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1.
Otolaryngol Head Neck Surg ; 169(5): 1247-1258, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37264983

RESUMO

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.


Assuntos
Doenças da Laringe , Pepsina A , Humanos , Prega Vocal/metabolismo , Autofagia , Células Epiteliais/metabolismo , Adenosina Trifosfatases , Proliferação de Células , Leucoplasia/metabolismo
2.
Ear Nose Throat J ; : 1455613231171828, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37194164

RESUMO

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.

3.
Pathol Res Pract ; 240: 154177, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36327815

RESUMO

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.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , Humanos , Transportadores de Ácidos Monocarboxílicos/metabolismo , Neoplasias Laríngeas/patologia , Proteínas Musculares/metabolismo , Prognóstico , Fibroblastos/patologia , Neoplasias de Cabeça e Pescoço/patologia
4.
Ear Nose Throat J ; : 1455613221116334, 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35968732

RESUMO

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.

5.
Ear Nose Throat J ; : 1455613221100030, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35730630

RESUMO

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.

6.
Ear Nose Throat J ; : 1455613221100031, 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35615989

RESUMO

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.

7.
J Cell Mol Med ; 26(10): 2881-2894, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35415942

RESUMO

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.


Assuntos
Carcinoma , Transportador de Glucose Tipo 1 , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neoplasias Laríngeas , Animais , Sistemas CRISPR-Cas , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/radioterapia , Linhagem Celular Tumoral , Glucose , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/radioterapia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tolerância a Radiação/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Wortmanina
8.
Eur Arch Otorhinolaryngol ; 279(6): 2981-2987, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35083516

RESUMO

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.


Assuntos
Refluxo Laringofaríngeo , Pepsina A , Adenosina Trifosfatases , Animais , Humanos , Hiperplasia/patologia , Mucosa Laríngea/patologia , Refluxo Laringofaríngeo/patologia , Camundongos , Pepsina A/análise
9.
Eur Arch Otorhinolaryngol ; 279(3): 1413-1424, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34800155

RESUMO

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.


Assuntos
Transportador de Glucose Tipo 1 , ATPase Trocadora de Hidrogênio-Potássio , Neoplasias Laríngeas , Refluxo Laringofaríngeo , Leucoplasia , Prega Vocal , Adenosina Trifosfatases/metabolismo , Transportador de Glucose Tipo 1/biossíntese , ATPase Trocadora de Hidrogênio-Potássio/biossíntese , Humanos , Neoplasias Laríngeas/patologia , Refluxo Laringofaríngeo/patologia , Leucoplasia/patologia , Pepsina A/análise , Pepsina A/farmacologia , Prega Vocal/patologia
10.
J Cell Mol Med ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955148

RESUMO

In this study, we investigated the ability of curcumin alone or in combination with GLUT1 siRNA to radiosensitize laryngeal carcinoma (LC) through the induction of autophagy. Protein levels in tumour tissues and LC cells were measured by immunohistochemistry and Western blotting. In vitro, cell proliferation, colony formation assays, cell death and autophagy were detected. A nude mouse xenograft model was established through the injection of Tu212 cells. We found that GLUT1 was highly expressed and negatively associated with autophagy-related proteins in LC and that curcumin suppressed radiation-mediated GLUT1 overexpression in Tu212 cells. Treatment with curcumin, GLUT1 siRNA, or the combination of the two promoted autophagy. Inhibition of autophagy using 6-amino-3-methypourine (3-MA) promoted apoptosis after irradiation or treatment of cells with curcumin and GLUT1 siRNA. 3-MA inhibited curcumin and GLUT1 siRNA-mediated non-apoptotic programmed cell death. The combination of curcumin, GLUT1 siRNA and 3-MA provided the strongest sensitization in vivo. We also found that autophagy induction after curcumin or GLUT1 siRNA treatment implicated in the AMP-activated protein kinase-mTOR-serine/threonine-protein kinase-Beclin1 signalling pathway. Irradiation primarily caused apoptosis, and when combined with curcumin and GLUT1 siRNA treatment, the increased radiosensitivity of LC occurred through the concurrent induction of apoptosis and autophagy.

11.
Front Oncol ; 11: 769310, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35117987

RESUMO

Langerhans cell sarcoma (LCS) is an extremely rare, malignant neoplasm that originates from Langerhans cells (LCs). Fewer than 70 cases have been reported in the English-language literature. LCS typically involves multiple organs, including the skin, lymph nodes, lungs, bone, bone marrow, liver, spleen, and soft tissues. Several etiological factors for LCS have been proposed, including immunosuppression, virus infection, and prior hematological disease. We report a rare case of LCS with Epstein-Barr virus (EBV) infection; bilateral cervical giant cysts were the initial manifestation. To our knowledge, this is the first report of LCS with EBV infection. The case information was complete, and the relevant literature was reviewed to gain insight into LCS. The case raises new questions on the oncogenic character of EBV.

12.
Otolaryngol Head Neck Surg ; 164(1): 160-165, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32692278

RESUMO

OBJECTIVE: To measure pepsin expression in patients with vocal fold leukoplakia and elucidate its clinical significance. STUDY DESIGN: Retrospective analysis of pathologic archive specimens. SETTING: Affiliated university hospital. SUBJECTS AND METHODS: The study included 45 patients with vocal fold leukoplakia and 19 with vocal fold polyps who underwent surgical treatment between December 2013 and July 2016. Masses were detected on both vocal cords in 5 patients with vocal fold leukoplakia and in 1 patient with vocal fold polyps. Immunohistochemistry was used to assess pepsin expression. In addition, the relationship of pepsin expression level with clinical characteristics of vocal fold leukoplakia was assessed. RESULTS: The rate of pepsin expression was high in the polyp group (75%) and the leukoplakia group (68%); however, the difference between groups was not significant (P > .05). Pepsin expression significantly increased according to grade of dysplasia (mild, 57.1%; moderate, 88.9%; severe, 100.0%; P = .034). Similarly, the percentage of lesions that exhibited strongly positive pepsin expression increased with the grade of dysplasia (mild, 37.1%; moderate, 66.7%; severe, 100.0%; P = .005). The leukoplakia recurrence rate was higher in patients with positive pepsin expression than in patients with negative pepsin expression but without a significant difference (P > .05). CONCLUSION: Our study suggests that pepsin was associated with the grade of dysplasia of vocal cord leukoplakia. Further investigation with appropriate control groups and controlling for other risk factors, such as smoking or alcohol consumption, is needed.


Assuntos
Doenças da Laringe/metabolismo , Leucoplasia/metabolismo , Pepsina A/metabolismo , Pólipos/metabolismo , Lesões Pré-Cancerosas/metabolismo , Prega Vocal/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Feminino , Humanos , Doenças da Laringe/patologia , Leucoplasia/patologia , Masculino , Pessoa de Meia-Idade , Pólipos/patologia , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos
13.
Onco Targets Ther ; 13: 12919-12931, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33363389

RESUMO

BACKGROUND: Several studies have suggested that laryngopharyngeal reflux disease (LPRD) or gastroesophageal reflux disease (GERD) is an independent risk factor for laryngeal carcinoma. However, it remains unclear whether either condition affects the level of H+/K+-ATPase expression in laryngeal carcinoma. MATERIALS AND METHODS: Immunohistochemistry, real-time RT-PCR, and Western blotting were used to explore the distributions of proton pump (H+/K+-ATPase) α- and ß-subunits in normal laryngeal tissue and laryngeal carcinoma. RESULTS: Messenger RNAs encoding both the α- and ß-subunits were found in the normal epiglottic, ventricular fold, vocal fold, and arytenoid mucosae, as well as epiglottic cartilage. The distributions and expression levels of H+/K+-ATPase α-subunits in various laryngeal subregions did not significantly differ in IHC, RT-PCR, or Western blotting. However, Western blotting revealed a significant difference between the expression level of the ß-subunit protein in the epiglottic cartilage and the levels in other sites. The expression levels of both subunits were significantly higher in carcinomatous than in paracarcinomatous tissue and normal laryngeal tissue. The mean follow-up duration was 66.2 months (range, 17-162 months). In all, 4 patients died during follow-up, 4 were lost to follow-up, and 22 were alive and free of disease at the end of follow-up. Two patients developed lung metastases and six developed disease recurrences (at 2, 8, 14, 16, 36, and 41 months). The 3- and 5-year overall survival (OS) rates were 93.0% and 77.0%, respectively. Univariate analyses showed that the 5-year OSs were significantly associated with the T, N, and clinical stages but not with age, alcohol use, pathological differentiation, or the expression levels of the α- or ß-subunits (as revealed by IHC, RT-PCR, or Western blotting). However, in multivariate regression analyses, the 5-year OSs were not significantly associated with any clinicopathological factor or the expression levels of either subunit. CONCLUSION: H+/K+-ATPase is expressed in the normal larynx, including in the epiglottic cartilage and the mucosae of the epiglottis, ventricular fold, and arytenoid vocal fold. The expression levels of the H+/K+-ATPase α- and ß-subunits in laryngeal carcinomas were higher than in normal laryngeal tissues.

14.
Int J Gen Med ; 13: 1509-1514, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33363399

RESUMO

PURPOSE: The presence of extra-gastric H+/K+ ATPases may explain the clinically significant effect of proton pump inhibitor (PPI) pharmacotherapy in patients with chronic laryngitis related to laryngopharyngeal reflux disease (LPRD) but without gastroesophageal reflux disease (GERD) symptoms. Given the need for a better understanding of GERD and LPRD, we review the various proton pumps with respect to their classification, function, and distribution. We then consider the potential role of the laryngeal H+/K+ ATPase pump in LPRD. METHODS: We searched databases of PubMed, EMBASE, and Web of Science to achieve related published before September 15, 2020. RESULTS: There were only seven English-literatures meeting inclusive criteria about laryngeal H+/K+ ATPases. Some studies provide convincing evidence of a laryngeal H+/K+ ATPase in normal laryngeal tissues but also suggest the potential role of the proton pump in the abnormal mucus secretion frequently seen in patients with chronic laryngitis. CONCLUSION: A laryngeal H+/K+ ATPase expresses in normal laryngeal tissues. These findings question the current understanding of GERD and LPRD.

15.
Head Neck ; 42(9): 2287-2297, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32314842

RESUMO

BACKGROUND: This study is to explore the role of curcumin and GLUT-1 antisense oligodeoxynucleotides (AS-ODN) on autophagy modulation-initiated radiosensitivity. METHODS: BALB/c mice were employed to establish xenograft model using Tu212 cell. The expression of autophagy- and apoptosis-related proteins was determined by WB. Autophagosome was observed under transmission electron microscope. Apoptosis of tumor tissue were detected by TUNEL staining. RESULTS: Combinations of curcumin and GLUT-1 AS-ODN with 10 Gy inhibited the tumor growth by inducing apoptosis of laryngeal cancer cells followed with the enhancement of autophagy. 3-MA also had a promotion effect on irradiation-mediated growth inhibition possibly by depressing PI3K and on curcumin/GLUT-1 AS-ODN-mediated growth inhibition potentially by regulating autophagic events. Of note, a de-escalation of radiotherapy dose (5 Gy) along with curcumin, GLUT-1 AS-ODN or 3-MA produced a stronger effect than high dosage of radiotherapy (10 Gy) alone. CONCLUSIONS: Curcumin and GLUT-1 AS-ODN improve the radiosensitivity of laryngeal carcinoma through regulating autophagy and inducing apoptosis.


Assuntos
Carcinoma , Curcumina , Neoplasias Laríngeas , Radiossensibilizantes , Animais , Apoptose , Autofagia , Linhagem Celular Tumoral , Curcumina/farmacologia , Transportador de Glucose Tipo 1 , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/radioterapia , Camundongos , Camundongos Endogâmicos BALB C , Oligodesoxirribonucleotídeos , Tolerância a Radiação , Radiossensibilizantes/farmacologia
16.
Onco Targets Ther ; 12: 9129-9142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31806998

RESUMO

BACKGROUND: Radiotherapy does not show good efficacy against laryngeal cancer due to radioresistance. Cancer stem cells (CSCs) are considered among the causes of radioresistance. Inhibition of glucose transporter-1 (GLUT-1) using GLUT-1 small interfering RNA (siRNA) may enhance the radiosensitivity of laryngeal cancer cells, but the underlying cellular mechanisms remain unclear. METHODS: The CD133+-Hep-2R cell line was established with repeated irradiation and magnetic-activated cell sorting. The effects of irradiation on CD133+-Hep-2R cells were examined by CCK-8 assay, Transwell assay, quantitative real-time polymerase chain reaction (RT-PCR), and Western blotting. The effects of GLUT-1 siRNA on the radiosensitivity of CD133+-Hep-2/2R cells were examined by RT-PCR, Western blotting, CCK-8 assay, colony formation assay, and Transwell assay in vitro and in a xenograft tumor model in nude mice. The cellular mechanism of enhanced radiosensitivity associated with GLUT-1 siRNA was investigated. The cell cycle and apoptosis rate were analyzed by flow cytometry, and the repair capability was examined by determining the levels of RAD51 and DNA-PKcs. RESULTS: CD133+-Hep-2/2R cells showed stronger proliferation, lower apoptosis rate, lower percentage of G0/G1 phase cells, higher percentages of S and G2/M phase cells, and higher expression levels of GLUT-1 than Hep-2/2R cells. Transfection with GLUT-1 siRNA inhibited the proliferation and invasive capability of CD133+-Hep-2R cells by inhibiting GLUT-1 expression, which also caused a redistribution of the cell cycle (higher proportion of cells in the G0/G1 phase and lower proportion in the S and G2/M phases), increased the apoptosis rate, and reduced DNA repair capability by suppressing RAD51 and DNA-PKcs expression. CONCLUSION: The results of this study suggest that GLUT-1 siRNA can enhance the radiosensitivity of CD133+-Hep-2R cells by inducing a redistribution of cell cycle phases, inhibiting DNA repair capability, and increasing apoptosis. Inhibition of GLUT-1 may have therapeutic potential for interventions to increase the radiosensitivity of laryngeal CSCs.

17.
Cancer Manag Res ; 11: 2087-2096, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30881132

RESUMO

BACKGROUND: Glucose transporter (GLUT)-mediated glucose uptake is an important process in the development of laryngeal carcinoma, one of the most common malignancies of the head and neck. GLUT-1, together with HIF-1α, is also an indicator of hypoxia. Both proteins play a critical role in glucose uptake and glycolysis in laryngeal carcinoma cells under hypoxic stress. A double gene knockout model in which HIF-1α and GLUT-1 are no longer expressed can provide important information about carcinogenesis in laryngeal carcinoma. PURPOSE: In this study we used the CRISPR/Cas 9 system to induce HIF-1α and GLUT-1 double gene knockout in HEp-2 cells and then used the knocked-out cells to study the role of these markers in laryngeal carcinoma, including in chemoradioresistance. METHODS: High-grade small-guide RNAs (sgRNAs) of HIF-1α and GLUT-1 were designed using an online tool and inserted into the pUC57-T7-gRNA vector. The recombinant plasmids were transfected into HEp-2 cells and positive cells were screened using the dilution method. Gene mutation and expression were determined by sequence analysis and immunoblotting. RESULTS: In HIF-1α and GLUT-1 double gene knockout HEp-2 cells, a 171-bp deletion in the HIF-1α genomic sequence was detected, whereas multiple base insertions resulted in frameshift mutations in the GLUT-1 gene. Neither HIF-1α nor GLUT-1 protein was expressed in positive cells. The proliferation, migration, and invasion of HEp-2 cells were significantly decreased afterward. The possible mechanism may be that the inhibition PI3K/AKT/mTOR pathway by HIF-1α and GLUT-1 double gene knockout using CRISPR/Cas9 technique lead to reduction of glucose uptake and lactic acid generation. CONCLUSION: Our HIF-1α and GLUT-1 double gene knockout HEp-2 cell model, obtained using a CRISPR/Cas9-based system, may facilitate studies of the pathogenesis of laryngeal carcinoma.

18.
World J Clin Cases ; 7(2): 242-252, 2019 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-30705902

RESUMO

BACKGROUND: Collision carcinoma is rare in clinical practice, especially in the head and neck region. In this paper, we report a case of squamous cell carcinoma (SCC) and neuroendocrine carcinoma (NEC) colliding in the larynx and review 12 cases of collision carcinoma in the head and neck to further understand collision carcinoma, including its definition, diagnosis, and treatment. CASE SUMMARY: A 61-year-old man presented with a 1-year history of hoarseness. Contrast-enhanced magnetic resonance imaging of the larynx revealed that the right vocal cord had a nodule-like thickening with obvious enhancement. Laryngoscopy revealed a neoplasm on the right vocal cord, and a malignant tumor was initially considered. A frozen section of right vocal cord was performed under general anesthesia. The pathological result showed a malignant tumor in the right vocal cord. The tumor was excised with a CO2 laser (Vc type). Routine postoperative pathology showed moderately differentiated SCC with small cell NEC in the right vocal cord. No metastatic lymph nodes or distant metastases were found on postoperative positron emission tomography/computed tomography. Because of the coexistence of SCC and NEC, the patient received adjuvant chemotherapy and radiotherapy. The patient was followed for 8 mo, and no recurrence or distant metastasis was found. CONCLUSION: The treatment of collision carcinoma in the head and neck region is uncertain due to the small number of cases.

19.
J Int Med Res ; 47(3): 1103-1113, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30526171

RESUMO

OBJECTIVE: Magnetic resonance imaging (MRI) provides important information regarding tumors in the parapharyngeal space (PPS), revealing their origin, whether they are benign or malignant, and their relationships with surrounding structures. METHODS: Twelve tumors in the PPS were completely excised using an endoscopically assisted transoral approach (EATA). The MRI features were analyzed. RESULTS: Ten pleomorphic adenomas confirmed on postoperative pathological examination had the parotid pedicle sign. A fat space between the tumor and parotid gland may distinguish such a tumor from a tumor arising from a minor salivary gland in the prestyloid space and a tumor arising from the deep lobe of the parotid gland. Both the jugular vein and carotid artery were displaced posteriorly in all 10 cases of pleomorphic adenomas. The principal features of the two schwannomas confirmed on postoperative pathological examination were separation of the internal carotid artery and internal jugular vein and anteromedial displacement of the internal carotid artery, suggesting that the tumors originated in the poststyloid space. In this review, 95 tumors were excised by the EATA in the English-language literature. CONCLUSIONS: MRI renders differential diagnosis possible. PPS tumors may be completely excised via an EATA guided by tumor features evident on preoperative MRI.


Assuntos
Adenoma Pleomorfo/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Neoplasias Faríngeas/cirurgia , Faringe/cirurgia , Adenoma Pleomorfo/patologia , Adulto , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Faríngeas/diagnóstico por imagem , Neoplasias Faríngeas/patologia , Faringe/diagnóstico por imagem , Faringe/patologia , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
20.
Medicine (Baltimore) ; 97(34): e11837, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30142775

RESUMO

RATIONALE: Basal cell adenoma (BCA) is a rare benign salivary gland tumor. It is difficult to be completely resected when arising in parapharyngeal space. A contemporary trend is to develop minimally invasive approaches on the premises of safety and complete resection. PATIENT CONCERNS: Three patients were referred to our ENT Outpatient Department with the chief complaint of an uncomfortable throat. CT or MRI revealed a unilateral mass in the parapharyngeal space, round or oval in shape, with well-defined borders. DIAGNOSES: CT and MRI provided useful information for the preoperative evaluation. The appearance of large-scale cystic components may be an important clue for the diagnosis of BCA. PET/CT images were also available in one case. The final diagnoses were all basal cell adenomas (tubular type) in parapharyngeal space according to the regular histopathological examination after surgery. INTERVENTIONS: All three cases were completely resected by a trans-oral approach. The average operative time and estimated blood loss were 86 (range, 61-106) min and 116.7 (range, 50-200) mL, respectively. Endoscopy was used in the largest case to further assess the residual cavity after the complete resection and hemostasis. OUTCOMES: Postoperative recovery courses were quick and uneventful, with no neurovascular complication. Patients were discharged on the 3-5 day after surgery on an oral diet. One patient reported symptoms of velopharyngeal incompetence, manifested as mild slurred speech and nighttime salivation, for up to 3 months, which recovered spontaneously thereafter. There was no evidence of recurrence in the follow-up period. LESSONS: In our experience, the trans-oral approach appeared to be effective, safe, and less invasive for extirpation of selected basal cell adenomas in the parapharyngeal space. An assistance of endoscopy facilitates the surgery.


Assuntos
Adenoma/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Neoplasias Faríngeas/cirurgia , Neoplasias das Glândulas Salivares/cirurgia , Adenoma/diagnóstico , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Neoplasias Faríngeas/diagnóstico , Neoplasias Faríngeas/patologia , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologia , Tomografia Computadorizada por Raios X
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