s******l
发帖数: 125 | 1 Checked the publications of Joe Gray, I can't find any papers for cancer
systems biology. He may just start to do cancer systems biology now and have
not published yet for the topic? |
|
j**a
发帖数: 165 | 2 我的背景是physics，做的是一些medical imaging方面的东西，因为所做项目和以后职
业的需要，我考虑修一门introduction to cancer biology的课，但我从大学开始就没
有学过生物了，这是那门课的lectures:
Histopathology of Cancer
Principles of Cell Transformation
Mouse Models of Carcinogenesis
Angiogenesis
Mechanisms of Carcinogenesis
Oncogenes
Tumor Suppressors
Cell Cycle Control
Genomic Integrity |
|
r***e
发帖数: 2539 | 3 Yes, that's why I raised the question at the beginning. It seems that most o
f the cancer cell line can initiate tumor, but is there a sub-population in
these cell lines that acts like CSC?
As for what is important, in clinical? It's hard to tell. Say, cell origin o
f cancer is hot in basic field, but does this question help curing the cance
r in clinical? |
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j***z
发帖数: 105 | 4 Good point.
My guess is that within a tumor or even cell line, there is always a
population of cells with better tumorigenesis potential / drug resistance.
Even if you get rid of those cells, other cells will replace.
Since cell lines are supposed to be genetically identical, epigenetics might
play a role here. It would be very interesting to identify the factors
involved in generating such population of cells.
And in terms of curing cancer, personally speaking I think too much focus
has been pl... 阅读全帖 |
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a*****g
发帖数: 543 | 5 It is interesting you mentioned the genetically similarity within cell line
s. Most of these studies would have been done using millions (if not billio
ns )of cells. The bias of sequencing or SNP would lead to identify the most
obvious low hanging fruit, such as KRAS, pten, p53 etc.
Apparently when single-cell level sequencing becomes widely available, iden
tifying subpopulations with genetic or epigenetic characteristics will be i
n a much better position.
http://www.genomeweb.com/sequencing/si... 阅读全帖 |
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Z**********g
发帖数: 222 | 6 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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s**********e
发帖数: 2888 | 7 我博士导师需要马上招一个博后，非常非常nice的一个美国人。广告全文在下面，有兴
趣的可以直接联系他，位置是在UW-Madison，谢谢。
这个工作是部分延续我们实验室以前做的一部分化学的工作，这个位置是AICR的
funding资助做后面的机理工作，所以相关的文章很多还没有发表出来。有兴趣的可以
直接联系他，或者想知道实验室情况的也可以问我，谢谢。
我已经毕业了，我的博士老板是我这么多年遇到的最nice和对我事业帮助最大的人，所
以帮他把广告贴在这里。
Department of Food Science Research Associate opportunity
Post-doctoral Research Associate. Project involves evaluation of
biological activities related to anti-cancer effects of naturally occurring
organosulfur components, including metabolic fate and cell signaling ... 阅读全帖 |
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n*********b
发帖数: 140 | 8 You made a good point. Age-related cancer seems to result from human living
condition.
However, the cancer with evolution potential is expected to occur before the
reproduction age. A long latency may not be desirable from God's point of
view because it misses the critical reproductive activity of the evolving
population.
|
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n*********b
发帖数: 140 | 9 Another good point here. Environmental carcinogenesis has significant
contributions to the age-related cancer. Changes in life style affect the
level of estrogen that has a direct implication in breast cancers.
BRAC1/2 are an example of evolving heritable changes for milk production.
When seeded in the population, BRAC1/2 or like mutations may be useful in
the event of either a failure in learning how to use animal milk as a safe
substitute or a need for the breeder/feeder when natural subst... 阅读全帖 |
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e*****t
发帖数: 642 | 10 我要的是whole cancer genome seq. 现在可以看到的好像只是snp （我不确定，在网
站上找不到）
在哪可以下你说的 cancer genome seq。我找不到。 |
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S*****s
发帖数: 242 | 11 Just look "Yale Cancer Center" and you will find those big sharks, a lot of
them are program directors
A example, Jose Schlessinger, designing small molecule compound to treat
cancer. Sutan, PLX4302? are all designed by his lab |
|
m*******r
发帖数: 7495 | 12 天上天下唯我至儒
不高不胖，身型fit，小撇胡子平添几分英俊中的正统。在lipid research及相关通路
在cancer中的机理研究方面，乃泰山北斗。语音不高，语速不慢，报告的严谨深刻度乃诸
牛之最。
猜猜这是哪位两院院士？
误入科学界的明日政坛之星
横看成Jay Leno，侧观似George Clooney. 以political campaign之气场驾驭报
告，侃侃而谈，声如洪钟。手起掌落挥臂迈步，无不尽煽动造势之能事。坐下华丽丽500多
听众，恨不得抓住类似“Yes, we can!”的slogan随之遥头晃尾，为science癫狂。
这位院士，是哪个著名cancer center的头？
翩翩单骑来者谁
这位是，风流倜傥，欧洲不落帝国贵族。举手投足，怎一个洒脱了得。90年代cell cycle
领域叱咤风云，无人能望其项背。如此风度翩翩，可曾想当年无缘诺奖也有几乎吐血而疯的
过去？
猜一下，贵族贵庚几何？
太极宗师
令老鼠闻风散胆的高人，生于中土，长于HK，扬名立腕于北美。吐词悠然，东方文化艺
术元素信手拈来，穿针引线于science之间。和两位院士联手，为某生物公司的M... 阅读全帖 |
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t**u
发帖数: 7 | 13 帮朋友贴一个---
Postdoctoral position for Microcell Mediated Chromosome Transfer in Sloan
Kettering Institution, New York, NY.Department of Cancer Biology and
Genetics Center for Cell Engineering Sloan Kettering Institute, New York
Affiliated with Weill Medical College of Cornell University
Looking for individual who has a prior research experience on microcell
mediated chromosome transfer (MMCT).
The positions will focus on mechanistic approaches to understand 1)
reprogramming of somatic cells to plu... 阅读全帖 |
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y****6
发帖数: 196 | 14 最近在读The Biology of Cancer (Robert A. Weinberg)，觉得真不错。内容翔实，通
俗易懂。推荐给做cancer的同学。 |
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y****6
发帖数: 196 | 15 Apple and peach comparison. The book is more on basic concepts of cancer.
The review article is about recent advances.
没看过，和他今年更新的HALLMARK OF CANCER比怎么样？ |
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e*******c
发帖数: 1479 | 16 投了一片文章到cancer research，被拒，做的蛋白太老了，多数的发现都是报道过的
，但做了几年又不想搞太低没用。各位同仁有无推荐的杂志？
internationall journal of cancer？这个如何？难否？ |
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S******l
发帖数: 14311 | 17 clinical cancer research,
Cancer
Oncogene |
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h*****t
发帖数: 103 | 18 为什么非要是突变呢？
CSC也是属于Cancer的吧？或者是良性的？一旦生长上面出现无法控制的情况，就变成
恶的了？另外，良性的肿瘤有没有tumor stem cell，原来遇见过子宫肌瘤，西瓜那样
大，里面是否也存在tumor stem cell呢？
CSC现在争论是否已经达成一致了？还是Cancer Initiating Cell?
不过从Leukemia来看，CSC应该是存在的，尽管不如HSC具有那样明确的hierarcy；对于
实体肿瘤，很多认为CSC也是存在的，尤其是今年Cell上发表Barret食管癌相关的那
篇paper也提示存在这么一个状态；而从lymphoma的研究来看，CSC好像还没有明确的找到，一方面可能因为lymphoma本身分类比较复杂，HL里面有人认为其中的小细胞可能是CSC，但也有人认为
患者体内CD20+的细胞为HL的CSC；而对于NHL，可能发展到leukemia的时候，会有CSC，
若只停留在lymphoma的状态，好像也还没有CSC的报道。其他器官如breast、prostate
、liver、brain等似乎都有很多CSC的报道。
但是有人质疑C... 阅读全帖 |
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s******s
发帖数: 13035 | 19 你是说cancer里面的CSC还是正常体内的CSC?
说起正常体内，上次听了Mina Bissel的seminar, 她基本就是类似的观点。她的理论是
phenotype control, 体内无数genotype是cancer的细胞由于环境等种种原因没法发作 |
|
e**o
发帖数: 345 | 20 谢谢各位。
还是想先在细胞里再测试一下。 准备多找几个cancer cell lines 试再检测一下。 问
题是正常的对照不好找。 比如hela 到哪里找control呢？
同时准备找个做cancer的MD 要几个samples。 |
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c****g
发帖数: 93 | 21 大家来讨论下cancer和cholesterol有没有直接或者间接的关联。我的观点是既然
cholesterol是cell membrane的重要成分，细胞要增值必然会保证足够的cholesterol
，所以抑制胆固醇或者许是potential treatment for some cancers. |
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o**i
发帖数: 1165 | 22 大家来讨论下cancer和H2O有没有直接或者间接的关联。我的观点是既然
H2O是cell的重要成分，细胞要增值必然会保证足够的H2O
，所以抑制H2O或者许是potential treatment for some cancers.
所以咱们就过上甘岭的日子吧 |
|
g*********3
发帖数: 177 | 23 呵呵 有意思的对话。
其实这本来应该是个有意思的帖子，可能LZ没有表达他自己的意思吧。
最近看到了两篇关于cholesterol和cancer的关系，其中一篇是UCLA的，另一篇好像是
关于glioma的.
并且关于cancer的一些cholesterol inhibitor临床测试很早很早以前就有了，据说效
果还不错，但是那基本上称不上临床测试，只是系里某位很老很老的教授告诉我他们以
前做过类似的研究，但是最后因为经费中断没有继续下去。不知道现在有关于
cholesterol inhibitor治疗癌症的例子没有。
LS说的其实虽然...但是好像也是对的 哈哈
以前说是glucose对癌症关键，后来发现fatty acid对癌细胞也重要(Tak去年就有一篇
genes and development,并且据说那篇文章的结果很早就有了)，现在又有了
cholesterol，不禁让我感到很失望，到最后我们不会发现真他妈连水也是关键的吧。
不过对于cholesterol，不只是作为component，有些蛋白比如ras的farnesylation也很
重要，并且我猜测（瞎猜的啊）chole... 阅读全帖 |
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i*e
发帖数: 352 | 24 biomark追求少比多好
J Natl Cancer Inst. 2012 Jan 18. [Epub ahead of print]
A Three-Gene Model to Robustly Identify Breast Cancer Molecular Subtypes.
Haibe-Kains B, Desmedt C, Loi S, Culhane AC, Bontempi G, Quackenbush J,
Sotiriou C.
PMID: 22262870 |
|
l**********1
发帖数: 5204 | 25 Oui
please refer Network-based genome-wide association studies (NWAS)
for identifying prognostic gene signatures to predict cancer recurrence.
report on
//www.cse.buffalo.edu/ACM-BCB2010/
by
Ying-Wooi Wan, Swetha Bose, James Denvir, and Nancy Lan Guo
Title:
A Novel Network Model for Molecular Prognosis
Abstracts:
Network-based genome-wide association studies (NWAS) utilize the molecular interactions between genes
and functional pathways in biomarker identification. This study presents a novel ne... 阅读全帖 |
|
s******l
发帖数: 125 | 26 This paper is nothing new except complaining, I rememberer to read a paper (
2010), they already reported that randomly genes have predictive power, but
often not roust. Then they focused on cancer hallmark genes (mechanism-based
?) and get very good results which are better than all others.
yes, I find it:
Nat Commun. 2010 Jul 13;1:34. doi: 10.1038/ncomms1033.
Identification of high-quality cancer prognostic markers and metastasis
network modules. |
|
V***b
发帖数: 3419 | 27 我现在不明白大规模测序之后，拿到一堆数据，和什么去比对？怎样定义“正常组织”
？比如说Steve Jobs的测序结果怎样？如果发现EGFR/PI3K/Ras这些常见突变倒好说（
其实即便这样也很难下定论），最怕就是发现很多突变，却无法将5%，甚至更少的
cancerous mutation，以及各种cancerous mutation组合，从95%的harmless mutation
中分离出来。把Jobs的胰腺癌细胞和他身上正常组织的序列比较，或者跟另一个“健康
人”的序列比较，肯定有非常多的不一样。
mutation. |
|
i*e
发帖数: 352 | 28 biomark追求少比多好
J Natl Cancer Inst. 2012 Jan 18. [Epub ahead of print]
A Three-Gene Model to Robustly Identify Breast Cancer Molecular Subtypes.
Haibe-Kains B, Desmedt C, Loi S, Culhane AC, Bontempi G, Quackenbush J,
Sotiriou C.
PMID: 22262870 |
|
l**********1
发帖数: 5204 | 29 Oui
please refer Network-based genome-wide association studies (NWAS)
for identifying prognostic gene signatures to predict cancer recurrence.
report on
//www.cse.buffalo.edu/ACM-BCB2010/
by
Ying-Wooi Wan, Swetha Bose, James Denvir, and Nancy Lan Guo
Title:
A Novel Network Model for Molecular Prognosis
Abstracts:
Network-based genome-wide association studies (NWAS) utilize the molecular interactions between genes
and functional pathways in biomarker identification. This study presents a novel ne... 阅读全帖 |
|
s******l
发帖数: 125 | 30 This paper is nothing new except complaining, I rememberer to read a paper (
2010), they already reported that randomly genes have predictive power, but
often not roust. Then they focused on cancer hallmark genes (mechanism-based
?) and get very good results which are better than all others.
yes, I find it:
Nat Commun. 2010 Jul 13;1:34. doi: 10.1038/ncomms1033.
Identification of high-quality cancer prognostic markers and metastasis
network modules. |
|
V***b
发帖数: 3419 | 31 我现在不明白大规模测序之后，拿到一堆数据，和什么去比对？怎样定义“正常组织”
？比如说Steve Jobs的测序结果怎样？如果发现EGFR/PI3K/Ras这些常见突变倒好说（
其实即便这样也很难下定论），最怕就是发现很多突变，却无法将5%，甚至更少的
cancerous mutation，以及各种cancerous mutation组合，从95%的harmless mutation
中分离出来。把Jobs的胰腺癌细胞和他身上正常组织的序列比较，或者跟另一个“健康
人”的序列比较，肯定有非常多的不一样。
mutation. |
|
i*e
发帖数: 352 | 32 也不能说“混在一起讨论就是不正确的”
毕竟subtype本身就乱七八糟
不作临床的完全可以说本来就只是打算address breast cancer这个大笼统的东西
只能说不分开分析ER status，尤其是这么established的参数
不够细致
说是有可能被Nature，Nature Genetics，PNAS等据稿
不提几大top的临床杂志
估计也有先见之明
就像你说的，压根没一丁点希望发在好的临床杂志上面
最终没到plos one就不错了
cancer.
没人报名我就单挑了，今天晚上就开工。要一起灌水的 |
|
p***a
发帖数: 5 | 33 I will be appointed as an Assistant Professor at Yale University School of
Medicine to establish a brain nanomedicine laboratory. My research focuses
on (1) nanotechnology based drug delivery to neurological disorders, and (2)
brain cancer stem cell biology and drug identification. Candidates with a
recent PhD in cancer biology, gene therapy, polymer synthesis, drug delivery
, blood-brain barrier, nanomedicine, stem cell biology, neuroscience or a
related field are encouraged to apply. Intereste... 阅读全帖 |
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g***s
发帖数: 60 | 34 可能要搬到Columbus去了，想找个千老的位置，
钻研了半天comprehensive cancer center的homepage，
PI们的名录不太方便发掘，有没有熟悉OSU的同学指点一下，
做cancer研究的老板们都集中在哪儿？有没有比较和蔼的老板
可以推荐。临床科系的老板们做researc的多吗，他们也跟做
基础的老板们在同一个program吗？ |
|
t********e
发帖数: 107 | 35 我们是专门做cancer research 的。 感觉有很多 Crap and Rubbish. 不过都不是特别
牛的组。厉害的组，比如 princeton, harvard medic, pennsylvania, or UT
southeast, 都有很好的数据。总的来说，Cancer Research 竞争太激烈，好拿钱。 |
|
h********n
发帖数: 4079 | 36 我只是预测, 不能当真. 我觉得它未来应该在cancer research之上.
如果你老板是cancer discovery的editor, 那不要犹豫, 赶紧投
助？ |
|
m*******m
发帖数: 127 | 37 谢谢。还有其他信息吗？到底算学校还是公司？
试图google，找不出什么信息。
我猜setup是不是和Belfer Institute for Applied Cancer Science类似？
有人了解Belfer Institute for Applied Cancer Science吗？ |
|
h****u
发帖数: 480 | 38
WOW! Ronald DePinho was pumping his company in CNBC interview! This
article also sheds light of Nobel prize laureate Alfred Gilman's resignation
due to the concerns over a speedy, US$18-million award to Lynda Chin's
Applied Cancer Science Institute.
There will probably be class action lawsuits against DePinho and his company
, and more investigations of Applied Cancer Science Institute. It seems
that this couple are shady... |
|
r***e
发帖数: 2539 | 39 公认的是
早期anti cancer，晚期promote cancer。
实际上一片糊涂账。 |
|
b****r
发帖数: 17995 | 40 谢谢回复
当然知道有类似工作，cancer genetics 这个领域不是一天两天了。本文主要是对将来
的发展和后果做一个主方向，主要技术路线和时间长度上的大致预期
对于你说的几点我有一些不同意见
1. 目前不是所有mutation能被targeted，但是只要肿瘤细胞和正常细胞有那么一点点
不同，能够被特意targeted的可能性就完全存在。比如说loss of function后，仍然要
造成其他基因的gain of function,这些基因可以被target。癌细胞也是活细胞，必须
要完成很多特别的生物行为才能在某个机体的某个部位生长，才能致癌
2. 这个我确实不太了解，有没有比较新的文章推荐一下。
3.细菌病毒也很少有不是heterogeneity的，目前办法就是广谱抗生素或者多抗联用
4. 所谓cancer stem cell到底是不是存在，据我所知并没有定论。我个人并不是特别
支持这个讲法，这个我以前在本版就发过主贴讨论过（http://weiming.info/zhuti/Biology/31430437/#post1）。即使存在，只要它们确实有独特
的致病mutati... 阅读全帖 |
|
p*****m
发帖数: 7030 | 41 我觉得测序最大的用处可能是categorize病人 至于之后怎么办那是另外一回事 测序结
果可能提供也可能更不能提供有用的信息（比如说，分型以后还是得靠盲筛去找药）。
至于mRNA/蛋白水平的变化，假设中心法则还是对的，假设cancer确实有遗传因素存在
，那即便是体细胞DNAseq也应该能提供足够的分型信息，甚至都不用到cancer cell
seq
性。
只是 |
|
b****r
发帖数: 17995 | 42 只要有维甲酸这样的例子，你就不能说小分子一定不如放疗化疗给力
类似的，易瑞沙也有证据比化疗更给力
Jackman DM, Miller VA, Cioffredi LA, Yeap BY, Jänne PA, Riely GJ, Ruiz
MG, Giaccone G, Sequist LV, Johnson BE (August 2009). "Impact of epidermal
growth factor receptor and KRAS mutations on clinical outcomes in previously
untreated non-small cell lung cancer patients: results of an online tumor
registry of clinical trials". Clin. Cancer Res. 15 (16): 5267–73. DOI:10.
1158/1078-0432.CCR-09-0888. PMID 19671843.
关键是这些肿瘤多半不是单个致癌突变引起，只抑制一条通路自然很难有... 阅读全帖 |
|
g*********3
发帖数: 177 | 43 我本人并不是说NGS对cancer研究没用，只是说不会产生革命性的突破~
1）NGS穷举出mutation不会很难，这也是NGS牛逼的地方，但是真正找到driver很难
2）在function研究方面，无论是RNA-Seq还是ChIP-Seq说的都是一个故事：
transcription，一些初步的数据已经证实protein level翻译水平的贡献率大概是2/3,
另外我觉得NGS的定量分析和microarray一样很丑陋
3）我比较赞同进化的观点，因为cancer不能完全归功于mutation~ LS有两位在讨论
reprogrammed signal pathway~ 这个当然有mutation的例子，但是和mutation无关的
例子简直是太多了~ e.g.a lot of weird metabolism pathways will totally rewire
the epigenetic profiling. Some abnormal metabolites can change the pathway.
.....the interaction between dif... 阅读全帖 |
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m**b
发帖数: 617 | 44 NGS assisted personalized medicine in cancer therapy has already underway.
Here is one of the first clinical example published in 2010:
http://genomebiology.com/content/11/8/R82
Key points:
1) Rare cancer with no standard chemo therapy
2) Initial treatment with radiation therapy and EGFR inhibitor (patient had
high EGFR expression) failed to stabilize disease progression
3) DNA sequencing + RNA expression identified new potential drug target RET
4) Used RET inhibitor to treat patient (off-label ... 阅读全帖 |
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H*****e
发帖数: 120 | 45 Very encouraging!
I just finished NGS for some colon cancer samples with the similar thought
in mind. From the result, I see common mutation on APC, which is expected
because I selected the samples with the "same" genetic background. However,
there are 100,000 SNP/mutation/deletion/insertion. I was lost and have no
idea what to do. This is a "old" cancer in terms of research since many
things are known. By using different tools (mainly on computer), it is now
narrowed down to 1,000. Among ... 阅读全帖 |
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j***z
发帖数: 105 | 46 几天不见楼这么高了啊，再次感叹下LZ的挖坑能力。
再谈谈NGS和targeted therapy的问题：
个人觉得NGS的作用是找到potential driver mutation，其意义一是可以为研究提供重
要的信息，二是如果这个mutation是直接druggable的话对于临床治疗有很大意义。和
LZ观点不同，我认为找到怎么target绝大部分的mutation还是一个非常大的挑战，例如
p53和ras, 被发现20多年了还是没有任何有效的治疗方法。所以就算90%的signaling
pathway in cancer的文章都是垃圾但是这方面的研究还是有很大意义的。
可以预见的是由于targeted therapy的发展，未来的十年很多癌症的治疗会有进展-病
人寿命延长，生活质量上升。但是从整体上来说癌症的攻克还是从prevention和early
detection上比较靠谱，lung and colon cancer就是好例子。这点NGS也会很有前景，
这期的science刚有一片文章关于这个：
http://www.sciencemag.org/content/337/6... 阅读全帖 |
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Z**********g
发帖数: 222 | 48 不认为Next Gen Seq在未来可以解决cancer问题。
1.可以认为cancer是基因病，但这是个复杂的基因病。每个肿瘤的突变谱都不一样，每
个肿瘤在不同阶段的突变谱不一样，每个肿瘤在同一阶段不同位置subclones突变
谱也不一样。肿瘤演化是divergent和branched的，如何找到属于特定时间和空间上的
某个肿瘤的真正元凶？在时空上你得知道下一阶段哪些个subclones会dominate。
2.很难说肿瘤的生长是否真正依赖于特定些个mutations。 Oncogene additive现象仅
仅发现于很少数的oncogene上。肿瘤很可能不会真正依赖于某个或某些个driving
mutations上。
3.即使找到了真正的driving/maintaining mutations,它们一定是可以druggable吗？
很多靶点根本不具有druggability。
4.耐药性往往是致命的问题。你还得通过Next Gen Seq建立耐药谱？！
5.肿瘤不单纯是基因病。Epigenetics是重要的因素，microenviroment也是重要的cell
non-aut... 阅读全帖 |
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g**********y
发帖数: 423 | 49 IF能比肩cancer cell?
cancer cell Impact Factor: 26.566 5-Year Impact Factor: 28.174 |
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G***G
发帖数: 16778 | 50 I know what the recurrence of disease is.
it means the disease occurs again.
but what is recurrence of cancer?
Does it mean the cancer was stable, but now not stable again? |
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