Shui-Hong Zhou

Expression of Glucose Transporter-1 and -3 in the Head and Neck Carcinoma – The Correlation of the Expression with the Biological Behaviors

Objective: The aim of this study was to determine the biological significance of glucose transporter (Glut)-1 and Glut-3 expression in head and neck carcinoma (HNC). Methods: We detected expression of Glut-1 and -3 in 38 HNCs and analyzed the relationship between increased expression and the biological behavior of HNCs. Results: The gene expression levels of Glut-1 and -3 in HNCs were significantly higher than those in adjacent cancer tissues or in normal tissues. The GLUT-1 gene level was correlated with the lymph node metastasis and clinical stage of 38 HNCs, and the GLUT-3 gene level was correlated with the lymph node metastasis of 38 HNCs. Of the 38 cases, 30 showed positive expression of Glut-1 protein. The Glut-1 protein expression level was related to the lymph node metastasis and clinical stage of 38 HNCs. However, there was no case that expressed Glut-3 protein. The high expression of Glut-1 gene and protein was associated with poor survival in the HNCs. GLUT-3 gene expression was not associated with the prognosis of HNCs. Conclusions:GLUT-1 gene expression level and protein expression were correlated with lymph node metastasis, poor survival and clinical stage of HNCs. The GLUT-3 gene expression level was high in HNCs, and its expression was associated with an increased incidence of lymph node metastasis of HNCs.

Effect of Antisense Oligodeoxynucleotides Glucose Transporter-1 on Enhancement of Radiosensitivity of Laryngeal Carcinoma

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.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography as an Effective Diagnostic Workup in Cervical Metastasis of Carcinoma from an Unknown Primary Tumor

PURPOSE The purpose of this study is to assess the potential of ¹⁸F-fluorodeoxyglucose (¹⁸FDG) positron emission tomography/computed tomography (PET/CT) imaging for the diagnosis of cervical metastasis of carcinoma of an unknown primary tumor (CUP) and to determine whether the maximum standardized uptake value (SUV(max)) is a prognostic factor. METHODS Twenty-five consecutive patients with cervical metastasis of CUP were retrospectively analyzed by PET/CT between July 2007 and July 2011. RESULTS FDG PET/CT suggested a primary tumor in 21 out of 25 patients (84.0%). The sensitivity of FDG PET/CT in detecting the primary tumor was 73.3% (11 of 15), and the positive predictive value was 52.4% (11 of 21). The median follow-up duration of survival patients was 10.4 months (range: 0-30 months). The estimated 2-year overall survival rate of all patients was 50.0%. Univariate analyses did not reveal a significant difference in overall survival between the group of 11 patients identified by pathology and the 14 patients not identified by pathology (overall survival was 57.1% and 49.1%, respectively; p=0.468). The median SUV(max) was 7.6. In the log-rank test, patients with a low SUV(max) (≤ 7.0) in cervical lymph nodes had a significantly higher survival rate at 2 years (87.5% vs. 21.2%; p=0.007) than patients with a high SUV(max) (>7.0). CONCLUSIONS Although our study was inconclusive due to the small sample size, our results suggest that FDG PET/CT may be an effective diagnostic workup in the cervical metastasis of carcinoma from an unknown primary tumor (UPT). In the present study, SUV(max) of PET/CT in the cervical lymph node may serve as a prognostic factor of cervical metastasis of carcinoma from a UPT based on the limited number of patients. Further studies are needed to confirm these findings.

Clinical significance of FDG single-photon emission computed tomography: Computed tomography in the diagnosis of head and neck cancers and study of its mechanism.

BACKGROUND The metabolic changes of malignant cells are earlier than these of morphology. (18)F-fluorodeoxyglucose (FDG) single-photon emission computed tomography (SPECT)-computed tomography (CT) systems provide functional and anatomic images that could significantly improve its diagnostic capability. The molecular mechanisms of increased FDG uptake are still not fully understood. The correlation between FDG uptake and the expression of Glut in various tumor cells is still under debate. Further study is necessary to correlate increased FDG uptake by tumors with their Glut-1 and Glut-3 expression, which will lead to a better understanding and interpretation of SPECT-CT imaging. In this study, we, therefore, investigated in patients with head and neck carcinoma (HNC) the relationship between tumor FDG accumulation and the mRNA expression and protein expression of Glut-1 and Glut-3. MATERIALS AND METHODS Overall, 25 patients with HNC who underwent SPECT-CT imaging and CT or magnetic resonance imaging (MRI) studies were performed between April 2002 and March 2004. Then, the mRNA and protein expression of Glut-1 and Glut-3 in these 25 surgical or biopsied samples were studied with HNC to determine the correlate increased FDG uptake by tumors with their Glut-1 and Glut-3 expression. RESULTS Visual analysis of (18)F-FDG SPECT-CT gave sensitivity, specificity, and accuracy levels of 100%, 62.5%, and 88%, respectively. The tumor-to-background (T/B) ratios were 94.1%, 87.5%, and 92.0% for (18)F-FDG SPECT/CT, and 64.7%, 50.0%, and 60.0% for CT and MRI. This indicates that (18)F-FDG SPECT-CT is superior to CT and MRI. Significant correlation was found between FDG and Glut-1 mRNA or Glut-1 protein (p < 0.001). There was no correlation between T/B ratio and Glut-3 mRNA (r = 0.14, p > 0.01). CONCLUSIONS (18)F-FDG SPECT-CT can be as a prospective tool that can judge the malignancy or benignity of head and neck tumor, stage and classify the tumor, distinguish recurrence or necrosis or fibrosis of the tumor after treatment by surgery or radiotherapy, and detect unknown primary tumor. Glut-1 may largely mediate basal glucose transport in HNC cells.

Interleukin-17A expression in patients with chronic rhinosinusitis and its relationship with clinical features

Objective To investigate the expression of interleukin (IL) 17A in Chinese patients with chronic rhinosinusitis (CRS) and analyse its correlation with clinical parameters. Methods Patients undergoing functional endoscopic sinus surgery and matched controls were included in this retrospective study. Clinical assessments (using a visual analogue scale of symptom severity, Johansson endoscopic score and Lund–Mackay computed tomography score) were performed preoperatively. Mucosal specimens were analysed for inflammatory infiltration and IL-17A expression, using immunohistochemistry. Results In total, 40 patients undergoing functional endoscopic sinus surgery and 16 controls were included in the study. IL-17A levels were significantly higher in tissues from patients with CRS (with or without nasal polyps) than in control tissues. In CRS, IL-17A expression tended to be higher in tissues with infiltrating neutrophils than in those with infiltrating eosinophils, but this difference was not significant. IL-17A expression in CRS was positively correlated with symptom severity, endoscopic findings and radiological appearance. Conclusions Expression of IL-17A was higher in Chinese patients with CRS than in controls, and was associated with infiltrating inflammatory cells, symptom severity, endoscopic findings and radiological appearance. These findings suggest that IL-17A may play a role in CRS pathogenesis and remodelling of nasal polyps.

Palatine Tonsil Schwannoma: Correlation between Clinicopathology and Computed Tomography Features

We describe the case of a 37-year old male who presented with a schwannoma in his right palatine tonsil. The tumour and tonsil were surgically removed transorally. Tonsillar schwannomas are slow growing, and the main symptoms were a foreign body feeling in the throat, dysphagia and snoring. The presence of a round, well-defined mass lesion with heterogeneous density on computed tomography (CT) may aid in differentiation from other tonsillar tumours. The CT findings in the reported case were different to those of schwannomas in other locations; the particular CT manifestations of tonsillar schwannomas seem to relate to the various pathological changes seen within the tumour.

Differentiating laryngeal carcinomas from precursor lesions by diffusion-weighted magnetic resonance imaging at 3.0 T: a preliminary study.

Background Diffusion-weighted magnetic resonance imaging (DWI) has been introduced in head and neck cancers. Due to limitations in the performance of laryngeal DWI, including the complex anatomical structure of the larynx leading to susceptibility effects, the value of DWI in differentiating benign from malignant laryngeal lesions has largely been ignored. We assessed whether a threshold for the apparent diffusion coefficient (ADC) was useful in differentiating preoperative laryngeal carcinomas from precursor lesions by turbo spin-echo (TSE) DWI and 3.0-T magnetic resonance. Methods We evaluated DWI and the ADC value in 33 pathologically proven laryngeal carcinomas and 17 precancerous lesions. Results The sensitivity, specificity, and accuracy were 81.8%, 64.7%, 76.0% by laryngostroboscopy, respectively. The sensitivity, specificity, and accuracy of conventional magnetic resonance imaging were 90.9%, 76.5%, 86.0%, respectively. Qualitative DWI analysis produced sensitivity, specificity, and accuracy values of 100.0, 88.2, and 96.0%, respectively. The ADC values were lower for patients with laryngeal carcinoma (mean 1.195±0.32×10−3 mm2/s) versus those with laryngeal precancerous lesions (mean 1.780±0.32×10−3 mm2/s; P<0.001). ROC analysis showed that the area under the curve was 0.956 and the optimum threshold for the ADC was 1.455×10−3 mm2/s, resulting in a sensitivity of 94.1%, a specificity of 90.9%, and an accuracy of 92.9%. Conclusions Despite some limitations, including the small number of laryngeal carcinomas included, DWI may detect changes in tumor size and shape before they are visible by laryngostroboscopy. The ADC values were lower for patients with laryngeal carcinoma than for those with laryngeal precancerous lesions. The proposed cutoff for the ADC may help distinguish laryngeal carcinomas from laryngeal precancerous lesions.

Role of atopy in chronic rhinosinusitis with nasal polyps: does an atopic condition affect the severity and recurrence of disease?

BACKGROUND The role of atopy in chronic rhinosinusitis is unclear: it is particularly controversial in chronic rhinosinusitis with nasal polyps. METHODS A prospective study of 210 patients with chronic rhinosinusitis with nasal polyps was performed. Patient demographics, visual analogue scale scores, Lund-Kennedy endoscopy scores, Lund-Mackay computed tomography scores, serum total immunoglobulin E levels, serum eosinophil cationic protein (ECP) levels and Phadiatop test findings were analysed. RESULTS There were no significant differences in age, sex, visual analogue scale score, Lund-Mackay computed tomography score, total serum immunoglobulin E level, serum ECP level or Phadiatop test results between patients with primary and recurrent chronic rhinosinusitis with nasal polyps. A total of 99 patients (47 per cent) had positive atopy tests. No significant differences in sex, visual analogue scale score, Lund-Kennedy endoscopy score, Lund-Mackay computed tomography score or recurrence rates were found between atopic and non-atopic patients; however, atopic patients were significantly younger than non-atopic patients. Atopy status did not correlate with disease severity. CONCLUSION There was no association between atopy status and either disease severity or recurrence in patients with chronic rhinosinusitis with nasal polyps, although atopic patients were younger than non-atopic patients.

Primary malignant myoepithelioma of the left maxillary sinus: a case report.

We describe the case of a 41-year-old woman who presented with a malignant myoepithelioma (MME) in her left maxillary sinus. Exploratory biopsy of the left maxillary sinus was performed and pathological examination demonstrated that the tumour was positive for calponin and cytokeratin 14, which are indicative of MME. Lateral rhinotomy and left total maxillectomy were undertaken and the patient received radiotherapy and chemotherapy post-surgery. Primary recurrence and metastasis to the left angle of the mandible occurred 9 months after the surgery. The patient died of cachexia 13 months after the surgery.

Co-Inhibition of GLUT-1 Expression and the PI3K/Akt Signaling Pathway to Enhance the Radiosensitivity of Laryngeal Carcinoma Xenografts In Vivo

In the present study, we investigated the role of GLUT-1 and PI3K/Akt signaling in radioresistance of laryngeal carcinoma xenografts. Volume, weight, radiosensitization, and the rate of inhibition of tumor growth in the xenografts were evaluated in different groups. Apoptosis was evaluated by TUNEL assay. In addition, mRNA and protein levels of GLUT-1, p-Akt, and PI3K in the xenografts were measured. Treatment with LY294002, wortmannin, wortmannin plus GLUT-1 AS-ODN, and LY294002 plus GLUT-1 AS-ODN after X-ray irradiation significantly reduced the size and weight of the tumors, rate of tumor growth, and apoptosis in tumors compared to that observed in the 10-Gy group (p<0.05). In addition, mRNA and protein expression of GLUT-1, p-Akt, and PI3K was downregulated. The E/O values of LY294002, LY294002 plus GLUT-1 AS-ODN, wortmannin, and wortmannin plus GLUT-1 AS-ODN were 2.7, 1.1, 1.8, and 1.8, respectively. Taken together, these data indicate that GLUT-1 AS-ODN as well as the inhibitors of PI3K/Akt signaling may act as radiosensitizers of laryngeal carcinoma in vivo.