Gallbladder abnormal with herceptin

[Lani]

to affect the respiratory system--another of the bodies systems beside the breast glandular system which is lined in epithelial cells. In the paper I piosted (in one patient who was biopsied during her time on herceptin and again when her symptoms resolved after herceptin was stopped) it was shown that while on herceptin something like 50%-70% less ciliated cells are found in the upper respiratory tract and there is approx 50% less of certain specialized cells lining the upper respiratory tract. Another paper, proposed/implied that the same thing happens in other systems lined by epithelial cells, particularly the GI tract. That is why, when I started the roll call on herceptin side effect, real and/or perceived, I included GI symptoms.

As I recall some had upper abdominal pain but I recall either in that thread or another several people describing gall bladder like problems. Now, gall bladder problems tend to occur in 40+ year old women yesterday and who knows if being on antiestrogens or having been put into early menopause by chemo potentiates it, or if it is just a long term side effect of radiation (which side was your breast cancer on?) or chemo(which affects all the epithelial cells of the GI tract including those lining the gall bladder and its duct, as they are some of the cells in the body which are replaced most often and therefore more rapidly dividing.

I hope people resurrect the roll call re herceptin side-effects. If I do, it will automatically get put into the "articles" category..... Anyone?

Sorry about my lack of correct statistics---tired! Feel free to search for my original post!(PS ciilated are hair-bearing cells which help filter germs in your nose and upper respiratory system)

[Hopeful]

Lani, how about the cilliated cells in the inner ear? I am still trying to determine whether my tinnitus is a result of the Herceptin, AI's or the combination.

thanks,

Hopeful

[Lani]

tinnitus is something which is not well understood in the first place

I suppose possibilities could include--late effect from chemo, late effect from radiation (is the ear on the same side radiated?), Herceptin or the ai

Not having ciliated cells has never been found to be the cause of tinnitus.

If I find something I'll let you know...

[penelope]

Does this mean that herceptin could cause upper repiratory problems. I have had two colds this year that went straight to my chest and have left me with a chronic cough. Incidently I had the CT scan and found that my luns are clear. Could herceptin be causing respiratory problems?

[Lani]

her2 is necessary to repair damage to airways. Many things damage airways--pollutants, household chemicals, as well as stab wounds and other trauma. Herceptin complexes with her2 making it unavailable for this function (usually a combined effort with other her family members)
: Nature. 2003 Mar 20;422(6929):322-6. Links
Comment in:
Nature. 2003 Mar 20;422(6929):267-8.
Segregation of receptor and ligand regulates activation of epithelial growth factor receptor.

Vermeer PD,
Einwalter LA,
Moninger TO,
Rokhlina T,
Kern JA,
Zabner J,
Welsh MJ.
Department of Internal Medicine, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, USA.
Interactions between ligands and receptors are central to communication between cells and tissues. Human airway epithelia constitutively produce both a ligand, the growth factor heregulin, and its receptors--erbB2, erbB3 and erbB4 (refs 1-3). Although heregulin binding initiates cellular proliferation and differentiation, airway epithelia have a low rate of cell division. This raises the question of how ligand-receptor interactions are controlled in epithelia. Here we show that in differentiated human airway epithelia, heregulin-alpha is present exclusively in the apical membrane and the overlying airway surface liquid, physically separated from erbB2-4, which segregate to the basolateral membrane. This physical arrangement creates a ligand-receptor pair poised for activation whenever epithelial integrity is disrupted. Indeed, immediately following a mechanical injury, heregulin-alpha activates erbB2 in cells at the edge of the wound, and this process hastens restoration of epithelial integrity. Likewise, when epithelial cells are not separated into apical and basolateral membranes ('polarized'), or when tight junctions between adjacent cells are opened, heregulin-alpha activates its receptor. This mechanism of ligand-receptor segregation on either side of epithelial tight junctions may be vital for rapid restoration of integrity following injury, and hence critical for survival. This model also suggests a mechanism for abnormal receptor activation in diseases with increased epithelial permeability.
PMID: 12646923 [PubMed - indexed for MEDLINE]

[Lani]

Links
Differentiation of human airway epithelia is dependent on erbB2.

Vermeer PD,
Panko L,
Karp P,
Lee JH,
Zabner J.
Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, 52242, 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. To test this hypothesis, we treated an in vitro model of well-differentiated human airway epithelia with trastuzumab or heregulin-alpha, an erbB ligand. In addition, coculturing 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 and decreased the number of metaplastic and nonciliated columnar cells, whereas 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. Cocultures 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 may direct various pathways of epithelial differentiation.
PMID: 16489114 [PubMed - indexed for MEDLINE]

another article says her1 is necessary to sense when the epithelial lining is breeched in order to recognize repair is necessary

How lapatinib will affect this (it inhibits both her1 and her2 ) is not known yet

Lack of ciliated cells can cause you to stop filtering out germs before they get further down, lack of differentiation of the airway cells may cause a lack of some secretions perhaps necessary to keep germs from invading I suppose.

[Lani]

and I noted someone else complaining of ringing in the ears and the next person stating they have all the same symptoms. Perhaps you should start a thread asking who has had tinnitus (ringing in ears) or contact those who listed it.

[Hopeful]

Lani, I did start a thread on tinnitus several weeks ago, and a few people responded, but it has died out. I did some research, and learned that tinnitus can be effected by estrogen levels. For the record, I have not had chemotherapy, I was radiated on the left side, and the tinnitus is in both ears. It started about 3 weeks after I began the AI, after I had already had three Herceptin treatments without a problem. I am trying switching AI's, to see if that makes a difference. The problem is it is hard to tell if it is one drug or the other or the combination of the two. Thanks for the information about cilliated cells and tinnitus - it does help me narrow down the research.

Hopeful