原帖地址：https://www.reddit.com/r/anime/comments/98zdow/hataraku_saibou_ep_7_doctors_notes/

My favorite topic, neoplasia. As a pathologist in training I probably spend a quarter or more of my time identifying and categorizing tumors, of which there are thousands described, involving virtually any type of nucleated cells--liver cells, neurons, sweat glands, lymphatic endothelium, you name it. Before we get too far into the episode, I want to define a few important terms, and try to explain what cancer actually is...

這集說的是我最喜歡的話題，“腫瘤形成”。作為在培的病理學(xué)家，我的時間有1/4或者更多，花在了鑒定和歸類腫瘤上。腫瘤，已知的就有幾千種，它幾乎牽涉到所有的有核細胞 - 肝細胞，神經(jīng)元細胞，汗腺，淋巴管內(nèi)皮細胞，等等等等。但在開聊本集劇情之前，我得先定義幾個重要的概念，以及解釋下癌癥究竟是什么……

Cancer is an uncontrolled, unregulated growth of cells that results usually from a genetic aberration. To throw around the phrase "cancer" implies that this growth is capable of metastatic spread, that is, can seed foreign sites in the body. Another word for this is a malignant tumor. Not all tumors, or neoplasia, will behave in a malignant fashion. Benign tumors, due to various nuances of their underlying biology, do not cause metastatic disease, but they are still monoclonal, meaning every cell is genetically identical and arose from a single "patient zero" mutated cell. "Hold on, aren't all of your cells genetically identical?" Normally, yes, but all cells can acquire somatic mutations from things like mutagens, replication errors, and viral infections. Cancers can range in lethality from insignificant (a low-grade prostate cancer that is best monitored but otherwise left alone) to immediately deadly (an infiltrative brain tumor or pancreatic tumor that kills in weeks after diagnosis). Their treatment is another topic altogether, I can go into more depth there if people are interested.

癌細胞是不受控制、不受管理成長的細胞，它形成的通常原因是基因異常?！鞍边@個詞，就代表細胞有‘轉(zhuǎn)移擴散’的能力，也就是可轉(zhuǎn)移到其他部分生長。它也叫做‘惡性腫瘤’。不是所有的腫瘤(瘤形成，neoplasia)，都是惡性的。由于各種自身問題產(chǎn)生的‘良性腫瘤’，并不會產(chǎn)生轉(zhuǎn)移擴散。但不管良性和惡性，癌細胞都是由“單細胞形成(monoclonal)”的，也就是說每個細胞在基因上都一致，都是由單個變異的‘初始病人（patient zero）’ 細胞產(chǎn)生。

“等等，細胞不都是基因一致嗎？”一般來說，是的。但所有細胞都可以出現(xiàn)‘體細胞突變’，這些突變可能來自于‘誘變劑’，復(fù)制錯誤，或者病毒感染等等。癌癥的致命程度，可以從無明顯危害（低危前列腺癌最好監(jiān)控下，但是放在那著不管也行）到快速斃命（滲透性的腦瘤，或者胰腺癌，會在診斷后的幾周內(nèi)斃命）。癌癥的治療方法是另一碼事了，如果大家有興趣的話，我會深入講解的。

Character Highlight

角色介紹

Natural Killer (NK) Cell

The natural killer cell! What an intimidating name, but an appropriate one. NK cells are very similar in appearance and function to the cytotoxic T-cells. Their chief role is to cause cytotoxicity, able to destroy both human and foreign cells using a variety of weapons, such as perforins and granzymes, which literally punch holes in target membranes.

NK細胞（自然殺傷細胞）??！好嚇人的名字，但是對它來說卻很合適。NK細胞的外觀和功能和細胞毒性T細胞（即殺手T細胞）類似。它們的主要功能是產(chǎn)生細胞毒素，它們能用各種武器——比如‘穿孔蛋白’和‘顆粒酶’——破壞人類和外來物細胞，就是在目標(biāo)細胞膜上噗噗噗打個洞。

So how should they be distinguished from cytotoxic T-cells? NK cells are more effective at destroying tumoral cells. While both cells can recognize abnormal protein antigens that are presented on the HLA molecules of tumor cells, the NK cell is furthermore capable of recognizing when the expression of the HLA itself is abnormal (as it is often decreased in tumor cells). They are also sensitive to danger signals and molecules that are over-expressed in cancerous transformation (PVR, Nectin-2). NK cells are also excellent at killing cancer stem cells, a highly malignant subpopulation that helps regenerate the tumor cell population. Finally, NK cells have the means by which to locally orchestrate immune responses, signaling to T and B lymphocytes.

所以該如何區(qū)分NK細胞和殺手T細胞呢？NK細胞能更有效地消滅腫瘤。腫瘤細胞上的HLA分子(人類白細胞抗原)，上面會呈現(xiàn)出異常的蛋白質(zhì)“抗原(antigen)”，可以被NK和殺手T細胞識別；但是，NK細胞還能識別HLA表達的異常（因為它在腫瘤細胞里會減少）。它們對那些過度呈現(xiàn)癌化的分子(PVR， 粘連蛋白-2)和信號也很敏感。NK細胞還很擅長于消滅癌癥干細胞；癌癥干細胞是高度惡性的細胞，會促進腫瘤細胞的再生。最后，NK細胞還可以組織局部免疫反應(yīng)，給T和B淋巴細胞發(fā)送信號。

Tumor cells have some ways to get around NK cell surveillance, however. By upregulating or downregulating certain signaling molecules, some can achieve “immune stealth”, going unnoticed by the immune system during their critical early phases. One can think of our immune system as providing a selective pressure towards this stealth, as any tumor that is detected otherwise is promptly destroyed. It is not really clear to me how often tumorigenesis occurs and is quashed by your immune system before coming to clinical attention, but it is definitely true that the role is significant, as immunocompromised patients are more prone to developing cancers from multiple causes.

但是，腫瘤細胞倒是有辦法躲開NK細胞的監(jiān)控。通過‘上調(diào)’或者‘下調(diào)’某些信號分子，有些腫瘤細胞會變身為‘免疫系統(tǒng)潛行者’，讓免疫系統(tǒng)無視掉腫瘤形成初期的重要階段。也就是說，免疫系統(tǒng)會對這種潛行者睜一只眼閉一只眼，因為被發(fā)現(xiàn)的腫瘤細胞，會被立刻干掉。我不太清楚腫瘤產(chǎn)生的頻率有多高，也不知道它在被醫(yī)生發(fā)現(xiàn)之前，會有多少被免疫系統(tǒng)壓制。但可以肯定的是，免疫系統(tǒng)的作用很大，因為‘免疫功能不全’的病人更容易得上癌癥。

In addition to killing tumor cells, NK cells will also kill any macrophages or other cells that have been shown to sometimes promote tumor growth. So don't cross her. There are currently millions (probably billions) of dollars in research right now developing means by which to reprogram/supercharge/otherwise administer NK cells that are specific towards tumors as a new form of clinical therapy.

除了殺死腫瘤細胞，NK細胞也會殺掉促進腫瘤生長的巨噬細胞和其他細胞。所以別惹她。目前投資在NK細胞上的資金有上百萬（甚至幾十億）美元，研究者通過改寫/加強/或者命令NK細胞，讓它們成為一種新的療法，去攻擊特定的腫瘤。

A fun and cruel irony is that as any nucleated cell is capable of becoming neoplastic, NK cells themselves can become cancerous (see: EBV-related NK proliferative diseases, extranodal NK/T-cell lymphoma, etc). I don’t think we’re going to get that far in depth though, as the cancer featured in this episode is not even named.

諷刺的是，因為任何有核細胞都可以腫瘤化，所以NK細胞自己也可以變成癌癥細胞（請參考：EBV相關(guān)的NK淋巴細胞增生性疾病，淋巴結(jié)外NK/T細胞淋巴瘤等等）。但我不會深入說這些，因為本集出現(xiàn)的癌細胞都不知道是哪種。

Episode 6.5 - Cancer cell pt 1

6.5集? 癌癥細胞part 1

15:30 - I wonder why U-1146 is always sipping green tea...or what that could be an allusion to. Immune cells mostly use the same cellular fuels as every other cell, namely simple sugars, ketone bodies, fatty acids, etc.

為什么U-1146總喝綠茶呢。。?；蛘撸谴硎裁?？免疫細胞的能量來源和其他細胞一樣，就是簡單的糖分子，酮體，脂肪酸等等。

15:40 - Very interesting, bizarre-appearing cell. It seems pretty reasonable for cancer cells to look awful, as cancers have abnormal looking architecture and cytomorphology as they acquire more mutations.?

長相奇葩的細胞。癌細胞很有可能蠻難看的，因為隨著突變的增多，它們結(jié)構(gòu)和細胞形態(tài)都會發(fā)生異常。

16:00 - Neutrophils should not be fighting cancer cells, as they would have no way to recognize that the cell is abnormal. An exception to this is when the tumor has grown so large that it outstrips its vascular supply and starts to necrose, spilling pro-inflammatory contents which the neutrophil could then respond to. Neutrophils are actually thought in a lot of cases to promote tumor formation, but research in this is ongoing.

中性粒細胞不應(yīng)該和癌細胞干架，因為它們根本看不出來這些細胞的異常。倒是也有例外，就是腫瘤長得太大了，以致所需的血量大大增加，并且開始壞死；這時，細胞就會吐出促進炎癥的物質(zhì)，讓中性粒細胞可以檢測出來。實際在很多情況下，中性粒細胞都會被認為是促進腫瘤形成，但這方面的研究還沒有定論。

17:00 - Intro to NK cell! I'm unsure what is with her competitive/adversarial dynamic with cytotoxic (CD8+) T-lymphocyte. They serve in a lot of similar roles, but as discussed above, she's a bit better at recognizing tumor cells, and also can orchestrate a T-lymphocyte response (I am unsure if the reverse applies, however). I could reasonably envision that they are capable of killing each other, though that would probably be inappropriate...

NK細胞登場。我不太清楚她為啥會對“殺手T細胞”有競爭/敵對情緒。它們功能的確有很多類似的地方，但之前說的那樣，她能更好識別腫瘤細胞，并且還可以組織T細胞的回應(yīng)（但我不確定反過來是不是可以）。我可以想象他們有能力殺死彼此，但那有點不太合適吧…

20:20 - Since this show focuses so heavily on the immune cells, we don't get to learn a lot about all of the other epithelial and stromal cells that make up organs, or the body more generally. It would be more interesting if this derelict complex were characterized as a particular organ...

因為本劇里免疫細胞戲份太重，我們都沒機會看組成器官、或者身體的上皮細胞和基質(zhì)細胞。如果這廢宅是某個特定的器官就好了…

21:00 - A rejection reaction, lol. That's pretty good. Cytotoxic T-lymphocytes are one of the main cells responsible for organ rejection in transplants (B-cells play a role as well). In fact, if we find a collection of them in eg an endomyocardial biopsy, we will call our clinicians who will immediately begin pulse-dosing steroids. "Compatibility" usually refers to antigens like the Human Leukocyte Antigens (HLA, or Major Histocompatibility Complex) that determine whether rejection will occur.

排斥反應(yīng)（笑）。很好很好。細胞毒性T淋巴細胞，是導(dǎo)致‘器官移植’時的發(fā)生‘排斥反應(yīng)’的元兇之一（B細胞也是一個）。如果我們在活體檢測中（比如‘心內(nèi)膜心肌活檢’）發(fā)現(xiàn)一堆T細胞，我們會叫醫(yī)生打脈動式類固醇(pulse-dosing steroid)?！嫒菪浴ǔＶ傅氖菦Q定排斥反應(yīng)是否發(fā)生的抗原，比如HLA（人類白細胞抗原）。

Episode 7 - Cancer cell pt 2

第7集 - 癌細胞 part 2

2:35 – Cancers, at least in their early stages, will generally resemble whatever cell lineage they arise from (well-differentiated), though their behavior will generally belie their neoplastic origin. As cancers mutate, they accrue more and more errors and abnormalities (as the normal mechanisms by which a cell would apoptose, or kill itself, are no longer being triggered).

癌細胞在初期階段，一般都像自己的本家。但它們的行為，一般最初并不像腫瘤。隨著癌細胞的變異，它們會累積越來越多的錯誤和異常，因為它們不會產(chǎn)生“細胞凋亡”，就是不會殺死自己。

3:05 – I should touch on what causes cancers to form a bit more. They almost all arise from genetic abnormalities, but the specifics can be varied and very important. Some may form because a growth signal system is mutated to always be “on”. Some form because a suicide pathway is permanently disabled. Any abnormality that leads to dysregulation of growth can form a cancer.

我得說下癌癥形成的原因，它基本都是基因異常引起的，但是具體情況還得具體分析。有些癌癥，可能是因為控制生長的‘按鈕’變異成一直‘開’著的狀態(tài)；有些可能是因為永遠不能走向自殺這條路。讓生長失控的任何異常，都可以形成癌癥。

4:15 – I’m not really familiar with cancer cells “attacking” immune cells, as they would generally not have the sort of complex machinery needed to do this. Most of their adaptations pertain to resisting and avoiding immune cells.

我都不知道癌細胞可以‘攻擊’免疫細胞，因為癌細胞一般缺少這種復(fù)雜的機制。它們一般能做的，就是抵抗或者逃離免疫細胞。

5:15 – Ooh, see that diagram on the bottom right of the board? Those are the phases of mitosis, the process by which a cell divides.

看到板子右下角的圖表了不？這是‘有絲分裂’—— 一種細胞分裂的過程。

10:00 - Let me elaborate a bit more on what I described earlier. As tumor cells grow, they require a constant influx of oxygen and nutrients to support their multiplication. As they begin to outstrip the local tissue infrastructure, they will promote formation of new blood vessels (angiogenesis) to support their growth. Drugs that block this signaling are approved for the treatment of certain cancers (eg. Bevacizumab in colorectal cancers). Remember, the red cells can't know any better! This very energy-demanding process often causes the patient to experience unintentional weight loss and cachexia.

我來詳細解釋下之前談的東西。隨著腫瘤細胞的增長，它們需要連續(xù)不斷的氧氣和營養(yǎng)供應(yīng)，方便自己的產(chǎn)生下一代。當(dāng)它們的成長蔓延出周邊的組織時，就會促進形成新的血管，以便自己的生長。有些藥可以阻止這種過程，它們被證實可以用來治療某些癌癥（比如治療直腸癌的‘貝伐單抗’）。紅細胞簡直不能更懂這點了！這個過程極其消耗能量，經(jīng)常導(dǎo)致病人無意識的掉體重。

11:30 - I've got nothing to say about the backstory here, but more on tumorigenesis: We talked about what the mutations can cause, but what causes the mutations? You've all heard of the effects of mutagens like radiation, smoking, and more exotic stuff like aflatoxins/vinyl chlorides/etc. Mutations also can occur as a result of copying errors--consider that the polymerase enzymes that encode DNA have to copy all 3 billion base pairs every time the cell divides. This process is not perfect, and errors do occur. Cells have ways of recognizing and correcting these errors, but they don't work every time. We can also look at oncogenic infections, where viruses integrate into or otherwise disrupt DNA. Epstein-Barr Virus (EBV or HHV5, the virus that causes infectious mono) is famous for this. Kaposi's sarcoma is caused by another member of the herpesvirus family (HHV8).

對這個癌細胞的身世嘛，我沒啥可說的，但我要說下腫瘤的形成過程。我們談了‘基因突變’的結(jié)果，但是，究竟是什么產(chǎn)生了‘突變’呢？你們可能都聽說過‘誘變劑’帶來的后果，誘變劑就是輻射、煙這種東西，也包括更有毒性的‘黃曲霉毒素’/氯乙烯等等。復(fù)制錯誤也可以導(dǎo)致突變；想想看，細胞一分裂，給DNA編碼的聚合酶就得復(fù)制30億個堿基對。這個過程并不完美，會產(chǎn)生錯誤。細胞倒是有方法識別和修正這些錯誤，但不是每次都能成功。我們也會看致癌性感染——致癌性感染就是病毒和DNA結(jié)合、或者是破壞DNA。著名的EB病毒（也叫HHV5,就是接吻病毒，學(xué)名叫‘傳染性單核細胞增多’）就是這種了。皰疹病毒的另一成員（HHV-8）會引起‘卡波濟氏肉瘤’。

12:00 - I do not know how many "cancer cells" form on a regular basis. This number is probably derived from mathematical models as it can be almost impossible for modern scientific methods to distinguish individual tumor cells from normal somatic cells in a living organism. I'd love if someone had a source though, I can't find one.

我不知道身體在一般情況下能產(chǎn)生多少‘癌細胞’。這個數(shù)字很可能來自數(shù)學(xué)模型，因為我們基本不可能用現(xiàn)代的科學(xué)方法區(qū)分正常體細胞和癌細胞。我自己是找不到這個數(shù)據(jù)的出處，如果有人能找到就好了。

13:00 - Why, exactly, are cancers dangerous? Metastatic spread will eventually disrupt the normal function of whatever tissues they invade. Mass effect can cause symptoms (see: a tumor compressing nerves, vessels, or ducts), and tumors can cause edema (very dangerous in the brain), malignant effusions, etc. Chunks of tumor that break off in circulation can cause embolism. The list goes on.

那么，癌癥究竟為什么這么危險呢？腫瘤會擴散、入侵到正常的組織里，最終破壞掉它們的功能?！罢嘉恍?yīng)”產(chǎn)生病狀（比如：被腫瘤壓迫的神經(jīng)、血管、或者管道），腫瘤會引起水腫（腦內(nèi)水腫非常危險），惡性擴散等等。如果大塊的腫瘤從循環(huán)系統(tǒng)里脫落，就會產(chǎn)生“栓塞”。諸如此類，等等等等。

14:00 - This macrophage doesn't seem phased...I wonder if she is a tumor-associated macrophage (TAM), which promotes tumorigenesis.

這個巨噬細胞看起來沒有突變… 我在想她是不是TAM(腫瘤相關(guān)巨噬細胞)呢，就是促進腫瘤形成的那種。

15:20 - This united front of all immune cells vs tumor is very dramatic and fun, but not very realistic.

所有免疫細胞聯(lián)合起來對抗腫瘤夠戲劇化、也夠好玩，但并不現(xiàn)實。

17:40 - This...is a stretch. I did a literature search and found a handful of Japanese research articles that looked at the effect of laughter on NK cell activity in multiple diseases, but they tended to be low-power and more generally low-quality studies. Not saying it's pure bullshit, but since this is not something that can be uniformly characterized and administered, there is not much in the literature about it.?

這…腦洞有點大。我查了下文獻；有些日本文獻里說了在一些疾病中，‘笑’對NK活性的影響，但是這些文章影響因數(shù)和質(zhì)量都不高。倒不是說這些文章鬼話連篇，只是我們不能這么下斷言，而且相關(guān)文獻也不多。

18:10 - A note from the manga: Cancer-boy says "Gaan", which sounds like an expression of dismay but also means "Crab"...appropriate considering what the zodiac symbol for Cancer is.

漫畫里的注釋：癌細胞說了聲“干(gan)”，這聽上去像嘆息，但是日語里，它也是癌癥的意思。

譯者注：這里的英文原文可能有誤，日語的癌發(fā)音是gan，而巨蟹座不是。所以我的翻譯也和原文不一樣。

21:30 - Red cells can't summon an immune response! But we've already established our two heroes are exceptional, right?

紅細胞不能召喚免疫反應(yīng)！但是我們已經(jīng)知道，兩個主角就是很特別嘛。

Summary

總結(jié)

A neoplastic growth that was able to be resolved without any clinical intervention. This does happen on at least a semi-regular basis. Usually, once a tumor reaches a critical size threshold (maybe 1cm or so), they rarely resolve on their own, and will grow until they manifest clinical symptoms, at which point they must be treated. Surgical resection can be simple, and curative in organ-confined disease. If the cancer has already spread, then surgery theoretically cannot be curative. Then we have an array of chemotherapeutics and radiation treatments, ranging from the old and barbaric (metabolic toxins that kill cancers cells on the basis of their high metabolism...but also poison the rest of you) to the cutting edge and laser-precise (small molecules that specifically target mutated proteins). If anyone is interested in the concept of personalized medicine, I'd be glad to talk about it more. But we're getting a little off track now.

本集的腫瘤君，沒用醫(yī)學(xué)手段就解決掉了。這應(yīng)該是日常會發(fā)生的情景。通常來說，一旦腫瘤到達了臨界值（大概1cm左右），就不太可能自行解決了。腫瘤會持續(xù)成長，直到它產(chǎn)生臨床病狀，那時就必須要治療了。腫瘤可以簡單地用手術(shù)切除，而且如果它只限于在一個器官里的話，也是可以根治的。但如果癌癥已經(jīng)擴散，那理論上就無法根治。我們有一系列化學(xué)和放射性療法，有些方法很古老、野蠻（用代謝毒素，它可以根據(jù)癌細胞的快速代謝率殺死它們，但是也會毒害其他的一切），有些很新式、精準(zhǔn)（只針對變異蛋白質(zhì)的小分子），如果有人想知道這些個性化藥物的話，我以后可以多聊聊。但是現(xiàn)在有點偏題了。

This was a fun one. If we see cancer again in the future, I would love for them to be distinguished a bit more. After all, the field of oncology is enormous, with thousands of different cancers all with different behaviors and appearances. They are about as varied as bacteria and viruses! But I'll take my neoplastic fix for now. Hope you all enjoyed it!

蠻有意思的一集。如果我們以后還能看到癌細胞的話，希望他能更細化一點。畢竟，腫瘤學(xué)是個大學(xué)科，有幾千種癌細胞，各自都有不同的行為和外表。它們和細菌、病毒的種類一樣多！但現(xiàn)在就這樣吧。希望大家喜歡！

生物相關(guān)單詞

neoplasia? 瘤形成

liver? 肝

neuron? 神經(jīng)元

sweat gland? 汗腺

lymphatic endothelium? 淋巴管內(nèi)皮細胞

metastatic （癌細胞的）轉(zhuǎn)移性的

malignant tumor? 惡性腫瘤

benign tumors 良性腫瘤

neoplasia? 瘤形成

monoclonal? 單細胞繁殖的

somatic mutation 體細胞突變

replication errors? 復(fù)制錯誤

prostate 前列腺

perforin? 穿孔蛋白

granzyme 顆粒酶

HLA = human leukocyte antigen? 人類白細胞抗原

vascular? 血管的

necrose? 壞死

epithelial? 上皮的

stromal 基質(zhì)

mitosis? 有絲分裂

somatic cells? 體細胞

surgical resection 手術(shù)切除

curative? 有療效的

chemotherapeutics? 化學(xué)治療法

oncology? 腫瘤學(xué)

apoptosis? ?脫噬