a*****s
发帖数: 131 | | p****n
发帖数: 9263 | | V*f
发帖数: 171 | | H*****e
发帖数: 120 | 4 Finally!
Amy is a star for long time. But almost like a joke although she and her
supporters fighted hard. Many years ago, she wrote a Cell review saying no
transdifferentiation. A few weeks later, there were 2 science paper did
transdifferentiation. When Cell launched Stem Cell, she was in the editor
board then she was elected for the senior post position in stem cell
association. How many AP could get this kind of treatment? I guess she
must make a big mistake in it this time.
Another rising star is C Kim on lung stem cells at Harvard. Almost everyone
in the field say her work was wrong. But she still can published high
profile paper saying others used wrong reagent. I cannot wait she retract
hers too!
Sad?! Well, this is at least a good news to people who are really
contributing. | a******g
发帖数: 129 | 5 They are both female scientists strongly backed by Irvine Weisman and Tyler
Jacks. So if they are not stars, who else dare to be?
no
everyone
【在 H*****e 的大作中提到】
: Finally!
: Amy is a star for long time. But almost like a joke although she and her
: supporters fighted hard. Many years ago, she wrote a Cell review saying no
: transdifferentiation. A few weeks later, there were 2 science paper did
: transdifferentiation. When Cell launched Stem Cell, she was in the editor
: board then she was elected for the senior post position in stem cell
: association. How many AP could get this kind of treatment? I guess she
: must make a big mistake in it this time.
: Another rising star is C Kim on lung stem cells at Harvard. Almost everyone
: in the field say her work was wrong. But she still can published high
| n********k
发帖数: 2818 | 6 yeah, have to agree on that...BTW, they both are reasonably pretty/stylish
when dress up:))...no personal contact with Kim, but have to say that Amy is
very sharp but very very aggressive and over-confident...didn't like her
once I had the first hand experience...
Tyler
【在 a******g 的大作中提到】
: They are both female scientists strongly backed by Irvine Weisman and Tyler
: Jacks. So if they are not stars, who else dare to be?
:
: no
: everyone
| h********n
发帖数: 4079 | 7 能不能详细说说为啥大家觉得C Kim的工作有问题? 我在lung cancer stem cell干过
一段时间, 以后可能还得做.
no
everyone
【在 H*****e 的大作中提到】
: Finally!
: Amy is a star for long time. But almost like a joke although she and her
: supporters fighted hard. Many years ago, she wrote a Cell review saying no
: transdifferentiation. A few weeks later, there were 2 science paper did
: transdifferentiation. When Cell launched Stem Cell, she was in the editor
: board then she was elected for the senior post position in stem cell
: association. How many AP could get this kind of treatment? I guess she
: must make a big mistake in it this time.
: Another rising star is C Kim on lung stem cells at Harvard. Almost everyone
: in the field say her work was wrong. But she still can published high
| r***e
发帖数: 2539 | 8 同求！我也在关注Kim在lung cancer stem cell上的东西。
不方便的话，请站信。谢谢！
【在 h********n 的大作中提到】
: 能不能详细说说为啥大家觉得C Kim的工作有问题? 我在lung cancer stem cell干过
: 一段时间, 以后可能还得做.
:
: no
: everyone
| H*****e
发帖数: 120 | 9 Well, nothing need to be hidden. If some experimental discussion is needed,
we can communicate privately.
From academic view, there are several questions that need to be answered (
Sorry my chinese input is very slow):
1.Whether stem cell is cancer stem cell is an issue. I read so many
literature that people are using tissue stem cell marker for identify cancer
stem cells. Frankly, I reject all of them, manuscript or grant application.
2.Whether there is Lung stem cell is rather unclear (could not find better
word). J Whitsett (?) never believe it. B. Hogan says every cell can act
like lung stem cells excepted those in the end differientation. Many others
never stop publishing new identity of lung stem cells. Kim found not the
stem cells (BASCs) but also extend them as cancer initiating cells.
3. Question about BASCs: she used FACS when she was not very good in it (I
used FACS for more than 3 years; like many other experienced fellow, every
new experiment is a new challenge). Some positive signals that she picked
in her Cell paper were found to be autoflourscence. Although she claimed
that the problem is not autoflou but the different antibody (means she was
using better and right antibody).
4. Is there real cancer stem cell in lung cancer situation? There are 4
types of NSLC and many be classfied into more by microarray data. One type
of stem cell cannot answer everything.
5. Her recent work is even amazing. She found that different genetic
background lung cancer, Kras or EGFR, set different cancer stem cells with
different potency.
Any way, this is just for pure academic discussion. Acutally, I was reading
Hogan's review on lung development on Dev Cell. Besides not mention Kim's
work, she even did not use this term "stem cell" in that 10 page long review
. On the other hand, I am not really 100% agree with Hogan although I
respect her. Talking about personality, Kim is much more aggressive than
Amy. Well too much! | r***e
发帖数: 2539 | 10 谢谢你的答复。我先看看你提到的hogan review，再私下请教些问题。
needed,
cancer
application.
others
【在 H*****e 的大作中提到】
: Well, nothing need to be hidden. If some experimental discussion is needed,
: we can communicate privately.
: From academic view, there are several questions that need to be answered (
: Sorry my chinese input is very slow):
: 1.Whether stem cell is cancer stem cell is an issue. I read so many
: literature that people are using tissue stem cell marker for identify cancer
: stem cells. Frankly, I reject all of them, manuscript or grant application.
: 2.Whether there is Lung stem cell is rather unclear (could not find better
: word). J Whitsett (?) never believe it. B. Hogan says every cell can act
: like lung stem cells excepted those in the end differientation. Many others
| | | h********n
发帖数: 4079 | 11 I think your point 1,2,3 are targeting the cancer stem cell research field,
not C Kim's work. I think you don't agree the concept of cancer stem cell.
I don't argue against you at this point because more data are required for
the field.
4. most lung cancer mouse models yield adenocarcinoma, including Kras and
EGFR model, which largely due to the promoter. And mechanistic study of
adenocarcinoma is much better then other subtype of lung cancers.
5. I have not read her recent work, but I was in her talk in AACR annual
meeting in Apr 2010.
In general, I think your critiques are on this field but not on her.
needed,
cancer
application.
others
【在 H*****e 的大作中提到】
: Well, nothing need to be hidden. If some experimental discussion is needed,
: we can communicate privately.
: From academic view, there are several questions that need to be answered (
: Sorry my chinese input is very slow):
: 1.Whether stem cell is cancer stem cell is an issue. I read so many
: literature that people are using tissue stem cell marker for identify cancer
: stem cells. Frankly, I reject all of them, manuscript or grant application.
: 2.Whether there is Lung stem cell is rather unclear (could not find better
: word). J Whitsett (?) never believe it. B. Hogan says every cell can act
: like lung stem cells excepted those in the end differientation. Many others
| r***e
发帖数: 2539 | 12 1. I don't like the concept of CSC either. It seems that more immuno-deficie
nt mice you use, you need less cells transplanted. I wonder if you just use
HELA cells, do you get the same result? then, there is a small number of CSC
in HELA cell culture too?
And what does this mean regarding to clinical practice?
4. More adencarcinomas are more due to mutations (Kras, EGFR), less due to
promoters. I tried different promoters, all leads to adenocarcinomas. I am
switching
to other mutations.
HGTPase:
Do you mean the double staining of BASCs is autofluo? I thought it is well
acepted, although I never see tumor cells that have double staining.
,
【在 h********n 的大作中提到】
: I think your point 1,2,3 are targeting the cancer stem cell research field,
: not C Kim's work. I think you don't agree the concept of cancer stem cell.
: I don't argue against you at this point because more data are required for
: the field.
: 4. most lung cancer mouse models yield adenocarcinoma, including Kras and
: EGFR model, which largely due to the promoter. And mechanistic study of
: adenocarcinoma is much better then other subtype of lung cancers.
: 5. I have not read her recent work, but I was in her talk in AACR annual
: meeting in Apr 2010.
: In general, I think your critiques are on this field but not on her.
| r*****m
发帖数: 231 | 13 just curious....
Did she marry a Korean man so that her name was changed to "Kim"?
Frankly, no one (I mean PIs, not ppl like us who dont even have the right to dislike her...) really likes Amy in
the H
community, but Carla has a better
reputation, at least to ppl outside of her field. Is she just hiding better?
needed,
cancer
application.
others
【在 H*****e 的大作中提到】
: Well, nothing need to be hidden. If some experimental discussion is needed,
: we can communicate privately.
: From academic view, there are several questions that need to be answered (
: Sorry my chinese input is very slow):
: 1.Whether stem cell is cancer stem cell is an issue. I read so many
: literature that people are using tissue stem cell marker for identify cancer
: stem cells. Frankly, I reject all of them, manuscript or grant application.
: 2.Whether there is Lung stem cell is rather unclear (could not find better
: word). J Whitsett (?) never believe it. B. Hogan says every cell can act
: like lung stem cells excepted those in the end differientation. Many others
| w**********9
发帖数: 242 | 14 Not in the field, but quite interested in knowing some basics
1), when we call stem cell, it means they have the ability to differentiate
multiple cell types. Well, as we know that cancers are monoclonal. It is
very very rare to find multiple types of cancers in the lungs or any organ
at the same time. So, how should I conceive the concept of "cancer" stem
cell ?
2), I do not understand what this means "every cell can act like lung stem
cells excepted those in the end differientation". As I can understand,
almost every cell in the lung is in end differentiation except those
neuroendocrine giving rise to small cell lung cancer, isn't it ?
needed,
cancer
application.
others
【在 H*****e 的大作中提到】
: Well, nothing need to be hidden. If some experimental discussion is needed,
: we can communicate privately.
: From academic view, there are several questions that need to be answered (
: Sorry my chinese input is very slow):
: 1.Whether stem cell is cancer stem cell is an issue. I read so many
: literature that people are using tissue stem cell marker for identify cancer
: stem cells. Frankly, I reject all of them, manuscript or grant application.
: 2.Whether there is Lung stem cell is rather unclear (could not find better
: word). J Whitsett (?) never believe it. B. Hogan says every cell can act
: like lung stem cells excepted those in the end differientation. Many others
| h********n
发帖数: 4079 | 15 I am so glad to read your thought. I would like to discuss a little more.
to 1: the term of CSC is controversy, but what if I say: "In lung adenocarcinoma, there is a population of tumor cells whose potency (in vivo) is much higher than other population in the same tumor. It is important to study this population of cells. How about we call it tumor initiating cell?"
what is your opinion to my above thought?
to 4: I don't agree with you on this point. Most lung cancer model use SPC or CCSP or CC10, SPC target AT2 cell or its progenitor cell, CCSP or CC10 target Clara cell or its progenitor. That's the reason that adenocarcinoma developed. The cellular origin of adenocarcinoma and BAC is quite sure, while cellular origin of other type of lung cancer is not so clear. ppl think squamous cell carcinoma may arise from NEB but the specific promoter is not clear. The specific promoter of the cell from which SCLC, LCLC and other types arise are largely unknown. I think this is the reason that making mouse model for lung cancer other than adenocarcinoma is hard.
However, Kwok-Kin Wong @ harvard did not agree with my above thought. He thought even use of SPC but different oncogene can yield different type of lung in mouse (We discussed in 2009 AACR meeting)
BTW, I have no relationship with Kim or Tylor Jacks or Kwok-Kin Wong.
Any critique is welcome.
1. I don't like the concept of CSC either. It seems that more immuno-deficie nt mice you use, you need less cells transplanted. I wonder if you just use HELA cells, do you get the same result? then, there is a small number of CSC in HELA cell culture too?
And what does this mean regarding to clinical practice?
4. More adencarcinomas are more due to mutations (Kras, EGFR), less due to promoters. I tried different promoters, all leads to adenocarcinomas. I am switching to other mutations.
【在 r***e 的大作中提到】
: 1. I don't like the concept of CSC either. It seems that more immuno-deficie
: nt mice you use, you need less cells transplanted. I wonder if you just use
: HELA cells, do you get the same result? then, there is a small number of CSC
: in HELA cell culture too?
: And what does this mean regarding to clinical practice?
: 4. More adencarcinomas are more due to mutations (Kras, EGFR), less due to
: promoters. I tried different promoters, all leads to adenocarcinomas. I am
: switching
: to other mutations.
: HGTPase:
| a****d
发帖数: 1919 | 16 I don't think cancers are monoclonal, most times they are heterogeneous
population, and cancer can be derived by different cell lineages, at least
in some types of cancer.
Plus I don't think people in cancer stem cell field thought the "cancer stem
cell" have the ability to differentiate into multiple cell types. They are
more like cancer initiating cells per se.
differentiate
【在 w**********9 的大作中提到】
: Not in the field, but quite interested in knowing some basics
: 1), when we call stem cell, it means they have the ability to differentiate
: multiple cell types. Well, as we know that cancers are monoclonal. It is
: very very rare to find multiple types of cancers in the lungs or any organ
: at the same time. So, how should I conceive the concept of "cancer" stem
: cell ?
: 2), I do not understand what this means "every cell can act like lung stem
: cells excepted those in the end differientation". As I can understand,
: almost every cell in the lung is in end differentiation except those
: neuroendocrine giving rise to small cell lung cancer, isn't it ?
| w**********9
发帖数: 242 | 17 Really? I always think that a malignant cancer arise from a single cell,
which in most cases may have a spontaneous mutation in one allele in
addition to an inherited mutation in another allele. I think I am correct.
stem
are
【在 a****d 的大作中提到】
: I don't think cancers are monoclonal, most times they are heterogeneous
: population, and cancer can be derived by different cell lineages, at least
: in some types of cancer.
: Plus I don't think people in cancer stem cell field thought the "cancer stem
: cell" have the ability to differentiate into multiple cell types. They are
: more like cancer initiating cells per se.
:
: differentiate
| o********r
发帖数: 775 | 18 Primary tumor is rarely a homogeneous population.
【在 w**********9 的大作中提到】
: Really? I always think that a malignant cancer arise from a single cell,
: which in most cases may have a spontaneous mutation in one allele in
: addition to an inherited mutation in another allele. I think I am correct.
:
: stem
: are
| h********n
发帖数: 4079 | 19 BTW, I think the key is how to validate the cells isolated by whatever
methods. My thought is in vivo and orthotopic implantation.
1.Whether stem cell is cancer stem cell is an issue. I read so many
literature that people are using tissue stem cell marker for identify cancer
stem cells. Frankly, I reject all of them, manuscript or grant application
.
【在 H*****e 的大作中提到】
: Well, nothing need to be hidden. If some experimental discussion is needed,
: we can communicate privately.
: From academic view, there are several questions that need to be answered (
: Sorry my chinese input is very slow):
: 1.Whether stem cell is cancer stem cell is an issue. I read so many
: literature that people are using tissue stem cell marker for identify cancer
: stem cells. Frankly, I reject all of them, manuscript or grant application.
: 2.Whether there is Lung stem cell is rather unclear (could not find better
: word). J Whitsett (?) never believe it. B. Hogan says every cell can act
: like lung stem cells excepted those in the end differientation. Many others
| w**********9
发帖数: 242 | 20 please !!! guys. Don't make fun of me.
Here is the simple example of monoclonal breast cancer. | | | o********r
发帖数: 775 | 21 Review
Many different tumor types have polyclonal tumor origin: Evidence and
implications
Barbara L. ParsonsCorresponding Author Contact Information, a, E-mail The
Corresponding Author
aDivision of Genetic and Reproductive Toxicology, National Center for
Toxicological Research, HFT-120, 3900 NCTR Road, USFDA, Jefferson, AR 72079,
United States
Received 7 February 2008;
revised 14 May 2008;
accepted 15 May 2008.
Available online 31 May 2008.
Abstract
Few ideas have gained such strong acceptance in the scientific community as
the monoclonal origin of tumors; the idea that tumors start with a single
mutated cell (or a single clone of cells) that go on to accumulate
additional mutations as a tumor develops. The certainty with which this
concept is held by the scientific community reflects the length of time it
has been unchallenged and the experimental difficulty in obtaining direct
evidence to the contrary. Yet, recent findings regarding X chromosome
inactivation patch size indicate that the X-linked marker data previously
interpreted as evidence of monoclonal tumor origin is actually more
consistent with polyclonal tumor origin, a situation where two or more cells
or clones of cells interact to initiate a tumor. Although most tumors show
homotypy for X-linked markers (as expected given the bias conferred by X
chromosome inactivation patch size), the literature contains numerous
examples of tumors with X-linked marker heterotypy, examples of which
encompass 24 different tumor types. Chimeric models have yielded direct
unequivocal demonstrations of polyclonality in rodent and human tumors. Also
, mutational data are consistent with polyclonal tumor origin. Methods that
analyze levels of tumor-associated oncogene and tumor suppressor gene
mutations demonstrate that initiated cells are much more common in normal
tissues than previously realized. Also, while tumors have higher levels of
mutation than normal tissues, oncogenic mutations frequently are present as
subpopulations within tumors, rather than as the pure mutant populations
expected to develop from a single initiated cell. Understanding the
mutational basis of tumor etiology has important practical significance for
assessing cancer risk, as well as in modeling and treating cancer. Therefore
, the scientific community needs to re-examine this issue and consider the
implications of polyclonal origin for, perhaps, a majority of tumors,
encompassing many different tumor types.
Keywords: Monoclonal; Tumor clonality; Somatic mutation; Tumor development;
Tumor etiology; X chromosome inactivation
Abbreviations: ACB-PCR, allele-specific competitive blocker polymerase chain
reaction; ACF, aberrant crypt foci; APC, adenomatous polyposis coli; CML,
chronic myelocytic leukemia; DGGE, denaturing gradient gel electrophoresis;
FAP, Familial Adenomatous Polyposis; G-6-PD, glucose-6-phosphate
dehydrogenase; HPRT, hypoxanthine-guanine phosophoribosyltransferase; HUMARA
, human androgen receptor gene; Ig, immunoglobulin; MF, mutant fraction;
RFLP, restriction fragment length polymorphism
samples
【在 w**********9 的大作中提到】
: please !!! guys. Don't make fun of me.
: Here is the simple example of monoclonal breast cancer.
| h********n
发帖数: 4079 | 22 In general a solid tumor arising from epithelial origin is often clonal. But as a tumor grows the cells will differentiate and recruit many other cells (endothelial and etc.)
stem
are
【在 a****d 的大作中提到】
: I don't think cancers are monoclonal, most times they are heterogeneous
: population, and cancer can be derived by different cell lineages, at least
: in some types of cancer.
: Plus I don't think people in cancer stem cell field thought the "cancer stem
: cell" have the ability to differentiate into multiple cell types. They are
: more like cancer initiating cells per se.
:
: differentiate
| y******8
发帖数: 1764 | 23 True.
【在 o********r 的大作中提到】
: Primary tumor is rarely a homogeneous population.
| y******8
发帖数: 1764 | 24 Eventhough the population is not homogeneous, I think they share some
signature changes, which define them as tumor cells.
So, the reference did not make a strong argument.
72079,
【在 o********r 的大作中提到】
: Review
: Many different tumor types have polyclonal tumor origin: Evidence and
: implications
: Barbara L. ParsonsCorresponding Author Contact Information, a, E-mail The
: Corresponding Author
: aDivision of Genetic and Reproductive Toxicology, National Center for
: Toxicological Research, HFT-120, 3900 NCTR Road, USFDA, Jefferson, AR 72079,
: United States
: Received 7 February 2008;
: revised 14 May 2008;
| l******u
发帖数: 936 | 25 其实tumor tissue 本身本来就是个heterogeneous 的一坨东西， tumor cells，
stroma cells， lymphoid cells， endothelial cells.....
即使只看tumor tissue 中的tumor cells， monoclonal 和 heterogeneous 也并不矛盾。
tumor tissue 里的monoclonal 的 tumor cells， 即使有相同的DNA 背景，
但是在transcription 水平，不同的cell populations 的 gene expression patterns
会很不一样。
stem
are
【在 a****d 的大作中提到】
: I don't think cancers are monoclonal, most times they are heterogeneous
: population, and cancer can be derived by different cell lineages, at least
: in some types of cancer.
: Plus I don't think people in cancer stem cell field thought the "cancer stem
: cell" have the ability to differentiate into multiple cell types. They are
: more like cancer initiating cells per se.
:
: differentiate
| t******y
发帖数: 716 | 26 我觉得CSC假设还是很靠谱的。大部分体细胞属于终末分化细胞，没有分裂能力。而干
细胞的定义就是自我更新和分化。癌症细胞显然至少保有自我更新这一干细胞的能力，
至于是否能够能够进一步分化，应该有很多证据证明这一点的。所以形成癌症细胞的分
裂细胞中，至少在理论上，存在CSC是完全说得通。
现在的分歧，我想应该纠结于在实证上能否找到这种既能自我更新，又能分化的癌细胞
。 | l******u
发帖数: 936 | 27 cancer stem cell 的理论本来就是个抄冷饭的东西， 这个概念上世纪上半页就有人
提出， 只不过当时没有好的工具和markers。 现在技术好了， 有了些不错的markers
（特别是在液态瘤中）一帮大牛又开始忽悠概念， 到处要钱了。
needed,
cancer
application.
others
【在 H*****e 的大作中提到】
: Well, nothing need to be hidden. If some experimental discussion is needed,
: we can communicate privately.
: From academic view, there are several questions that need to be answered (
: Sorry my chinese input is very slow):
: 1.Whether stem cell is cancer stem cell is an issue. I read so many
: literature that people are using tissue stem cell marker for identify cancer
: stem cells. Frankly, I reject all of them, manuscript or grant application.
: 2.Whether there is Lung stem cell is rather unclear (could not find better
: word). J Whitsett (?) never believe it. B. Hogan says every cell can act
: like lung stem cells excepted those in the end differientation. Many others
| n********k
发帖数: 2818 | 28 layman on cancer stuff and no intent to argue but discuss...
First don't like Amy and have no knowledge about Kim before ur post...
that said, Most of the points you made here are points for discussions or
personal scientific standing, and more or less representing the challenging
for the entire cancer (or CSC) field and highly debatable...with that, your
strong opinion towards them kind of not justified...
I think we all have heard too much of pro and con concerning the various
theory regarding cancer of origins...the question: is/shall there (be) a
unified theory? for all cancers, or even for cancer of a same organ site or
even of a same cell of origin...my naive/layman thoughts regarding CSC is it
could bear some true essence of tumorigenesis but no one shall expect it
would be a one fit all.
With that, I might disagree with you No 1 point "using tissue stem cell
marker for identify cancer stem cells. Frankly, I reject all of them,
manuscript or grant application"...
alright time to go back to my boring MS....
needed,
cancer
application.
others
【在 H*****e 的大作中提到】
: Well, nothing need to be hidden. If some experimental discussion is needed,
: we can communicate privately.
: From academic view, there are several questions that need to be answered (
: Sorry my chinese input is very slow):
: 1.Whether stem cell is cancer stem cell is an issue. I read so many
: literature that people are using tissue stem cell marker for identify cancer
: stem cells. Frankly, I reject all of them, manuscript or grant application.
: 2.Whether there is Lung stem cell is rather unclear (could not find better
: word). J Whitsett (?) never believe it. B. Hogan says every cell can act
: like lung stem cells excepted those in the end differientation. Many others
| n********k
发帖数: 2818 | 29 I heard it is almost one hundred or more ys old...Of course it is a concept.
..if we look around, how many hot stuff are not a concept? but to me, the
critical question is " does the concept bear some truth and can be
applicable", instead is it wrong or not? rarely anything can stand
absolutely scrutinization...
markers
【在 l******u 的大作中提到】
: cancer stem cell 的理论本来就是个抄冷饭的东西， 这个概念上世纪上半页就有人
: 提出， 只不过当时没有好的工具和markers。 现在技术好了， 有了些不错的markers
: （特别是在液态瘤中）一帮大牛又开始忽悠概念， 到处要钱了。
:
: needed,
: cancer
: application.
: others
| l******u
发帖数: 936 | 30 it was in 1937
http://www.nature.com/milestones/milecancer/full/milecancer06.html
In bioscience, what is truth? very few observations are "real", most people
described things in very artificial ways, very few things could be really
translated to clinical application. but so what? This is life, this is
biology.
concept.
【在 n********k 的大作中提到】
: I heard it is almost one hundred or more ys old...Of course it is a concept.
: ..if we look around, how many hot stuff are not a concept? but to me, the
: critical question is " does the concept bear some truth and can be
: applicable", instead is it wrong or not? rarely anything can stand
: absolutely scrutinization...
:
: markers
| | | i*********0
发帖数: 915 | 31 这篇nature最后还是被retract了,igf-1这个东西太扯淡了.
不过他们作的很多的parabiosis assay去rejuvenate其他的组织还是很有意思的. | O******e
发帖数: 4845 | 32 大多数数据是真的吧，但怎么解释就仁者见仁了。
people
【在 l******u 的大作中提到】
: it was in 1937
: http://www.nature.com/milestones/milecancer/full/milecancer06.html
: In bioscience, what is truth? very few observations are "real", most people
: described things in very artificial ways, very few things could be really
: translated to clinical application. but so what? This is life, this is
: biology.
:
: concept.
| p******d
发帖数: 3737 | 33 Several different concepts are being discussed here:
1. The origin of tumor/cancer(single cell or multiple cells)
2. The existence of CSC. Even if the tumor origin is only one cell (
differentiated or tissue-specific stem cell), the whole tumor is
phenotypically heterogeneous, which has been proven by many many
experiments
. Then do all these cells have the same potential to initiate a new tumor?
Or to be more practical, do all these cells have the same potential to met
or relapse after chemo? | p******d
发帖数: 3737 | 34 Personally, I see the virtue of CSC study. Although immunodeficiency level
seems to affect the data of limiting dilution, the congenic mice tumor model
still highly support the existence of CSC or tumor-initiating cells. As to
the markers for tissue stem cells or CSC, since we don't even know the
function of most of these "markers", I think it is ok to use then, as long
as the data is real. | r***e
发帖数: 2539 | 35 Thank everyone for the discussion!
As pineseed pointed out, too many topics were discussed here.
But my personal interests are:
1. what is the cell origin of different type of lung cancers?
2. does cell origin or mutation decide tumor types?
3. how to model different type of lung cancer?
HGTPase, it seems you are working in this field (more lung development than
lung cancer?), and I hope you can give your opinions. We can also discuss in
private mails for technique details.
1. Cancer initiating cells
I agree on that cancer initiating cells are better than CSCs, since CICs are
not necessary to give rise to all linage of cells as SCs do. My question he
re is, do most of the cells in the tumor mess proliferate and contribute to
the growing tumor mess? In normal tissue, most of the cells are terminal dif
ferentiated and not dividing any more. But tumor cells have mutations and ha
ve the potential to expand. I did clonal experiment from primary tumor. Most
of the clones I got can form tumor again. Does that mean most of the cells
in the tumor are CICs? Of course there is possibility that I have already se
lected a sub population during the cloning (which survived in the cloning).
But, in one cell clone, every cell has same genotype and should behave simil
arly. Are these cells all CICs? Actually, if you do CD133 staining, still on
ly very small set of cells are CD133+. So should this be epigentical regulat
ion? Very confusing to me….
2. Cell origin
I am more interested in this part. Originally Jacks lab used adeno virus to
deliver cre and in Kras or Kras/p53 mice, and they got adenocarcinoma. Wong
KK used Kras/LKB mice and got adenocarcinoma and squamous tumor. They think
LKB leads to squamous tumor. However we compared adeno and lenti cre. With l
enti we never got squamous tumor. One possible reason is adeno and lenti are
hitting different cell population. So cell origin is important.
One other experiment we did is using different promoter cre in Kras mice, ho
wever we always got adenocarcinomas. As for the SCLC model published before,
they used adenovirus too, to hit p53/Rb mice, and they got SCLC! So mutatio
n is also important.
I am now very interested in modeling different tumor types with different co
mbinations of promoter, infection techniques and mutations.
3. heterogeneity
As for the heterogeneity of primary tumor, my understanding is that tumor st
arted from one cell that got original mutation and started to divide. When c
ell expanded, some of the cells accumulated other mutations. Although the ce
lls with more mutations have better growth advantage, those original cells s
till expand and accumulate other mutations, so on and so on, tumor becomes a
mixture.
adenocarcinoma, there is a population of tumor cells whose potency (in vivo)
is much higher than other population in the same tumor. It is important to
study this population of cells.
SPC or CCSP or CC10, SPC target AT2 cell or its progenitor cell, CCSP or
CC10 target Clara cell or its progenitor. That's the reason that
adenocarcinoma developed. The cellular
thought even use of SPC but different oncogene can yield different type of
lung in mouse (We discussed in 2009 AACR meeting)
deficie nt mice you use, you need less cells transplanted. I wonder if you
just use HELA cells, do you get the same result? then, there is a small
number of CSC in HELA cell cultu
promoters. I tried different promoters, all leads to adenocarcinomas. I am
switching to other mutations.
【在 h********n 的大作中提到】
: I am so glad to read your thought. I would like to discuss a little more.
: to 1: the term of CSC is controversy, but what if I say: "In lung adenocarcinoma, there is a population of tumor cells whose potency (in vivo) is much higher than other population in the same tumor. It is important to study this population of cells. How about we call it tumor initiating cell?"
: what is your opinion to my above thought?
: to 4: I don't agree with you on this point. Most lung cancer model use SPC or CCSP or CC10, SPC target AT2 cell or its progenitor cell, CCSP or CC10 target Clara cell or its progenitor. That's the reason that adenocarcinoma developed. The cellular origin of adenocarcinoma and BAC is quite sure, while cellular origin of other type of lung cancer is not so clear. ppl think squamous cell carcinoma may arise from NEB but the specific promoter is not clear. The specific promoter of the cell from which SCLC, LCLC and other types arise are largely unknown. I think this is the reason that making mouse model for lung cancer other than adenocarcinoma is hard.
: However, Kwok-Kin Wong @ harvard did not agree with my above thought. He thought even use of SPC but different oncogene can yield different type of lung in mouse (We discussed in 2009 AACR meeting)
: BTW, I have no relationship with Kim or Tylor Jacks or Kwok-Kin Wong.
: Any critique is welcome.
:
: 1. I don't like the concept of CSC either. It seems that more immuno-deficie nt mice you use, you need less cells transplanted. I wonder if you just use HELA cells, do you get the same result? then, there is a small number of CSC in HELA cell culture too?
: And what does this mean regarding to clinical practice?
| w**********9
发帖数: 242 | 36 俺觉得这个polyclonal origin 很山寨. 难以置信. 等大牛或教科书改了后俺跟着就是
了.
As of heterogeneity, is this you made up or you got from somewhere ? Did
you ever read Volgestin's work about tumorigenesis in spontaneous colon
cancer ?
=======================================================
3. heterogeneity
As for the heterogeneity of primary tumor, my understanding is that tumor st
arted from one cell that got original mutation and started to divide. When c
ell expanded, some of the cells accumulated other mutations. Although the ce
lls with more mutations have better growth advantage, those original cells s
till expand and accumulate other mutations, so on and so on, tumor becomes a
mixture.
=======================================================
than
in
【在 r***e 的大作中提到】
: Thank everyone for the discussion!
: As pineseed pointed out, too many topics were discussed here.
: But my personal interests are:
: 1. what is the cell origin of different type of lung cancers?
: 2. does cell origin or mutation decide tumor types?
: 3. how to model different type of lung cancer?
: HGTPase, it seems you are working in this field (more lung development than
: lung cancer?), and I hope you can give your opinions. We can also discuss in
: private mails for technique details.
: 1. Cancer initiating cells
| r***e
发帖数: 2539 | 37 你是说一步一步地积累mutation吗？和我说的应该差不多意思吧。可能我没说清楚。我
就是想说有些细胞虽然没获得最有效的组合，但也可能生存下来，当然是很少的一部分
。如果它们没生存下来，那肿瘤里的tumor cell应该接近monoclonal了。
欢迎指正。
st
c
ce
【在 w**********9 的大作中提到】
: 俺觉得这个polyclonal origin 很山寨. 难以置信. 等大牛或教科书改了后俺跟着就是
: 了.
: As of heterogeneity, is this you made up or you got from somewhere ? Did
: you ever read Volgestin's work about tumorigenesis in spontaneous colon
: cancer ?
: =======================================================
: 3. heterogeneity
: As for the heterogeneity of primary tumor, my understanding is that tumor st
: arted from one cell that got original mutation and started to divide. When c
: ell expanded, some of the cells accumulated other mutations. Although the ce
| w**********9
发帖数: 242 | 38 指正啥啊,俺就一外行. 俺还想知道这个tumor heterogeneity是怎么回事. 没这个概念
啊, 俺一直以为是monoclonal的. 上面好多同学都在说这个heterogeneity. 能不能
educate俺一下?
是啊, 那个一步一步mutation. 最后到p53,引起肿瘤. 你那个先tumor后突变有点古怪.
不过那也能解释heterogeneous.是你想出来的? 还是大家都在这么说啊?
【在 r***e 的大作中提到】
: 你是说一步一步地积累mutation吗？和我说的应该差不多意思吧。可能我没说清楚。我
: 就是想说有些细胞虽然没获得最有效的组合，但也可能生存下来，当然是很少的一部分
: 。如果它们没生存下来，那肿瘤里的tumor cell应该接近monoclonal了。
: 欢迎指正。
:
: st
: c
: ce
| r***e
发帖数: 2539 | 39 我表述有问题，当然是先突变，积累突变才最后变肿瘤。
heterogeneity我的理解是 1.有不同的cell type，比如tumor cell, 和正常细胞，包括
endothelial cell, infiltrated immune cell和stromal cell。2.tumor cell本身也应
该是混合的，包括占大部分的获得最佳mutation组合的tumor cell，它们应该是clonal
的，另外获得其他突变的tumor cell应该也存在。
怪.
【在 w**********9 的大作中提到】
: 指正啥啊,俺就一外行. 俺还想知道这个tumor heterogeneity是怎么回事. 没这个概念
: 啊, 俺一直以为是monoclonal的. 上面好多同学都在说这个heterogeneity. 能不能
: educate俺一下?
: 是啊, 那个一步一步mutation. 最后到p53,引起肿瘤. 你那个先tumor后突变有点古怪.
: 不过那也能解释heterogeneous.是你想出来的? 还是大家都在这么说啊?
| w**********9
发帖数: 242 | 40 2 appears to make some sense. maybe it is it. thx
包括
也应
clonal
【在 r***e 的大作中提到】
: 我表述有问题，当然是先突变，积累突变才最后变肿瘤。
: heterogeneity我的理解是 1.有不同的cell type，比如tumor cell, 和正常细胞，包括
: endothelial cell, infiltrated immune cell和stromal cell。2.tumor cell本身也应
: 该是混合的，包括占大部分的获得最佳mutation组合的tumor cell，它们应该是clonal
: 的，另外获得其他突变的tumor cell应该也存在。
:
: 怪.
| | | p******d
发帖数: 3737 | 41 累积mutation的概念应该叫做clonal evolution吧？这个概念能解释很多现象，例如肿
瘤发生过程中可以观察到的不同恶性程度的癌前病变。但是这个概念不涉及cell of
origin的问题。 |
|
