Parapharyngeal and retropharyngeal infections in children: Kawasaki disease needs vigilance.

OBJECTIVE: Kawasaki Disease (KD) may mimic Parapharyngeal (PPI) and Retropharyngeal Infections (RPI), leading to misdiagnosis as Deep Neck Infections (DNIs). The treatment plans for the two diseases are different, and delayed treatment can lead to serious complications. Therefore, prompt diagnosis and management are necessary. This study was performed to evaluate the clinical features of KD mimicking DNIs and explore the treatment options. METHODS: Children with cellulitis or abscess in parapharyngeal or retropharyngeal space in neck CT were included in this study. The medical records of enrolled children were retrospectively reviewed. RESULTS: In total, 56 children were diagnosed with PPI or/and RPI. Twenty-two (39.3%) participants were eventually diagnosed with KD, and 34 (60.7%) were diagnosed with DNIs. Compared with the DNIs group, the KD group had a higher body temperature (p=0.007), and higher levels of AST (p=0.040), ALT (p=0.027), and ESR (p=0.030). Deep cervical cellulitis (p=0.005) were more common in the KD group. However, deep neck abscess often occurred in the DNIs group (p=0.002), with parapharyngeal abscess being the most common type of abscess (p=0.004). The KD mimicking DNIs cases did not respond to antibiotic treatment, but symptoms significantly improved after the use of Immunoglobulin (IVIG) and aspirin. CONCLUSION: Children with KD may exhibit retropharyngeal or parapharyngeal inflammation in the early stages. KD should be considered a differential diagnosis for children with DNIs, high fever, and no response to antibiotic therapy. Surgery in KD mimicking deep neck abscess requires caution. LEVEL OF EVIDENCE: I.

The role of radiotherapy in tumor immunity and the potential of PET/CT in detecting the expression of PD-1/PD-L1.

Upregulation of PD-1/PD-L1 allows cancer cells to escape from host immune systems by functionally inactivating T-cell immune surveillance. Clinical blockade strategies have resulted in an increased prevalence of patients with late-stage cancers. However, many cancer patients had limited or no response to current immunotherapeutic strategies. Therefore, how to improve the sensitivity of immunotherapy has become the focus of attention of many scholars. Radiotherapy plays a role in the recruitment of T cells in the tumor microenvironment, increases CD4 + and CD8 + T cells, and increases PD-L1 expression, resulting in the synergistically enhanced antitumor effect of irradiation and PD-L1 blockade. Radiotherapy can cause changes in tumor metabolism, especially glucose metabolism. Tumor glycolysis and tumor immune evasion are interdependent, glycolytic activity enhances PD-L1 expression on tumor cells and thus promotes anti-PD-L1 immunotherapy response. Therefore, the mechanism of radiotherapy affecting tumor immunity may be partly through intervention of tumor glucose metabolism. Furthermore, some authors had found that the uptake of 2'-deoxy-2'-[18F]fluoro-D-glucose(18F-FDG) was correlated with PD-1/PD-L1 expression. Positron emission tomography/computed tomography (PET/CT) is a non-invasive detection method for PD-1/PD-L1 expression and has several potential advantages over immunohistochemical (IHC), PET/CT can dynamically reflect the expression of PD-1/PD-L1 inside the tumor and further guide clinical treatment.

Successful surgery with preservation of laryngeal function in a patient with collision primary squamous cell carcinoma and adenoid cystic carcinoma in the hypopharynx and synchronous esophageal carcinoma: A case report.

BACKGROUND: The definition of "collision tumor" is the coexistence of two histologically and morphologically distinct tumors within the same anatomical area without histological admixture. Collision tumors featuring primary squamous cell and adenoid cystic carcinomas of the hypopharynx, combined with synchronous esophageal carcinoma, are very rare. METHODS: We describe a patient with a collision tumor of the hypopharynx and synchronous esophageal carcinoma who underwent partial laryngectomy, with preservation of laryngeal function, and radical esophageal resection featuring esophageal reconstruction using a gastric tube. Surgery was successful. RESULTS: Postoperative radiotherapy was recommended after surgery; the patient exhibited no recurrence or distant metastasis to the 17-month follow-up. CONCLUSION: To the best of our knowledge, this is the first report of collision of primary squamous cell carcinoma and adenoid cystic carcinoma in the hypopharynx and synchronous esophageal carcinoma. We performed appropriate surgery and prescribed postoperative radiotherapy. This preserved laryngeal function.

Enhanced Mitophagy in Cholesteatoma Epithelial Cells.

HYPOTHESIS: Mitophagy may have a potential role in the pathogenesis of acquired cholesteatoma. BACKGROUND: Enhanced mitophagy has been proven to be involved in various cancers. However, its role in the pathogenesis of cholesteatoma, which shares some common features with cancer, is controversial. This study investigated mitophagy in cholesteatoma epithelial cells. METHODS: The autophagy protein markers LC3-II and p62 and mitophagy proteins BNIP3, Parkin, and PINK1 were analyzed in cholesteatoma epithelial cells and external auditory canal epithelium cells by immunoblotting. The results were confirmed by immunohistochemistry. Adenovirus Ad-mCherry-GFP-LC3B and Ad-GFP-LC3B were used to evaluate autophagic activity. Transmission electron microscopy was used to observe and analyze autophagosomes. RESULTS: LC3-II expression was increased in cholesteatoma cells, whereas soluble and insoluble p62 levels were decreased. The expressions of BNIP3, Parkin, and PINK1 were higher in total protein and mitochondrial protein of cholesteatoma cells compared with normal external auditory canal epithelium cells. Autophagic activity was increased in cholesteatoma cells compared with normal external auditory canal epithelium cells. CONCLUSION: Mitophagy was enhanced in cholesteatoma epithelial cells and may have a potential role in the pathogenesis of acquired cholesteatoma.

Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy.

OBJECTIVE: To investigate the role of H+ /K+ ATPase in the proliferation of pepsin-induced vocal cord leukoplakia (VCL) cells. STUDY DESIGN: Translation research. SETTING: Affiliated Hospital of University. METHODS: Immunohistochemistry was used to detect pepsin, H+ /K+ ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+ /K+ -ATPase distribution of VCL cells were investigated. RESULTS: The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate-to-severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning- and autophagy-promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+ /K+ -ATPase and lysosomes in VCL cells; it also mediated lysosome acidification. CONCLUSION: Pepsin and H+ /K+ -ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+ /K+ -ATPase.

Multiple Thyroglossal Duct Cysts: Clinical Experience and Literature Review.

Thyroglossal duct cysts (TDCs) are generally single cyst, multiple TDCs are rare. We describe a case of multiple TDCs, discuss its characteristic features and management, and provide a review of the literature, to improve clinical diagnosis and treatment. We report an extremely rare case of multiple TDCs containing five cysts, together with a review of the relevant English medical literature. To the best of our knowledge, this is the first reported case of TDCs containing more than three cysts in the anterior cervical region. The five cysts were completely excised in a Sistrunk operation. Histological examination of the cystic lesions revealed TDCs. The patient recovered well and no recurrence was found during the 6-year of follow-up. Multiple TDCs are extremely rare, and may be misdiagnosed as a single cyst. Clinicians should be aware of the possibility of multiple thyroglossal duct cysts. Adequate preoperative radiological examinations should be performed, and careful interpretation of the CT or MRI scans is important to diagnosis and surgery.

Factors Influencing Postoperative Prognosis in Patients with Hypopharyngeal and Laryngeal Carcinoma.

OBJECTIVES: Despite the increasingly modern surgical techniques in the oncology field, the factors that influence postoperative prognosis in patients with hypopharyngeal and laryngeal carcinoma (HLC) remain unclear. The study aimed to evaluate the factors influencing the prognosis of HLC patients with pathological diagnosis of squamous cell carcinoma, and the findings are intended to direct follow-up management strategies. METHODS: A retrospective cohort study was performed. The study population included 407 postoperative patients with HLC from 2011 to 2015. Univariate and multivariate analyses were used to examine the prognostic factors identified. RESULTS: Based on univariate analysis results, smoking and alcohol history, tumor differentiation, preoperative radiotherapy, primary tumor sites, flap reconstruction, lymph node invasion (LNI), and preoperative albumin levels (PAL) significantly affects the prognosis of HLC patients (P < .05). Meanwhile, multivariate analysis revealed that smoking pack-year (OR = 1.002, 95% CI = 1.001 ∼ 1.003), primary tumor sites (OR = 6.241, 95% CI = 1.715 ∼ 18.433), LNI (OR = 2.869, 95% CI = 1.095 ∼ 8.743), and PAL (OR = .020, 95% CI = .004 ∼ 0.104) were associated with complications. Tumor differentiation (OR = 0.650, 95% CI = .383 ∼ 0.855), primary tumor sites (OR = 12.392, 95% CI = 3.290 ∼ 26.679), LNI (OR = 16.323, 95% CI = 2.726 ∼ 47.729), preoperative radiotherapy (OR = 9.300, 95% CI = 3.182 ∼ 27.181), and PAL (OR = .321, 95% CI = .141 ∼ .732) were associated with overall survival rates. CONCLUSION: Smoking and alcohol history, tumor differentiation, LNI, primary tumor sites, flap reconstruction, PAL, and preoperative radiotherapy are crucial factors that influence the postoperative prognosis of patients with HLC. In addition, a monogram of five factors was established to predict the survival rates of HLC patients.

Pepsin enhances glycolysis to promote malignant transformation of vocal fold leukoplakia epithelial cells with dysplasia.

PURPOSE: The mechanism underlying malignant transformation of vocal fold leukoplakia (VFL) and the precise role of the expression of pepsin in VFL remain unclear. This study aimed to investigate the effects of acidified pepsin on VFL epithelial cell growth and migration, and also identify pertinent molecular mechanisms. METHODS: Immunochemistry and Western blotting were performed to measure glucose transporter type 1 (GLUT1), monocarboxylate transporters 4 (MCT4), and Hexokinase-II (HK-II) expressions. Cell viability, cell cycle, apoptosis, and migration were investigated by CCK-8 assay, flow cytometry and Transwell chamber assay, respectively. Glycolysis-related contents were determined using the corresponding kits. Mitochondrial HK-II was photographed under a confocal microscope using Mito-Tracker Red. RESULTS: It was found: the expression of pepsin and proportion of pepsin+ cells in VFL increased with the increased dysplasia grade; acidified pepsin enhanced cell growth and migration capabilities of VFL epithelial cells, reduced mitochondrial respiratory chain complex I activity and oxidative phosphorylation, and enhanced aerobic glycolysis and GLUT1 expression in VFL epithelial cells; along with the transfection of GLUT1 overexpression plasmid, 18FFDG uptake, lactate secretion and growth and migration capabilities of VFL epithelial cell were increased; this effect was partially blocked by the glycolysis inhibitor 2-deoxy-glucose; acidified pepsin increased the expression of HK-II and enhanced its distribution in mitochondria of VFL epithelial cells. CONCLUSION: It was concluded that acidified pepsin enhances VFL epithelial cell growth and migration abilities by reducing mitochondrial respiratory complex I activity and promoting metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis.

Fibroblast-epithelial metabolic coupling in laryngeal cancer.

OBJECTIVES: To explore the Fibroblast-epithelial metabolic coupling among laryngeal cancers and its prognostic roles METHODS: We reviewed the clinical information of patients with laryngeal cancer in our department. Paraffin-embedded tissues from included patients were immune-stained with antibodies towards MCT4 and TOMM20 and evaluated for stromal and epithelial expression. Survival analysis and Cox regression analysis were applied to investigate the prognostic factor of laryngeal squamous cell carcinoma. TCGA database was used to validate our result. RESULTS: Stromal MCT4 and TOMM20 were both significantly associated with each other among laryngeal cancer tissues. High expression of both Stromal MCT4 and TOMM20 is related to poor prognosis in laryngeal cancer. Stromal MCT4 expression was an independent prognostic indicator for laryngeal cancer. Furthermore, cancer cell MCT4 expression has no relationship with the clinical characteristics of laryngeal cancer. CONCLUSIONS: Our results support that the phenomenon of metabolic symbiosis was exist in the laryngeal cancer tissue. In addition, TOMM20 and stromal MCT4 could be used as new therapeutic targets for laryngeal cancer.

Epstein-Barr virus-associated leiomyosarcoma of the larynx in an adult patient with human immunodeficiency virus infection: Case report and review of the literature.

We investigated the clinical features, treatment, and prognosis of laryngeal leiomyosarcoma (LLMS) and Epstein-Barr virus-associated (EBV-associated) LMS. We report a case of EBV-associated LLMS in an adult patient with HIV infection. We also conducted a review of the English-language literature on LLMS and EBV-associated leiomyosarcoma. To the best of our knowledge, 62 cases of LLMS and EBV-associated leiomyosarcoma have been reported to date. Of patients with LLS, 18.9% had distant metastases and 17.0% had local recurrence. The overall 5-year survival rate was 64.0%. Distant metastases affected the survival of patients with LLMS (p = 0.04). EBV-positive patients had a low survival rate (p = 0.01). Among patients with EBV-associated LMS, 8.2% had distant metastases and recurrence and the overall 5-year survival rate was 50.0%. EBV-associated LLMS is rare. The EBV infection might be a poor prognostic factor of LLMS.

Transcervical Exploration via the Posterolateral Approach to Extract a Fishbone Embedded in the Paraglottic Space.

Ingested foreign bodies occasionally migrate to the paraglottic space. The external transcervical approach is almost always required to extract completely embedded foreign bodies. We report a case of an ingested fishbone embedded in the paraglottic space, which was successfully removed through transcervical exploration of the paraglottic space via the posterolateral approach. The posterolateral approach is safe and effective for the removal of foreign bodies completely embedded in the paraglottic space.

Thyroglossal duct cyst with hoarseness as the sole symptom and an intralaryngeal extension masquerading as a laryngeal mass: Clinical experience and literature review.

A thyroglossal duct cyst is the most common congenital disease in the neck. There are two age groups usually associated with thyroglossal duct cysts: 1-11 years in children and 30-60 years in adults. These midline neck masses are typically located anteriorly in the neck, inferior to the hyoid bone. We report an extremely rare case of an intralaryngeal thyroglossal duct cyst without a neck mass, presenting with hoarseness as the sole symptom. A 64-year-old man presented with a 3-month history of hoarseness. On physical examination, no neck mass or swelling was observed during cervical palpation. Laryngostroboscopy revealed a large submucosal mass in the right glottis and supraglottis, and mobility of the right vocal cord was restricted. Surgery was performed via an external approach to completely resect the cyst, together with the middle part of the hyoid bone. Histopathologic examination of the cyst led to a diagnosis of thyroglossal duct cyst. The patient recovered well and his voice returned to normal. Attention should be paid to the occurrence of rare types of thyroglossal duct cyst in unusual clinical sites. Adequate radiological examinations should be performed, and reading the computed tomography or magnetic resonance imaging scans carefully before surgery is important to avoid misdiagnosis.

Awareness about laryngopharyngeal reflux disease among Chinese otolaryngologists: a nationwide survey.

OBJECTIVES: This study aimed to investigate the status of the current knowledge about laryngopharyngeal reflux disease (LPRD) among Chinese otolaryngologists. DESIGN: Multi-centre cross-sectional survey. SETTING: 220 medical centres in different regions of China. PARTICIPANTS: A total of 2254 otolaryngologists from 220 medical centres in China who were successfully on-site surveyed between November 2019 and December 2020. MAIN OUTCOME MEASURES: Awareness about LPRD included knowledge about risk factors, symptoms, laryngoscope signs, related diseases, current diagnostic methods and treatments. RESULTS: The percentage of participants who had heard of LPRD was 96.4%, with academic conferences as the most common source of information (73.3%). The most commonly known risk factor, symptom, laryngoscope sign, related disease, diagnostic method and treatment were alcohol consumption (44.0%), pharyngeal foreign body sensation (66.9%), hyperaemia (52.4%), pharyngolaryngitis (54.8%), pH monitoring (47.6%) and medication (82.1%), respectively. Only 28.3% of all participants knew that 24 h pH or multichannel intraluminal impedance pH monitoring was the most accurate diagnostic test. As many as 73.1% of all participants knew that proton pump inhibitors were the first-line treatment drugs. An analysis of the overall status of awareness using a scoring system suggested that otolaryngologists were better aware owing to more access, working at 3A hospitals, and postgraduate or above educational background (all p<0.05). CONCLUSION: Although the majority of Chinese otolaryngologists had heard of LPRD, their overall awareness about the disease was not encouraging. More efforts are needed to increase the knowledge about LPRD among this group of physicians. TRIAL REGISTRATION NUMBER: ChiCTR1900025581.

Angioleiomyoma of the Epiglottis Mimicking Epiglottic Hemangioma: Clinical Experience and Literature Review.

We describe a case of laryngeal angioleiomyoma, discuss its characteristic features and management, and provide a review of the literature, to improve clinical diagnosis and treatment. We report the oldest patient with a laryngeal angioleiomyoma to date and analyze the clinicopathological features reported in the literature. To the best of our knowledge, a total of 36 cases have been described in the English and Chinese medical literature (including our case). The male-to-female ratio was 5:1 and the mean age was 53.89 years. The most common laryngeal site was the supraglottic region (23 cases; 63.89%), followed by the subglottic region (8 cases; 22.22%), and glottis (5 cases; 13.89%). The most common and serious intra- and postoperative complication was massive bleeding. Angioleiomyoma is a benign tumor that rarely occurs in the larynx. Biopsy of this lesion should not be performed; complete surgical resection is the best treatment. Recurrence and malignant transformation are extremely rare.

MicroRNA-203a-3p may prevent the development of thyroid papillary carcinoma via repressing MAP3K1 and activating autophagy.

BACKGROUND: Papillary thyroid carcinoma (PTC) grows slowly but has a great risk of metastasis. MicroRNAs are well known as vital tumor-related gene regulators. In PTC, the role of miR-203a-3p and the underlying mechanisms remain not completely understood. METHODS: We conducted CCK8 assay, wound healing assay, transwell experiment and flow cytometry analyses to investigate the function of miRNA-203a-3p. The interaction of miRNA-203a-3p with its gene MAP3K1 was characterized by quantitative real-time polymerase chain reaction, western blotting and luciferase assay. RESULTS: We found that the levels of miRNA-203a-3p were statistically decreased in PTC tissues. When mimics were delivered to TPC-1 and KTC-1 cells to upregulate miR-203a-3p, it was observed that cell proliferation, metastatic abilities and cell cycle process were prevented but cell apoptosis was enhanced. Furthermore, we proved the interaction between MAP3K1 and miR-203a-3p. Intriguingly, similar to miR-203a-3p mimics, siMAP3K1 showed a tumor-suppressive effect, and this effect could be reversed when miR-203a-3p was simultaneously inhibited. Finally, selected autophagy-linked proteins such as LC3 Beclin-1 were detected and found to be increased when miR-203a-3p was upregulated or MAP3K1 was inhibited. CONCLUSION: Overall, miR-203a-3p inhibits the oncogenic characteristics of TPC-1 and KTC-1 cells via suppressing MAP3K1 and activating autophagy. Our findings might enrich the understanding and the therapeutic strategies of PTC.

Effect of Glut-1 and HIF-1α double knockout by CRISPR/CAS9 on radiosensitivity in laryngeal carcinoma via the PI3K/Akt/mTOR pathway.

Hypoxic resistance is the main obstacle to radiotherapy for laryngeal carcinoma. Our previous study indicated that hypoxia-inducible factor 1α (HIF-1α) and glucose transporter 1 (Glut-1) double knockout reduced tumour biological behaviour in laryngeal carcinoma cells. However, their radioresistance mechanism remains unclear. In this study, cell viability was determined by CCK8 assay. Glucose uptake capability was evaluated by measurement of 18 F-fluorodeoxyglucose radioactivity. A tumour xenograft model was established by subcutaneous injection of Tu212 cells. Tumour histopathology was determined by haematoxylin and eosin staining, immunohistochemical staining, and TUNEL assays. Signalling transduction was evaluated by Western blotting. We found that hypoxia induced radioresistance in Tu212 cells accompanied by increased glucose uptake capability and activation of the PI3K/Akt/mTOR pathway. Inhibition of PI3K/Akt/mTOR activity abolished hypoxia-induced radioresistance and glucose absorption. Mechanistic analysis revealed that hypoxia promoted higher expressions of HIF-1α and Glut-1. Moreover, the PI3K/Akt/mTOR pathway was a positive mediator of HIF-1α and/or Glut-1 in the presence of irradiation. HIF-1α and/or Glut-1 knockout significantly reduced cell viability, glucose uptake and PI3K/Akt/mTOR activity, all of which were induced by hypoxia in the presence of irradiation. In vivo analysis showed that knockout of HIF-1α and/or Glut-1 also inhibited tumour growth by promoting cell apoptosis, more robustly compared with the PI3K inhibitor wortmannin, particularly in tumours with knockout of both HIF-1α and Glut-1. HIF-1α and/or Glut-1 knockout also abrogated PI3K/Akt/mTOR signalling transduction in tumour tissues, in a manner similar to wortmannin. HIF-1α and/or Glut-1 knockout facilitated radiosensitivity in laryngeal carcinoma Tu212 cells by regulation of the PI3K/Akt/mTOR pathway.

Roles Played by the PI3K/Akt/HIF-1α Pathway and IL-17A in the Chinese Subtype of Chronic Sinusitis with Nasal Polyps.

BACKGROUND: The Chinese subtype of CRSwNP may have a unique pathogenesis. This study was designed to seek the role of the PI3K/Akt/HIF-1α pathway and IL-17A in CRSwNP. METHODS: The total IgE, ECP, and IL-17A levels were determined by UniCAP100 and ELISA. The activity of MPO was detected by the biochemical techniques. The protein expressions of HIF-1α, p-Akt, and PI3K were detected by the WB method. HIF-1α and IL-17A mRNA levels were measured by RT-PCR. RESULTS: The CRSwNP group showed significantly elevated MPO activity, PI3K, p-AKT protein, HIF-1α, and IL-17A mRNA levels in nasal polyps. Stimulated by the TNF-α, the PI3K, p-AKT, HIF-1α, and IL-17A levels significantly elevated in the fibroblasts. Inhibited by the Wortmannin, those indicators significantly declined in the fibroblasts. CONCLUSION: The PI3K/Akt/HIF-1α pathway played a role in the pathogenesis of CRSwNP. The elevated IL-17A level might be responsible for the neutrophilic inflammation in CRSwNP. The PI3K/Akt/HIF-1α pathway might regulate the IL-17A-related inflammation in CRSwNP.

The role of Glut-1 and H+/K+-ATPase expression in hyperplasia of mice laryngeal epithelium induced by pepsin.

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, ß 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, ß.

Role and mechanism of Glut-1 and H+/K+-ATPase expression in pepsin-induced development of vocal cord leukoplakia.

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, ß significantly increased in HVCLCs compared to in the absence of pepsin (p < 0.05). The expression of Glut-1 and H+/K+-ATPase α, ß 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 role of cancer stromal fibroblasts in mediating the effects of tobacco-induced cancer cell growth.

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.