[Lani]

those on herceptin (are you still?) may have a more prolonged period of recovery from inflammation/infection of the upper airways and perhaps some lower ones.

I posted several times here the case of a woman who developed a chronic cough on herceptin which resolved once she stopped herceptin. She agreed to have biopsies done both during AND AFTER her coughing which was attributed to the herceptin.

I used the search function and put in cough herceptin Lani and came up with three times I had posted on the topic since 2007. Here is one:

For those complaining of nasal/sinus symptoms/coughing which they relate to Herceptin, I submit the following two articles. The nose, like the more distant airways/bronchiols have ciliated epithelial cells (lining cells with tiny hairs which help trap bacteria, molds and other particulates) . 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]



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--thhey 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.