第6-7集 癌细胞(Cancer)
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...
这集说的是我最喜欢的话题，“肿瘤形成”。作为在培的病理学家，我的时间有1/4或者更多，花在了鉴定和归类肿瘤上。肿瘤，已知的就有几千种，它几乎牵涉到所有的有核细胞 - 肝细胞，神经元细胞，汗腺，淋巴管内皮细胞，等等等等。但在开聊本集剧情之前，我得先定义几个重要的概念，以及解释下癌症究竟是什么……
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.
癌细胞是不受控制、不受管理成长的细胞，它形成的通常原因是基因异常。“癌”这个词，就代表细胞有‘转移扩散’的能力，也就是可转移到其他部分生长。它也叫做‘恶性肿瘤’。不是所有的肿瘤(瘤形成，neoplasia)，都是恶性的。由于各种自身问题产生的‘良性肿瘤’，并不会产生转移扩散。但不管良性和恶性，癌细胞都是由“单细胞形成(monoclonal)”的，也就是说每个细胞在基因上都一致，都是由单个变异的‘初始病人（patient zero）’ 细胞产生。
“等等，细胞不都是基因一致吗？”一般来说，是的。但所有细胞都可以出现‘体细胞突变’，这些突变可能来自于‘诱变剂’，复制错误，或者病毒感染等等。癌症的致命程度，可以从无明显危害（低危前列腺癌最好监控下，但是放在那着不管也行）到快速毙命（渗透性的脑瘤，或者胰腺癌，会在诊断后的几周内毙命）。癌症的治疗方法是另一码事了，如果大家有兴趣的话，我会深入讲解的。
Character Highlight
角色介绍
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细胞（自然杀伤细胞）！！好吓人的名字，但是对它来说却很合适。NK细胞的外观和功能和细胞毒性T细胞（即杀手T细胞）类似。它们的主要功能是产生细胞毒素，它们能用各种武器——比如‘穿孔蛋白’和‘颗粒酶’——破坏人类和外来物细胞，就是在目标细胞膜上噗噗噗打个洞。
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.
所以该如何区分NK细胞和杀手T细胞呢？NK细胞能更有效地消灭肿瘤。肿瘤细胞上的HLA分子(人类白细胞抗原)，上面会呈现出异常的蛋白质“抗原(antigen)”，可以被NK和杀手T细胞识别；但是，NK细胞还能识别HLA表达的异常（因为它在肿瘤细胞里会减少）。它们对那些过度呈现癌化的分子(PVR， 粘连蛋白-2)和信号也很敏感。NK细胞还很擅长于消灭癌症干细胞；癌症干细胞是高度恶性的细胞，会促进肿瘤细胞的再生。最后，NK细胞还可以组织局部免疫反应，给T和B淋巴细胞发送信号。
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，肿瘤细胞倒是有办法躲开NK细胞的监控。通过‘上调’或者‘下调’某些信号分子，有些肿瘤细胞会变身为‘免疫系统潜行者’，让免疫系统无视掉肿瘤形成初期的重要阶段。也就是说，免疫系统会对这种潜行者睁一只眼闭一只眼，因为被发现的肿瘤细胞，会被立刻干掉。我不太清楚肿瘤产生的频率有多高，也不知道它在被医生发现之前，会有多少被免疫系统压制。但可以肯定的是，免疫系统的作用很大，因为‘免疫功能不全’的病人更容易得上癌症。
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.
除了杀死肿瘤细胞，NK细胞也会杀掉促进肿瘤生长的巨噬细胞和其他细胞。所以别惹她。目前投资在NK细胞上的资金有上百万（甚至几十亿）美元，研究者通过改写/加强/或者命令NK细胞，让它们成为一种新的疗法，去攻击特定的肿瘤。
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.
讽刺的是，因为任何有核细胞都可以肿瘤化，所以NK细胞自己也可以变成癌症细胞（请参考：EBV相关的NK淋巴细胞增生性疾病，淋巴结外NK/T细胞淋巴瘤等等）。但我不会深入说这些，因为本集出现的癌细胞都不知道是哪种。
Episode 6.5 - Cancer cell pt 1
6.5集 癌症细胞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.
为什么U-1146总喝绿茶呢。。。或者，那代表什么？免疫细胞的能量来源和其他细胞一样，就是简单的糖分子，酮体，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.
长相奇葩的细胞。癌细胞很有可能蛮难看的，因为随着突变的增多，它们结构和细胞形态都会发生异常。
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.
中性粒细胞不应该和癌细胞干架，因为它们根本看不出来这些细胞的异常。倒是也有例外，就是肿瘤长得太大了，以致所需的血量大大增加，并且开始坏死；这时，细胞就会吐出促进炎症的物质，让中性粒细胞可以检测出来。实际在很多情况下，中性粒细胞都会被认为是促进肿瘤形成，但这方面的研究还没有定论。
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细胞登场。我不太清楚她为啥会对“杀手T细胞”有竞争/敌对情绪。它们功能的确有很多类似的地方，但之前说的那样，她能更好识别肿瘤细胞，并且还可以组织T细胞的回应（但我不确定反过来是不是可以）。我可以想象他们有能力杀死彼此，但那有点不太合适吧…
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...
因为本剧里免疫细胞戏份太重，我们都没机会看组成器官、或者身体的上皮细胞和基质细胞。如果这废宅是某个特定的器官就好了…
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.
排斥反应（笑）。很好很好。细胞毒性T淋巴细胞，是导致‘器官移植’时的发生‘排斥反应’的元凶之一（B细胞也是一个）。如果我们在活体检测中（比如‘心内膜心肌活检’）发现一堆T细胞，我们会叫医生打脉动式类固醇(pulse-dosing steroid)。‘兼容性’通常指的是决定排斥反应是否发生的抗原，比如HLA（人类白细胞抗原）。
Episode 7 - Cancer cell pt 2
第7集 - 癌细胞 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).
癌细胞在初期阶段，一般都像自己的本家。但它们的行为，一般最初并不像肿瘤。随着癌细胞的变异，它们会累积越来越多的错误和异常，因为它们不会产生“细胞凋亡”，就是不会杀死自己。
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.
我得说下癌症形成的原因，它基本都是基因异常引起的，但是具体情况还得具体分析。有些癌症，可能是因为控制生长的‘按钮’变异成一直‘开’着的状态；有些可能是因为永远不能走向自杀这条路。让生长失控的任何异常，都可以形成癌症。
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.
我都不知道癌细胞可以‘攻击’免疫细胞，因为癌细胞一般缺少这种复杂的机制。它们一般能做的，就是抵抗或者逃离免疫细胞。
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.
看到板子右下角的图表了不？这是‘有丝分裂’—— 一种细胞分裂的过程。
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.
我来详细解释下之前谈的东西。随着肿瘤细胞的增长，它们需要连续不断的氧气和营养供应，方便自己的产生下一代。当它们的成长蔓延出周边的组织时，就会促进形成新的血管，以便自己的生长。有些药可以阻止这种过程，它们被证实可以用来治疗某些癌症（比如治疗直肠癌的‘贝伐单抗’）。红细胞简直不能更懂这点了！这个过程极其消耗能量，经常导致病人无意识的掉体重。
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).
对这个癌细胞的身世嘛，我没啥可说的，但我要说下肿瘤的形成过程。我们谈了‘基因突变’的结果，但是，究竟是什么产生了‘突变’呢？你们可能都听说过‘诱变剂’带来的后果，诱变剂就是辐射、烟这种东西，也包括更有毒性的‘黄曲霉毒素’/氯乙烯等等。复制错误也可以导致突变；想想看，细胞一分裂，给DNA编码的聚合酶就得复制30亿个碱基对。这个过程并不完美，会产生错误。细胞倒是有方法识别和修正这些错误，但不是每次都能成功。我们也会看致癌性感染——致癌性感染就是病毒和DNA结合、或者是破坏DNA。著名的EB病毒（也叫HHV5,就是接吻病毒，学名叫‘传染性单核细胞增多’）就是这种了。疱疹病毒的另一成员（HHV-8）会引起‘卡波济氏肉瘤’。
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.
我不知道身体在一般情况下能产生多少‘癌细胞’。这个数字很可能来自数学模型，因为我们基本不可能用现代的科学方法区分正常体细胞和癌细胞。我自己是找不到这个数据的出处，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，癌症究竟为什么这么危险呢？肿瘤会扩散、入侵到正常的组织里，最终破坏掉它们的功能。“占位效应”产生病状（比如：被肿瘤压迫的神经、血管、或者管道），肿瘤会引起水肿（脑内水肿非常危险），恶性扩散等等。如果大块的肿瘤从循环系统里脱落，就会产生“栓塞”。诸如此类，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.
这个巨噬细胞看起来没有突变… 我在想她是不是TAM(肿瘤相关巨噬细胞)呢，就是促进肿瘤形成的那种。
15:20 - This united front of all immune cells vs tumor is very dramatic and fun, but not very realistic.
所有免疫细胞联合起来对抗肿瘤够戏剧化、也够好玩，但并不现实。
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.
这…脑洞有点大。我查了下文献；有些日本文献里说了在一些疾病中，‘笑’对NK活性的影响，但是这些文章影响因数和质量都不高。倒不是说这些文章鬼话连篇，只是我们不能这么下断言，而且相关文献也不多。
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.
漫画里的注释：癌细胞说了声“干(gan)”，这听上去像叹息，但是日语里，它也是癌症的意思。
译者注：这里的英文原文可能有误，日语的癌发音是gan，而巨蟹座不是。所以我的翻译也和原文不一样。
21:30 - Red cells can't summon an immune response! But we've already established our two heroes are exceptional, right?
红细胞不能召唤免疫反应！但是我们已经知道，两个主角就是很特别嘛。
Summary
总结
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.
本集的肿瘤君，没用医学手段就解决掉了。这应该是日常会发生的情景。通常来说，一旦肿瘤到达了临界值（大概1cm左右），就不太可能自行解决了。肿瘤会持续成长，直到它产生临床病状，那时就必须要治疗了。肿瘤可以简单地用手术切除，而且如果它只限于在一个器官里的话，也是可以根治的。但如果癌症已经扩散，那理论上就无法根治。我们有一系列化学和放射性疗法，有些方法很古老、野蛮（用代谢毒素，它可以根据癌细胞的快速代谢率杀死它们，但是也会毒害其他的一切），有些很新式、精准（只针对变异蛋白质的小分子），如果有人想知道这些个性化药物的话，我以后可以多聊聊。但是现在有点偏题了。
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!
蛮有意思的一集。如果我们以后还能看到癌细胞的话，希望他能更细化一点。毕竟，肿瘤学是个大学科，有几千种癌细胞，各自都有不同的行为和外表。它们和细菌、病毒的种类一样多！但现在就这样吧。希望大家喜欢！
生物相关单词
neoplasia 瘤形成
liver 肝
neuron 神经元
sweat gland 汗腺
lymphatic endothelium 淋巴管内皮细胞
metastatic （癌细胞的）转移性的
malignant tumor 恶性肿瘤
benign tumors 良性肿瘤
neoplasia 瘤形成
monoclonal 单细胞繁殖的
somatic mutation 体细胞突变
replication errors 复制错误
prostate 前列腺
perforin 穿孔蛋白
granzyme 颗粒酶
HLA = human leukocyte antigen 人类白细胞抗原
vascular 血管的
necrose 坏死
epithelial 上皮的
stromal 基质
mitosis 有丝分裂
somatic cells 体细胞
surgical resection 手术切除
curative 有疗效的
chemotherapeutics 化学治疗法
oncology 肿瘤学
apoptosis 脱噬
