z********i
发帖数: 610 | 1 kang yibin,massague实验室出来的 |
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l******u
发帖数: 936 | 2 Kang is just a xiaoniu, louzhu is asking daniu. |
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h******y
发帖数: 1374 | 5 Sha gave a talk in Dept. of Cancer Biology about miRNA and metastasis |
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h********n
发帖数: 4079 | 6 我做的这个基因是tumor suppressor and/or metastasis suppressor, 这个才是我做
的方向, 有好多老鼠的活要做.
embryonic lethal这种事有点难, 主要是我没啥development的经验. 先干着吧. 我本
来跟老板说我不想lead这个project, 现在估计只有我能lead, 除非老板再招一个人干
活, 我就可以把这个脱手了.
上个月刚刚写了一个新的关于cancer的animal protocol(实验室以前没有独立的animal
protocol), 还好以前phd的时候写过不少类似的. 现在又写一个development的
protocol, 这两个月都在写东西. 老板坚决不肯在animal protocol上出现他老人家的
名字, 所以这两个animal protocol的PI是我, 有啥事都是我的责任啊.... |
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w*******2
发帖数: 2199 | 7 It's not a fair word.
there is NO solid evidence that she manipulated her cell paper.
But her nature paper about the role of a miRNA in cancer metastasis
may be an artifact that does not happen in cancer patients. |
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l*h
发帖数: 4124 | 8 There is no clinically available migration/metastasis inhibitor.
There are quite some research efforts trying to figure out what causes
cancer cells to metastasize. No real answer has been found yet (A lot of
molecules are involved.) For research, as the last time I did a literature
survey, there is no cancer cell (even for a specific cancer type) specific
migration inhibitor.
metatasis, |
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y**s
发帖数: 6809 | 9 弱弱的问一下，发育完成之后，成体的哪些细胞需要migrate啊？
There is no clinically available migration/metastasis inhibitor.
There are quite some research efforts trying to figure out what causes
cancer cells to metastasize. No real answer has been found yet (A lot of
molecules are involved.) For research, as the last time I did a literature
survey, there is no cancer cell (even for a specific cancer type) specific
migration inhibitor.
metatasis, |
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r****r
发帖数: 379 | 10 我觉得更有可能的是两类途径：
1，依据一些metastasis中出现的突变蛋白的那些突变位点设计specific rani therapy
2，发展delivery tools，用专一性的载体比如单抗结合迁移肿瘤的一些特异表面受体
去delivery the drug
对于tumor therapy而言，想着纯粹从化学角度开发专一性药物，可能不是个很有效的
方法。
for |
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r****r
发帖数: 379 | 11 metastasis也分阶段的，所以这些抑制剂还是有用的。
但他讲的是一个悖论的问题，我倒觉得从另外一个角度来说，是非常对的，没有发现转
移的时候，你不能无的放矢去用药，包括剂量，给药方式都无法确定一个最佳效果，你
虽然可以依据以往的经验预判可能出现的转移类型而且用药，但可能还是抵不过癌细胞
的突变筛选，最后逃过你这个抑制剂的作用。
我觉得更多的作用还是在：1），怎么更好的预判，以及迅速在早期发现癌转移；2），
怎么更有效杀死发生癌转移的细胞；3），怎么抑制癌转移（更现实的可能不是抑制起
始，而是中间阶段）。
其实所有的癌相关的东西，检测远比治疗更重要，而靶向性治疗远比所谓的专一性治疗
更重要。 |
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s******y
发帖数: 28562 | 12 Most immortalized cell line indeed has some cancer cell properties.
However, depending on what cancer stage you are testing, some immortalized
cell line can be used as normal control as well.
For example, Human Foreskin Fibroblast (HFF) would be a good control for
metastasis.
I suggest you to try HFF first because it is easy to culture and easy to buy
or borrow from other labs.If the results looks promising, then you should
contact several companies to order the primary normal human cells. |
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m****r
发帖数: 383 | 13 是不是只有通过打tail vein,才能看到metastasis? 俺打了两次subcutaneous,primary
tumor两周内长得硕大，可是没有mets. 郁闷。：（ |
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s******y
发帖数: 28562 | 14 呵呵，不同的细胞系的metastasis 的速度不同 |
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h********n
发帖数: 4079 | 15 周五跟老板聊天的时候我说, 我觉得Weinberg有些文章的有些实验我不太相信(我指的
是有些metastasis exp data), 结果老板说, 你说的是2007年那篇miR-10b的文章吗?
我说不是, 我说的不是miRNA的文章.
那篇miRNA的文章我看过, 因为我以前一直做miRNA, 但我们老板也看, 不太合理; 也可
能他听到什么流言.
感慨一下. |
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s******r
发帖数: 2876 | 16 那篇不是直接被人在nature上质疑了，
而且Weinberg的回答也不是很有力。
周五跟老板聊天的时候我说, 我觉得Weinberg有些文章的有些实验我不太相信(我指的
是有些metastasis exp data), 结果老板说, 你说的是2007年那篇miR-10b的文章吗?
我说不是, 我说的不是miRNA的文章.
那篇miRNA的文章我看过, 因为我以前一直做miRNA, 但我们老板也看, 不太合理; 也可
能他听到什么流言.
感慨一下. |
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s******l
发帖数: 125 | 17 这篇Nature Communications paper也太猛了，把一个领域十年的工作给否定了？
Identification of high-quality cancer prognostic markers and metastasis
network modules
http://www.nature.com/ncomms/journal/v1/n4/pdf/ncomms1033.pdf
"In summary, we showed that the concept of 'one-step-clustering' of gene
expression profiles, which has been dominantly used in the past decade, is
not suitable for generating robust gene signatures. Therefore, we developed
an algorithm for identifying prognostic markers that can be used in
combinat |
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w******y
发帖数: 8040 | 19 Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary
tumor model.
貌似合作者进一步证实了它的结果？ |
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d*****r
发帖数: 2583 | 20 ☆─────────────────────────────────────☆
wsbioguy (postdog) 于 (Thu Sep 9 22:47:26 2010, 美东) 提到:
Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary
tumor model.
貌似合作者进一步证实了它的结果？
☆─────────────────────────────────────☆
oboi (心率50 非运动员) 于 (Thu Sep 9 22:48:29 2010, 美东) 提到:
牛人
☆─────────────────────────────────────☆
wop168 (wop168) 于 (Fri Sep 10 06:26:46 2010, 美东) 提到:
她怎么还不去找工作啊，一直做博后？
☆─────────────────────────────────────☆
amedio (Boasting Father) 于 (Fri Se |
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b*****e
发帖数: 288 | 21 随便去pubmed搜了下：
A large intergenic noncoding RNA induced by p53 mediates global gene
repression in the p53 response.
Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D,
Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T,
Rinn JL.
Cell. 2010 Aug 6;142(3):409-19.
Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer
metastasis.
Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T,
Argani P, Rinn JL, Wang Y, Brzoska P, ... 阅读全帖 |
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a*****g
发帖数: 543 | 22 Jumping to a deep water hole...
I would caution the widely "credited" potential of CSC(technically here refe
ring to the tumor-inititating cells identified in immune-deficient mice) ass
ociated with relapse, drug resistance and metastasis.
Can anyone point out an original research paper with some experimental data
showing these cells have any of the three major capabilities? My impression
is sadly none...But we read it everywhere...
Second, CSCs are defined vaguely. The standards mentioned by ht... 阅读全帖 |
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Z**********g
发帖数: 222 | 23 感觉很promising,可以解决不少争议问题:
1.CSC or clonal evolution:我觉得cancer genomics数据还是比较支持clonal
evolution模型的.从现有的ancer genomics数据来看,任何一个肿瘤里面可能存在成千
上万的突变,而且各个突变(包括点突变,拷贝数,重排等)的发生率迥异,表明随机突变和
克隆进化必然存在.这种genetic heterogeneity不太容易由CSC模型解释.毕竟CSC模型
从本质上来说更强调epigenetics.另外,把一个肿瘤里的CSC和nonCSC拿出来测序对比,
我觉得突变图谱肯定也不一样(虽然目前我还没有看到这方面的证据)
肿瘤本质上是基因病,根源是基因组不稳定性,所以我支持clonal evolution.
2.The relationship between primary and metastasis:对于转移,一个关键的问题是
早期还是晚期事件.如果转移发生在早期,原发瘤和转移瘤应该是平行进化,那么各自的
突变图谱应该比较divergent,而发生在晚期的话,应该convergence... 阅读全帖 |
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a*****g
发帖数: 543 | 24 Just my two cents:
1. 我不反对也不支持CSC的model.但是光从mutation的普遍性来说并不能否定CSC. 我
们现在还没法确定这些genetic heterogeneity是driver 还是passager.大多数只是ca
ncer的result而不是cause。Moreover, it is possible that CSC and Non-CSCs all
have genetic changes;remember the so-called CSCs don't have to follow the
biology of typical stem cells.
If cancer strictly follows evolution model, should one imagine certain gene
tic lesions gain dominance?
As for the genomic stability, why should we believe it is promoting tumor?
As far as I know,... 阅读全帖 |
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b*****l
发帖数: 9499 | 25 临床意义就是 metastasis 啊。
but |
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o********r
发帖数: 775 | 26 先说你后面的：
：consistency
不试验证明找到的新的发现是真的，而且有biological significance以前，啥都不算
，俺永远predict RB1和RB有关，这个基本上永远没错，而且永远consistent。
：sensitivity/selectivity
By simulation?没用，每个人都可以找到一个model说明自己的方法是世界上最牛的（
别人也可以设计另一个model证明你的东西完全错了）。用俺前老板的话，simulation
只能证明你的方法没用，不能证明有用。
：BIOLOGICAL RELEVANCE.
如果你是通过翻文献或者GO code/IPR之类的，算了，太主观了。比如找到一个set和
Ubiquitin有关，估计啥phenotype都能往上套。想要证明这个东西是对的，唯一的方法
是做试验，比如说你predict某些gene overexpression会引起 metastasis，那就去动
物体内去验证，至少也要在cell line里证实。当然，现在绝大多数bioinfo的文章都是
主观说biologically relevant... 阅读全帖 |
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s*******g
发帖数: 3332 | 28 你误解了，我是想知道用什么样的high throughput model，不是用什么库
siRNA, small molecules library都已经有了 |
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s*******g
发帖数: 3332 | 29 谢谢，我去研究下
ta
的
的要
R
c
65 |
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n***3
发帖数: 663 | 30 Cancer Cell. 2011 Jan 18;19(1):125-37.
Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch
Signaling.
Sonoshita M, Aoki M, Fuwa H, Aoki K, Hosogi H, Sakai Y, Hashida H,
Takabayashi A, Sasaki M, Robine S, Itoh K, Yoshioka K, Kakizaki F,
Kitamura T, Oshima M, Taketo MM.
Please send the paper to e*********[email protected]
Thanks~ |
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h********n
发帖数: 4079 | 31 你是说杂交下来一窝老鼠没有任何两只一样吗? 这个我可以理解.
但是, 比如说, FVB X B6, 我们通常说得到的老鼠50%FVB;50%B6, 类似的情况下, 那么
有没有可能通过查很多gene/microsatelite/SNP看看一个大概的情况, 比如FVB为主还
是B6为主. 我的老鼠的phenotype(metastasis)的程度跟background相关的, 所以我很
关心这个.
谢谢. |
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a****d
发帖数: 1919 | 32 鸥鸟兄能否解释一下EMT领域的状况，我最近读了一些相关的工作，还是觉得一头雾水
。EMT是否只是在tumor metastasis中的现象，还是更加普遍的一种细胞组织水平
behavior的变化？比如发育阶段的某些细胞类群从epithelial type cell
differentiate到multi-polar type cell，是否也属于EMT的一种？另外理想的real in
vivo model应该是什么样呢？ |
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S*********s
发帖数: 304 | 33 Dear Colleagues:
In collaboration with Children’s Medical Center, I’m delighted to announce
the recruitment of Dr. Sean Morrison, an internationally recognized leader
in adult stem cell research, to lead new pediatric research initiatives. In
addition to pursuing his own important research, he also will direct efforts
to attract the highest caliber of scientists and clinicians interested in
further strengthening the groundbreaking pediatric research already taking
place at UT Southwestern and Ch... 阅读全帖 |
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k******2
发帖数: 81 | 34 A role for cancer stem cells in drug resistance and metastasis in non-small-
cell lung cancer
Clin Transl Oncol. 2011 May;13(5):289-93.
Thanks a lot.
k********[email protected] |
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h********n
发帖数: 4079 | 36 做个几年miRNA的工作, 现在不做, 说说我的看法吧.
你的第一个问题,"是否可以从biology的角度去推测一个基因的表达是否受microRNA调
控", 我觉得这个问题一一不大. 多数基因都会或多或少的受到miRNA的调控, 但是这
一个调控不是universal的, 而是tissue specific, 或者说跟某个生理/病理过程相关.
比如某个基因在肺上皮细胞受miR-X调节, 而在大肠上皮里主要受miR-Y调节.
另一个问题是尺度的问题. 对某个基因来说, 如果确定在某种细胞里受miR-X调节, 这
个量有多大, 是微调还是大尺度调节. 这个问题可能是现在miRNA领域很多人都认识到
却不愿意面对的.
你的第二个问题, 用那些网上软件去预测, 比如TargetScan, 可以得到一大堆
candidate. 同时再看看这些miRNA在这个组织或者疾病的profile, 挑出一些candidate
做functional assay. 不要被别人的发现所限制.
比如当时我们投文章(miR-xxx is an oncomiR in lung cancer)的时候发现一... 阅读全帖 |
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s*********t
发帖数: 600 | 37 metastasis? 许田不是在做么
还有卵巢癌？ |
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h********n
发帖数: 4079 | 38 没人做metastasis mouse model吗? |
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h********n
发帖数: 4079 | 39 I agree. heterozygous mutant p53 can help to develop tumor and metastasis
when combined with an oncogene.
since
enough |
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h********n
发帖数: 4079 | 40 我的目的是想做一个新的GEMM metastasis model. 从cancer model的角度来说, 越接
近human cancer的老鼠就越好. |
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q*****n
发帖数: 331 | 41 Why not try female mice?
MDA-MB-231 is not a very aggressive model for breast cancer. Joan Massague'
group have developed some derivative cell lines, such as LM2, which grows
faster and metastasize better. here is the reference:
Nature. 2005 Jul 28;436(7050):518-24.
Genes that mediate breast cancer metastasis to lung.
Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB,
Gerald WL, Massagué J.
You can write and request LM2 cells and they will give for free. |
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y****6
发帖数: 196 | 42 Thanks a lot for the information. However I already made a stable cell line
from the original MDA-MB-231, which means I cannot use the derivatives. I
will try female mice, and inject more cells (as suggested by "ArtyArty").
MDA-MB-231 is not a very aggressive model for breast cancer. Joan Massague'
group have developed some derivative cell lines, such as LM2, which grows
faster and metastasize better. here is the reference:
Nature. 2005 Jul 28;436(7050):518-24.
Genes that mediate breast cancer m... 阅读全帖 |
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h*****x
发帖数: 147 | 43 Qun Li,Chaoyu Chen,Amit Kapadia,Qiong Zhou,Mary Kay Harper,Jerome Schaack,
Daniel V. Labarbera
3D Models of Epithelial-Mesenchymal Transition in Breast Cancer Metastasis:
High-Throughput Screening Assay Development, Validation, and Pilot Screen
J Biomol Screen 2011 16: 141-154
http://jbx.sagepub.com/content/16/2/141.full.pdf+html
email: h************[email protected]
Thanks so much! |
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s******y
发帖数: 28562 | 44 对了，有一个好奇的问题问一下做血癌的同学啊，
固体瘤里面如果metastasis 了就很容易到处播种新colonies,
这个血癌能变成colonies 么？比方说能不能转移到别的器官上长出一个由
血癌细胞发展来的固体瘤？ |
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s******y
发帖数: 28562 | 46 哎，大家能不能不要吵中医了？
先来解决生物学的问题吧：） |
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O******e
发帖数: 4845 | 47 直接证明很难吧，不过间接证据肯定有，象hypoxia inducible factor 1，干掉它好像
肿瘤生长或者癌细胞生长都变慢或者停止了。 |
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j**e
发帖数: 582 | 48 The problem is, even there are massive blood vessels in tumor, cancer cells
are still in hypoxic condition. |
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p********t
发帖数: 411 | 50 这可能部分的解释了为什么VEGF单抗在临床效果不好。我猜的。不是前一段时间还有人
讨论清华某PI么？
另外，HIF确实是一个很好很强大的转录因子。 |
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