)量每個(gè)患者基因表達(dá)的編號(hào)食管癌N24賁門癌N24合計(jì)N48081523141523033325444850116213食管切除術(shù)后患者N46的1年，3年，5年精確生存率為85,41,AND24。R0切除術(shù)后患者N37的1年，3年，5年精確生存率為89,51,AND30。在第一組生存分析中，樣本被分為兩個(gè)隊(duì)列由基因表達(dá)和無基因表達(dá)。在所有的ESCC和CAC患者組中，發(fā)現(xiàn)兩個(gè)隊(duì)列與生存無顯著的差異。進(jìn)而分析MAGEBAGEGAGE基因，只有

簡(jiǎn)介：RADIOLOGYORIGINALARTICLEVALUEOFAPPARENTDIFFUSIONCOEFFICIENTMEASUREMENTFORDISCRIMINATIONOFFOCALBENIGNANDMALIGNANTHEPATICMASSESOKILICKESMEZ,1SBAYRAMOGLU,2EINCI2ANDTCIMILLI21DEPARTMENTOFRADIOLOGY,SCHOOLOFMEDICINE,YEDITEPEUNIVERSITYAND2DEPARTMENTOFRADIOLOGY,ISTANBULBAKIRKOYDRSADIKONUKTRAININGANDRESEARCHHOSPITAL,ISTANBUL,TURKEYOKILICKESMEZMDSBAYRAMOGLUMDEINCIMDTCIMILLIMDCORRESPONDENCEDROZGURKILICKESMEZ,DEPARTMENTOFRADIOLOGY,SCHOOLOFMEDICINE,YEDITEPEUNIVERSITY,DEVLETYOLUANKARASTREET102/104,KOZYATAGI34752,ISTANBUL,TURKEYEMAILOKILICKESMEZYAHOOCOMCONFLICTSOFINTERESTNONESUBMITTED30JULY2008ACCEPTED31JULY2008DOI101111/J17549485200902036XSUMMARYTHEPURPOSEOFOURSTUDYWASTOINVESTIGATETHEVALUEOFDIFFUSIONWEIGHTEDMAGNETICRESONANCEIMAGINGDWMRITODISCRIMINATEBENIGNANDMALIGNANTFOCALLESIONSOFTHELIVERUSINGPARALLELIMAGINGTECHNIQUEATOTALOF77PATIENTSAND65HEALTHYCONTROLSWEREENROLLEDINTHESTUDYDWMRIWASPERFORMEDWITHBFACTORSOF0,500AND1000S/MM2,ANDTHEAPPARENTDIFFUSIONCOEFFICIENTSADCVALUESOFTHENORMALLIVERANDTHELESIONSWERECALCULATEDTHEMEANADCVALUEOFTHEFOCALLIVERLESIONSWEREASFOLLOWSSIMPLECYSTS316±018?1023MM2/S,HYDATIDCYSTS258±053?1023MM2/S,HEMANGIOMAS197±049?1023MM2/S,METASTASES114±041?1023MM2/SANDHEPATOCELLULARCARCINOMASHCC115±036?1023MM2/STHEMEANADCVALUESOFALLTHEDISEASEGROUPSWERESTATISTICALLYSIGNIFICANTWHENCOMPAREDWITHTHEMEANADCVALUEOFTHENORMALLIVER156±014?1023MM2/S,P001THEREWEREALSOSTATISTICALLYSIGNIFICANTDIFFERENCESAMONGTHEADCVALUESOFHEMANGIOMASANDHCCMETASTASESP001,ANDSIMPLEANDHYDATIDCYSTSP0008HOWEVER,THEREWASNOSTATISTICALLYSIGNIFICANTDIFFERENCEBETWEENHCCANDMETASTASESTHEPRESENTSTUDYSHOWEDTHATADCMEASUREMENTHASTHEPOTENTIALTODIFFERENTIATEBENIGNANDMALIGNANTFOCALHEPATICLESIONSWEPROPOSETOADDDWSEQUENCEINTHEMRPROTOCOLFORTHEDETECTIONANDQUANTITATIVEDISCRIMINATIONOFHEPATICPATHOLOGIESKEYWORDSABDOMENDIFFUSIONWEIGHTEDIMAGINGLIVERMAGNETICRESONANCEIMAGINGINTRODUCTIONMAGNETICRESONANCEIMAGINGISCONSIDEREDTHEMOSTACCURATEMODALITYTOIMAGETHELIVERFORDETECTIONANDCHARACTERIZATIONOFDIFFUSEANDFOCALLIVERDISEASESANDTODISCRIMINATEBENIGNFROMMALIGNANTTUMORS,REFLECTINGITSABILITYONTHEBASISOFVARIOUSDATAACQUIRED,SUCHAST1,T2,ANDEARLYANDLATEPOSTGADOLINIUMIMAGES1,2CHARACTERIZATIONOFFOCALLIVERLESIONSISVERYIMPORTANTBECAUSEPATIENTSWITHKNOWNPRIMARYMALIGNANTNEOPLASMSOFTENHAVEBENIGNFOCALLIVERLESIONS,WHICHMUSTBEDIFFERENTIATEDFROMMETASTASESTHELACKOFIONIZINGRADIATIONWITHMRIMAGINGANDTHESAFETYOFGADOLINIUMCHELATES,ASCOMPAREDWITHIODINATEDCONTRASTAGENTS,ARETWOIMPORTANTCONSIDERATIONSFORTHEPREFERENTIALUSEOFMRIMAGINGOVERCTSCANNINGINTHEINVESTIGATIONOFLIVERDISEASE3FURTHERMORE,DWIHASEMERGEDASANEWDIAGNOSTICTOOLWITHTHEABILITYTODETECTFOCALLESIONSANDTODISCRIMINATEMALIGNANTONESWITHOUTTHENEEDFORCONTRASTMATERIAL4–7WEAIMEDTOINVESTIGATEWHETHERDWIHASTHEABILITYTODETECTMALIGNANCYANDTODISCRIMINATEMETASTASESANDHEPATOCELLULARCARCINOMASMETHODSTHISWASARETROSPECTIVESTUDYCONDUCTEDATOURINSTITUTIONBETWEENJANUARY2006ANDMARCH2007ATOTALOF77PATIENTS42WOMEN,35MENMEANAGE,59YEARSAND65HEALTHYCONTROLS35WOMEN,30MENMEANAGE,35YEARSWITHCOMPLETELYNORMALLIVERMRIANDLABORATORYFINDINGSWEREENROLLEDINTHESTUDYTHERESEARCHPROTOCOLWASAPPROVEDBYTHEETHICSCOMMITTEEOFOURINSTITUTIONWRITTENCONSENTWASOBTAINEDFROMALLPATIENTSPRIORTOCOMMENCEMENTOFTHESTUDYMAGNETICRESONANCEIMAGINGWASPERFORMEDONA1,5TBODYSCANNERAVANTOSIEMENS,ERLANGEN,GERMANYJOURNALOFMEDICALIMAGINGANDRADIATIONONCOLOGY53200950–5550a2009THEAUTHORSJOURNALCOMPILATIONa2009THEROYALAUSTRALIANANDNEWZEALANDCOLLEGEOFRADIOLOGISTSCLOSESTTHREEMEASUREMENTSINTHEPATIENTGROUP,AFREEHANDROIWASDEFINEDFORTHELESIONSDETECTEDONTHET2WEIGHTEDEPIIMAGEB0,WHILEREFERRINGTOTHECONVENTIONALSEQUENCESFORVERIFICATIONOFTHELESIONBOUNDARIESTHEROIWASTHENCOPIEDTOTHECORRESPONDINGADCMAPSTATISTICALANALYSISALLSTATISTICALANALYSESWEREPERFORMEDUSINGSPSSSTATISTICALPACKAGEFORSOCIALSCIENCESFORWINDOWS100THEADCVALUESOFCASESAREREPORTEDASTHEMEAN±STANDARDDEVIATIONVARIANCEANALYSISANDPAIREDSAMPLESTESTWEREALSOCONDUCTEDFORCOMPARISONOFSEGMENTSOFABDOMINALORGANSAPVALUEOFLESSTHAN005WASCONSIDEREDTOINDICATEASTATISTICALLYSIGNIFICANTDIFFERENCERESULTSAPPARENTDIFFUSIONCOEFFICIENTVALUESOFALLTHEPATIENTSWHOUNDERWENTCONVENTIONALANDDIFFUSIONWEIGHTEDMREXAMINATIONSARELISTEDASBOXPLOTSINFIGURE1THEMEANADCVALUEOFTHELIVERLESIONSWEREASFOLLOWSTABLE1SIMPLECYSTS,20CASES316±018?1023MM2/SHYDATIDCYSTS,13CASES258±053?1023MM2/SHEMANGIOMAS,15CASES197±049?1023MM2/SMETASTASES,13CASES114±041?1023MM2/SANDHEPATOCELLULARCARCINOMASHCC13CASES115±036?1023MM2/STHEMEANADCVALUESOFALLOFTHEDISEASEGROUPSWERESTATISTICALLYSIGNIFICANTWHENCOMPAREDWITHMEANADCVALUEOFTHENORMALLIVERGROUP156±014?1023MM2/S,P001THEREWEREALSOSTATISTICALLYSIGNIFICANTDIFFERENCESAMONGTHEADCVALUESOFHEMANGIOMASANDHCCMETASTASESP001,ANDSIMPLEANDHYDATIDCYSTSP0008HOWEVER,THEREWASNOSTATISTICALLYSIGNIFICANTDIFFERENCEBETWEENHCCANDMETASTASESREPRESENTATIVECASESARESHOWNINFIGURES2–5DISCUSSIONDIFFUSIONISTHETERMUSEDTODESCRIBETHERANDOMBROWNIANMOTIONOFWATERMOLECULES8WITHAVERYSTRONGBIPOLARGRADIENTPULSEINSERTEDINTOEITHERASPINECHOPULSESEQUENCEIESTEJSKALTANNERTECHNIQUEORAGRADIENTECHOPULSESEQUENCE,MRIMAGINGCANBEMADESENSITIVETOTHEDIFFUSIONOFWATERMOLECULESINTHETISSUE6,9DIFFUSIONRESTRICTIONINCREASESINHIGHLYCELLULARTISSUESINCONTRAST,ITDECREASESINLOWCELLULARTISSUESWITHLARGEEXTRACELLULARSPACEORWITHBROKENDOWNCELLULARMEMBRANES7STUDIESHAVEBEENPUBLISHEDCONCERNINGTHEDIFFUSIONPROPERTIESOFFOCALHEPATICLESIONSMOSTOFTHESTUDIESREVEALEDTHATADCVALUESOFBENIGNLESIONSCYSTSANDHEMANGIOMASWERESIGNIFICANTLYHIGHERTHANTHOSEOFMALIGNANTLESIONSATTRIBUTEDTOHIGHCELLULARITYOFMALIGNANTMASSES10–12ASWITHTHEPREVIOUSSTUDIES,WEFOUNDTHATHEPATICCYSTSHADTHEHIGHESTADCBECAUSEOFTHEIRFLUIDCONTENT,WITHNONRESTRICTEDMOTIONOFWATERMOLECULES4,10TABLE1ADCVALUESOFTHEFOCALLIVERLESIONSLESIONSNMEANADCMM2/SNORMALLIVER65156±014?1023MM2/SSIMPLECYSTS20316±018?1023MM2/SHYDATIDCYSTS13258±053?1023MM2/SHEMANGIOMAS15197±049?1023MM2/SHEPATOCELLULARCARCINOMAS13115±036?1023MM2/SMETASTASES13114±041?1023MM2/SADC,APPARENTDIFFUSIONCOEFFICIENTSFIG2FORTYYEAROLDWOMANWITHHEMANGIOMAAAXIALFST2WIMAGEREVEALSAMARKEDHYPERINTENSELESIONBAXIALDIFFUSIONWEIGHTEDB1000S/MM2IMAGEREVEALSMODERATEHYPERINTENSITYCAPPARENTDIFFUSIONCOEFFICIENTSADCWERECALCULATEDTUMORONADCIMAGESHOWSMILDHYPERINTENSITYSLIGHTLYINCREASEDDIFFUSIONCOMPAREDWITHNORMALPARENCHYMAREGIONOFINTERESTWASPLACEDONMASSROI1,CADCOFLESIONWAS192?1023MM2/SOKILICKESMEZETAL52a2009THEAUTHORSJOURNALCOMPILATIONa2009THEROYALAUSTRALIANANDNEWZEALANDCOLLEGEOFRADIOLOGISTS

簡(jiǎn)介：MAGE,BAGE,ANDGAGEGENEEXPRESSIONINPATIENTSWITHESOPHAGEALSQUAMOUSCELLCARCINOMAANDADENOCARCINOMAOFTHEGASTRICCARDIAANNALISAZAMBON,PHD1SUSANNAMANDRUZZATO,PHD1ANNAPARENTI,MD2BEATRICEMACINO,PHD1PIERODALERBA,MD1ALBERTORUOL,MD3STEFANOMERIGLIANO,MD3GIOVANNIZANINOTTO,MD3PAOLAZANOVELLO,PHD11DEPARTMENTOFONCOLOGYANDSURGICALSCIENCES,ONCOLOGYSECTION,UNIVERSITYOFPADOVA,PADOVA,ITALY2DEPARTMENTOFONCOLOGYANDSURGICALSCIENCES,PATHOLOGYSECTION,UNIVERSITYOFPADOVA,PADOVA,ITALY3DEPARTMENTOFMEDICALANDSURGICALSCIENCES,CLINICACHIRURGICA4,UNIVERSITYOFPADOVA,PADOVA,ITALYPRESENTEDATTHE33RDCONGRESSOFTHEEUROPEANSOCIETYFORSURGICALRESEARCHESSR,PADOVA,ITALY,APRIL22–25,1998ANDATTHEINTERNATIONALSOCIETYFORTHEDISEASESOFTHEESOPHAGUSISDESEVENTHWORLDCONGRESS,MONTREAL,QUEBEC,CANADA,SEPTEMBER1–41998SUPPORTEDBYTHEASSOCIAZIONEITALIANAPERLARICERCASULCANCROAIRC,MILAN,ITALYANDTHEREGIONEVENETOGRANT657/02/96,RICERCASANITARIAFINALIZZATASMWASSUPPORTEDBYAPOSTDOCTORALFELLOWSHIPFROMICGEB,TRIESTE,ITALYANDBMWASSUPPORTEDBYAPERSONALGRANTFROMAIRCTHEAUTHORSAREGRATEFULTODRGLDESALVOANDMEPIFANIFORSTATISTICALANALYSISANDTOPSEGATOFORHELPINARTICLEPREPARATIONADDRESSFORREPRINTSALBERTORUOL,MD,CLINICACHIRURGICA4,UNIVERSITYOFPADOVA,VIAGIUSTINIANI,2,35128PADOVA,ITALYFAX?390498213152EMAILARUOLUX1UNIPDITRECEIVEDJUNE28,2000REVISIONRECEIVEDJANUARY10,2001ACCEPTEDJANUARY19,2001BACKGROUNDTHEMAGE,BAGE,ANDGAGEGENEFAMILIESCODEFORDISTINCT,TUMORSPECIFICANTIGENSTHATARERECOGNIZEDBYCYTOTOXICTLYMPHOCYTESINTHECONTEXTOFHLAMOLECULESTHEPURPOSEOFTHISSTUDYWASTOANALYZEMAGE,BAGE,ANDGAGEGENEEXPRESSIONINTHETWOMAJORHISTOLOGICTYPESOFESOPHAGEALCARCINOMA,SQUAMOUSCARCINOMAESCCANDADENOCARCINOMACAC,ANDTOCORRELATETHEIREXPRESSIONPATTERNSWITHTHEPRINCIPALPROGNOSTICPARAMETERSANDLONGTERMSURVIVALMETHODSGENEEXPRESSIONWASANALYZEDINSURGICALSAMPLESFROM24PATIENTSWITHESCCAND24PATIENTSWITHCACBYREVERSETRANSCRIPTASEPOLYMERASECHAINREACTIONAMPLIFICATIONRTPCRNONEOFTHEPATIENTSHADRECEIVEDPREOPERATIVECHEMOTHERAPYORRADIOTHERAPY,ANDALLWEREFOLLOWEDUNTILDEATHORFORAMINIMUMOF4YEARSRESULTSSIXTEENESCCSAMPLES67AND9CACSAMPLES375EXPRESSEDATLEASTONEOFTHEGENESUNDERSTUDYTHEEXPRESSIONOFEACHMAGEGENEINTHETWOHISTOLOGICTYPESWASNOTSIGNIFICANTLYDIFFERENT,WITHTHEEXCEPTIONOFMAGE4,WHICHWASEXPRESSEDMOREINESCCSAMPLESTHANINCACSAMPLESBAGEANDGAGEEXPRESSIONWASRATHERLOWAND,INEVERYCASE,WASASSOCIATEDWITHTHEEXPRESSIONOFATLEASTONEMAGEGENECONCLUSIONSINTHEGROUPASAWHOLE,ANDINBOTHESCCANDCACSUBGROUPS,NOSIGNIFICANTCORRELATIONEMERGEDBETWEENTHEEXPRESSIONOFANYGENEANDPROGNOSTICPARAMETERS,SUCHASPATHOLOGICTUMOR,LYMPHNODE,ORDISEASESTAGENEVERTHELESS,BAGEORGAGEEXPRESSIONWASRELATEDSIGNIFICANTLYTOAPOORPROGNOSIS,WHEREASTHEEXPRESSIONOFMAGEGENESINTHEABSENCEOFBAGEANDGAGEEXPRESSIONWASRELATEDSIGNIFICANTLYTOAGOODPROGNOSISCANCER2001911882–8?2001AMERICANCANCERSOCIETYKEYWORDSESOPHAGEALCARCINOMA,TUMORANTIGENS,MAGE,BAGE,GAGEINRECENTYEARS,NUMEROUSHUMANTUMORANTIGENSTHATARERECOGNIZEDBYAUTOLOGOUSCYTOTOXICTLYMPHOCYTESCTLSHAVEBEENIDENTIFIED1ANIMPORTANTCATEGORYOFTHESESOCALLEDTCELLDEFINEDTUMORANTIGENSCONSISTSOFNORMALGENEPRODUCTSTHATARENOTEXPRESSEDINMOSTBODYTISSUES,WITHTHEEXCEPTIONOFMALEGERMLINECELLSANDPLACENTA,ANDAREACTIVATEDINANUMBEROFDIFFERENTTUMORSANTIGENICPEPTIDESENCODEDBYTHEMAGE,BAGE,ANDGAGEGENEFAMILIESAREPROTOTYPESOFTHISCATEGORYOFSHAREDTUMORANTIGENS2–5ALTHOUGHTHEYINITIALLYWEREDESCRIBEDINMELANOMA,THESEGENESHAVEBEENFOUNDTOBEEXPRESSEDINASUBSTANTIALNUMBEROFSOLIDTUMORSINVARIOUSORGANS,SUCHASLUNG,BREAST,BLADDER,HEADANDNECK,ESOPHAGUS,ANDSTOMACH,ASWELLASINSEVERALTUMORCELLLINES2BECAUSEOFTHEIRSTRICTTUMORSPECIFICITY,THEYAREOFPARTICULARINTERESTFORCANCERIMMUNOTHERAPY1882?2001AMERICANCANCERSOCIETYDEOXYNUCLEOTIDESDNTPS,1?LOFA500?G/MLSOLUTIONOFOLIGODT12–18PRIMERS,20UNITSOFRNASEOUTGIBCOBRL,2?LOF01M1,4DITHIOTHREITOL,AND200UNITSOFMOLONEYMURINELEUKEMIAVIRUSREVERSETRANSCRIPTASEGIBCOBRLTHEREACTIONWASINCUBATEDAT42°CFOR60MINUTESANDTHENDILUTEDTO40?LWITHWATERTWOMICROLITERSOFTHECDNAMIXTUREWEREUSEDFOREACHPOLYMERASECHAINREACTIONPCRAMPLIFICATIONINA50?LREACTIONVOLUMECONTAINING1?LOFEACHPRIMER40?M,1?LEACHOF25MMDNTP,15MMMGCL2,AND2UNITSTAQDNAPOLYMERASEPROMEGA,MADISON,WIINBUFFERA,WHICHWASSUPPLIEDBYTHEMANUFACTURERTHEPRIMERSUSEDINTHISSTUDYTOENSURESPECIFICITYFOREACHGENEWEREDESCRIBEDPREVIOUSLY3,4,9THIRTYTWOAMPLIFICATIONCYCLESWERERUN1MINUTEAT94°CAND3MINUTESAT72°CFORMAGE1ANDMAGE31MINUTEAT94°C,2MINUTESAT68°C,AND2MINUTESAT72°CFORMAGE2ANDMAGE41MINUTEAT94°C,2MINUTESAT70°C,AND2MINUTESAT72°CFORMAGE61MINUTEAT94°C,2MINUTESAT62°C,AND2MINUTESAT73°CFORBAGEAND1MINUTEAT94°C,2MINUTESAT55°C,AND2MINUTESAT72°CFORALLOFTHEGAGEGENESCYCLINGWASCONCLUDEDWITHAFINALEXTENSIONSTEPOF15MINUTESAT72°CTOVERIFYRNAINTEGRITYINEACHSAMPLE,23CYCLESFOR1MINUTEAT94°C,2MINUTESAT68°C,AND2MINUTESAT72°CWERERUNWITHPRIMERSSPECIFICFOR?ACTINAFTERAMPLIFICATION,PCRPRODUCTSWEREANALYZEDBYAGAROSEGELELECTROPHORESISSTATISTICALANALYSISSTATISTICALANALYSESWEREPERFORMEDUSINGTHESASSTATISTICALPACKAGESAS,INC,CARY,NCDIFFERENCESBETWEENGROUPSWEREASSESSEDBYCHISQUAREANALYSIS,FISHEREXACTTEST,ORSTUDENTTTEST,ASINDICATEDALLPVALUES?005WERECONSIDEREDSIGNIFICANTSURVIVALWASMEASUREDFROMTHEDATEOFSURGERYTODEATHORLASTDATEOFFOLLOWUPSURVIVALRATESANDSTANDARDERRORSWERECALCULATEDBYTHEKAPLAN–MEIERMETHOD,INCLUDINGDEATHSFROMALLCAUSES,EXCEPTTHETWOHOSPITALDEATHSTHATWERERELATEDTOPOSTOPERATIVECOMPLICATIONSTHESTATISTICALSIGNIFICANCEOFDIFFERENCESINSURVIVALWASANALYZEDBYTHELOGRANKTEST,WITHP?005CONSIDEREDSIGNIFICANTTHEPROGNOSTICIMPORTANCEOFCLINICALVARIABLESWASEVALUATEDBYACOXPROPORTIONALHAZARDREGRESSIONUSINGMULTIVARIATEANALYSISRESULTSMAGE1,MAGE2,MAGE3,MAGE4,MAGE6,BAGE,ANDGAGEGENEEXPRESSIONWASEVALUATEDIN48SURGICALSPECIMENS,OFWHICH24SPECIMENSWEREESCC,AND24SPECIMENSWERECACTABLE1,ANDIN5SAMPLESOFNORMALESOPHAGEALTISSUEADJACENTTOTHETUMORSIXTYSEVENPERCENTOFTHEESCCTUMORSAND375OFTHECACTUMORSEXPRESSEDATLEASTONEOFTHESEGENESFIGURE1SHOWSTHEDIFFERENTPATTERNSOFMAGEBAGEGAGEGENEEXPRESSIONINEIGHTREPRESENTATIVECACSAMPLESTOGETHERWITHAPPROPRIATECONTROLSTABLE2SHOWSTHATTHEPATTERNOFMAGEGENEEXPRESSIONWASVERYSIMILARINBOTHESCCANDCACSAMPLES,EXCEPTFORMAGE4,WHICHWASEXPRESSEDSIGNIFICANTLYMOREINTHEESCCSAMPLES58VS25,RESPECTIVELYP?0019TWOESCCSAMPLES8,BUTNONEOFTHECACSAMPLES,EXPRESSEDBAGEP?0149GAGEGENEEXPRESSIONWASOBSERVEDINFOURESCCSAMPLES17ANDINTHREECACSAMPLES13P?0683NONEOFTHEGENESUNDERSTUDYWASEXPRESSEDINNORMALESOPHAGEALTISSUESAMPLESDATANOTSHOWNWEINVESTIGATEDTHEASSOCIATIONBETWEENMAGE,BAGE,ANDGAGEGENEEXPRESSION,ANDTHECLINICOPATHOLOGICPARAMETERSLISTEDINTABLE1INTHEGROUPOFPATIENTSASAWHOLEANDINBOTHESCCANDCACSUBGROUPS,NOSIGNIFICANTCORRELATIONEMERGEDBETWEENTHEEXPRESSIONOFANYOFTHESEGENES,ANDPATIENTGENDERANDAGE,HISTOLOGICTUMORTYPEANDGRADINGPT,PN,ANDPSTAGE,ANDTYPEOFRESECTION,WITHTHESINGLEEXCEPTIONOFTHEGAGEGENE,WHICHWASEXPRESSEDSIGNIFICANTLYMOREINTUMORSAMPLESOBTAINEDFROMPATIENTSWHOUNDERWENTR1–R2RESECTIONP?0027DATANOTSHOWNMAGE,BAGE,ANDGAGEGENEEXPRESSIONAPPEAREDTOBECLUSTEREDINASUBSETOFTHETUMORSEXAMINED,BECAUSEMOSTLESIONSEITHERDIDNOTEXPRESSANYGENE4823OF48PATIENTSORSIMULTANEOUSLYCOEXPRESSEDTHREEORMOREGENES3517OF48PATIENTSTABLE3BAGEANDGAGEGENESALWAYSWERECOEXPRESSEDWITHONEORMOREMEMBERSOFTHEMAGEFAMILYTHEOVERALL1YEAR,3YEAR,AND5YEARACTUARIALSURVIVALRATESOFPATIENTSSURVIVINGESOPHAGECTOMYN?46PATIENTSWERE85,41,AND24,RESPECTIVELYTHE1YEAR,3YEAR,AND5YEARACTUARIALSURVIVALRATESAFTERR0RESECTIONN?37PATIENTSWERE89,51,AND30,RESPECTIVELYTABLE4SUMMARIZESTHEUNIVARIATEANALYSISOFTHEPROGNOSTICVALUEOFSEVERALCLINICOPATHOLOGICPARAMETERSINTHEFIRSTSETOFSURVIVALANALYSES,THESAMPLESWEREDIVIDEDINTOTWOCOHORTSTHOSEEXPRESSINGONEORMOREOFTHEGENESSTUDIEDANDTHOSESHOWINGNOGENEEXPRESSIONINTHEENTIREGROUPOFPATIENTSANDINBOTHESCCANDCACSUBGROUPS,WHICHWEREEVALUATEDSEPARATELY,NOSIGNIFICANTASSOCIATIONWASFOUNDBETWEENTHEABOVETWOCOHORTSANDSURVIVALDATANOTSHOWNASIMILARANALYSISWASCARRIEDOUTFOREACHOFTHEMAGE,BAGE,ANDGAGEGENESSEPARATELYONLYBAGEORGAGEEXPRESSIONWASRELATEDSIGNIFICANTLYTOAPOORPROGNOSISTABLE4FINALLY,WEGROUPEDTHEPATIENTSACCORDINGTOTHE1884CANCERMAY15,2001/VOLUME91/NUMBER10

簡(jiǎn)介：中文中文3650字，字，2660單詞，單詞，14000英文字符英文字符出處出處TORRICELLIFCM,DES,SARKISSIANC,ETALHYDROPHILICGUIDEWIRESEVALUATIONANDCOMPARISONOFTHEIRPROPERTIESANDSAFETYJUROLOGY,2013,82511821186親水導(dǎo)絲親水導(dǎo)絲評(píng)估和比較其性能與安全性評(píng)估和比較其性能與安全性FABIOCESARMIRANDATORRICELLI，SHUBHADE，CARLSARKISSIAN，ANDMANOJMONGA目的目的比較10種市售親水導(dǎo)絲的物理和機(jī)械性能方法方法進(jìn)行體外測(cè)試評(píng)估10種不同的直型親水導(dǎo)絲（5種普通導(dǎo)絲和5種硬導(dǎo)絲）GLIDEWIRE，NICORE，EZGLIDER，HIWIRE與ZIPWIRE。測(cè)量所有這10種導(dǎo)絲的頭端穿刺力，頭端彎曲力，桿彎曲力以及在運(yùn)動(dòng)中的摩擦力。采用高倍光學(xué)顯微鏡測(cè)量頭端輪廓。結(jié)果結(jié)果GLIDEWIRE穿刺我們的模型所需的力最大（P01）。EZGLIDER，ZIPWIRE和GLIDEWIRE頭端彎曲力最?。≒＜001）。GLIDEWIRE桿最硬（P＜001）。EZGLIDER和GLIDEWIRE在摩擦力測(cè)試中力最大。就硬導(dǎo)絲而言，GLIDEWIRES在穿刺測(cè)試中力最大（P≤05）。GLIDEWIRES和EZGLIDERS頭端彎曲力最小。ZIPWIRES和NICORES桿最硬（P≤01）GLIDEWIRES在摩擦測(cè)試中力最大（P≤001）。頭端輪廓測(cè)試顯示ZIPWIRE，HIWIRES以及EZGLIDERS頭端最圓。結(jié)論結(jié)論每一種導(dǎo)線都有其獨(dú)特的優(yōu)點(diǎn)和缺點(diǎn)。雖然GLIDEWIRE（硬導(dǎo)絲和普通導(dǎo)絲兩種）潤(rùn)滑性較差，但是其刺穿的可能性最低。GLIDEWIRE和EZGLIDER頭端彎曲的力最小。在腔道泌尿外科手術(shù)過程中選擇正確的導(dǎo)絲可以幫助提高成功率，減少發(fā)病率。當(dāng)通過狹窄的輸尿管段或嵌頓結(jié)石時(shí)，可以使用親水性柔韌導(dǎo)絲繞過阻塞，不會(huì)發(fā)生穿孔或創(chuàng)傷。目前存在大量的市售導(dǎo)絲，每個(gè)都有其獨(dú)特的屬性，這些屬性可以影響它們的性能和潛在的發(fā)病率。導(dǎo)絲的功能是在輸尿管撕裂的情況下提供連續(xù)性和作為器械能夠通過的引導(dǎo)。由于術(shù)中對(duì)導(dǎo)絲的需求在不同情況下是不一樣的，可以使用各種不同的組成材料、形狀、桿剛性、潤(rùn)滑性，表面涂層、頭端設(shè)計(jì)和柔韌性的導(dǎo)絲?？紤]所有這些屬性是為臨床應(yīng)用選擇合適的導(dǎo)絲的關(guān)鍵。在遇到嚴(yán)重曲折、障礙物或嘗試用普通導(dǎo)絲失敗等復(fù)雜的情況下，親水導(dǎo)絲通常會(huì)被用來幫助疏通通道。這些導(dǎo)絲通常有一個(gè)堅(jiān)實(shí)的鎳鈦或金屬合金核心，以及持久的親水涂層，親水涂層顯著減少了其濕潤(rùn)時(shí)的摩擦系數(shù)。圖1A穿刺實(shí)驗(yàn)；B桿彎曲試驗(yàn)；C頭端彎曲試；D摩擦實(shí)驗(yàn)統(tǒng)計(jì)分析導(dǎo)絲被分為2組（普通VS硬），使用單向方差分析來確定各組中的各個(gè)測(cè)試的所有導(dǎo)絲之間的統(tǒng)計(jì)學(xué)差異。T檢驗(yàn)用于各試驗(yàn)中的導(dǎo)線之間的成對(duì)比較。使用MICROSOFTEXCEL分析工具庫(kù)（微軟，華盛頓州雷蒙德市）來分析所收集的數(shù)據(jù)。顯著性被定為P005。結(jié)果所有導(dǎo)絲的直徑為0889毫米，長(zhǎng)150厘米，帶3厘米軟頭。單因素方差分析結(jié)果顯示，在所有測(cè)試每個(gè)組內(nèi)導(dǎo)絲之間平均力測(cè)量有顯著的統(tǒng)計(jì)學(xué)差異（P0001表1）。普通硬導(dǎo)絲普通GLIDEWIRE刺穿我們的模型需要約的力量比其他導(dǎo)絲大約40（0363±0704N），其次是ZIPWIRE（0328±0085N，P340），EZGLIDER（0261±0071N，P06），HIWIRE（0259±0038N，P001），以及NICORE（0257±0048N，P01）。桿彎曲測(cè)試表明GLIDEWIRE最硬（0134±0005），明顯比其他導(dǎo)絲需要更大

簡(jiǎn)介：PROCNATLACADSCIUSAVOL95,PP8801–8805,JULY1998MEDICALSCIENCESMYOCYTEPROLIFERATIONINENDSTAGECARDIACFAILUREINHUMANSMITOTICINDEX?CYTOKINESISJANKAJSTURA?,ANNAROSALERI,NICOLETTAFINATO?,CARLADILORETO?,CARLOABELTRAMI?,ANDPIEROANVERSADEPARTMENTOFMEDICINE,NEWYORKMEDICALCOLLEGE,VALHALLA,NY10595AND?DEPARTMENTOFPATHOLOGY,UNIVERSITYOFUDINE33100,UDINE,ITALYCOMMUNICATEDBYEUGENEBRAUNWALD,PARTNERSHEALTHCARESYSTEM,INC,BOSTON,MA,MAY18,1998RECEIVEDFORREVIEWJANUARY14,1998ABSTRACTINTRODUCEDSEVERALDECADESAGO,THEDOGMAPERSISTSTHATCARDIACMYOCYTESARETERMINALLYDIFFERENTIATEDCELLSANDTHATDIVISIONOFMUSCLECELLSISIMPOSSIBLEINTHEADULTHEARTMORERECENTLY,NUCLEARMITOTICDIVISIONSINMYOCYTESOCCASIONALLYWERESEEN,BUTTHOSEOBSERVATIONSWERECHALLENGEDONTHEASSUMPTIONTHATTHERATEOFCELLPROLIFERATIONWASINCONSEQUENTIALFORACTUALTISSUEREGENERATIONMOREOVER,MITOSESWERENEVERDETECTEDINNORMALMYOCARDIUMHOWEVER,THEANALYSISOFROUTINEHISTOLOGICPREPARATIONSCONSTITUTEDTHEBASISFORTHEBELIEFTHATMYOCYTESWEREUNABLETOREENTERTHECELLCYCLEANDDIVIDE,IGNORINGTHELIMITATIONSOFTHESETECHNIQUESWEREPORTHEREBYCONFOCALMICROSCOPYTHAT14MYOCYTESPERMILLIONWEREINMITOSISINCONTROLHUMANHEARTSANEARLY10FOLDINCREASEINTHISPARAMETERWASMEASUREDINENDSTAGEISCHEMICHEARTDISEASE152MYOCYTESPERMILLIONANDINIDIOPATHICDILATEDCARDIOMYOPATHY131MYOCYTESPERMILLIONBECAUSETHELEFTVENTRICLECONTAINS58?109MYOCYTES,THESEMITOTICINDICESIMPLYTHAT812?103,882?103,AND760?103MYOCYTESWEREINMITOSISINTHEENTIREVENTRICULARMYOCARDIUMOFCONTROLHEARTSANDHEARTSAFFECTEDBYISCHEMICANDIDIOPATHICDILATEDCARDIOMYOPATHY,RESPECTIVELYADDITIONALLY,MITOSISLASTSLESSTHAN1HR,SUGGESTINGTHATLARGENUMBERSOFMYOCYTESCANBEFORMEDINTHENONPATHOLOGICANDPATHOLOGICHEARTWITHTIMEEVIDENCEOFCYTOKINESISINMYOCYTESWASOBTAINED,PROVIDINGUNEQUIVOCALPROOFOFMYOCYTEPROLIFERATIONITISAGENERALCONTENTIONTHATCARDIACMYOCYTESAREUNABLETODIVIDEINTHEADULTHEART1,2HOWEVER,QUANTITATIVERESULTSSUGGESTTHATANINCREASEINMYOCYTENUMBEROCCURSWITHSEVEREMYOCARDIALHYPERTROPHY3,4,BUTBECAUSEMITOSESINMYOCYTESWERENOTIDENTIFIED,THISDEFICIENCYLEDTODISBELIEFOFTHESEMORPHOMETRICRESULTSTHEOCCASIONALDETECTIONOFNUCLEARMITOTICDIVISIONSINTHEPATHOLOGICHEART5,6,WASCONSIDEREDOFNOVALUEINTERMSOFACTUALREGENERATIONOFMYOCARDIALMASSADDITIONALLY,MITOSESWERENEVEROBSERVEDINCONTROLMYOCARDIUMSIMILARLY,DOCUMENTATIONOFCYTOKINESISINMYOCYTESWASLACKINGISCHEMICANDIDIOPATHICDILATEDCARDIOMYOPATHIESINHUMANSARECHARACTERIZEDSTRUCTURALLYBYSEVEREMYOCARDIALSCARRINGCONSISTINGOFMULTIPLESITESOFREPLACEMENTFIBROSISANDDIFFUSEINTERSTITIALFIBROSIS7–10MOREOVER,AREASOFSEGMENTALFIBROSISAREPRESENTINALLCASESOFISCHEMICMYOPATHIES7,9SEGMENTAL,REPLACEMENT,ANDINTERSTITIALFIBROSISARETHECONSEQUENCEOFMYOCYTENECROSISHOWEVER,ADISCREPANCYEXISTSBETWEENTHEEXTENSIVECOLLAGENACCUMULATIONANDTHEMODESTREDUCTIONINTHENUMBEROFVENTRICULARMYOCYTESINTHEPOSTINFARCTEDHUMANHEART9THEDEPOSITIONOF1MM3OFCOLLAGENREFLECTSTHELOSSOF50?103MUSCLECELLS11,ANDTHEMAGNITUDEOFFIBROSISINENDSTAGEISCHEMICCARDIOMYOPATHYWOULDIMPLYANEARLY90DECREASEINTHETOTALNUMBEROFLEFTVENTRICULARMYOCYTES9CONVERSELY,DECREASESOFLESSTHAN30HAVEBEENREPORTED9THISDISCREPANCYISEVENMOREAPPARENTINIDIOPATHICDILATEDCARDIOMYOPATHYINWHICHMYOCARDIALFIBROSISISASSOCIATEDWITHPRESERVATIONOFTHENUMBEROFMYOCYTESINTHEVENTRICLES10UNDERSTANDINGOFTHECELLULARBASISOFWALLRESTRUCTURINGINTHEDISEASEDHEARTISCOMPLICATEDFURTHERBYTHEDOCUMENTATIONTHATPROGRAMMEDMYOCYTECELLDEATHOCCURSWITHVENTRICULARDECOMPENSATION12,13APOPTOSISDOESNOTRESULTINTISSUEFIBROSISDYINGMYOCYTESAREREMOVEDFROMNEIGHBORINGCELLSINTHEABSENCEOFANINFLAMMATORYREACTION14THESEPHENOMENA,INDICATINGSEVEREONGOINGNECROTICANDAPOPTOTICMYOCYTEDEATH,POINTTOTHEPOSSIBILITYTHATMYOCYTESARENOTTERMINALLYDIFFERENTIATEDANDCELLPROLIFERATIONMAYBESTIMULATEDINTHEPATHOLOGICHEARTIMMUNOCYTOCHEMISTRYANDCONFOCALMICROSCOPYWEREUSEDHERETOMEASUREAMITOTICINDEXINMYOCYTESOFHEARTSOBTAINEDFROMPATIENTSUNDERGOINGCARDIACTRANSPLANTATIONASARESULTOFCHRONICISCHEMICHEARTDISEASEANDDILATEDCARDIOMYOPATHYHEARTSCOLLECTEDATAUTOPSYWEREUSEDASCONTROLSMATERIALSANDMETHODSCARDIACCHARACTERISTICSTWENTYSEVENPATIENTSUNDERGOINGCARDIACTRANSPLANTATION,12FORISCHEMICAND15FORIDIOPATHICDILATEDCARDIOMYOPATHY,WERESTUDIEDTHEFIRSTGROUPINCLUDED11MALESANDONEFEMALE,WITHANAVERAGEAGEOF52?9YEARS,ANDTHESECOND11MALESANDFOURFEMALES,WITHANAVERAGEAGEOF55?11YEARSNINECONTROLHEARTS,SEVENMALESANDTWOFEMALES,WITHANAVERAGEAGEOF48?15YEARS,WERECOLLECTEDATAUTOPSYWITHIN15HRAFTERDEATHDEATHOCCURREDFROMCAUSESOTHERTHANCARDIOVASCULARDISEASEMITOTICINDEXINTHE27EXPLANTEDANDNINECONTROLHEARTS,SPECIMENSCOMPRISINGTHEENTIRETHICKNESSOFTHEANTERIORANDPOSTERIORASPECTSOFTHELEFTVENTRICULARWALLWEREOBTAINEDHALFWAYBETWEENTHEAPEXANDTHEBASEOFTHEHEARTSAMPLESWEREFIXEDINFORMALINANDEMBEDDEDINPARAFFINSECTIONSWERESTAINEDWITHPROPIDIUMIODIDE20?G?MLAND?SARCOMERICACTINANTIBODYCLONE5C5,SIGMATOVISUALIZEDNAANDMYOFIBRILLARSTRUCTURESTHESESECTIONSWEREEXAMINEDBYCONFOCALMICROSCOPYMRC1000,BIORADWITHANOPTICALSECTIONTHICKNESSOF057?MTHEPERCENTAGEOFMYOCYTENUCLEIUNDERGOINGMITOSISWASOBTAINEDBYSAMPLINGANUMBEROFMYOCYTENUCLEI,VARYINGFROM12,000TO67,000VALUESINCONTROLHEARTSWERE75,000AND230,000THEEVALUATIONOFAMITOTICINDEXININTERSTITIALCELLSINCLUDEDSEVENCASESWITHISCHEMICCARDIOMYOPATHY,FIVEWITHDILATEDCARDIOMYOPATHY,ANDFOURCONTROLHEARTSINEACHPATHOLOGICANDNORMALHEART30,000AND100,000NUCLEIWERESAMPLED,RESPECTIVELYDATACOLLECTIONANDANALYSISRESULTSAREPRESENTEDASMEAN?SDSIGNIFICANCEBETWEENTWOMEASUREMENTSWASDETERMINEDBYTHESTUDENT’STTEST,ANDINMULTIPLECOMPARISONSWASEVALUATEDBYTHEBONFERRONIMETHOD15P?005WASCONSIDEREDSIGNIFICANTTHEPUBLICATIONCOSTSOFTHISARTICLEWEREDEFRAYEDINPARTBYPAGECHARGEPAYMENTTHISARTICLEMUSTTHEREFOREBEHEREBYMARKED‘‘ADVERTISEMENT’’INACCORDANCEWITH18USC§1734SOLELYTOINDICATETHISFACT?1998BYTHENATIONALACADEMYOFSCIENCES00278424?98?9588015200?0PNASISAVAILABLEONLINEATHTTP??WWWPNASORG?TOWHOMREPRINTREQUESTSSHOULDBEADDRESSEDATDEPARTMENTOFMEDICINE,VOSBURGHPAVILION,ROOM302,NEWYORKMEDICALCOLLEGE,VALHALLA,NY105958801RESULTSPATIENTSALLPATIENTSHADNEWYORKHEARTASSOCIATIONFUNCTIONALCLASSIIIORIVLEFTANDRIGHTVENTRICULARWEIGHTSWERE189?26AND62?18G,RESPECTIVELY,INCONTROLS,281?51AND110?33G,RESPECTIVELY,INISCHEMICCARDIOMYOPATHY,AND362?129AND96?36G,RESPECTIVELY,INDILATEDCARDIOMYOPATHYTHE49P?005AND92P?0001INCREASEINLEFTVENTRICULARWEIGHT,AND77P?001AND55P?005INCREASEINRIGHTVENTRICULARWEIGHTWITHISCHEMICANDDILATEDCARDIOMYOPATHY,RESPECTIVELY,WERESIGNIFICANTTISSUESAMPLINGOFTHELEFTVENTRICLEWASRESTRICTEDTOREGIONSINWHICHAREASOFSCARRINGWERENOTMACROSCOPICALLYVISIBLEHOWEVER,SMALLFOCIOFREPLACEMENTFIBROSISANDDIFFUSEINTERSTITIALFIBROSISWEREPRESENTINTHETISSUESECTIONSFROMPATHOLOGICHEARTSAREASOFREPARATIVEANDINTERSTITIALFIBROSISOCCASIONALLYWERESEENINTHELEFTVENTRICLEOFCONTROLHEARTSCONFOCALMICROSCOPYSECTIONSOFMYOCARDIUMWERELABELEDWITHPROPIDIUMIODIDEAND?SARCOMERICACTINANTIBODYTHISANTIBODYISSPECIFICFORIBANDSOFCARDIACANDSKELETALMUSCLECELLSANDDOESNOTREACTWITHOTHERACTINISOFORMS16CONFOCALMICROSCOPYALLOWEDANACCURATEIDENTIFICATIONOFMITOSISINMYOCYTESCHROMOSOMESWEREDEPICTEDBYTHEGREENCOLORASSIGNEDTOPROPIDIUMIODIDEFLUORESCENCE,ANDMYOFIBRILLARSTRUCTURESWERERECOGNIZEDBYTHEREDCOLORASSIGNEDTOTHEFLUORESCENCEOF?SARCOMERICACTINANTIBODYLABELINGFIG1A–CILLUSTRATESANUCLEUSINMITOSISANDTWODAUGHTERCELLSATTHECOMPLETIONOFCYTOKINESISINAPATIENTAFFECTEDBYDILATEDCARDIOMYOPATHYINTHISLATTEREXAMPLE,THEAGGREGATESOFCHROMOSOMESMIRROREACHOTHERINTHETWONEWLYGENERATEDMYOCYTESFIG1ESHOWSALATEPROPHASETHATISCHARACTERIZEDBYTHEPRESERVATIONOFNUCLEARSHAPEINTHEABSENCEOFNUCLEARMEMBRANETWOMOREMYOCYTENUCLEIEXHIBITINGMETAPHASECHROMOSOMESAREDEPICTEDINFIG1DANDFTHEINITIALSEPARATIONOFCHROMOSOMESINFIG1DMAYCORRESPONDTOLATEMETAPHASEORONSETOFANAPHASETHESETHREEMITOTICFIGURESWEREFOUNDINACASEOFISCHEMICCARDIOMYOPATHY,DILATEDCARDIOMYOPATHY,ANDACONTROLHEART,RESPECTIVELYAMITOTICIMAGEINANINTERSTITIALCELLANDTHREEADDITIONALMITOSESINMYOCYTESAREDEPICTEDINFIG1G–LUNDIFFERENTIATEDCYTOPLASMSURROUNDINGTHENUCLEUSUNDERGOINGDIVISIONFIG1IWASOBSERVEDIN52OFTHECASES74OF142ORGANELLESBREAKUPINTOSMALLFRAGMENTSTOALLOWMOREUNIFORMDISTRIBUTIONOFTHESECOMPONENTSINTHETWODAUGHTERCELLSTHEDISTINCTIONBETWEENMYOCYTEANDNONMYOCYTENUCLEIWASEXTREMELYSIMPLE,BECAUSEINTERSTITIALCELLSWERENOTSTAINEDBY?SARCOMERICACTINANTIBODYANDONLYTHENUCLEUSCOULDBEIDENTIFIEDBYPROPIDIUMIODIDESTAININGFIG1G,H,ANDJ–LTHISWASAPPARENTINNONDIVIDINGANDDIVIDINGINTERSTITIALCELLSFIG1GTHEREWASNOAPPARENTDIFFERENCEINTHELOCALIZATIONOFMITOSESINTHEANTERIORANDPOSTERIORASPECTSOFTHELEFTVENTRICLEINCONTROLANDPATHOLOGICHEARTSTHEAVERAGEAREAOFMYOCARDIUMEXAMINEDBYCONFOCALMICROSCOPYINEACHPATIENTWAS609?240MM2INCONTROLS,327?193MM2INISCHEMICCARDIOMYOPATHY,AND341?194MM2INDILATEDCARDIOMYOPATHYCORRESPONDINGNUMBERSOFMYOCYTENUCLEICOUNTEDWERE141,136?56,699,38,854?16,766,AND36,013?17,134VALUESFORMYOCYTEMITOTICFIGURESWERE18?06,51?35,AND43?20,RESPECTIVELYTHESEDATAALLOWEDTHECOMPUTATIONOFAMYOCYTEMITOTICINDEXINEACHGROUPFIG2INNORMALLEFTVENTRICLES,ANAVERAGEOF14MYOCYTESPERMILLIONCELLSWEREUNDERGOINGMITOSIS,BUTAMUCHHIGHERMITOTICINDEXWASMEASUREDINPATHOLOGICHEARTSINISCHEMICCARDIOMYOPATHY,152MYOCYTESPERMILLIONWEREDIVIDING,ANDINDILATEDCARDIOMYOPATHY,131MYOCYTESPERMILLIONWEREINMITOSISTHESMALLDIFFERENCEBETWEENTHETWOGROUPSOFPATIENTSWITHCARDIACFAILUREWASNOTSIGNIFICANT,YIELDINGANAVERAGEVALUEOF140PROLIFERATINGMYOCYTESPERMILLIONCELLSINCOMPARISONWITHHEALTHYMYOCARDIUM,CARDIACFAILUREWASCHARACTERIZEDBYA10FOLDINCREASEINTHENUMBEROFDIVIDINGMYOCYTESP?00001NOGENDERDIFFERENCEINTHISPARAMETERCOULDBEDETECTEDTHEMITOTICINDEXININTERSTITIALCELLSWAS18?13PERMILLIONCELLSINCONTROLSN?4AND106?42PERMILLIONCELLSINFAILINGHEARTSN?12SEVENISCHEMICANDFIVEIDIOPATHICMYOPATHIESWITHRESPECTTOMYOCYTES140?50N?27,THE24LOWERVALUEININTERSTITIALCELLSWASNOTSIGNIFICANTDISCUSSIONCARDIACHYPERTROPHYINTHEEARLY1920S,ANATOMICALSTUDIESEMPHASIZEDTHEDIFFICULTIESOFDETECTINGMITOTICFIGURESINMYOCYTESAND,ONTHISBASIS,INTRODUCEDTHECONCEPTTHATMUSCLECELLPROLIFERATIONISABSENTINTHEADULT,FULLYDIFFERENTIATED,MAMMALIANMYOCARDIUM1MOREOVER,EXPERIMENTALRESULTSOFACUTECARDIACHYPERTROPHYINRODENTSDEMONSTRATEDTHEINABILITYOFMYOCYTESTOREENTERTHECELLCYCLE,SYNTHESIZEDNA,ANDUNDERGOMITOTICDIVISION17–19THESEOBSERVATIONSWERERESPONSIBLEFORTHECREATIONOFTHEDOGMATHAT,SHORTLYAFTERBIRTH,VENTRICULARMYOCYTESWITHDRAWPERMANENTLYFROMTHECELLCYCLEANDAREDESTINEDTODIEWITHOUT

簡(jiǎn)介：中文中文3500字出處出處CHOIWH,KWONSU,JWAYJ,ETALTHEPULMONARYEMBOLISMSEVERITYINDEXINPREDICTINGTHEPROGNOSISOFPATIENTSWITHPULMONARYEMBOLISMJKOREANJOURNALOFINTERNALMEDICINE,2009,242123127肺栓塞嚴(yán)重程度指數(shù)預(yù)測(cè)肺栓塞患者的預(yù)后分析肺栓塞嚴(yán)重程度指數(shù)預(yù)測(cè)肺栓塞患者的預(yù)后分析CHOIWH,KWONSU,JWAYJ,ETAL【摘要】背景/目的許多預(yù)后模型已經(jīng)被建立來幫助醫(yī)生做出醫(yī)療決定以更好的治療肺栓塞患者。在這些模型中，肺栓塞嚴(yán)重程度指數(shù)（PESI）已被證明是一個(gè)成功的急性肺栓塞患者危險(xiǎn)分層工具。然而，PESI，沒有被應(yīng)用在韓國(guó)的肺栓塞患者。方法在這項(xiàng)研究中的患者由仁濟(jì)大學(xué)一山白醫(yī)院進(jìn)行計(jì)算機(jī)斷層掃描，時(shí)間1999年12月至2007年3月。為病人進(jìn)行危險(xiǎn)分層使用的PESI。根據(jù)PESI計(jì)算死亡風(fēng)險(xiǎn)。結(jié)果在這項(xiàng)研究中，90例患者中，有10例為PESI，29例為PESIII類，22例Ⅲ類，8例IV級(jí)，10例V級(jí)。30天之后，在每個(gè)級(jí)別的死亡率分別為0，103，91，0和50％（P00016），而分別的醫(yī)院內(nèi)死亡率為48，138，136，125，和50％（P值00065）?？傮w死亡率為95，276，318，500和60％（P00019）。死亡率與PESI分級(jí)顯著相關(guān)。結(jié)論P(yáng)ESI分級(jí)被發(fā)現(xiàn)與30天死亡率，醫(yī)院內(nèi)死亡率和整體死亡率顯著相關(guān)。我們的數(shù)據(jù)表明的PESI可以被用來預(yù)測(cè)肺栓塞患者的預(yù)后和決定患者的治療?！娟P(guān)鍵詞】急性肺栓塞預(yù)后簡(jiǎn)介肺動(dòng)脈栓塞發(fā)生比較頻繁，在美國(guó)每年每10萬人有23例1，但是，由于其臨床特點(diǎn)是非特異的，因此診斷肺栓塞不是容易的。進(jìn)而，如果沒有適當(dāng)?shù)闹委?，肺栓塞是致命的。因此，恰?dāng)?shù)膽岩珊瓦m當(dāng)?shù)脑u(píng)估對(duì)于預(yù)后是很重要的。一旦預(yù)后被預(yù)測(cè)，通過適當(dāng)?shù)闹委?，死亡率可以降低。雖然已經(jīng)取得了明確的肺栓塞的危險(xiǎn)因素分類及治療方法，預(yù)后指標(biāo)數(shù)據(jù)仍是相對(duì)少。然而，自2000年日內(nèi)瓦評(píng)分發(fā)現(xiàn)2和2005年肺栓塞嚴(yán)重性指數(shù)（PESI）3被提出，這兩種模型已被引入。PESI評(píng)分被證明具有更高的預(yù)測(cè)精度4。表面上，韓國(guó)人可能會(huì)有較少肺栓塞的危險(xiǎn)因素，如肥胖或深靜脈血栓形成，與西方人相比，并可能有較好的預(yù)后5,6。然而，在目前的較少有數(shù)據(jù)支持這一論斷。出于這個(gè)原因，我們分析了用的PESI3分析韓國(guó)肺栓塞患者的預(yù)后預(yù)測(cè)。方法病人選擇1999年12月至2007年3月，我們招收在仁濟(jì)大學(xué)的一山白醫(yī)院的195例確診為急性肺栓塞的住院病人或門診病人，根據(jù)韓國(guó)疾病指南（KCD）。在這些患者中，84診斷不充分（即沒有經(jīng)計(jì)算機(jī)斷層掃描（CT）證實(shí)肺栓塞），21人生存或死亡沒能由醫(yī)療記錄錄或電話或保存病歷中獲得，將他們排除在外。在這項(xiàng)研究中，共對(duì)90名患者進(jìn)行了評(píng)價(jià)。研究設(shè)計(jì)1999年12月，我們選擇經(jīng)胸部CT檢查證實(shí)肺栓塞的患者，對(duì)他們的醫(yī)療記錄進(jìn)行了分析。除了11項(xiàng)的被認(rèn)為包括在PESI指數(shù)中的項(xiàng)目外，還記錄了年齡，性別，既往病史，合并癥，臨床癥狀3。根據(jù)AUJESKY等人3提出的方法，分?jǐn)?shù)計(jì)算如下年齡每歲為1分，男性10分，心率110次/分鐘為20分，癌癥為30分，心臟衰竭10分，慢性肺疾病10分，收縮壓30次/分鐘為20分，體溫36℃為20分，精神狀態(tài)改變?yōu)?0討論肺栓塞患者的死亡率報(bào)告的各種各樣（從2％到95％）79。根據(jù)我們的數(shù)據(jù)，30天的死亡率為111％，而住院期間的死亡率為156％，總死亡率為300％。我們懷疑該報(bào)告的死亡率，因?yàn)槊總€(gè)病人有一些混雜因素，可能會(huì)影響他/她的預(yù)后，如不同的合并疾病和不同程度的肺栓塞。然而，很少有報(bào)告中均提到的因素，可以影響預(yù)后或肺栓塞的預(yù)測(cè)因素。要?jiǎng)?chuàng)建一個(gè)肺栓塞患者預(yù)后預(yù)測(cè)系統(tǒng)，日內(nèi)瓦評(píng)分22000年開發(fā)，PESI評(píng)分3在2005年首次提出。自那時(shí)以來，PESI評(píng)分已被證明是一個(gè)較好的預(yù)后模型4。AUJESKY等3報(bào)道，PESI評(píng)分IV級(jí)的患者30天的死亡率為08271％，意味著PESI評(píng)分越高的患者死亡率有增加的傾向。PESI被應(yīng)用于韓國(guó)，30天的死亡率，住院期間死亡率和總死亡率為060％。由于所有的結(jié)果都有顯著的意義，PESI預(yù)測(cè)韓國(guó)肺栓塞患者的預(yù)后是有意義的（30天死亡率P00016，住院死亡率P00065，整體死亡率P00019）。AUJESKY等人3斷言，PESI可以被用來確定低風(fēng)險(xiǎn)群體，并制定一個(gè)治療計(jì)劃。他們報(bào)告說，PESI評(píng)分I和II的患者30天的死亡率為16％和35％以下。治療過程中出血的危險(xiǎn)肺動(dòng)脈栓塞復(fù)發(fā)的頻率要低一些。他們還聲稱，在I級(jí)和II級(jí)的患者，低分子量肝素可以安全地使用，即使在門診病人，這些患者實(shí)際上是一個(gè)低風(fēng)險(xiǎn)組10。然而，當(dāng)根據(jù)PESI計(jì)算韓國(guó)患者30天的死亡率，I級(jí)患者為0％，而II級(jí)患者為103％，組間有顯著差異。AUJESKY等報(bào)道3，PESI為II級(jí)的病人難以通過日間護(hù)理治療。住院期間死亡率（I級(jí)48％，Ⅱ級(jí)138％）（P0029）和總死亡率（I級(jí)95％，Ⅱ級(jí)276％）（P0115），但兩組之間的差異無統(tǒng)計(jì)學(xué)意義。這可能因?yàn)镻ESI評(píng)分I級(jí)患者21個(gè)，II級(jí)患者的數(shù)量為29人。因此，對(duì)于兩個(gè)PESIⅠ和Ⅱ級(jí)為低風(fēng)險(xiǎn)群體門診治療可能是危險(xiǎn)的。IIIV級(jí)的患者表現(xiàn)出了類似的30天死亡率，住院期間的死亡率和總死亡率。等級(jí)越高沒有死亡率增加的傾向（P0424，0995和0281），當(dāng)PESI評(píng)分IIIV被重新分組為中等風(fēng)險(xiǎn)組，分級(jí)越高，死亡率明顯增加（30天死亡率P00016→00003，住院死亡率P00065→00038，整體死亡率P00019→00034）。因此，如果的PESI分級(jí)被重新分為低危（I級(jí)），中危（IIIV級(jí)），高危（V級(jí)），可改善后預(yù)測(cè)指標(biāo)的便利性，可行性和準(zhǔn)確性。比較各組死亡率，在低，中，高危人群分別為0，82％和50％，而30天死亡率住院期間死亡率分別為48，131和50％。相比較而言，總死亡率為95，311，和60％（表2）。肺栓塞要確定合適的治療方案，最重要的考慮病人的血流動(dòng)力學(xué)穩(wěn)定和超聲心動(dòng)圖結(jié)果。在這項(xiàng)研究中，觀察右心室運(yùn)動(dòng)障礙三個(gè)75例患者采取了心電圖，值得注意的是，這些患者中1人是在PESIⅢ級(jí)和其他兩個(gè)人在IV級(jí)，表明所有實(shí)例發(fā)生在相對(duì)較高的PESI類。這表明，可以用來確定高危人群以及低風(fēng)險(xiǎn)人群治療方案。這項(xiàng)研究有任何追溯性研究，包括在病人的選擇和治療計(jì)劃不一致的內(nèi)在限制。根據(jù)患者組（N90），對(duì)他們來說，死亡原因未分類的數(shù)量相對(duì)較少。然而，我們的研究結(jié)果的精度提高，只有那些情況下，肺栓塞，通過胸部CT確認(rèn)都包括在內(nèi)。此外，使用的電話使我們能夠進(jìn)行相對(duì)長(zhǎng)期隨訪，以確認(rèn)在30天的死亡率，以及死亡率住院期間總死亡率。這項(xiàng)研究表明，PESI是一個(gè)有用的預(yù)測(cè)，不只是30天的死亡率，也包括住院期間死亡率及總死亡率。風(fēng)險(xiǎn)組分類使用PESI可以預(yù)測(cè)不僅是30天的死亡率，也包括住院期間死亡率及總死亡率，這表明它是一個(gè)相對(duì)準(zhǔn)確的預(yù)后預(yù)測(cè)的指標(biāo)。

簡(jiǎn)介：中文中文3400字出處出處KILICKESMEZO,BAYRAMOGLUS,INCIE,ETALVALUEOFAPPARENTDIFFUSIONCOEFFICIENTMEASUREMENTFORDISCRIMINATIONOFFOCALBENIGNANDMALIGNANTHEPATICMASSESJJOURNALOFMEDICALIMAGINGRADIATIONONCOLOGY,2009,5315055表觀擴(kuò)散系數(shù)對(duì)肝臟良惡性腫塊的鑒別表觀擴(kuò)散系數(shù)對(duì)肝臟良惡性腫塊的鑒別KILICKESMEZO,BAYRAMOGLUS,INCIE,ETAL摘要我們研究的目的是探討使用并行成像技術(shù)的磁共振彌散加權(quán)成像（DWI）區(qū)分肝臟良性和惡性局灶性病變的價(jià)值。77例患者和65例健康對(duì)照者被納入研究中。DWI選取B值0，500和1000S/毫米2，計(jì)算出病灶及正常肝臟表觀擴(kuò)散系數(shù)（ADC）值。肝局灶性病變的ADC值如下單純性囊腫（316±01810?3毫米2／S），包蟲囊腫（258±05310?3毫米2／S），血管瘤（197±04910?3毫米2／S），轉(zhuǎn)移（114±04110?3毫米2／S）和肝細(xì)胞癌（HCC）（115±03610?3毫米2／S）。與正常肝平均ADC值（156±01410?3毫米2／S）相比，所有疾病組的ADC值差異均有統(tǒng)計(jì)學(xué)意義（P＜001）。血管瘤和肝癌轉(zhuǎn)移瘤間的ADC值也有統(tǒng)計(jì)上的顯著差異（P001），兩者與單純的包蟲囊腫間也有統(tǒng)計(jì)學(xué)差異（P＜0008。然而，HCC和轉(zhuǎn)移瘤之間有無統(tǒng)計(jì)學(xué)差異。目前的研究表明，ADC的測(cè)量對(duì)鑒別肝臟局灶性良、惡性病變有很大潛力。我們建議添加DWI序列在MR掃描中和肝臟病理定量鑒別檢測(cè)。前言磁共振成像是檢測(cè)肝臟彌漫性和局灶性病變及區(qū)分良惡性腫瘤的特性最準(zhǔn)確的方法，其反映了其對(duì)各種數(shù)據(jù)采集的基礎(chǔ)能力，如T1，T2和注射造影劑釓后的早期和晚期增強(qiáng)圖像。肝臟局灶性病變的表征是非常重要的，患者知道原發(fā)惡性腫瘤長(zhǎng)需與已知的常見良性肝臟局灶性病變及轉(zhuǎn)移灶相鑒別。在肝臟疾病的調(diào)查中，也由于磁共振成像缺少電離輻射，且釓螯合物與碘造影劑相比相對(duì)安全等以上兩個(gè)重要因素使MR成像優(yōu)先使用CT掃描。此外，DWI已經(jīng)成為一個(gè)新的無對(duì)比材料的診斷工具來檢測(cè)和區(qū)分惡性局灶性病變。4我們的目的是研究DWI是否有檢測(cè)和區(qū)分惡性腫瘤的轉(zhuǎn)移和原發(fā)性肝細(xì)胞癌的能力。這是我們的機(jī)構(gòu)2006年1月至2007年3月進(jìn)行了一項(xiàng)回顧性研究。77例患者（42名女性，35名男性；平均年齡，59歲）和65名健康對(duì)照者（35名女性，30名男性；平均年齡，35歲）與完全正常的肝臟MRI及實(shí)驗(yàn)室檢查患者的研究。研究方案是經(jīng)我們機(jī)構(gòu)的道德委員會(huì)批準(zhǔn)。所有患者的書面同意書已在研究開始之前獲得。統(tǒng)計(jì)分析統(tǒng)計(jì)分析所有的統(tǒng)計(jì)分析采用SPSSWINDOWS100分析。病例的ADC值表示為平均值±標(biāo)準(zhǔn)偏差。方差分析和配對(duì)樣本的測(cè)試也被用于腹部器官段進(jìn)行比較。一個(gè)P值小于005被認(rèn)為是表示統(tǒng)計(jì)上有顯著差異。結(jié)果結(jié)果所有患者行常規(guī)及彌散加權(quán)MR檢查表觀擴(kuò)散系數(shù)的值列為箱形圖。肝臟病變的平均ADC值為（表1）單純性囊腫，20例（316±01810?3毫米2／S）；包蟲囊腫，13例（258±05310?3毫米2／S）；血管瘤，15例（197±04910?3毫米2／S）；轉(zhuǎn)移，13例（114±04110?3毫米2／S）；與肝細(xì)胞癌（HCC）13例（115±03610?3毫米2／S）。與正常肝組平均ADC值相比，所有的疾病組的平均ADC值差異有統(tǒng)計(jì)學(xué)意義（156±01410?3毫米2／S），（P＜001）。肝臟血管瘤和肝癌轉(zhuǎn)移瘤的ADC值也有統(tǒng)計(jì)上的顯著差異，（P001），它們與單純的包蟲囊腫間也有統(tǒng)計(jì)學(xué)意義（P＜0008）。然而，HCC和轉(zhuǎn)移瘤之間差異無統(tǒng)計(jì)學(xué)意義。討論討論擴(kuò)散加權(quán)成像是用來描述水分子的隨機(jī)（布朗）運(yùn)動(dòng)。插入一個(gè)自旋回波脈沖序列的一個(gè)非常強(qiáng)大的雙極性梯度脈沖或梯度回波脈沖序列，MRI可以對(duì)在組織中的水分子的擴(kuò)散更敏感。在多細(xì)胞組織擴(kuò)散限制增加；相反，它減少了在大細(xì)胞外空間或破壞細(xì)胞膜的低細(xì)胞組織。7很多關(guān)于肝臟局灶性病變的擴(kuò)散特性的文章已經(jīng)被發(fā)表。大多數(shù)研究表明，良性病變的ADC值（囊腫、血管瘤）明顯高于惡性病變高細(xì)胞的惡性腫塊。與先前的研究中，我們發(fā)現(xiàn)肝囊腫有最高的ADC值，無限制運(yùn)動(dòng)的水分子。有人發(fā)現(xiàn)基于擴(kuò)散信號(hào)的不同，單純肝囊腫與其他病變有顯著的統(tǒng)計(jì)學(xué)差異。作者認(rèn)為這種差異是由于粘性包蟲囊腫由頭節(jié)，小鉤，氯化鈉，葡萄糖，蛋白質(zhì)，脂類和多糖的離子。同樣，我們也發(fā)現(xiàn)了單純肝囊腫與其他病變有顯著間有統(tǒng)計(jì)學(xué)差異。與以往的研究中相比，我們的研究表明，定性和定量指標(biāo)容易區(qū)分血管瘤、囊腫及惡性腫塊。血管瘤相比囊腫有較低的ADC值，這可能與血管瘤成分是相關(guān)的。陳等人的報(bào)道稱，DWI可以鑒別膿腫與囊性腫瘤。在這項(xiàng)研究中所有膿腫腔顯示有較低的ADC值與腫瘤壞死部分不重疊。

簡(jiǎn)介：中文中文4125字出處出處OKOCHIM,OHTAH,TANAKAT,ETALELECTROCHEMICALPROBEFORONCHIPTYPEFLOWIMMUNOASSAYIMMUNOGLOBULINGLABELEDWITHFERROCENECARBOALDEHYDEJBIOTECHNOLOGYKOJIMAETAL,2003LIMETAL,2002,2003SALEH和SOHN,2003SATOETAL,2002WANGETAL,1998,2002WANG和JIN,2003二茂鐵衍生物常被用來做免疫分析LIMETAL,2002,2003PADESTEETAL,2000WANGETAL,2002以及DNA雜化測(cè)定的（FIG1B）。在兩種方法中，未標(biāo)記的二茂鐵是通過YM30超濾而除去的。超濾常進(jìn)行1215次，直至二茂鐵的響應(yīng)峰消失。與IGG結(jié)合的二茂鐵數(shù)目的確定結(jié)合的二茂鐵數(shù)目的確定羊抗人IGEIGG結(jié)合的二茂鐵平均數(shù)目通過原子吸收光譜儀（AA6600G型號(hào)，SHIMAZU,KYOTO,JAPAN）檢測(cè)鐵離子濃度而測(cè)定。FCCOOH的水溶液作為鐵離子的標(biāo)準(zhǔn)溶液。IGG的濃度可以通過BCA蛋白質(zhì)分析方法檢測(cè)（SMITHETAL,1985）。蛋白質(zhì)的濃度是通過三次測(cè)定而最終確定。FCCHO標(biāo)記標(biāo)記IGG的ELISA分析分析將抗原溶液（10MM人抗原IGE，100ΜL/WELL）置于96孔的聚苯乙烯高密度檢測(cè)板（CORNINGGLASS,CORNING,NY）中，室溫下培育1小時(shí)。此板用含005％TWEEN20的PBS溶液沖洗三次，然后將200ΜL含有01％BSA（W/V）的PBS溶液加入每個(gè)孔中，室溫下培育1小時(shí)以抑制活性位點(diǎn)的非特異性吸收。經(jīng)過清洗步驟之后，加入10MM標(biāo)記FCCHO的羊抗人IGEIGG100ΜL，反應(yīng)1小時(shí)。然后再次清洗實(shí)驗(yàn)板，加入100ΜL的ALP兔抗羊IGG在PBS中稀釋100倍二次抗體，反應(yīng)1小時(shí)；每次親合反應(yīng)后，實(shí)驗(yàn)板用PBST洗三次。將ALP的底物魯米諾530，滴入每個(gè)孔中，然后用LUCY2ANTHOSLABTECINSTRUMENTS,SALZBURG,AUSTRIA檢測(cè)光的強(qiáng)度。

簡(jiǎn)介：THEPULMONARYEMBOLISMSEVERITYINDEXINPREDICTINGTHEPROGNOSISOFPATIENTSWITHPULMONARYEMBOLISMWONHOCHOI1,SUNGUKKWON1,2,YOONJUNGJWA1,JUNGAKIM1,YUNHOCHOI1,JEHOCHANG1,HOONJUNG1,JOONHYUNGDOH1,2,JUNENAMGUNG1,2,SUNGYUNLEE1,2ANDWONROLEE1,2DEPARTMENTSOF1INTERNALMEDICINEAND2VISION21CARDIAC24123127KEYWORDSPULMONARYEMBOLISMPROGNOSISRECEIVEDAPRIL13,2008ACCEPTEDJULY28,2008CORRESPONDENCETOSUNGUKKWON,MDDEPARTMENTOFINTERNALMEDICINE,INJEUNIVERSITYILSANPAIKHOSPITAL,2240DAEHWADONG,ILSANGU,GOYANG411706,KOREATEL82319107830,FAX82319107219,EMAILMDKSUILSANPAIKACKRINTRODUCTIONPULMONARYEMBOLISMSOCCURRELATIVELYFREQUENTLY,WITH23CASESPER100,000ANNUALLYINTHEUNITEDSTATES1HOWEVER,SINCEITSCLINICALFEATURESARENONSPECIFIC,ADIAGNOSISOFPULMONARYEMBOLISMISNOTEASYTOMAKEFURTHERMORE,WITHOUTAPPROPRIATETREATMENT,APULMONARYEMBOLISMCANBEFATALTHEREFORE,SUSPECTINGSUCHACONDITIONANDEVALUATINGITAPPROPRIATELYISIMPORTANTINMAKINGAPROGNOSISONCEAPROGNOSISHASBEENMADE,THEMORTALITYRATECANBELOWEREDTHROUGHPROPERTREATMENTHOWEVER,WHILESIGNIFICANTEFFORTHASBEENMADETOCLARIFYTHERISKFACTORSANDTREATMENTOFPULMONARYEMBOLISM,RELATIVELYLITTLEDATAAREAVAILABLEREGARDINGAPROGNOSTICINDEXNEVERTHELESS,SINCETHEDEVELOPMENTOFTHEGENEVASCORE2IN2000ANDTHEPULMONARYEMBOLISMSEVERITYINDEXPESI3IN2005,TWOMODELSHAVEBEENINTRODUCEDASPROGNOSTICPREDICTIVEINDEXESOFTHESE,THEPESIHASBEENSHOWNTOHAVEHIGHERPREDICTIVEACCURACY4OSTENSIBLY,KOREANSMAYAPPEARTOHAVEFEWERRISKFACTORSFORPULMONARYEMBOLISM,SUCHASOBESITYORDEEPVEINTHROMBOSIS,COMPAREDTOPEOPLEINTHEWEST,ANDMAYTHUSBEEXPECTEDTOSUFFERFROMPULMONARYEMBOLISMS133HADDIABETES,AND16178HADEITHERBEENDIAGNOSEDWITHCANCERORWEREBEINGTREATEDFORCANCERNINEPATIENTS10WERECONFIRMEDASHAVINGEMPHYSEMATHROUGHCHESTCT,WHILETENPATIENTS111HADACEREBRALHEMORRHAGEANDCEREBRALINFARCTION,AND26289HADASURGICALHISTORYTABLE1PESICLASSIFICATICHWITHREGARDTOTHEDISTRIBUTIONOFTHEPATIENTSACCORDINGTOTHEIRPESIRISKCLASS,2123,3465POINTS,AVERAGE499POINTSPATIENTSWEREINCLASSI126PESIPOINTSTHUS,MOSTOFTHEPATIENTSWEREINCLASSIIWHILETHESMALLESTNUMBERWEREINCLASSIVFIG1MORTALITYRATEBASEONTHEPESITHEMORTALITYRATEAFTER30DAYS,MORTALITYRATEDURINGHOSPITALIZATION,ANDTOTALMORTALITYRATEWERECOMPAREDACCORDINGTOTHEPESIRISKCLASSESOFTHEPATIENTSAT30DAYS,THEMORTALITYRATEWAS111WHENTHISRESULTWASANALYZEDACCORDINGTOPESICLASS,ASIGNIFICANTTRENDTOWARDINCREASEDMORTALITYWITHAHIGHERCLASSWASDETECTEDP00016,WITH0INCLASSI,103INCLASSII,91INCLASSIII,0INCLASSIV,AND50INCLASSVINCONSIDERINGTHE0MORTALITYRATEDETECTEDFORCLASSIV,NOTETHATTHEAVERAGEHOSPITALSTAYFORTHISGROUPWAS10DAYSSHORTERTHANTHATFORTHEOTHERGROUPSTHUS,THEPOSSIBILITYOFUNDERESTIMATIONEXISTSINCOMPARISON,THEHOSPITALMORTALITYRATEWAS156WHENITWASANALYZEDACCORDINGTOPESICLASS,ASIGNIFICANTTRENDP00065WASOBSERVED,WITH48INCLASSI,138INCLASSII,136INCLASSIII,125INCLASSIV,AND50INCLASSVFIG2THETOTALMORTALITYRATEWAS30WHENITWASANALYZEDACCORDINGTOPESICLASS,ANINCREASINGTENDENCYTOWARDTHEHIGHERCLASSWASOBSERVED,WITH95INCLASSI,276INCLASSII,318INCLASSIII,50INCLASSIV,AND60INCLASSVP00019FIG3MORTALITYRATEOFTHEREDISTRIBUTEDPESIGROUPINGOFTHEPESICLASSESINTOLOWCLASSI,INTERMEDIATECLASSESIIIV,ANDHIGHRISKCLASSVGROUPSPRODUCEDA30DAYMORTALITYRATEOF0,82,AND50,RESPECTIVELYCOMPAREDTOTHERESULTSBEFORETHEREDISTRIBUTION,THETENDENCYWASQUITECLEARP00016→00003THEMORTALITYRATEDURINGHOSPITALIZATIONWAS48,131,AND50FORTHELOW,INTERMEDIATE,ANDHIGHRISKGROUPS,RESPECTIVELY,ANDTHETENDENCYWASMUCHCLEARERP00065→00038,ASWASTHE30DAYMORTALITYRATETHETOTALMORTALITYRATEWAS95,311,AND60FORTHELOW,INTERMEDIATE,ANDHIGHRISKGROUPS,RESPECTIVELY,CHOIWH,ETALUSEOFPESITOPREDICTPROGNOSISOFPULMONARYEMBOLISM125FIGURE1PATIENTSDISTRIBUTIONACCORDINGTOPESIRISKCLASS23N2132N2925N229N811N10CLASSICLASSIICLASSIIICLASSIVCLASSVFIGURE2HOSPITALMORTALITYACCORDINGTOPESIRISKCLASSIFICATIONPESI,PULMONARYEMBOLISMSEVERITYINDEXNS,NOTSIGNIFICANT5000000000000000CLASSICLASSIICLASSIIICLASSIVCLASSVHOSPITALMORTALITYP0026PNS4808013601250PFIGURE3OVERALLMORTALITYACCORDINGTOPESIRISKCLASSIFICATIONPESI,PULMONARYEMBOLISMSEVERITYINDEXNS,NOTSIGNIFICANT6000P00000000000000CLASSICLASSIICLASSIIICLASSIVCLASSVOVERALLMORTALITYP0038PNS950603180P00

簡(jiǎn)介：SAGEHINDAWIACCESSTORESEARCHMOLECULARBIOLOGYINTERNATIONALVOLUME2011,ARTICLEID437301,7PAGESDOI104061/2011/437301REVIEWARTICLEMIR146AINIMMUNITYANDDISEASENICOLERUSCAANDSILVIAMONTICELLIINSTITUTEFORRESEARCHINBIOMEDICINE,VIAVINCENZOVELA6,6500BELLINZONA,SWITZERLANDCORRESPONDENCESHOULDBEADDRESSEDTOSILVIAMONTICELLI,SILVIAMONTICELLIIRBUNISICHRECEIVED17DECEMBER2010ACCEPTED17FEBRUARY2011ACADEMICEDITORALESSANDRODESIDERICOPYRIGHT?2011NRUSCAANDSMONTICELLITHISISANOPENACCESSARTICLEDISTRIBUTEDUNDERTHECREATIVECOMMONSATTRIBUTIONLICENSE,WHICHPERMITSUNRESTRICTEDUSE,DISTRIBUTION,ANDREPRODUCTIONINANYMEDIUM,PROVIDEDTHEORIGINALWORKISPROPERLYCITEDMICRORNASMIRNASAREREGULATORYMOLECULESABLETOINFLUENCEALLASPECTSOFTHEBIOLOGYOFACELLTHEYHAVEBEENASSOCIATEDWITHDISEASESSUCHASCANCER,VIRALINFECTIONS,ANDAUTOIMMUNEDISEASES,ANDINRECENTYEARS,THEYALSOEMERGEDASIMPORTANTREGULATORSOFIMMUNERESPONSESMIR146AINPARTICULARISRAPIDLYGAININGIMPORTANCEASAMODULATOROFDIFFERENTIATIONANDFUNCTIONOFCELLSOFTHEINNATEASWELLASADAPTIVEIMMUNITYGIVENITSIMPORTANCEINREGULATINGKEYCELLULARFUNCTIONS,ITISNOTSURPRISINGTHATMIR146AEXPRESSIONWASALSOFOUNDDYSREGULATEDINDIFFERENTTYPESOFTUMORSINTHISPAPER,WESUMMARIZERECENTPROGRESSINUNDERSTANDINGTHEROLEOFMIR146AININNATEANDADAPTIVEIMMUNERESPONSES,ASWELLASINDISEASE1INTRODUCTIONMICRORNASMIRNASREPRESENTAPERVASIVEFEATUREOFALLCELLS,ASTHEYREGULATELARGEFRACTIONSOFTHECELL’STRANSCRIPTOMESOFAR,672MOUSEMIRNASAND1048HUMANMIRNASHAVEBEENDESCRIBEDINTHEMIRBASEDATABASEHTTP//WWWMIRBASEORG/,RELEASESEPT2010WITHEACHMIRNAPOTENTIALLYREGULATINGTHEEXPRESSIONOFHUNDREDSOFTARGETGENES,HIGHLIGHTINGTHEEXTENTOFTHISFORMOFREGULATION1WHEREASSOMEMIRNASAREWIDELYEXPRESSED,OTHERSEXHIBITONLYLIMITEDDEVELOPMENTALSTAGE,TISSUE,ORCELLTYPESPECIFICPATTERNS2SIMILARTOANYOTHERMAMMALIANCELLTYPE,CELLSOFTHEIMMUNESYSTEMRELYONMIRNASTOREGULATELINEAGECOMMITMENT,PROLIFERATION,MIGRATION,ANDDIFFERENTIATIONINMOSTCASES,THESEACTIVITIESAREORCHESTRATEDBYBOTHUBIQUITOUSLYEXPRESSEDANDCELLTYPESPECIFICMIRNASPECIES3–7THEIMPORTANCEOFMIRNASINREGULATINGDIFFERENTIATIONANDFUNCTIONOFIMMUNECELLSISUNDERLINEDBYTHEPHENOTYPICALPERTURBATIONSTHATOCCURWHENMIRNAEXPRESSIONISALTEREDGIVENTHEEMERGINGROLESOFMIRNASINMODULATINGIMMUNERESPONSES,ITISLIKELYTHATANYDYSREGULATIONOFMIRNAEXPRESSIONMAYCONTRIBUTETOTHEPATHOGENESISOFAUTOIMMUNEDISEASES,CHRONICINFLAMMATION,ANDMALIGNANCIESINDEED,SEVERALHUMANDISEASESHAVENOWBEENASSOCIATEDWITHDYSREGULATEDMIRNAEXPRESSION,ANDMIRNASHAVEBEENSHOWNTOFUNCTIONBOTHASONCOGENESANDTUMORSUPPRESSORGENES8,9MIR146AHASBEENRECENTLYSHOWNTOBEANIMPORTANTMODULATOROFDIFFERENTIATIONANDFUNCTIONOFCELLSOFINNATEASWELLASADAPTIVEIMMUNITYHERE,WESUMMARIZERECENTPROGRESSINUNDERSTANDINGTHEROLEOFMIR146AINIMMUNERESPONSESANDINDISEASESEEALSOTABLE12WHATAREMICRORNASMIRNASARESMALL20–25NUCLEOTIDES,NONCODINGRNAMOLECULESINVOLVEDINPOSTTRANSCRIPTIONALGENEREGULATIONTHEYDERIVEFROMPRIMARYTRANSCRIPTSPRIMIRNATHATAREPROCESSEDINTOHAIRPINPRECURSORSPREMIRNASWITHINTHENUCLEUSOFTHECELLBYTHEMICROPROCESSORCOMPLEX,WHICHINCLUDESTHERNASEIIIENZYMEDROSHAPREMIRNASARETRANSLOCATEDINTOTHECYTOPLASMANDPROCESSEDBYDICERINTOTHEIRMATUREFORMFORARECENTREVIEWSEE25ANEXCEPTIONTOTHISRULEISREPRESENTEDBYTHELESSABUNDANT“MIRTRONS”,THATBYPASSDROSHAANDAREPROCESSEDONLYBYDICER26MATUREMIRNASLOADEDONTOTHERNAINDUCEDSILENCINGCOMPLEXRISCRECOGNIZESITESLOCATEDMOSTLYINTHE3?UNTRANSLATEDREGION3?UTROFTARGETMRNASTHROUGHCANONICALBASEPAIRINGBETWEENTHESEEDSEQUENCEOFTHEMIRNANUCLEOTIDES2–8ATITS5?ENDANDITSCOMPLEMENTARYSEQUENCEINTHETARGETMRNATHISLEADSTOABLOCKINTRANSLATIONWITHORWITHOUTDESTABILIZATIONANDDEGRADATIONOFTHETARGETEDMRNAMIRNASMODULATEAMOLECULARBIOLOGYINTERNATIONAL3TCELLSUBSETSINDEED,TCELLSLACKINGDICERSHOWEDINCREASEDDIFFERENTIATIONTOTHETH1SUBSETWITHACORRESPONDINGLYREDUCEDPOLARIZATIONTOTH229ADDINGTOTHECOMPLEXITYOFGENEREGULATORYNETWORKS,PROLIFERATINGTCELLSEXPRESSGENESWITHSHORTER3?UTRSTHANTHOSEEXPRESSEDINRESTINGTCELLS,MAKINGTHESEMRNASLESSSUSCEPTIBLETOREGULATIONBYMIRNASDUETOTHELOSSOFMIRNABINDINGSITES41FINALLY,INDIVIDUALMIRNASWEREALSOSHOWNTOPLAYIMPORTANTROLESINTCELLDIFFERENTIATIONANDFUNCTIONFOREXAMPLE,MIR181A,WHICHISUPREGULATEDDURINGTCELLDEVELOPMENT,WASSHOWNTOENHANCETCELLRECEPTORTCRSIGNALLINGSTRENGTHBYDIRECTLYTARGETINGANUMBEROFPROTEINPHOSPHATASES32,WHILEMICELACKINGMIR155SHOWEDANALTEREDTH1/TH2POLARIZATIONWITHABIASTOWARDSTH2,INDICATINGTHATMIR155PROMOTESDIFFERENTIATIONTOWARDSTH1CELLS35ASFORTHEROLEOFMIR146AINTCELLS,BYANALYZINGTHEEXPRESSIONOFMIRNASINHIGHLYPURIFIEDSUBSETSOFCELLSOFTHEIMMUNESYSTEM,WESHOWEDTHATMIR146AISONEOFTHEVERYFEWMIRNASDIFFERENTIALLYEXPRESSEDBETWEENTH1ANDTH2CELLSINTHEMOUSE,SUGGESTINGTHATITMIGHTBEINVOLVEDINFATEDETERMINATIONOFTHESECELLS5RECENTWORKPERFORMEDINMIR146ADEFICIENTMICESHOWEDANINCREASEINTHEPERCENTAGEOFINFΓPRODUCINGTCELLSUBSETINTHEABSENCEOFMIR146A10INHUMANTCELLS,MIR146AISEXPRESSEDATLOWLEVELSINNA¨IVETLYMPHOCYTESWHILEITISABUNDANTLYEXPRESSEDINMEMORYTCELLSANDITISINDUCEDUPONTCRSTIMULATION,CONSISTENTWITHITSEXPRESSIONBEINGDEPENDENTONNFΚBINDUCTION12,13INDEED,NFΚBANDCETSBINDINGSITESWERESHOWNTOBEREQUIREDFORTHEINDUCTIONOFMIR146ATRANSCRIPTIONINHUMANTCELLS,ANDSUCHINDUCTIONPOTENTIALLYMODULATEDCELLDEATHINTHESECELLSBYTARGETINGFADDANDBYIMPAIRINGBOTHAP1ACTIVITYANDIL2PRODUCTION13TREGCELLSCONSTITUTEASPECIALIZEDTCELLSUBSETABLETOMAINTAINIMMUNEHOMEOSTASISBYLIMITINGTHEINFLAMMATORYRESPONSES,ANDTHEIRSUPPRESSIVEFUNCTIONISINDISPENSABLEFORIMMUNEHOMEOSTASISANDSURVIVALOFHIGHERORGANISMSRECENTLY,LUANDCOLLEAGUESREPORTEDTHATMIR146AISAMONGTHEMIRNASPREVALENTLYEXPRESSEDINTREGCELLSANDSHOWEDTHATITISCRITICALFORTREGFUNCTIONSINDEED,DEFICIENCYOFMIR146ARESULTEDININCREASEDNUMBERSBUTIMPAIREDFUNCTIONOFTREGCELLSANDASACONSEQUENCE,BREAKDOWNOFIMMUNOLOGICALTOLERANCEWITHMASSIVELYMPHOCYTEACTIVATION,ANDTISSUEINFILTRATIONINSEVERALORGANS10THEIMMUNEMEDIATEDLESIONSINDUCEDBYTHELACKOFMIR146AINTREGSWEREDEPENDENTONINFΓANDSTAT14MIR146ININNATEIMMUNITYANDNONIMMUNESYSTEMSCELLSOFTHEINNATEIMMUNESYSTEM,SUCHASGRANULOCYTES,NATURALKILLERNKCELLS,MONOCYTES,ANDMACROPHAGES,PROVIDEANIMPORTANTFIRSTLINEOFDEFENSEFORTHEORGANISMAGAINSTINVADINGPATHOGENSMIRNASHAVEBEENIMPLICATEDINBOTHTHEDEVELOPMENTANDFUNCTIONSOFINNATEIMMUNECELLSFOREXAMPLE,THEMACROPHAGEINFLAMMATORYRESPONSETOINFECTIONINVOLVESTHEUPREGULATIONOFSEVERALMIRNAS,SUCHTLR4ADAPTERMOLECULESIKKCOMPLEXPPIRAK1TRAF6CYTOPLASMNUCLEUSPRIMIR146AMIR146ARISCCOMPLEXIΚBΑNFΚBNFΚBFIGURE1MIR146ANEGATIVELYREGULATESSIGNALTRANSDUCTIONPATHWAYSLEADINGTONFΚBACTIVATIONUPONACTIVATIONOFACELLSURFACERECEPTORSUCHASTLR4,AMOLECULARCASCADEINCLUDINGTRAF6ANDIRAK1LEADSTOIΚBΑPHOSPHORYLATIONANDDEGRADATIONANDTONFΚBACTIVATIONANDNUCLEARTRANSLOCATION12,42NFΚBACTIVATIONINDUCESTRANSCRIPTIONOFMANYGENES,INCLUDINGPRIMIR146AONCETRANSLOCATEDTOTHECYTOPLASMANDLOADEDONTOTHERISCCOMPLEX,MATUREMIR146ACONTRIBUTESTOATTENUATERECEPTORSIGNALINGTHROUGHTHEDOWNMODULATIONOFIRAK1ANDTRAF6ASMIR155,MIR146,MIR147,MIR21,ANDMIR912,43–46SEVERALSTUDIESLINKEDMIR146AEXPRESSIONTONFΚBSIGNALINGWITHINTHEINNATEIMMUNESYSTEMFIGURE1ANDWEREINITIATEDBYASTUDYSHOWINGTHATMIR146AISQUICKLYINDUCEDUPONACTIVATIONOFHUMANMONOCYTES12INTHISSTUDY,MIR146AWASFOUNDTOBEINDUCIBLEUPONSTIMULATIONWITHLPSINANFΚBDEPENDENTMANNER,ANDTOTARGETTHETNFRECEPTORASSOCIATEDFACTOR6TRAF6ANDIL1RECEPTORASSOCIATEDKINASE1IRAK1GENESTHESEGENESENCODETWOKEYADAPTERMOLECULESDOWNSTREAMOFCYTOKINEANDTOLLLIKERECEPTORSTLR,POINTINGTOWARDSAROLEFORMIR146AINCONTROLLINGSIGNALINGFROMTHESERECEPTORSTHROUGHANEGATIVEFEEDBACKREGULATORYLOOPINVOLVINGDOWNREGULATIONOFTRAF6ANDIRAK112ITWASALSOSUGGESTEDTHATMIR146ACONTRIBUTESTOTHEESTABLISHMENTOFENDOTOXINTOLERANCEINMONOCYTESANDTOTHEREGULATIONOFTNFΑPRODUCTION14INTHISCONTEXT,MIR146AWOULDTHEREFOREACTASATUNINGMECHANISMTOPREVENTANOVERSTIMULATEDINFLAMMATORYSTATEINHUMANLANGERHANSCELLSLCS,MIR146AWASFOUNDTOBECONSTITUTIVELYEXPRESSEDATHIGHLEVELS,ASCOMPAREDTOINTERSTITIALDENDRITICCELLSINTDCS15INTHESECELLS,HIGHMIR146AEXPRESSIONWASINDUCEDBYTHETRANSCRIPTIONFACTORPU1INRESPONSETOTGFΒ1,AKEY

簡(jiǎn)介：中文中文5200字出處出處KAJSTURAJ,LERIA,FINATON,ETALMYOCYTEPROLIFERATIONINENDSTAGECARDIACFAILUREINHUMANSJPROCEEDINGSOFTHENATIONALACADEMYOFSCIENCES,1998,951588018805心臟衰竭末期的心肌細(xì)胞再生心臟衰竭末期的心肌細(xì)胞再生KAJSTURAJ,LERIA,FINATON,DILORETOC,BELTRAMICA,ANVERSAP前言前言在幾十年前，人們一直堅(jiān)信心肌細(xì)胞是一種終極分化細(xì)胞，在成人心臟中心肌細(xì)胞分裂是不可能的。然而最近，偶爾有在心肌細(xì)胞中發(fā)現(xiàn)細(xì)胞核有絲分裂的報(bào)道，但是這種發(fā)現(xiàn)被一種假設(shè)所質(zhì)疑如果心肌細(xì)胞存在有絲分裂，但現(xiàn)實(shí)中的卻沒有心肌組織再生。此外，心肌細(xì)胞有絲分裂的現(xiàn)象從來沒有在正常心肌細(xì)胞中被發(fā)現(xiàn)。然而，通過分析常規(guī)的組織組成的基礎(chǔ)需求，忽略設(shè)備的限制，確信心肌細(xì)胞沒有能力進(jìn)入細(xì)胞周期及細(xì)胞分裂。在這里我們的研究通過顯微鏡發(fā)現(xiàn)在每100萬個(gè)心肌細(xì)胞中有14個(gè)在進(jìn)行有絲分裂。在在缺血性心臟疾病及先天性擴(kuò)張型心肌病中這個(gè)數(shù)字將是正常心臟的10倍（在缺血性心臟病中每100萬個(gè)心肌細(xì)胞中有152個(gè)，在先天性擴(kuò)張性心肌病中每100萬個(gè)心肌細(xì)胞中有131個(gè)）。由于左心室大約有58109個(gè)心肌細(xì)胞，這些有絲分裂指數(shù)暗示在正常心肌，缺血性心肌病及先天性心肌病的整個(gè)左心室中將分別有812103,882103,76103個(gè)心肌細(xì)胞在進(jìn)行有絲分裂。與此同時(shí)，有絲分裂時(shí)間通常少于一小時(shí)，提示在非病理及病理心臟中隨時(shí)間發(fā)展將有大量的心肌細(xì)胞生成。我們已經(jīng)發(fā)現(xiàn)了細(xì)胞質(zhì)分裂的證據(jù)，這清楚地證明了心肌細(xì)胞有絲分裂的存在。心肌細(xì)胞在成人心臟中是否能夠分裂一直是人們爭(zhēng)論的話題。然而大量證據(jù)提示在心肌嚴(yán)重肥厚時(shí)存在心肌細(xì)胞數(shù)目大量增長(zhǎng)，但是心肌細(xì)胞是否進(jìn)行有絲分裂卻沒有被證實(shí)，這個(gè)證據(jù)的缺乏質(zhì)疑了體視學(xué)結(jié)論的可信性。偶有發(fā)現(xiàn)在有病理性心臟疾病的心臟中存在細(xì)胞核的有絲分裂，但是這個(gè)發(fā)現(xiàn)對(duì)證實(shí)心肌細(xì)胞的大量再生沒有任何價(jià)值。另外，心肌細(xì)胞的有絲分裂從沒有在正常心臟的心肌細(xì)胞中發(fā)現(xiàn)。于此同時(shí)，心肌細(xì)胞細(xì)胞質(zhì)的有絲分裂證據(jù)也是不足的。人類缺血性心臟疾病及先天性擴(kuò)張性心臟疾病的結(jié)構(gòu)特征是由多處心肌纖維化及彌漫性的間質(zhì)纖維化構(gòu)成的心肌瘢痕。此外，在心肌缺血所有樣本中都有發(fā)現(xiàn)纖維片段。心肌細(xì)胞的壞死導(dǎo)致了纖維片段、纖維替代及間質(zhì)纖維化的現(xiàn)象。然而，大量膠原的積累與梗死后人左心室心肌細(xì)胞的大量減少出現(xiàn)明顯的差異。每減少1MM3的膠原反映了大約50103心肌細(xì)胞的丟失，在缺血性心肌病末期，大量纖維化暗示了大約有90的心肌細(xì)胞減少。相反的，曾經(jīng)報(bào)道實(shí)際心肌細(xì)胞的減少小于30。這種差異在先天性擴(kuò)張性心肌病中更加明顯。在有先天性擴(kuò)張性心肌病患者的心室肌中心肌纖維化，但是心肌細(xì)胞的數(shù)目卻沒有減少。在細(xì)胞基礎(chǔ)層面上研究疾病心臟的的心肌重塑機(jī)制是非常復(fù)雜的，遠(yuǎn)遠(yuǎn)超出心室的失代償導(dǎo)致的心肌細(xì)胞程序化死亡這樣的解釋。細(xì)胞凋亡不會(huì)導(dǎo)致組織纖維化；死亡的細(xì)胞被周圍細(xì)胞清除因此不會(huì)有炎癥反應(yīng)的發(fā)生。在嚴(yán)重的心肌細(xì)胞死亡及凋亡中，這些現(xiàn)象指出心肌細(xì)胞可能不是終極分化細(xì)胞，細(xì)胞的再生可能由病理性刺激誘導(dǎo)。我們用免疫細(xì)胞化學(xué)及共焦顯微鏡來計(jì)算由于慢性缺血性心臟病機(jī)擴(kuò)張性心肌病而需進(jìn)行心臟移植的患者的心臟心肌細(xì)胞的有絲分裂指數(shù)。用來做解剖的心臟都是受法律保護(hù)的。性心肌病組327±193MM2，在擴(kuò)張性心肌病組341±194MM2相應(yīng)的細(xì)胞核的數(shù)目分別為14136±56699,38854±16766，36013±17134細(xì)胞分裂指數(shù)分別為18±06,51±35,43±20用這些數(shù)據(jù)可以估算在各個(gè)組中心肌細(xì)胞的有絲分裂指數(shù)。在正常的左心室中平均每100萬個(gè)心肌細(xì)胞有14個(gè)心肌細(xì)胞在進(jìn)行有絲分裂，但在病理心臟左心室中這個(gè)指數(shù)要高得多。在缺血性心肌病中平均每100萬個(gè)心肌細(xì)胞中有152個(gè)在進(jìn)行有絲分裂，在擴(kuò)張性心肌病中每100萬中有131個(gè)心肌細(xì)胞在進(jìn)行有絲分裂。在有心臟衰竭的這兩組患者中這種指數(shù)很小的差別沒有意義，平均一下每100萬個(gè)心肌細(xì)胞中有140個(gè)心肌細(xì)胞在進(jìn)行著有絲分裂。與健康心肌相比，有絲分裂細(xì)胞數(shù)目在有心臟衰竭的患者總是正常健康人的10倍。實(shí)驗(yàn)中沒有性別差異。在正常組有絲分裂指數(shù)為18±13/100萬細(xì)胞中，在衰竭的心臟中有106±42/100萬心肌細(xì)胞中。（N127個(gè)缺血性心肌病，5個(gè)先天性心肌病）。與心肌細(xì)胞相比，間質(zhì)細(xì)胞有絲分裂指數(shù)下降24是沒有意義的。討論討論心肌肥厚心肌肥厚在20世紀(jì)20年代初，在許多解剖研究中都強(qiáng)調(diào)，在心肌細(xì)胞中檢測(cè)核分裂有許多困難，并在此基礎(chǔ)上，介紹了細(xì)胞的增殖在成人、完全分化的生物及哺乳動(dòng)物的心肌中是不存在的的概念（1）。此外，實(shí)驗(yàn)結(jié)果證明，急性心肌肥厚的嚙齒類動(dòng)物心肌細(xì)胞沒有再一次進(jìn)入細(xì)胞周期、合成DNA并進(jìn)行有絲分裂的能力。這些發(fā)現(xiàn)都證明了一個(gè)學(xué)說，在出生后不久，心室肌細(xì)胞就永久的不再進(jìn)入細(xì)胞周期并注定不再?gòu)?fù)制最終細(xì)胞死亡。在20世紀(jì)50年代中期這種論點(diǎn)被LINZBACH在形態(tài)學(xué)研究中的成果所質(zhì)疑。形態(tài)學(xué)研究表明在心衰患者的心肌中有發(fā)現(xiàn)心肌細(xì)胞增生。最近的數(shù)據(jù)結(jié)果支持LINZBACH的假說，并確認(rèn)在人類心臟失代償期，心室肌細(xì)胞的數(shù)量幾乎增加了一倍（4，20，21）。定量分析未能成功記載心肌細(xì)胞的有絲分裂，更偏向于應(yīng)用體視學(xué)定律分析心肌細(xì)胞數(shù)量上的變化。缺乏有絲分裂使得對(duì)心肌細(xì)胞分化機(jī)制的解釋更加復(fù)雜，其中包括心肌細(xì)胞的縱向分裂而細(xì)胞核卻不分裂。這種現(xiàn)象將導(dǎo)致在每個(gè)細(xì)胞中細(xì)胞核含量的減少。然而在人類心臟中單核細(xì)胞與雙核細(xì)胞的比例是不變的。如果細(xì)胞沒有完成最終分裂，在細(xì)胞處于G0期時(shí)，給予細(xì)胞一定刺激，細(xì)胞將再次進(jìn)入細(xì)胞周期完成細(xì)胞核及細(xì)胞質(zhì)的分裂。只有這種增長(zhǎng)方式才會(huì)出現(xiàn)心肌細(xì)胞數(shù)量的增長(zhǎng)與心肌細(xì)胞的再生。早期的發(fā)現(xiàn)及近期的數(shù)據(jù)都堅(jiān)持了這種增值方式的可能性，因?yàn)樵谛牧λソ叩男呐K心機(jī)中已經(jīng)被證實(shí)存在細(xì)胞核與細(xì)胞質(zhì)的分裂。心肌細(xì)胞增殖心肌細(xì)胞增殖根據(jù)學(xué)說中提到，心室肌細(xì)胞是一種沒有再生能力的細(xì)胞，細(xì)胞壽命完全與個(gè)體或生物的壽命相對(duì)應(yīng)。在人類試驗(yàn)研究中證實(shí)，在人類出生幾個(gè)月后心肌細(xì)胞數(shù)量就已達(dá)到成人水平，他們一直以每分鐘70次的頻率收縮，直到細(xì)胞死亡。由于有一部分人口壽命能達(dá)到100歲或是更長(zhǎng)，一個(gè)不可避免的結(jié)論由此產(chǎn)生心肌細(xì)胞在功能與形態(tài)上可能是不朽的。這種假說與細(xì)胞衰老、細(xì)胞程序化死亡及隨著哺乳動(dòng)物心臟的衰老，細(xì)胞翻新速度減慢的邏輯產(chǎn)生矛盾。然而后者的可能性更大，在沒有疾病的正常心臟發(fā)現(xiàn)，從17歲到89歲，心肌細(xì)胞每年將減少64106個(gè)，這暗示了細(xì)胞是隨診年齡增長(zhǎng)死亡的。除此之外，盡管缺少生理負(fù)荷需求，心肌細(xì)胞也可以再進(jìn)入細(xì)胞周期，合成DNA。那些對(duì)與心臟細(xì)胞衰老及心肌細(xì)胞不斷更新的研究表明，在正常情況下，每100萬個(gè)心肌細(xì)胞中有14個(gè)細(xì)胞能進(jìn)行有絲分裂。在衰竭的心肌中，心肌細(xì)胞這種再生與代替死亡細(xì)胞的能力明顯增強(qiáng)，每100

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