for those with nasal/sinus complaints with herceptin--new clues

For those complaining of nasal/sinus symptoms which they relate to Herceptin, the following two articles may hold clues as to what may be going on. The nose/airways have ciliated epithelial cells (lining cells with tiny hairs which help trap bacteria, molds and other particulates) and other specialized cells (including further down the "airways" in the bronchi and bronchioles). These articles raise questions which may help explain symptoms while on Herceptin--showing that her2 is necessary not just in embryogenesis, but also in adulthood for repair of these kinds of cells. They may help explain your nasal complaints, the reports of rare pulmonary problems in patients on Herceptin and perhaps the dry-eye problem I posted on before. The more they look into what her2 does, the more they find!:


Am J Physiol Lung Cell Mol Physiol. 2006 Feb 17; [Epub ahead of print]
Related Articles, Links
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Differentiation of Human Airway Epithelia Is Dependent on ErbB2.

Vermeer PD, Panko L, Karp P, Lee JH, Zabner J.

Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.

A clinical case documented a reversible change in airway epithelial differentiation that coincided with the initiation and discontinuation of trastuzumab, an anti-erbB2 antibody. This prompted the investigation into whether blocking the erbB2 receptor alters differentiation of the airway epithelium. If so, blocking or exogenously stimulating the receptor would lead to consequences on differentiation. To test this hypothesis, an in vitro model of well-differentiated human airway epithelia was treated with trastuzumab or heregulin-alpha, an erbB ligand. In addition, co-culturing with human lung fibroblasts tested whether in vivo subepithelial fibroblasts function as an endogenous source of ligands able to activate erbB receptors expressed by the overlying epithelial cells. Epithelia were stained with hematoxylin and eosin and used for morphometric analysis. Trastuzumab treatment decreased the ciliated cell number by 49% and increased the metaplastic, flat cell number by 640%. Heregulin-alpha treatment increased epithelial height, decreased the number of metaplastic and non-ciliated columnar cells while it increased the goblet cell number. We found that normal human lung fibroblasts express transforming growth factor-alpha, heparin binding-epidermal-like growth factor, epiregulin, heregulin-alpha, and amphiregulin, all of which are erbB ligands. Co-cultures of airway epithelia with primary fibroblasts increased epithelial height comparable to that achieved following heregulin-alpha treatment. These data show that erbB2 stimulation is required for maintaining epithelial differentiation. Furthermore, the mesenchyme underlying the airway epithelium secretes a variety of erbB ligands that might direct various pathways of epithelial differentiation.

PMID: 16489114 [PubMed - as supplied by publisher]


1: FASEB J. 2005 Aug;19(10):1374-6. Epub 2005 May 27.
Related Articles, Links
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ErbB2 activity is required for airway epithelial repair following neutrophil elastase exposure.

Fischer BM, Cuellar JG, Byrd AS, Rice AB, Bonner JC, Martin LD, Voynow JA.

Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.

In cystic fibrosis and chronic bronchitis, airways are chronically injured by exposure to neutrophil elastase (NE). We sought to identify factors required for epithelial repair following NE exposure. Normal human bronchial epithelial cells were treated with NE (50 nM, 22 h) or control vehicle. Following NE treatment, we found a marked and sustained decrease in epithelial proliferation as detected by Ki67 immunostaining. 3H-thymidine incorporation was also initially depressed but increased over 72 h in NE-treated cells, which suggests that DNA synthesis constitutes an early repair process following NE exposure. We hypothesized that ErbB2 receptor tyrosine kinase, a regulator of cancer cell proliferation, was required for epithelial DNA synthesis following NE exposure. Immediately following NE treatment, by flow cytometry analysis, we found a decrease in ErbB2 surface expression. Protein levels of the full-length 185 kD ErbB2 receptor significantly decreased following NE treatment and smaller ErbB2-positive bands, ranging in size from 23 to 40 kD, appeared, which suggests that NE caused ErbB2 degradation. By real-time RT-PCR analysis, we found no change in ErbB2 mRNA expression following NE treatment, which suggests that changes in ErbB2 protein levels were regulated at the post-translational level. Following NE treatment, full-length 185 kD ErbB2 levels increased to pretreatment levels, correlating with the increase in thymidine incorporation during the same time period. Importantly, inhibition of ErbB2 activity with AG825 (5 microM) or Herceptin (3.1 microM), an ErbB2-neutralizing antibody, blocked thymidine incorporation only in NE-treated cells. These results suggest ErbB2 is a critical factor for epithelial recovery following NE exposure.

PMID: 15923396 [PubMed - in process]

Re your comment on embryogenesis - were not they talking about using olefactory cells as a source of stem cell for nerve repair etc.

Technically beyond me but a fascinating post.

Good find, or suggests dedication or a very deep knowledge or both!

Thanks.

RB

[Lolly]

I agree with RB, technically beyond me also; in addition, being currently on chemo and suffering cognitive dysfunction, my brain becomes "full" very quickly.

If those who post such interesting finds could take the time to compose a brief summary in layperson's terms, it would be very much appreciated by us laypeople!

<3 Lolly

[Marlys]

I agree with Lolly. Sometimes these posts have no meaning in themselves. I am a nurse and they can be above me. Asummary in layman's terms would be more useful to many of us.
Marlys

[IndyAnnie]

Lolly,

I saw that you were on line now and wanted to tell you how often I have read your posts and have usually had a smile after doing so! I know that you have been thru struggles yourself but you're always quick with the optimistic word for folks....it is so uplifting.

I've been on this site often since my diagnosis in July 2003...I received neo adjuvant treatment for a large tumor and then Herceptin and Navelbine after my lumpectomy. I feel as though I was in the right place at the right time to receive such innovative treatment at the time and am still benefitting from it... I've been NED for almost two years now and am getting Herceptin, too. Keep those great posts coming.

Best regards,
Ann

[Lolly]

Hi Ann! Thanks for the kind words, they're much appreciated
I'm thrilled for you that you're closing in on your two year mark for NED. You and the other adjuvant Herceptin girls are writing the NEXT chapter on Herceptin and survival!
Keep up the good work.

<3 Lolly

I believe anyone with enough motivation can learn enough to find relevant articles and even interpret them on a basic level.

Not everyone on this site is a pharmaceutical rep, nurse, pharmaceutical rep or biochemist.

Joe and Al had no background in the biologic sciences from what I understand, yet they have quickly "boned up" by not being intimidated.

I was discouraged to read the term "layman" as it is a self-fulfilling title. I do not doubt in the least the ability of each of the women posting on this site to understand the issues--especially as it turns out MUCH MORE IS UNKNOWN THAN IS KNOWN and everything has to be read "with a grain of salt" Rather than "laymen" there are only persons who have not yet overcome the inertia to start helping themselves in the best way possible--becoming knowledgeable.

If you were transported to Mongolia, you would start to learn the language as it was necessary for you to survive. Your diagnosis has transported you even further away, and, although it is nice to trust your doctor, there is no one more motivated than you to fight your cancer and in all likelihood, kids, husband and all, no doctor with more time than you to research only your type of cancer.

I have voluntarily supplied literature and attended lectures/conferences for friends with NK Tcell lymphoma, alveolar rhabdomyosarcoma, triple negative breast cancer etc--these people ranged from 70 year old bond traders to 40 year old file clerks to 50 year old art dealers. Each took the effort and educated themselves and understood the articles almost as well as someone who had had chemistry and physiology in high school or college--and none of them had! I do my best communicating with individuals on a one on one basis. I had NEVER posted to an online board prior to her2 and have found it often frustrating. It is not my FORTE' and I constantly waver between wishing to share information (like Rhonda H) and feeling it is not a productive use of my time.

I never mind "translating" and educating, but find it fulfilling on a one on one basis and mostly annoying in this forum as I sense people just want to be "spoon-fed". It is natural to become passive and hope someone else will get them out of this fix but you are not babies, but multi- talented women albeit with little sense of intellectual self-worth.

YOU CAN DO IT!!!!!!!!!!!!!!!!!Don't underestimate yourself. The web has dictionaries, your local library has physiology texts and there are a lot of lectures available on CD.

I hesistated posting these two articles anyway as I thought they might only cause concern without providing a positive message. But seeing that people are looking to find side-effects of Herceptin should not only be frightening, but reassuring, as it shows someone is looking and until one recognizes the problem, they can't look for a solution!

So here is a short translation--perhaps my last!(sorry for the rant):

I started the post with my summary:
"For those complaining of nasal/sinus symptoms which they relate to Herceptin, the following two articles may hold clues as to what may be going on. The nose/airways have ciliated epithelial cells (lining cells with tiny hairs which help trap bacteria, molds and other particulates) and other specialized cells (including further down the "airways" in the bronchi and bronchioles). These articles raise questions which may help explain symptoms while on Herceptin--showing that her2 is necessary not just in embryogenesis, but also in adulthood for repair of these kinds of cells. They may help explain your nasal complaints, the reports of rare pulmonary problems in patients on Herceptin and perhaps the dry-eye problem I posted on before. The more they look into what her2 does, the more they find!:"

A “translation” of the “Greek” of the two articles:

Because of a case of a patient whose airways changed when Herceptin treatment was started and when Herceptin was stopped in terms of which types of specialized cells were present/absent they tried in a petri dish to see what happens to airway cells and found:

Trastuzumab treatment decreased the ciliated cell number by 49% and increased the metaplastic, flat cell number by 640%.

Thus the cells necessary to fight infection were more than halved and the cells with little specialized function, which do not secrete or trap bacteria, mold or particles went up by more than 6 fold.

In the other article, after bronchitis or other diseases where a white blood cell enzyme injures airway (bronchial) lining tissue her2 is necessary to repair the damage caused by this enzyme in an adult. The "Greek" is just describing how they proved the mechanism of how this occurs, at what step it occurs and whether the changes were on a gene or protein level.

Both articles emphasize that her2 fulfills physiologic functions in an adult and Herceptin can potentially adversely affect those functions. Epithelial cells are numberous throught the body--they line organs facing the "outside world"(which is sometimes inside as in the stomach and intestines) they function to keep infectious and dangerous particles out, secrete substances to lubricate and or digest, etc. Her2 seems to be necessary to keep these cells specializiing to serve different necessary functions and to repair/replace damaged cells.

Thus it seems it is not just the heart that Herceptin affects.

Her 2 also is suggested to act in arthritis so herceptin may be having some impact positive or negative there too.

http://www.her2support.org/vbulletin...ad.php?t=22855

I accept and agree with your comment - time is an issue for some - but overall this site is a co-operative effort, and human nature is what it is. For my own part I spend most of my "spare" time on the issue of fats and trying to make some sense of it and have to limit the areas I try and explore in depth, and try not to give the impression I have an specific understanding of some sort where I dont and hence my comment.

The general jist of the post was clear.

Knowledge is power, and the raising of a wider understanding hopefully in time will lead to positive change.

Please keep posting - the bits begin to fit together after a while - I often find myself going back to a post some time later as I realise its significance or see a link somewhere else.

Your posts do make a differnence, and the site would be very much the poorer for the lack of them.

RB

[Karen t]

Thank you to everyone who helps to lift our spirits when we need it, educate us when we need it, hold our hand when we need it, spoon-feed us when we need it, care about us when we need it. This site is a lifeline for many of us and since some days are better than others, we do appreciate all the extra efforts that are made to ease us through each day.

Having trouble signing in tonight, but want to thank you for posting the two articles on nasal/sinus complaints d/t Herceptin. This is exactly the information I needed, and I'm VERY thankful you were willing to provide it.
merryg