Purpose To explore the role played by Glut-1 and H+/K+-ATPase in pepsin-induced, mouse laryngeal epithelial proliferation, growth, and development. Methods We established a mouse model of laryngopharyngeal reflux and measured Glut-1 and H+/K+-ATPase expression levels in mouse laryngeal epithelium treated with artificial gastric juice containing pepsin. Results Artificial pepsin-containing gastric juice induced significant hyperplastic changes in mouse laryngeal epithelium compared to control mice at 15, 30, and 45 days. Inhibition of Glut-1 expression by 2-DG significantly suppressed such hyperplasia compared to mice exposed to artificial gastric juice containing pepsin at 15, 30, and 45 days. After treatment with pepsin-containing artificial gastric juice, RT-PCR and Western blotting showed that the levels of Glut-1 and H+/K+-ATPase α, β increased significantly. Conclusions Pepsin-containing artificial gastric juice promoted mouse laryngeal epithelial hyperplasia associated with abnormal expression of Glut-1 and H+/K+-ATPase α, β.

Purpose We investigated the role of Glut-1 and H+/K+-ATPase expression in pepsin-induced development of human vocal cord leukoplakia cells (HVCLCs). Next, we analyzed the relationship between Glut-1 and H+/K+-ATPase expression with the clinicopathological features of laryngeal carcinoma. Methods Glut-1 and H+/K+-ATPase expression levels in HVCLCs were determined after treatment with artificial gastric juice containing pepsin and laryngeal carcinoma tissues. Results Exposure to pepsin-containing artificial gastric juice significantly enhanced the migration and proliferation of VSCLCs in a time-dependent manner. The apoptotic rate of VSCLCs decreased over time after exposure to pepsin and reached a nadir on day 7 (p < 0.01). With increasing duration of exposure to pepsin, the proportion of VSCLCs in G0/G1 phase decreased and the proportions in the S and G2/M phases significantly increased (p < 0.05). After treatment with pepsin-containing artificial gastric juice, RT-PCR and Western blotting showed that the expression of Glut-1 and H+/K+-ATPase α, β significantly increased in HVCLCs compared to in the absence of pepsin (p < 0.05). The expression of Glut-1 and H+/K+-ATPase α, β gradually increased from vocal cord leukoplakia (VLC) to laryngeal carcinoma (p < 0.05). Lentivirus-mediated inhibition of Glut-1 expression in VCL significantly inhibited the cells’ migration and proliferation (p < 0.05) but enhanced their apoptosis (p < 0.05). Also, inhibition of Glut-1 expression resulted in an increased proportion of cells in G0/G1 phase and a significantly decreased proportion in G2/M phase (p < 0.05). Conclusions Elevated Glut-1 expression may promote the development of VCL by upregulating laryngeal H+/K+-ATPase expression to reactivate absorbed pepsin, thus damaging the laryngeal mucosa.

The incidence of primary poorly differentiated neuroendocrine carcinoma (PDNC) of the hypopharynx iŝ4%. However, the disease pathogenesis, natural history, and prognostic factors remain poorly understood. We report the case of a 66-year-old man who presented with multiple metastases from primary PDNC of the hypopharynx. Physical examination revealed ã3×4 cm left cervical mass located at the level III, with tenderness and an unclear boundary. Laryngoscopy revealed a large mass arising from the posterior hypopharynx; glottis and vocal cord movements were invisible. After consultation with our head and neck oncological multidisciplinary team, diagnosis and specific treatment plan were made. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed small cell carcinoma. Immunohistochemical staining identified neoplastic cells that were positive for cytokeratins, CD56, chromogranin A, and synaptophysin. The Ki-67 mitotic index approached 80%. These findings confirmed hypopharyngeal PDNC, and chemotherapy was prescribed. After 7 months, the tumor metastasized to the left side of the anterior chest wall, bilateral lungs, left liver, and skeleton. The soft tissue of the chest wall was biopsied, and pathology revealed PDNC. Subsequent examinations over the next 4 months confirmed multiple liver metastatic lesions. The patient succumbed to the cancer progression a month later. Here, we systematically review the clinical manifestations, pathogenesis, prognostic factors, and treatment of the disease. In conclusion, patients always have a poor prognosis due to a lack of optimal treatment.

Hypothesis: Autophagy and its enhancement may have a role in the pathogenesis of acquired cholesteatoma. Background: The etiopathogenesis of acquired cholesteatoma remains unclear. Some clinical features of cholesteatoma are similar to those of cancer. The study of autophagy in cancer has indicated that enhanced autophagy enables tumor cell survival and growth. Methods: Cholesteatoma epithelium and normal external auditory canal (EAC) epithelium were obtained from patients with acquired cholesteatoma, and marginal epithelium of the tympanic membrane perforation was obtained from patients with chronic otitis media (COM). Immunohistochemistry (IHC) was performed to detect the expression of light chain 3 (LC3) in cholesteatoma and EAC epithelium. Western blotting (WB) was performed to detect the expression of LC3, Beclin-1, or the PI3K/AKT pathway in cholesteatoma, EAC, and COM epithelium. Results: LC3 staining of IHC was stronger in cholesteatoma epithelium compared with normal EAC epithelium. The ratios of LC3-II/I and Beclin-1 expression on WB were significantly higher in cholesteatoma epithelium compared with EAC epithelium or COM epithelium, and there was a significantly higher ratio of p-PI3K/PI3K and p-AKT/AKT in cholesteatoma epithelium compared with EAC epithelium. Conclusions: Enhanced autophagy might play a role in the pathogenesis of acquired cholesteatoma. PI3Ks might have different regulatory functions on autophagy in the cholesteatoma epithelium.

Tobacco products cause a variety of cancers, nicotine and carcinogens are two major factors to link the tobacco products and various cancers. The mechanism of tobacco inducing carcinogenesis and promoting cancer progression have been studied for a long time. However, mainstream studies just focus on the mutagenic characteristics of tobacco product and its properties to induce carcinogenesis of epithelial cells. In the past decades, people began to aware of the significant role of tumor stroma in cancer development and progression. Fibroblasts, which is associated with various cancer in all stage of disease progression, are the dominant cell type in the tumor microenvironment. While only a few studies explore the crosstalk between tobacco-induced fibroblasts and surrounding epithelial cells. Our purpose is to systematically review the effects of tobacco products on fibroblasts and further discuss how these effects affect the development of cancer cells.