The early stages of polyp formation

Larsen, Peter; Tos, Mirko; Kuijpers, W.; Beek, J.M.H. van der

doi:10.1288/00005537-199206000-00013

Cited by 59 publications

(39 citation statements)

References 15 publications

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“…The real surprise in our results was the different distribution of pSTAT3 in the cells of the epithelium of polyps and inferior turbinates, which had not been reported previously. In the 1990s, a rupture of the basal membrane, which was followed by interstitial oedema, was suspected as the cause of polyp formation based on light-microscopic findings in a rat model [34,35]. Our studies provide clear indications, obtained using an immunohistochemical method, that the STAT3 pathway is turned on, which is known in oncology, and that the phosphorylation rate of a key signalling molecule is up-regulated in the basal cell layer of the pathologically altered epithelium of nasal polyps.…”

Section: Discussionmentioning

confidence: 99%

Increased Activation and Differentiated Localization of Native and Phosphorylated STAT3 in Nasal Polyps

Linke

Pries²,

Könnecke³

et al. 2013

Int Arch Allergy Immunol

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Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disease; the underlying mechanisms of cell signalling are not fully understood. STAT3 (signal transducer and activator of transcription 3) is a phosphokinase and a key signalling molecule implicated in cell cycle regulation. We studied the distribution and expression of STAT3 to examine the role of STAT3 in the pathogenesis of CRSwNP. Methods: We investigated tissue samples of the nasal polyps and inferior turbinate of patients with CRSwNP as well as samples of the inferior turbinate of subjects without chronic sinusitis. The expression levels of STAT3 and its activated form pSTAT3 were analysed using Western blotting, protein array, DNA microarray and immunohistochemistry. Results: No significant differences were found in STAT3-mRNA levels between the samples of nasal polyps and inferior turbinates of the same patient. However, the amount of pSTAT3 was increased in the polyp tissue compared to the inferior turbinates from both CRSwNP patients and control subjects (p < 0.01), indicating an activation of STAT3 in polyps. We identified a varying distribution pattern of pSTAT3; pSTAT3 was primarily found in superficial epithelial cells but not in the basal layer of the epithelium of the turbinate, whereas pSTAT3 was located in all layers of the epithelium of the polyp and mostly noted in the basal layer. Conclusions: Our results of the activation and varying localisation of STAT3 and its phosphorylated form in nasal polyps suggest that pSTAT3 plays a crucial role in the proliferative development of nasal polyps.

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Section: Discussionmentioning

confidence: 99%

Increased Activation and Differentiated Localization of Native and Phosphorylated STAT3 in Nasal Polyps

Linke

Pries²,

Könnecke³

et al. 2013

Int Arch Allergy Immunol

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“…In addition, the developmental delay in palate fusion found in Eya4 -/-mice might superimpose dysfunction at the nasopharyngeal end of the eustachian tube, as occurs in human palate clefting. Both structural malformations and eustachian tube dysfunction would mechanically impede clearance of normal middle ear secretions in Eya4 -/-mice and predispose to polyp formation and loss of cilia (Figure 6), as occurs in experimentally induced eustachian tube malfunction (34). Taken together, the primary anatomic defects produced by genetic loss of Eya4 -/-would so impair ventilation and clearance functions of the eustachian tube that mice become uniformly susceptible to otitis media as manifest by secondary responses (e.g., effusion, polyp formation, and loss of cilia).…”

Section: Discussionmentioning

confidence: 99%

Eya4-deficient mice are a model for heritable otitis media

Depreux¹,

Darrow²,

Conner³

et al. 2008

J. Clin. Invest.

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Otitis media is an extremely common pediatric inflammation of the middle ear that often causes pain and diminishes hearing. Vulnerability to otitis media is due to eustachian tube dysfunction as well as other poorly understood factors, including genetic susceptibility. As EYA4 mutations cause sensorineural hearing loss in humans, we produced and characterized Eya4-deficient (Eya4 -/-) mice, which had severe hearing deficits. In addition, all Eya4 -/-mice developed otitis media with effusion. Anatomic studies revealed abnormal middle ear cavity and eustachian tube dysmorphology; thus, Eya4 regulation is critical for the development and function of these structures. We suggest that some human otitis media susceptibility reflects underlying genetic predisposition in genes like EYA4 that regulate middle ear and eustachian tube anatomy.

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“…Although it would appear, to the best of our knowledge, that very few studies have dealt with vascular remodelling within nasal-polyp tissue, the neovascularization of vessels observed in nasal polyps are suggestive of the involvement of angiogenic processes [15]. Moreover, from animal models of nasal-polyp formation, numerous blood vessels have been reported to have been present within the stroma of the growing polyps [21,22]. Quite a number of studies have used a specific antibody directed against factor VIII-related antigen in order to determine, microscopically, the blood vessel count and density within nasal-polyp tissue [23][24][25].…”

Section: Discussionmentioning

confidence: 99%