再见干细胞

pujixing

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回复 knowtumor 的帖子6 M- X1 K$ y+ O* V1 W" C2 y
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诚如楼上所说，要找到一个能代表所有肿瘤的抽象的肿瘤是有很大困难的。但如果去重温一下Weinberg和Hanahan所写的两篇Cancer Hallmark（2000年和2011年发表于Cell杂志）的文章后，应该会有一个较为清晰的轮廓。在前文中说描述的是畸胎瘤的特殊性。首先，畸胎瘤这个概念是个非常宽松的定义，其实其来源是非常多样的（具体种类在此不细述，可在网上找到很多资料）。畸胎瘤中绝大多数是成熟的，或说是良性的，只有很小的比例是恶性的，而恶性的这部分才是真正的cancer。癌症的致命性并不在于其无限生长的特性，而是转移性。在这一点来说，畸胎瘤这个马群里的绝大多数马，都不具有这种代表性（malignancy中最重要的部分）。* [0 y. z, L& N, w. W1 Q) `
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因为目前在下所能认识到的范围内，癌细胞可变为正常细胞的观点并不是主流观点，而且在下对这个有趣的问题的确心存很多疑问。也或许是遇到一些超前的但没来得及正确认识到的观点（历史上的确有一些案例表明某些超前的理论在初期并没有得到应有的承认，比如转座子，比如HPV和宫颈癌的关系等等）。在此情形下，Know Tumor大侠可否和我们分享一下畸胎瘤（良性畸胎瘤还是恶性？）/肝癌细胞（癌细胞存活状况？）移植变为正常的文献，以及豹蛙（豹蛙肾癌细胞移植后没有影响其生育能力，但是否就终止了癌症发生呢？）的文献。
( V* B2 d; s" h$ [) r看是否能从中找出我们没有提及的重要细节呢？
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& q  T; G1 J4 @/ D, r6 t这里有篇文章可参考关于移植畸胎瘤细胞的一些引起注意的事实（teratoma v.s teratocarcinoma）：# y) N' d* F* y8 C9 l3 S
Correspondence7 x/ Y& r( P" m: e; G
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7 T, [' j/ x# n. k* vNature Biotechnology 25, 1212 (2007)
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$ d7 R5 f  s/ o" i4 l( aThe terminology of teratocarcinomas and teratomas5 Q/ c/ m' M, l6 I
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Ivan Damjanov1 & Peter W Andrews2
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From our point of view, most of the problems and controversies mentioned in this correspondence have arisen from the inconsistent usage of the terms teratoma and teratocarcinoma by many scientists working in this field. Thus, we encourage the editors of Nature Biotechnology to standardize the terminology, at least for human embryonic stem (ES) cell–derived xenografts.3 I3 U7 r- J% E
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In our view, the term teratocarcinoma should be used only for malignant tumors, which in this context are malignant by virtue of the continued presence of stem cells—the embryonal carcinoma (EC) cells1. EC cells, as suggested by almost all studies on mouse- and human-derived cells, are the malignant equivalents or cognates of ES cells2. Any pathologist trained to identify human EC cells should be able to distinguish malignant teratocarcinomas from benign teratomas, which are defined as tumors composed only of somatic tissues and devoid of EC cells. In an experimental setting, the malignancy of a tumor due to the presence of morphologically identifiable EC cells can be tested by re-transplantation to a new host.
& C, s! d; X0 y8 S* MThe distinction between teratomas and teratocarcinomas is crucial, especially for the future usage of ES cells in human medicine. [[[[[[Using xenografting as an essential preclinical safety control, one could predict that the ES cell lines that form only teratomas are 'benign' or 'safe' for human usage, whereas the cell lines that produce teratocarcinomas are 'malignant' and not safe for injection into humans3]]]]]]. Thus, we would discourage the indiscriminate usage of terms 'teratoma' and 'teratocarcinoma', even though in the past some eminent scientists have used those term interchangeably and even as synonyms. Previous imprecision is, in our opinion, not a valid justification for future use of a confusing terminology.
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A minor but not insurmountable problem pertains to the usage of 'teratocarcinoma' for tumors produced from human ES cells. Even though the term 'teratocarcinoma' has been used as a synonym for malignant teratoma in mice for more than four decades, most leaders in human pathology have consistently refused to accept it. In the recent consensus book on human testicular tumors compiled by the experts of the World Health Organization (WHO; Geneva, Switzerland)4, the term teratocarcinoma is mentioned only in passing for the animal model of human germ cell tumors. Because the work on human ES cells is, in a sense, a continuation of the experiments first performed on mouse ES cells and teratocarcinoma-derived EC cells, we feel that the term 'teratocarcinoma' will be more readily accepted by laboratory researchers than diagnostic pathologists. At least it is less cumbersome than the WHO-recommended term “mixed embryonal carcinoma and teratoma” or indeed the British classification “malignant teratoma intermediate4”.
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Nature Biotechnology 25, 1212 (2007)
4 z2 B8 l. o1 O/ ?doi:10.1038/nbt1107-1212b
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Response to The terminology of teratocarcinomas and teratomas
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2 Q% ^; h% T4 o# v5 P  rNature Biotechnology responds:8 O! w4 ?/ Y1 |+ u, q8 f" h# k0 M

& K, B' F4 @: yA survey of the literature indicates no consensus on how to distinguish the terms 'teratoma' and 'teratocarcinoma'. The term 'teratocarcinoma' is used as a synonym for human tumors clinically known as “teratoma with embryonal carcinoma” (according to the World Health Organization) or “teratoma intermediate” (according to the British classification of germ cell tumors). Some pathologists include these tumors in the group of testicular 'nonseminomas' (also known as 'nonseminomatous germ cell tumors (NSGCT)') or use imprecise terms, such as 'malignant teratoma'. The somatic tissues in teratocarcinoma may be fully differentiated (equivalent to adult tissue) or only partially differentiated (corresponding to immature tissues in fetal organs).
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: p1 N& t: g, y/ \  p; G! jOn the basis of the above exchange and after expert consultation, Nature Biotechnology will adopt the term 'teratocarcinoma' to describe malignant tumors comprising both somatic tissues and undifferentiated malignant stem cells, identifiable as EC cells. EC cells are malignant equivalents of ES cells. Human EC cells should be identifiable microscopically according to the pathologic and immunohistochemical criteria used to identify human EC cells in malignant germ cell tumors of the ovary or testis or extragonadal sites. In an experimental setting, the malignancy of a tumor due to the presence of morphologically identifiable undifferentiated EC cells may be defined by their ability to form a new tumor after transplantation to a new host.6 [- f' J( i' S7 j0 Z
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We will apply the term 'teratoma' only to tumors composed of normal, 'benign' somatic tissue and their immature (fetal) precursors derived from more than one of the three embryonic germ layers (ectoderm, mesoderm and endoderm). Teratomas comprising nonproliferating somatic tissue may be further labeled as 'benign', 'mature' or 'fully differentiated'. Teratomas composed of immature, proliferating fetal-like tissues may be labeled 'immature'.$ t3 L0 D, g8 C! A) M4 n6 ?

: |0 W" F: L$ D$ S) q" `It should be noted that almost all tumors produced in immunosuppressed mice from xenografted human ES cells have proven to be teratomas. Some data suggest that teratocarcinomas may occasionally be produced from human ES cells upon xenografting, but these tumors have not been fully documented.
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以上拙见欢迎指正。

marrowstem

      有感而发，问个问题：把一个正常的干细胞或一群还具分化潜能的细胞放进一个恶性质的niche中，会有癌肿发生吗？
* I# b& {9 h$ b! M      或者把恶性的具有成瘤能力的肿瘤启始细胞放进一个正常的干细胞巢中，结果会与以上的问题答案是一样的吗？

knowtumor

回复 marrowstem 的帖子& q( P: x3 [* ^) F* o+ O: J
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说的就是这个。干细胞在坏环境中变坏，在好环境中变好。“癌之初，性本善”---环境使之恶化也。就是老狼的那句话 ”a good cell in bad niche“。: m/ X3 s0 c+ N  h  x1 Z* H

# s4 a! }% K5 L' @- h. B# }* L中国人不排队，不是中国人的基因突变了，到了美国照样排队。老外来了中国也不排队。当年晏子使楚讲的故事”淮南为橘，淮北为枳“， 一样的道理。但这样说白了，就没有牛人了。

knowtumor

回复 pujixing 的帖子
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不要拘泥于这些文献。大鼻子的个人观点而已。
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- p, c/ O! b' n- M' @如果说一定致死的肿瘤，那只有胰腺癌了，近乎100%。 乳腺癌的病死率在30%左右。即便远隔部位转移了，也不一定死。见过骨转移18年后仍然很健康的乳腺癌患者。Neuroblastoma 晚期多器官转移，可以戏剧性的自愈。甲状腺癌常见颈部淋巴结转移，但并不影响生存。* g% n# t+ E* x) I1 C% `. P& `) i9 |

  x' a: l- m3 U/ I- ~良与恶之间，没有截然的分界。你如果从非整倍体的角度定义”恶性“， 我告诉你，培养的小鼠胚胎成纤维细胞大部分细胞都是非整倍体。我自己做过，乱地一塌糊涂。

knowtumor

回复 pujixing 的帖子: u5 v& D, Q7 q2 V! c* s, S
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见老狼的帖子。
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5 h/ k' o( }1 D/ p9 f癌细胞的发生可能是一种“返祖”现象？ http://www.stemcell8.cn/thread-32073-1-1.html1 k9 S*  % Z2 r( {) {* Y4 w0 x
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wl23wl

要知道量变才产生质变，你处在不同阶段看肯定有你当时的想法。

neohunter

楼主之所以有这样的感觉，我觉得跟国内的科研现状是分不开的。+ {, W; a3 I' H

# ~" R; r- `/ l5 c5 H- u0 Y恕我直言，尽管跟帖充满了中国人的人情世故和叫好，但我感觉你说的这些话是很粗浅的。很多刚做科研的人当初都会跟你一样有各种迷惘，抱怨，甚至觉得自己的理论假说比其他人的都要合理全面，事实是当你静下心来慢慢的阅读文献，然后根据文献之间的关联再去阅读更多文献的时候，你会发现你所迷惑纠结的问题，你提出的自以为很新的理念，国外早就有学者在做，而且做得很深刻，甚至已经有肯定的证据来证明你的想法是对的还是错的。这时候你会有严重的挫败感，但同时也明白了无知者无畏这个残酷的道理。
/ e" a4 `( `0 d/ X+ v造成这种结果的原因自然不能怪你，这似乎也在为我自己开脱。事实上国内的科研，基本是跟风，模仿。相当一部分科研工作都是研究生完成的，做了两年出不了结果急了，为了毕业各种数据都出来了。而研究生阶段很多学校都没有系统的培养规范和计划，临床型研究生做肿瘤基础研究这一点尤为明显，临床研究生大部分的导师只会看病做手术，都不明白学生在做什么更谈何从理论的高度指导学生？这时候研究生就只有靠实验室的师兄师姐漏点实验技巧给自己了。情商高的，碰到好师兄师姐的能多学点，情商低的就基本只能一知半解了。硕士三年你最多只能掌握些基本的实验技能，如果你能够针对实验中的一些状况分析下就已经很了不起了。博士三年你可能可以开始在没有师兄师姐的帮助自己一个人独立的慢慢上路了，可以根据已有的计划去做一些课题，但具有独立思考能力的博士是极少的。在博士毕业后两年，随着你实验知识的积累，更重要的是你文献阅读量的增大，最最重要的是你发现你做的课题跟别人相比没有创新性的时候，发现你的一些IDEA总是有人已经付诸实践的时候，你会对科研产生敬畏、绝望的心情。恰恰这时候你开始真正步入了科学研究的大门。记住，这仅仅是入门，你仍然需要仰望那些坐在庙堂之上的前辈，聆听他们的见解。他们的见解似乎并不晦涩难懂，甚至很简单，几句话就说完了，但这几句话的背后，需要付出的太多了。
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相比佛教、道教等虚无缥缈的社会科学而言，自然科学毫无疑问是人类史上一颗璀璨的明珠，它推动着人类文明的发展，揭示生命生生不息的秘密，曾有人劝我信佛，说一切都是因果，看透就好，没有信佛我将来会后悔，需要找个大师普度下我让我不受轮回之苦。我笑笑说，我更信仰我所投身的科研事业，即使真需要轮回，这跟我所热爱的事业相比又算得了什么。$ |8 q7 D# H  j; r+ ^' v

+ r1 [' s  V, C& k" K与楼上诸君共勉。$ Q5 `  }' C$ j6 M* e1 g
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哈252769344

想法大胆，各抒己见，大家观点不一样