Effect of the Radioprotector WR2721 on Irradiation-Induced Injury to Ciliated Cells of Eustachian Tube

Jung, Timothy T. K.; Park, Young Min; Panossian, David H.; Weeks, Douglas A.; Miller, Sharon; Sandefur, Jere; Krohn, Kenneth A.

doi:10.1177/000348949210100504

Cited by 14 publications

(3 citation statements)

References 22 publications

(4 reference statements)

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“…8 Middle ear mucosal injury is thought to be related to radiation-induced toxicity leading to impairment of the mucosal and ciliary function. 8,9 Prior investigations on radiation to the temporal bone emphasised ciliary dyskinesis as a factor contributing to MEE after radiotherapy, with Panossian et al 8 showing a decrease in cilia, and Elwany et al 9 observing various epithelial changes in the middle ear mucosa of patients with post-radiotherapy hearing loss. Additionally, changes in the mucosal microbiome, according to Zagury-Orly et al 10 were also observed.…”

Section: Discussionmentioning

confidence: 99%

“…The aetiology of post‐radiation MEE is hypothesized to be associated with either obstruction or functional impairment of the ET; and/or middle ear mucosal injury 8 . Middle ear mucosal injury is thought to be related to radiation‐induced toxicity leading to impairment of the mucosal and ciliary function 8,9 …”

Section: Discussionmentioning

confidence: 99%

“…Prior investigations on radiation to the temporal bone emphasised ciliary dyskinesis as a factor contributing to MEE after radiotherapy, with Panossian et al 8 showing a decrease in cilia, and Elwany et al 9 observing various epithelial changes in the middle ear mucosa of patients with post‐radiotherapy hearing loss. Additionally, changes in the mucosal microbiome, according to Zagury‐Orly et al 10 were also observed.…”

Section: Discussionmentioning

confidence: 99%

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Post‐radiation middle ear effusion in NPC patients: Analysis of patient, tumour, and radiation factors

Vainer,

Tzelnick,

Kurman

et al. 2024

Clinical Otolaryngology

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ObjectiveThe purpose of this study was to investigate whether patient, tumour and radiation therapy factors are associated with development of middle ear effusion (MEE) in nasopharyngeal carcinoma (NPC) patients.Deign, Settings, and ParticipantsA retrospective review of NPC patients treated between January 2000 and June 2018 at Rabin Medical Center.Patient factors, tumour factors, radiation doses, and radiation fields were collected and outlined if needed (middle ear, eustachian tube [ET], tensor veli palatini [TVP], and levator palatini [LVP] muscles), then analysed and compared between patients with MEE and those without and between sides in patients with unilateral MEE.Main Outcome Measures and ResultsSeventy‐three patients were enrolled. Most were males (71.2%) with advanced‐stage diseases (78%). At the time of diagnosis 14 patients (19.2%) presented with MEE. Following radiation, 18 patients, with no evidence of MEE at presentation, developed MEE. Tumour stage, histology, and laterality were not associated with development of MEE. Comparison of mean radiation field dosages including—gross target volume, clinical target volume, and patient target volume showed no association with post‐radiation MEE. In addition, no difference was found in the radiation doses to the middle ear, ET or the LVP nor the TVP between ears with and without MEE.ConclusionsPost‐irradiation MEE remains a common adverse effect in NPC patients. Surprisingly, tumour stage, tumour laterality, and histology were not associated with MEE. Similar findings were observed for total radiation doses and specific doses to the middle ear, ET, and ET muscles.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Post‐radiation middle ear effusion in NPC patients: Analysis of patient, tumour, and radiation factors

Vainer,

Tzelnick,

Kurman

et al. 2024

Clinical Otolaryngology

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Histopathologic Study of the Human Eustachian Tube and Its Surrounding Structures Following Irradiation for Carcinoma of the Oropharynx

Takasaki¹,

Hirsch²,

Sando³

2000

Arch Otolaryngol Head Neck Surg

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Ionizing radiation increases primary cilia incidence and induces multiciliation in C2C12 myoblasts

Filipová

Díaz-García

Bezrouk

et al. 2015

Cell Biology International

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Primary cilia act as physical-chemical sensors and their functions include the perception of the extracellular milieu, regulation of organogenesis, and cell polarity. In general, these cells are monociliated and the single cilium possesses diverse receptors and channels which are involved in morphogenesis and growth signaling, and are, therefore, important for cell proliferation and differentiation. In this study, we used an in vitro model of C2C12 myoblasts to evaluate the effect of DNA damage induced by gamma ionizing radiation on primary cilia incidence. A significantly higher number of ciliated cells were observed after 1 day post-irradiation with 2-20 Gy when compared with non-irradiated cells. After 3 days post-irradiation, the cilia incidence in cells had decreased slightly when treated with 2, 6, and 10 Gy, although an increase in incidence rate was observed in cells treated with 20 Gy. Multi-ciliated cells were also detected in myoblasts irradiated with 10 and 20 Gy but not in non-irradiated cells or after low irradiation (2-6 Gy). Irradiation also caused a dose-dependent decrease in cell viability and proliferation and corresponding cell cycle arrest. Furthermore, an activation of caspases 3/7, 8, and 9 was observed after higher radiation (10 and 20 Gy) with increased apoptosis. Together, our results show that irradiation by gamma rays promotes myoblast ciliogenesis, with pronounced effects observed after 3 days post-irradiation. We conclude that irradiation doses of 10 and 20 Gy are sufficient to induce cell death and are responsible for the formation of multiple cilia originating from multiple basal bodies.

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Effect of the Radioprotector WR2721 on Irradiation-Induced Injury to Ciliated Cells of Eustachian Tube

Cited by 14 publications

References 22 publications

Post‐radiation middle ear effusion in NPC patients: Analysis of patient, tumour, and radiation factors

Post‐radiation middle ear effusion in NPC patients: Analysis of patient, tumour, and radiation factors

Histopathologic Study of the Human Eustachian Tube and Its Surrounding Structures Following Irradiation for Carcinoma of the Oropharynx

Ionizing radiation increases primary cilia incidence and induces multiciliation in C2C12 myoblasts

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