Dear Ladies,
Lisa and friends, here are the links you requested:
http://annonc.oxfordjournals.org/cgi...ull/14/10/1477
Here is one link suggesting the activation of HER2 during the healing process:
http://content.kluweronline.com/arti...7/fulltext.pdf
Here is a transcipt about the same issue:
Rapid Decline After Surgery
1 September 2003
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Researchers in Italy investigated why some people go downhill rapidly after having surgery for cancer.
Program Transcript
Norman Swan: Welcome to the program.
Today on The Health Report, what Middle East terrorism is doing to the psyche of its citizens: some surprising findings. What obesity is doing or not doing to the psyche of Australians, and the impact of weight loss.
Plus a common belief that you might think is just anecdotal, with no evidence. It’s the story many of us have heard: the granny, the father, the spouse who was fine till the surgeons opened him up, or her up, then after the operation the cancer ran wild and she or he was dead in no time.
Well it turns out this is real, although not always or not often as dramatic, and it could be a missed cause of cancer relapse. The good news is there may now be an explanation and indeed a solution.
Research from Italy has been investigating this phenomenon in women with breast cancer. Dr Sylvie Menard is Director of the Molecular Targeting Unit at the National Cancer Institute in Milan.
Sylvie Menard: It’s important first of all to identify at time of surgery who are these kind of patients in order to be ready to do something in terms of what surgical therapy. Probably with this oncogene overexpression and amplification we have identified this kind of patient.
Norman Swan: Sylvie Menard’s laboratory in Milan has been studying what she referred to there as oncogenes: genes which produce substances involved in the growth and multiplication of cells. One of these is called the HER2 receptor, which is turned on by growth factors. And when the HER2 receptors are in high numbers in women with breast cancer, it tends to predict a poor outcome. It turns out that women who have an early worsening of their breast cancer after surgery, tend to be HER2 positive.
Sylvie Menard: HER2 is a receptor for growth factors, so it’s very likely to be stimulated by growth factors. So we have tried to identify the mechanism, why these patients have a probability of relapse, and this is why we addressed the issue. What happened at the time of surgery, which kind makes a difference?
Norman Swan: So what did you find that it was about surgery that seemed to cause the problem?
Sylvie Menard: The surgery you must have, wound healing, to repair the damage of the surgery through growth factors.
Norman Swan: So the very facts that you’ve created a wound, and the wound has got to repair itself, the stuff that the wound –
Sylvie Menard: Yes, and with reparation of the wound occur through factors that in some way stimulate the tumour.
Norman Swan: So in a tragic biological irony, the growth factors which are needed to promote wound healing seem to target this HER2 receptor on the tumour cells, promoting their growth as well.
Sylvie Menard again.
Sylvie Menard: The same receptor, and therefore the same kind of proliferation. There are many, many different factors that can stimulate this kind of receptor, and therefore you have stimulation of the wound, but stimulation also of the tumour.
Norman Swan: Now you might be able to imagine that if you got these factors at the site of the wound, it might induce a recurrence of a tumour at the site of the breast, but not necessarily further away.
Sylvie Menard: This factor can go to stimulate dormant tumour cells anywhere. So if you have tumour cells in the bone marrow, tumour cells in the liver.
Norman Swan: So these growth factors go from the wound into the blood stream and spread throughout the body?
Sylvie Menard: Yes.
Norman Swan: So there are two solutions to this: one is you don’t do the operation, and the other presumably is –
Sylvie Menard: This is an impossible situation because surgery is the most important therapy for tumour. The point is that we can plan some therapy in order to operate. Maybe the wound will take a little bit more time to be repaired, but the tumour will not be stimulated.
Norman Swan: And in fact there is an antibody available which blocks the HER2 receptor. It’s called trastuzumab and Dr Menard and her colleagues tried it in the lab and found it works in the test tube. Now they’re doing a trial of it in women undergoing surgery. But this observation that surgery can speed the downhill path of a person with cancer applies to other tumours as well.
Sylvie Menard: There have been a reports for example with colon cancer, which in some cases it has been well demonstrated that after surgery there’s been an early recurrence of disease with multiple metastases. There are many different factors and looking at them and the corresponding receptors on the tumour cell, we will be able to say which tumours will be stimulated by surgery and which not. For HER2 it’s very specific for breast carcinoma.
Norman Swan: So you’re not convinced it’s HER2 in the others, and you’ve got to find out which ones it is?
Sylvie Menard: Yes. So we have to investigate now what kind of factor and what kind of receptor on the tumour cells for all the tumours.
Norman Swan: And then you’ve got to find the blocker that works for them?
Sylvie Menard: Yes, from any kind of surgery, not necessarily an oncological surgery. This may happen even with any kind of surgery which requires repair of the surgical damage.
Norman Swan: So you could have a tumour and have appendicitis, have your appendix out, and the appendix operation could cause this, because the wound for the appendicectomy would produce these growth factors as well?
Sylvie Menard: Yes, this is something that we are looking at, looking at recurrence of the disease later and seeing if the patient has had surgery in between or not. This is not something that’s easy, because the record of the patients are not always very complete. But this may be a possibility that some recurrences occur because dormant cells have been “rescued” from dormancy just because of an operation, which was not a cancer operation, it was for some other problem.
Norman Swan: And what about injuries, like fractures and things like that? Could they also produce these growth factors?
Sylvie Menard: It depends if you have blood clotting. The growth factor is released during the activation of platelets. If you don’t have blood clotting you don’t have release of growth factors. So it’s something that is very specific when you have damage of the tissue and you have blood clotting at the level of the damage.
Norman Swan: And the challenge now is to take this out of the lab into the clinic, using real people to confirm the relevance of the findings.
Dr Sylvie Menard runs the Molecular Targeting Unit at the National Cancer Institute in Milan.
Reference:
Tagliabue E et al Role of HER2 in wound-induced breast carcinoma proliferation. The Lancet August 16, 2003;362:527-533
Guests on this program:
Dr Sylvie Menard
Director,
Molecular Targeting Unit
Department of Experimental Oncology,
Istituto Nazionale Tumori,
via Venezian 1,
20133 Milano, Italy
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