Cancer therapy

　　癌癥治療

　　Checkpoint Charlie

　　查理檢查站

　　A new class of drugs is being deployed in thestruggle against cancer

　　部署新藥部隊投入抗癌戰斗

　　THE lexicon of oncology is filled with military metaphors: the war on cancer, aggressivetumours, magic bullets.

　　腫瘤學詞典里充斥著軍事比喻：抗癌戰，侵襲性腫瘤，魔術彈。

　　And although these are indeed only metaphors, they do reflect an underlying attitudethatit is the clinician s job to attack and destroy his patient s tumour directly, with whateverweapons are to hand.

　　雖然只是些比喻，它們卻凸顯出人們對待腫瘤的態度。臨床醫生的工作就是直接攻擊和摧毀病人體內的腫瘤，無論是用什么武器裝備。

　　As in real warfare, those weapons may be conventional, chemical or nuclear.

　　就像在真實的戰場上一樣，這些武器可能是常規武器，化學武器，或者核武器。

　　There is even talk of biological agents,in the form of viruses specifically tailored to seek out and eliminate their tumorous targets.

　　有時甚至會使用生物制劑，即能找出并消滅腫瘤標靶的特制病毒。

　　Which is all well and good as strategies go. But as Sun Tzu observed, the wisest general is notone who wins one hundred victories in one hundred battles, but rather one who overcomesthe armies of his enemies without having to fight them himself.

　　癌癥治療和兵法一樣好用。但是正如孫子所言，善用兵的將軍不是指百戰不殆，而是能不戰而屈人之兵。

　　And one way to do that is to get someone else to do your fighting for you.

　　有個辦法就可以做到，那便是讓別人幫你戰斗。

　　That, in an oncological context, is where immunotherapy comes in.

　　在腫瘤學領域，這就需要免疫療法出山。

　　Instead of attacking cancer directly, immunotherapy recruits a patient s immune system todo the attacking.

　　免疫療法并不直接攻擊癌癥，而是招募病人的免疫系統來做這件事，最新的方法是解除那些為保護人體在健康時期免受免疫系統傷害而對其進行檢查的控制機制。

　　The latest way of doing so is by removing the controls which keep the immune system incheck during times of bodily peace, lest it damage the person it is supposed to be protecting.Such checkpoint-inhibitor immunotherapy has proved itself over the past three years in thetreatment of advanced melanoma, hitherto a death sentence.

　　晚期黑色素瘤目前被視為對病人判了死刑，而過去三年的這類病癥相關治療證明檢查抑制劑免疫療法確實有效。

　　Now, as a series of papers presented this week to the annual meeting of the AmericanSociety of Clinical Oncology, in Chicago, shows, its range is being extended.

　　現在，在芝加哥舉辦的美國臨床腫瘤學協會年度會議上，研究人員發表一系列論文表明該療法可以推廣到其它腫瘤治療領域。

　　More effective versions are being brought to bear on melanoma.

　　目前更多有效的同類治療手段正在用于治療黑色素瘤，

　　And the whole approach is being tried outoften successfullyon lots of other cancers,including those of the lungs, the kidneys, the bladder, the colon, the stomach, the head andthe neck.

　　這種方法正在經受其它癌癥的考驗，如肺部、腎臟、膀胱、結腸、胃部、頭部和頸部等出現的癌癥，并且常常很有效果。

　　Checkout time

　　檢查時間到

　　The treatment of melanoma that started the ball rolling employed a drug called ipilimumab.

　　這種黑色素瘤治療是研究人員在三年前的協會會議上公布的。

　　This belongs to a class known as monoclonal antibodies.

　　它使用一種名為易普利姆瑪的單克隆抗體藥物。

　　An antibody is an immune-system protein shaped to lock onto a particular chemicaltarget. And specific varieties of antibody, aimed at specific targets, can be generatedfrom cultures of genetically identical cells created for the taskin other words, cellularclones.

　　抗體是一種能夠鎖定特異化學標靶的免疫系統蛋白。不同類型的抗體針對不同的特定性標靶，可以通過培養那些為實現特定功能而出現且具有相同基因的細胞獲取，換句話說就是采用細胞克隆的方法。

　　Ipilimumab locks onto and thus blocks the action of a protein, CTLA-4, which sits on theouter membranes of immune-system cells called T-lymphocytes.

　　易普利姆瑪鎖定并抑制CTLA-4的活動，這種蛋白位于T淋巴細胞的細胞膜外層。

　　These lymphocytes exist to kill body cells that pose a threat, such as cells infected byviruses, and also cancer cells.

　　這些T淋巴細胞殺死構成威脅的身體細胞，比如被病毒感染的細胞或者癌細胞等。

　　CTLA-4 s role is to calm lymphocytes down and stop them proliferating.

　　CTLA-4的作用是讓淋巴細胞冷靜下來，阻止它們增殖。

　　That is a good thing when there is no threat around.

　　這在人體未受威脅時是件好事，但是有些癌細胞非常善于躲避免疫系統。

　　But some cancer cells are skilled at hiding from the immune system, so a drug that switchesCTLA-4 off can unleash lymphocytes in circumstances when they are needed but otherwiseunavailable.

　　在需要淋巴細胞活動卻無法激活的情況下，一種關閉CTLA-4功能的藥物可以解放更多的淋巴細胞。

　　Ipilimumab s success has spurred the development of further antibodies that work in similarways.

　　易普利姆瑪的成功激勵研究人員深入研究有著類似工作機制的抗體。

　　Nivolumab and lambrolizumab gum up another surface protein, PD-1; and a fourth, so newthat it still goes by its laboratory identifier of MPDL3280A, binds to PD-L1, a protein thatwould otherwise help PD-1 to do its job.

　　Nivolumab和lambrolizumab擾亂另一種表面蛋白PD-1。第四種蛋白最近才發現，還使用著實驗室標識符MPDL3280A，它可以綁定到PD-L1上，而PD-L1會反過來協助PD-1蛋白完成任務。

　　Though they have slightly different modi operandi, all four antibodies work by shutting downbiochemical checkpoints that limit the proliferation of lymphocytes.

　　盡管方式稍微不同，四種抗體采取關閉生物檢查站，解除淋巴細胞擴散限制的方法，

　　Hence the name checkpoint inhibitors.

　　因此得名檢查抑制劑

　　In the original trials of ipilimumab, 11% of patients responded.

　　易普利姆瑪在最初進行試驗時，有11%的病人對藥物產生反應。

　　That might not sound many, but those who did respond often did so stronglysurviving insome cases for years with no evidence of disease.

　　雖然人數不是很多，但這些病人的反應很強烈。有些人可以存活幾年而沒有疾病特征。

　　Ipilimumab s successors have pushed the response rate up while maintaining the long-termbenefits.

　　易普利姆瑪的后續制劑提高了反應比例，同時維持長期效果。

　　A trial of nivolumab, led by Mario Sznol of the Yale Cancer Centre, showed a success rate ofalmost a third in a group of 107 melanoma patients, when success was defined as a tumourshrinking by 30% or more.

　　耶魯大學癌癥中心Mario Sznol 對Nivolumab進行了試驗，按照腫瘤縮小至少30%的標準，參與該試驗的107名黑色素瘤病人中有三分之一取得了良好的治療效果，

　　The median survival time of these successes has so far been 16.8 months, quite a gain overthe nine months that might have been expected for such people just a few years ago.

　　目前存活時間的中位數為16.8個月，這要比前些年對這類病人存活期的預期增加了9個月，已經算相當長了。

　　Lambrolizumab, too, looks promising.

　　Lambrolizumab也很有前景。

　　Antoni Ribas of the University of California, Los Angeles, and his colleagues reported to themeeting that the tumours of more than a third of the 135 advanced-melanoma patientswhom they had treated with it have shrunk.

　　洛杉磯加利福尼亞大學的Antoni Ribas及其同事在會議上報告稱，135名接受Lambrolizumab治療的黑色素瘤病人中，有超過三分之一的腫瘤縮小了。

　　Some of these people had previously been treated, unsuccessfully, with ipilimumab,confirming that the two drugs really do work in different ways.

　　有些人之前接受ipilimumab治療卻沒有成效，證明了這兩種藥物確實有著不同的工作機制。

　　Those separate modes of action were also confirmed by work announced to the meetingby Jedd Wolchok of the Memorial Sloan-Kettering Cancer Centre, in New York.

　　兩種制劑相互獨立的作用機制也由Jedd Wolchok向大會所做的工作匯報證明。

　　He and his colleagues reported that a combination of ipilimumab and nivolumab causesfaster and more complete responses than either does on its own. So far, they have treated 52people.

　　Jedd來自紐約斯隆凱特林癌病中心，他和同事們稱ipilimumab和nivolumab結合使用比單獨使用產生更快更徹底的效果。

　　The tumours of around three-quarters of these patients began shrinking in the first 12 weeksof treatment.

　　目前他們治療了52位病人，約有四分之三的的腫瘤在治療初的12周內開始縮小，

　　In a third of cases tumours shrank by 80% or more in that period and in 90% the patient wascontinuing to respond at his last check-up.

　　同時有三分之一的腫瘤縮小了至少80%。在最后一次的檢查中，這種治療對90%的病人繼續有效。

　　This, then, is good news for those with melanoma.

　　這對于患有黑色素瘤的病人是個莫大的好消息。

　　But the most intriguing paper of the series was delivered by Roy Herbst, who also works atYale.

　　然而這些論文中最令人激動的要數同在耶魯工作的Roy Herbst所發表的論文。

　　He and his colleagues are testing MPDL3280A in a trial open to people who have any type ofmetastatic or otherwise incurable tumourthose, in other words, for whom establishedtreatments offer no hope.

　　他和同事們在一輪實驗中測試MPDL3280A，并且面向所有患有任何轉移性或者不可治愈腫瘤的人，換句話說，這些病人的腫瘤是目前成熟的治療手段所不能治療的。

　　Preliminary results suggest a fifth of the 140 patients in this trial are responding. And, as inthe case of Dr Wolchok s work, these responses are long-lasting.

　　該實驗的初步結果顯示140名病人中有五分之一產生反應，并且這些反應長期持續，恰如Wolchok博士研究中觀察到的那樣。

　　The crucial point in the MPDL3280A trial is that those who have responded have a range ofcancersnot just melanoma.

　　MPDL3280A試驗的關鍵點在于那些產生反應的病人患有的癌癥多種多樣，不局限在黑色素瘤。

　　What was once a treatment specifically for melanoma now looks as if it might work for atleast some cases of half a dozen common cancers.

　　曾經專門用于黑色毒瘤的治療現在看似至少對六種常見腫瘤的部分病例起效。

　　If such results are confirmed by future studies, a new front will have opened in the war oncancer.

　　這一結論如果能在未來的研究中得以驗證，抗癌戰爭就開拓了新前線。

　　Moreover, the troops on this front will be not untested conscripts but confederates who arefamiliar with the enemy and just needed a little encouragement to join the battle.

　　此外，守在前線的部隊不是沒有經驗的新兵，他們對敵人十分了解，只需要一點點鼓勵參加戰斗，

　　Sun Tzu would surely have approved.

　　而孫子必定會批準下命令。

　　詞語解釋

　　1.seek out 找出;物色

　　Instead, seek out relevant information for yourselfto set your expectations to a reasonable level.

　　替代的是，為自己找出相關的信息，把你的期望訂立在合理的水平上。

　　Seek out healthy choices in potential partners.

　　在潛在的伴侶中找到健康的那些。

　　2.instead of 代替，而不是

　　Consider renting or borrowing instead of buying.

　　考慮用租賃或者借用代替購買。

　　I wish mother was here instead of you!

　　我寧可是媽媽在這里而不是您!

　　3.bear on 靠在壓在對產生影響

　　It is unclear whether marshall used the same teddy bear on each occasion.

　　還不清楚馬歇爾是否每次都使用的是同一只泰迪熊。

　　To get the justice we deserve, we would do well to bring a similar approach to bear on ourcriminal courts.

　　為了追求我們應得的公正，我們應該在我們的刑事法庭的評價上也應采取類似的措施。

　　4.such as 例如;譬如;諸如

　　What about future steps such as euro bonds?

　　諸如歐元聯盟之類的未來計劃怎樣?

　　Imaginary problems such as these are usually hiding real ones.

　　像這樣的臆想的問題通常隱藏真實性的。

　　Cancer therapy

　　癌癥治療

　　Checkpoint Charlie

　　查理檢查站

　　A new class of drugs is being deployed in thestruggle against cancer

　　部署新藥部隊投入抗癌戰斗

　　THE lexicon of oncology is filled with military metaphors: the war on cancer, aggressivetumours, magic bullets.

　　腫瘤學詞典里充斥著軍事比喻：抗癌戰，侵襲性腫瘤，魔術彈。

　　And although these are indeed only metaphors, they do reflect an underlying attitudethatit is the clinician s job to attack and destroy his patient s tumour directly, with whateverweapons are to hand.

　　雖然只是些比喻，它們卻凸顯出人們對待腫瘤的態度。臨床醫生的工作就是直接攻擊和摧毀病人體內的腫瘤，無論是用什么武器裝備。

　　As in real warfare, those weapons may be conventional, chemical or nuclear.

　　就像在真實的戰場上一樣，這些武器可能是常規武器，化學武器，或者核武器。

　　There is even talk of biological agents,in the form of viruses specifically tailored to seek out and eliminate their tumorous targets.

　　有時甚至會使用生物制劑，即能找出并消滅腫瘤標靶的特制病毒。

　　Which is all well and good as strategies go. But as Sun Tzu observed, the wisest general is notone who wins one hundred victories in one hundred battles, but rather one who overcomesthe armies of his enemies without having to fight them himself.

　　癌癥治療和兵法一樣好用。但是正如孫子所言，善用兵的將軍不是指百戰不殆，而是能不戰而屈人之兵。

　　And one way to do that is to get someone else to do your fighting for you.

　　有個辦法就可以做到，那便是讓別人幫你戰斗。

　　That, in an oncological context, is where immunotherapy comes in.

　　在腫瘤學領域，這就需要免疫療法出山。

　　Instead of attacking cancer directly, immunotherapy recruits a patient s immune system todo the attacking.

　　免疫療法并不直接攻擊癌癥，而是招募病人的免疫系統來做這件事，最新的方法是解除那些為保護人體在健康時期免受免疫系統傷害而對其進行檢查的控制機制。

　　The latest way of doing so is by removing the controls which keep the immune system incheck during times of bodily peace, lest it damage the person it is supposed to be protecting.Such checkpoint-inhibitor immunotherapy has proved itself over the past three years in thetreatment of advanced melanoma, hitherto a death sentence.

　　晚期黑色素瘤目前被視為對病人判了死刑，而過去三年的這類病癥相關治療證明檢查抑制劑免疫療法確實有效。

　　Now, as a series of papers presented this week to the annual meeting of the AmericanSociety of Clinical Oncology, in Chicago, shows, its range is being extended.

　　現在，在芝加哥舉辦的美國臨床腫瘤學協會年度會議上，研究人員發表一系列論文表明該療法可以推廣到其它腫瘤治療領域。

　　More effective versions are being brought to bear on melanoma.

　　目前更多有效的同類治療手段正在用于治療黑色素瘤，

　　And the whole approach is being tried outoften successfullyon lots of other cancers,including those of the lungs, the kidneys, the bladder, the colon, the stomach, the head andthe neck.

　　這種方法正在經受其它癌癥的考驗，如肺部、腎臟、膀胱、結腸、胃部、頭部和頸部等出現的癌癥，并且常常很有效果。

　　Checkout time

　　檢查時間到

　　The treatment of melanoma that started the ball rolling employed a drug called ipilimumab.

　　這種黑色素瘤治療是研究人員在三年前的協會會議上公布的。

　　This belongs to a class known as monoclonal antibodies.

　　它使用一種名為易普利姆瑪的單克隆抗體藥物。

　　An antibody is an immune-system protein shaped to lock onto a particular chemicaltarget. And specific varieties of antibody, aimed at specific targets, can be generatedfrom cultures of genetically identical cells created for the taskin other words, cellularclones.

　　抗體是一種能夠鎖定特異化學標靶的免疫系統蛋白。不同類型的抗體針對不同的特定性標靶，可以通過培養那些為實現特定功能而出現且具有相同基因的細胞獲取，換句話說就是采用細胞克隆的方法。

　　Ipilimumab locks onto and thus blocks the action of a protein, CTLA-4, which sits on theouter membranes of immune-system cells called T-lymphocytes.

　　易普利姆瑪鎖定并抑制CTLA-4的活動，這種蛋白位于T淋巴細胞的細胞膜外層。

　　These lymphocytes exist to kill body cells that pose a threat, such as cells infected byviruses, and also cancer cells.

　　這些T淋巴細胞殺死構成威脅的身體細胞，比如被病毒感染的細胞或者癌細胞等。

　　CTLA-4 s role is to calm lymphocytes down and stop them proliferating.

　　CTLA-4的作用是讓淋巴細胞冷靜下來，阻止它們增殖。

　　That is a good thing when there is no threat around.

　　這在人體未受威脅時是件好事，但是有些癌細胞非常善于躲避免疫系統。

　　But some cancer cells are skilled at hiding from the immune system, so a drug that switchesCTLA-4 off can unleash lymphocytes in circumstances when they are needed but otherwiseunavailable.

　　在需要淋巴細胞活動卻無法激活的情況下，一種關閉CTLA-4功能的藥物可以解放更多的淋巴細胞。

　　Ipilimumab s success has spurred the development of further antibodies that work in similarways.

　　易普利姆瑪的成功激勵研究人員深入研究有著類似工作機制的抗體。

　　Nivolumab and lambrolizumab gum up another surface protein, PD-1; and a fourth, so newthat it still goes by its laboratory identifier of MPDL3280A, binds to PD-L1, a protein thatwould otherwise help PD-1 to do its job.

　　Nivolumab和lambrolizumab擾亂另一種表面蛋白PD-1。第四種蛋白最近才發現，還使用著實驗室標識符MPDL3280A，它可以綁定到PD-L1上，而PD-L1會反過來協助PD-1蛋白完成任務。

　　Though they have slightly different modi operandi, all four antibodies work by shutting downbiochemical checkpoints that limit the proliferation of lymphocytes.

　　盡管方式稍微不同，四種抗體采取關閉生物檢查站，解除淋巴細胞擴散限制的方法，

　　Hence the name checkpoint inhibitors.

　　因此得名檢查抑制劑

　　In the original trials of ipilimumab, 11% of patients responded.

　　易普利姆瑪在最初進行試驗時，有11%的病人對藥物產生反應。

　　That might not sound many, but those who did respond often did so stronglysurviving insome cases for years with no evidence of disease.

　　雖然人數不是很多，但這些病人的反應很強烈。有些人可以存活幾年而沒有疾病特征。

　　Ipilimumab s successors have pushed the response rate up while maintaining the long-termbenefits.

　　易普利姆瑪的后續制劑提高了反應比例，同時維持長期效果。

　　A trial of nivolumab, led by Mario Sznol of the Yale Cancer Centre, showed a success rate ofalmost a third in a group of 107 melanoma patients, when success was defined as a tumourshrinking by 30% or more.

　　耶魯大學癌癥中心Mario Sznol 對Nivolumab進行了試驗，按照腫瘤縮小至少30%的標準，參與該試驗的107名黑色素瘤病人中有三分之一取得了良好的治療效果，

　　The median survival time of these successes has so far been 16.8 months, quite a gain overthe nine months that might have been expected for such people just a few years ago.

　　目前存活時間的中位數為16.8個月，這要比前些年對這類病人存活期的預期增加了9個月，已經算相當長了。

　　Lambrolizumab, too, looks promising.

　　Lambrolizumab也很有前景。

　　Antoni Ribas of the University of California, Los Angeles, and his colleagues reported to themeeting that the tumours of more than a third of the 135 advanced-melanoma patientswhom they had treated with it have shrunk.

　　洛杉磯加利福尼亞大學的Antoni Ribas及其同事在會議上報告稱，135名接受Lambrolizumab治療的黑色素瘤病人中，有超過三分之一的腫瘤縮小了。

　　Some of these people had previously been treated, unsuccessfully, with ipilimumab,confirming that the two drugs really do work in different ways.

　　有些人之前接受ipilimumab治療卻沒有成效，證明了這兩種藥物確實有著不同的工作機制。

　　Those separate modes of action were also confirmed by work announced to the meetingby Jedd Wolchok of the Memorial Sloan-Kettering Cancer Centre, in New York.

　　兩種制劑相互獨立的作用機制也由Jedd Wolchok向大會所做的工作匯報證明。

　　He and his colleagues reported that a combination of ipilimumab and nivolumab causesfaster and more complete responses than either does on its own. So far, they have treated 52people.

　　Jedd來自紐約斯隆凱特林癌病中心，他和同事們稱ipilimumab和nivolumab結合使用比單獨使用產生更快更徹底的效果。

　　The tumours of around three-quarters of these patients began shrinking in the first 12 weeksof treatment.

　　目前他們治療了52位病人，約有四分之三的的腫瘤在治療初的12周內開始縮小，

　　In a third of cases tumours shrank by 80% or more in that period and in 90% the patient wascontinuing to respond at his last check-up.

　　同時有三分之一的腫瘤縮小了至少80%。在最后一次的檢查中，這種治療對90%的病人繼續有效。

　　This, then, is good news for those with melanoma.

　　這對于患有黑色素瘤的病人是個莫大的好消息。

　　But the most intriguing paper of the series was delivered by Roy Herbst, who also works atYale.

　　然而這些論文中最令人激動的要數同在耶魯工作的Roy Herbst所發表的論文。

　　He and his colleagues are testing MPDL3280A in a trial open to people who have any type ofmetastatic or otherwise incurable tumourthose, in other words, for whom establishedtreatments offer no hope.

　　他和同事們在一輪實驗中測試MPDL3280A，并且面向所有患有任何轉移性或者不可治愈腫瘤的人，換句話說，這些病人的腫瘤是目前成熟的治療手段所不能治療的。

　　Preliminary results suggest a fifth of the 140 patients in this trial are responding. And, as inthe case of Dr Wolchok s work, these responses are long-lasting.

　　該實驗的初步結果顯示140名病人中有五分之一產生反應，并且這些反應長期持續，恰如Wolchok博士研究中觀察到的那樣。

　　The crucial point in the MPDL3280A trial is that those who have responded have a range ofcancersnot just melanoma.

　　MPDL3280A試驗的關鍵點在于那些產生反應的病人患有的癌癥多種多樣，不局限在黑色素瘤。

　　What was once a treatment specifically for melanoma now looks as if it might work for atleast some cases of half a dozen common cancers.

　　曾經專門用于黑色毒瘤的治療現在看似至少對六種常見腫瘤的部分病例起效。

　　If such results are confirmed by future studies, a new front will have opened in the war oncancer.

　　這一結論如果能在未來的研究中得以驗證，抗癌戰爭就開拓了新前線。

　　Moreover, the troops on this front will be not untested conscripts but confederates who arefamiliar with the enemy and just needed a little encouragement to join the battle.

　　此外，守在前線的部隊不是沒有經驗的新兵，他們對敵人十分了解，只需要一點點鼓勵參加戰斗，

　　Sun Tzu would surely have approved.

　　而孫子必定會批準下命令。

　　詞語解釋

　　1.seek out 找出;物色

　　Instead, seek out relevant information for yourselfto set your expectations to a reasonable level.

　　替代的是，為自己找出相關的信息，把你的期望訂立在合理的水平上。

　　Seek out healthy choices in potential partners.

　　在潛在的伴侶中找到健康的那些。

　　2.instead of 代替，而不是

　　Consider renting or borrowing instead of buying.

　　考慮用租賃或者借用代替購買。

　　I wish mother was here instead of you!

　　我寧可是媽媽在這里而不是您!

　　3.bear on 靠在壓在對產生影響

　　It is unclear whether marshall used the same teddy bear on each occasion.

　　還不清楚馬歇爾是否每次都使用的是同一只泰迪熊。

　　To get the justice we deserve, we would do well to bring a similar approach to bear on ourcriminal courts.

　　為了追求我們應得的公正，我們應該在我們的刑事法庭的評價上也應采取類似的措施。

　　4.such as 例如;譬如;諸如

　　What about future steps such as euro bonds?

　　諸如歐元聯盟之類的未來計劃怎樣?

　　Imaginary problems such as these are usually hiding real ones.

　　像這樣的臆想的問題通常隱藏真實性的。