Improving understanding of cell behaviour in breast cancer

Jul 15, 2008 | Posted by: roboblogger | Full story: Medical News

The invasion and spread of cancer cells to other parts of the body, known as metastasis, is a principal cause of death in patients diagnosed with breast cancer.

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1 - 13 of 13 Comments Last updated Aug 9, 2008

Since: Dec 05

Union, NJ

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#1
Jul 17, 2008
 
In normal tissue, new blood vessels are formed during tissue growth and repair, and the development of the fetus during pregnancy. In cancerous tissue, tumors cannot grow or spread (metastasize) without the development of new blood vessels. Blood vessels supply tissues with oxygen and nutrients necessary for survival and growth.

Endothelial cells, the cells that form the walls of blood vessels, are the source of new blood vessels and have a remarkable ability to divide and migrate. The creation of new blood vessels occurs by a series of sequential steps. An endothelial cell forming the wall of an existing small blood vessel (capillary) becomes activated, secretes enzymes that degrade the extracellular matrix (the surrounding tissue), invades the matrix, and begins dividing. Eventually, strings of new endothelial cells organize into hollow tubes, creating new networks of blood vessels that make tissue growth and repair possible.

Most of the time endothelial cells lie dormant. But when needed, short bursts of blood vessel growth occur in localized parts of tissues. New capillary growth is tightly controlled by a finely tuned balance between factors that activate endothelial cell growth and those that inhibit it.

About 15 proteins are known to activate endothelial cell growth and movement, including angiogenin, epidermal growth factor, estrogen, fibroblast growth factors (acidic and basic), interleukin 8, prostaglandin E1 and E2, tumor necrosis factor-, vascular endothelial growth factor (VEGF), and granulocyte colony-stimulating factor. Some of the known inhibitors of angiogenesis include angiostatin, endostatin, interferons, interleukin 1 ( and ), interleukin 12, retinoic acid, and tissue inhibitor of metalloproteinase-1 and -2.(TIMP-1 and -2).

At a critical point in the growth of a tumor, the tumor sends out signals to the nearby endothelial cells to activate new blood vessel growth. Two endothelial growth factors, VEGF and basic fibroblast growth factor (bFGF), are expressed by many tumors and seem to be important in sustaining tumor growth.

Since angiogenesis is also related to metastasis, it is generally true that tumors with higher densities of blood vessels are more likely to metastasize and are correlated with poorer clinical outcomes. Also, the shedding of cells from the primary tumor begins only after the tumor has a full network of blood vessels. In addition, both angiogenesis and metastasis require matrix metalloproteinases, enzymes that break down the surrounding tissue (the extracellular matrix), during blood vessel and tumor invasion.

A microvascular viability biomarker was developed based upon the principle that microvascular cells are present in tumor cell microclusters obtained from solid tumor specimens. A major modificaton of the DISC (cell death) assay allows for the study of anti-microvascular drug effects of standard and targeted agents, such as Avastin, Nexavar, and Sutent. The assay which has a morphological endpoint, allows for visualization of both tumor and microvascular cells and direct assessment of both anti-tumor and anti-microvascular drug effect (clinical responders).

Source: Eur J Clin Invest, Volume 37(suppl. 1):60, April 2007
Gail Perry

Bradenton, FL

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#2
Jul 20, 2008
 
Unfortunately we aren't anywhere having those tests. Without the copy of your study there's now way for anyone else to evaluate what you're saying, so the citation isn't really enough. If you have a website that provides the text of your source I would willingly read it.

There is no test yet that will tell us what, exactly, is the best chemotherapy for any one person. The best our oncologists can currently do is compare research on specific groups to the individual patient. That is not a guarantee of success, something as someone who has had cancer I am acutely aware of.

Since: Dec 05

Union, NJ

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#3
Jul 20, 2008
 
I would guess you are the only one who will have to actually research it Gail, since you haven't done any research yourself.
Gail Perry

Bradenton, FL

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#4
Jul 20, 2008
 
gdp, once again you have responded with insults. I really would like to see your source.
Gail Perry

Bradenton, FL

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#5
Jul 21, 2008
 
(metastasize) without the development of new blood vessels. Blood vessels supply tissues with oxygen and nutrients necessary for survival and growth.

Endothelial cells, the cells that form the walls of blood vessels, are the source of new blood vessels and have a remarkable ability to divide and migrate. The creation of new blood vessels occurs by a series of sequential steps. An endothelial cell forming the wall of an existing small blood vessel (capillary) becomes activated, secretes enzymes that degrade the extracellular matrix (the surrounding tissue), invades the matrix, and begins dividing. Eventually, strings of new endothelial cells organize into hollow tubes, creating new networks of blood vessels that make tissue growth and repair possible.

Most of the time endothelial cells lie dormant. But when needed, short bursts of blood vessel growth occur in localized parts of tissues. New capillary growth is tightly controlled by a finely tuned balance between factors that activate endothelial cell growth and those that inhibit it.

About 15 proteins are known to activate endothelial cell growth and movement, including angiogenin, epidermal growth factor, estrogen, fibroblast growth factors (acidic and basic), interleukin 8, prostaglandin E1 and E2, tumor necrosis factor-Proportional to, vascular endothelial growth factor (VEGF), and granulocyte colony-stimulating factor. Some of the known inhibitors of angiogenesis include angiostatin, endostatin, interferons, interleukin 1 (Proportional to and ), interleukin 12, retinoic acid, and tissue inhibitor of metalloproteinase-1 and -2.(TIMP-1 and -2).

At a critical point in the growth of a tumor, the tumor sends out signals to the nearby endothelial cells to activate new blood vessel growth. Two endothelial growth factors, VEGF and basic fibroblast growth factor (bFGF), are expressed by many tumors and seem to be important in sustaining tumor growth.

Angiogenesis is also related to metastasis. It is generally true that tumors with higher densities of blood vessels are more likely to metastasize and are correlated with poorer clinical outcomes. Also, the shedding of cells from the primary tumor begins only after the tumor has a full network of blood vessels. In addition, both angiogenesis and metastasis require matrix metalloproteinases, enzymes that break down the surrounding tissue (the extracellular matrix), during blood vessel and tumor invasion."

The actual source is:
http://www.nih.gov/news/pr/july98/nci-07.htm

I have not been able to find the actual research you have been citing. You should share it so we can all look at it and not rely solely on your posts, since you are juxtaposing scientific work the originators did not intend to connect.

The rest of your post appears to be based on this information, which is summarized here:

http://www.medicalnewstoday.com/articles/8918...

This is Phase II trials, not anything 'ready for prime time.' It is on Avastin, which so far has not held up to its original promise.

There's a lot of information out there on both old and new approaches to cancer, but the only place I find "microvascular viability biomarkers" being discusses are in your other posts.

It's time for you to lead the rest of us to the information you are using to make these claims.
Gail Perry

Bradenton, FL

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#6
Jul 21, 2008
 
I'm sorry, somehow the first part of that post got cut off. My point was that you just copied and pasted, verbatim, a long section from the NIH, without attribution. You selectively choose what you take from research.

This is why I want to see the source you see so frequently. You put so much work into your posts; I would like to know how much credence to give them. For that, I need to see the source.

Since: Dec 05

Union, NJ

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#7
Jul 22, 2008
 
I have stated my sources whenever applicable. If you do not want to do any further research on your own, I cannot answer for your lack of performance. If someone cites a source, you'll want a website, if someone cites a website, you'll want a literature citation, if someone gives a literature citation, you'll want something else. You're all over yourself Gail. I cannot help someone who enjoys arguing for arguments sake. You'll have to chase your own tail.
Gail Perry

Bradenton, FL

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#8
Jul 22, 2008
 
I am respectfully asking you to provide the actual text of the source you keep citing. I genuinely would like to see it.
Gail Perry

Bradenton, FL

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#9
Jul 24, 2008
 
gdp, I think you are afraid to provide the actual source (either text or a link to the actual text). I think the research you keep citing doesn't state what you claim it does.

But you're right. Other websites or articles won't do -- only the one from that European oncology annal you keep citing. That's the one.

Since: Dec 05

Union, NJ

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#10
Aug 5, 2008
 
History of the ER Assay

The ER assay is used to determine a number of very important things. Which patients with early breast cancer should receive adjuvant chemotherapy. Whether or not chemotherapy should include hormonal therapy. In the advanced setting, whether chemotherapy should be given versus hormonal therapy. These are all very important decisions. The stakes are high with the ER assay, in terms of potentially harming the patient.

The ER assay was developed in the mid 1970s. First generation technology was a complicated lab test called the radioligand binding assay (RLB assay). The accuracy of this assay was mainly documented by retrospective correlations, in hundreds and not thousands of patients. Patients who were ER negative were said to have about 10% chance of responding to hormonal therapy and were more likely to recur after "curative" surgery. Patients who were ER positive had about a 60% chance of responding and were less likely to recur. No one ever did a prospective randomized trial to prove that doing the assay made a difference; there were just retrospective studies correlating assay results with clinical response to treatment.

In the early 1980s, the technology was changed from the complicated RLB assay, which could be done only in a few highly specialized laboratories to a much more simple immunohistochemical (microscope slide) assay, which could be done in most pathology labs. This newer assay was initially validated by comparison of the RLB assay in the specialized labs. The new assay correlated reasonably well with the older assay and it replaced the older assay. No one ever did a prospective or even retrospective study to show how the newer assay correlated with and predicted for response to treatment. It was just "the old assay works and the new assay correlates (in a few, highly specialized laboratories) with the old assay; so the new assay is OK to use."

In 2006, there was finally a study (in a highly sophisticated laboratory) showing how well the new assay predicts. In a very small study, which was retrospective, meaning they could draw the best possible cut off lines after the fact, they found that ER positive patients had a 56% response rate, while ER negative patients had a 20% response rate. Correlations which are vastly inferior to those obtained in much bigger and better studies with cell culture assays.

If a highly sophisticated lab gets such lousy correlations, then you can imagine the accuracy of tests done in community hospitals. And yet every patient with breast cancer gets this test and in almost every patient the information is used to make much more critical decisions than in the cases of both the Her2/neu assay and also the cell culture assay.

Questions regarding the best methodology of HER2 testing as well as the clinical applications of such testing remain. Ultimately, the most useful test will be the one that correlates best with HER2-mediated cellular biology and clinical outcome. The comparison of HER2 detection with clinical end points will allow clarification of the predictive value of a particular method.
Gail Perry

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#11
Aug 6, 2008
 
When a highly sophisticated lab gets inconsistent results, the test simply isn't ready for prime time. Yes, questions remain. There will be questions for the foreseeable future. And yes, of course, the goal is clinical success.

What article did you pharaphrase here? We ought to have a footnote so we can read the original for ourselves.

Since: Dec 05

Union, NJ

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#12
Aug 9, 2008
 
I realized you do not have any original thought Gail.
Gail Perry

Bradenton, FL

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#13
Aug 9, 2008
 
Once again, gdp, you can only descend to insults. What article did you pharaphrase?

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