Purpose: Laryngeal carcinomas always resist to radiotherapy. Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngeal carcinoma. Methods: We assessed the effect of GLUT-1 expression on radioresistance of laryngeal carcinoma and the effect of GLUT-1 expressions by antisense oligodeoxynucleotides (AS-ODNs) on the radiosensitivity of laryngeal carcinoma in vitro and in vivo. Results: After transfection of GLUT-1 AS-ODNs: MTS assay showed the survival rates of radiation groups were reduced with the prolongation of culture time (p<0.05); Cell survival rates were significantly reduced along with the increasing of radiation dose (p<0.05). There was significant difference in the expression of GLUT-1mRNA and protein in the same X-ray dose between before and after X-ray radiation (p<0.05). In vivo, the expressions of GLUT-1 mRNA and protein after 8Gy radiation plus transfection of GLUT-1 AS-ODNs were significant decreased compared to 8Gy radiation alone (p<0.001). Conclusion: Radioresistance of laryngeal carcinoma may be associated with increased expression of GLUT-1 mRNA and protein. GLUT-1 AS-ODNs may enhance the radiosensitivity of laryngeal carcinoma mainly by inhibiting the expression of GLUT-1.
Eight patients underwent ansa cervicalis anastomosis to the adductor branch of the recurrent laryngeal nerve for unilateral vocal cord paralysis. They were followed long enough (at least 1 year) to determine if the procedure was successful. All cases have been subjected to preoperative and postoperative voice recording, acoustic analysis, and videolaryngoscopy. Some of them have been subjected to stroboscopy and electromyography (EMG). Data from these cases indicate that satisfactory phonatory quality may be achieved after the procedure. The reinnervated vocal cord neither abducted nor adducted, but it presented itself in midline for precise apposition with the normal cord. Synchronous mucosal waves in both vocal cords could be observed. EMG showed that the procedure produced satisfactory reinnervation of the adductory muscles. Therefore, the authors believe that the procedure could be proposed as an alternative to Teflon injection or thyroplasty in selected cases.
Abstract. Malignant cells show increased glucose uptake in vitro and in vivo. This process is considered to be mediated by glucose transporters (GLUTs). Hypoxia-inducible factor-1α (HIF-1α) may upregulate GLUT-1 expression. Little is known about the correlation between HIF-1α and GLUT-1 expression in laryngeal carcinoma. The current study investigated this correlation immunohistochemically, according to various clinical and pathological features, in 49 paraffin-embedded archival tissue blocks from patients with laryngeal squamous cell carcinoma. HIF-1α and GLUT-1 expression was detected in 63.3 (31/49) and 55.1% (27/49) of the tumour samples, respectively. HIF-1α expression was significantly correlated with lymph node classification (P= 0.018), recurrence (P= 0.02) and metastasis (P= 0.031). GLUT-1A expression was significantly associated with recurrence (P=0.02) and metastasis (P=0.01). Univariate analyses revealed that HIF-1α (χ 2 =8.2; P=0.004) and GLUT-1 expression (χ 2 =9.0; P=0.003) were significantly associated with a poorer survival rate. In a multivariate analysis, GLUT-1 expression (P=0.006) was a significant predictor of poor survival rate, as well as the primary tumour site, lymph node invasion and distant metastasis. Based on Spearman's analysis, GLUT-1 expression and phosphatidylinositol 3-kinase (PI3K) expression were significantly correlated (r=0.504; P=0.000). This is the first study to demonstrate a significant correlation between GLUT-1 and HIF-1α expression in laryngeal carcinoma and to show increased GLUT-1 expression as an independent survival rate predictor. These results suggest that GLUT-1 is a potential new therapeutic target for laryngeal carcinoma.
Laryngeal tuberculosis may occur even without pulmonary tuberculosis, and the characteristics of the lesions appear to be more nonspecific. It is important to consider tuberculosis in the differential diagnosis of laryngeal disease.
Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is an important hypoxic marker in malignant tumors, including laryngeal carcinoma. Apigenin is a natural phytoestrogen flavonoid that has potential anticancer effects. Various studies have reported that the effects of apigenin on lowering GLUT-1 expression were involved in downregulation of the PI3K/Akt pathway. Thus, apigenin may improve the radiosensitivity of laryngeal carcinoma by suppressing the expression of GLUT-1 via the PI3K/Akt pathway. The effect of GLUT-1 and PI3K/Akt pathway-related factor expressions by apigenin or antisense oligonucleotides (AS-ODNs) on the radiosensitivity of laryngeal carcinoma in vivo was assessed. The xenograft volume, xenograft weight and apoptosis detection were performed to determine radiosensitivity. The results showed that apigenin or apigenin plus GLUT-1 AS-ODNs improved the radiosensitivity of xenografts. Apigenin or apigenin plus GLUT-1 reduced the expression of GLUT-1, Akt, and PI3K mRNA after X-ray radiation. We found similar results at the protein level. The results suggest that the effects of apigenin on inhibiting xenograft growth and enhancing xenograft radiosensitivity may be associated with suppressing the expression of GLUT-1 via the PI3K/Akt pathway. In addition, apigenin may enhance the effects of GLUT-1 AS-ODNs via the same mechanism.
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