Zhou Sh

Glucose transporter-1 as a new therapeutic target in laryngeal carcinoma.

Treatment options for laryngeal carcinoma, one of the most common head and neck malignancies, consist of radiotherapy, surgery, chemotherapy or a combination thereof. The functional treatment of laryngeal carcinoma poses a considerable challenge because of its resistance to chemotherapy and radiotherapy, and its tendency for local recurrence. Finding ways to inhibit the energy supply of malignant tumours is becoming an increasingly attractive proposition. Glucose transporter-1 (Glut-1; encoded by the SLC2A1 gene in humans) is the main transporter of glucose in solid carcinomas and has become a focus of cancer research. Recently, it was shown that the increased expression of SLC2A1 in head and neck carcinomas is correlated with lymph node metastasis, poor survival and clinical stage, and revealed that the suppression of SLC2A1 expression by antisense oligodeoxynucleotides decreased glucose uptake and inhibited the proliferation of Hep-2 cells. Thus, the authors propose the suppression of SLC2A1 expression as a new therapeutic target for laryngeal carcinoma.

Differential Diagnosis of Inflammatory Myofibroblastic Tumour and Low-Grade Myofibroblastic Sarcoma: Two Case Reports with a Literature Review

Inflammatory myofibroblastic tumour (IMT) and low-grade myofibroblastic sarcoma (LGMS) have similar morphological and immunophenotypic features, but LGMS is more malignant than IMT and the treatment requires a wider surgical margin plus post-operative chemotherapy or radiotherapy. To date, only 28 cases of IMT and two cases of LGMS have been reported in the laryngopharynx. Recent studies have suggested that anaplastic lymphoma kinase (ALK) and cytokeratin are important markers for differentiating between the two tumours. Here, two cases involving different myofibroblastic tumours of the larynx are reported. Based on the histological and immunohistochemical results, case 1 was diagnosed as IMT involving the right arytenoepiglottic fold, while case 2 was diagnosed as LGMS involving the epiglottic–glossal surface. There was no recurrence or metastasis in either case after post-operative follow-up (12 and 14 months, respectively). It is difficult to distinguish IMT from LGMS; both morphological and immunohistological analyses are required.

Glucose transporter-1 expression in CD133+ laryngeal carcinoma Hep-2 cells.

CD133 is a useful putative marker of cancer stem cells (CSCs) in human laryngeal tumors. Numerous studies have demonstrated that CD133+ CSCs possess higher clonogenicity, invasiveness and tumorigenesis compared with CD133- cells. Recently, interest in the Warburg effect in the microenvironment of CSCs has escalated. The Warburg effect dictates that cancer cells rely on glycolysis rather than oxidative phosphorylation under aerobic conditions. In numerous cancer cells, glucose is used mainly for the glycolytic pathway. Stem cells express high levels of glycolytic enzymes and rely mostly on glycolysis to meet their energy demands. Glucose is transported through cell membranes by glucose transporters (Glut). Studies of Glut-1 expression in CSCs are limited. In the present study, we investigated the proliferation of CD133+ Hep-2 cells and whether Glut-1 is expressed in laryngeal carcinoma CD133+ Hep-2 cells. Real-time reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that the size of the CD133 product was 213 bp. Dissociation curve analysis demonstrated only the expected peaks at 82.1˚C for CD133. The mean ΔCt of CD133 expression was 10.98. Prior to isolation, the CD133+ fraction was 1.2% by fluorescence-activated cell sorting (FACS) analysis. Following isolation, the CD133+ fraction was increased to 76.1%. Successive tests also demonstrated that cells grew well following isolation. The proliferation of CD133+ and CD133- cells was not different during the first 3 days (P>0.05). From day 4, the proliferation capacity of CD133+ cells in vitro was higher than that of CD133- cells (P<0.05). The mean ΔCt of Glut-1 mRNA expression was 1.78 for CD133+ cells and 1.00 for CD133- cells (P<0.05). The mean Glut-1 protein values in CD133+ and CD133- Hep-2 cells relative to β-tubulin were 0.48 ± 0.02 and 0.21 ± 0.03 (µg/µl), respectively (P<0.05). In conclusion, CD133+ cells demonstrated higher proliferation. Glut-1 mRNA and protein levels were higher in CD133+ than in CD133- cells. Our results suggest that Glut-1 is important in the energy supply of laryngeal CD133+ Hep-2 cells and Glut-1 may represent a potential therapeutic target for the inhibition of the proliferation of laryngeal CSCs.

Computed tomography and pathological findings of five nasal neurilemmomas

ObjectivesNeurilemmomas are benign tumors deriving from Schwann cells of the nerve sheath. They occur in all parts of the body. The highest incidence of neurilemmoma is in the head and neck region (38–45%), but involvement of the nose and paranasal sinus is quite rare, with only sporadic cases having been reported in the world literature. Fewer than 4% of these tumors involve the nasal cavity and paranasal sinuses. We describe the clinical, pathologic, and computed tomography (CT) features of five nasal neurilemmomas.MethodologyCT features of five patients with nasal schwannoma proved by operation and pathology were investigated.ResultsSchwannomas tend to be solitary and are usually well-circumscribed tumors with an oval, round or fusiform shape in the unilateral nasal cavity. The lesions usually have a mottled central lucency with peripheral intensification on contrast-enhanced CT scans. The heterogeneous appearance is related to areas of increased vascularity with adjacent non-enhancing cystic or necrotic regions.ConclusionsSchwannoma should be considered in the differential of unusual nasal masses. Certain clinical and CT patterns may be of use in the differential diagnosis.

Correlation of Computed Tomography with Pathological Features in Angiomatous Nasal Polyps

Background Angiomatous nasal polyps (ANPs), also known as angiectatic polyps, have rarely been reported in the literature. ANPs are characterized by extensive vascular proliferation and ectasia. ANPs can grow rapidly and exhibit aggressive clinical behavior that could simulate malignancy preoperatively, and they are easily confused with other diseases. In the present study, we analyzed the correlation between the computed tomography (CT) findings of nasal angiomatous polyps and their pathological features. Methods We evaluated CT findings and pathological features of 31 surgically proven ANPs. Results The study population included 16 males and 15 females aged between 27 and 81 years (mean age, 53.5 years). On CT, the masses were heterogeneous; they had a soft tissue density and filled the maxillary and/or nasal cavities. Calcifications were found in 2 of the 31 cases. The lesions showed a clear boundary (15/31). The low-density shading on CT was related to the inflammatory, necrotic, and cystic changes, and the high-density shading on CT was related to hemorrhagic areas of the mass. On contrast-enhanced CT, the center of the lesions was non-enhanced with peripheral intensification due to occlusion or compression of feeder vessels of the polyp center, and the inflammatory cells and neovascularization around the edge of the mass. The most common site of maxillary wall erosion was the medial wall (21/31), followed by the posterior lateral wall (3/31), upper wall (2/31), and septum (3/31). Of these, the nasal cavity and/or maxillary sinus were enlarged in 28 cases. These findings were associated with the chronic progress of nasal angiomatous changes. Conclusions CT of ANPs may demonstrate benign bone changes associated with the lesions and may also reflect the fact that ANPs do not invade peripheral soft tissue. CT demonstrated these lesions consistently and provided information useful for surgical planning.

Expression of Hypoxia Inducible Factor-1α and Its Significance in Laryngeal Carcinoma

This study examined levels of hypoxia inducible factor-1α (HIF-1α) protein in 40 laryngeal squamous cell carcinoma specimens using immunohistochemistry. Correlations between HIF-1α immunoreactivity and patient age, tumour lymph node metastasis stage, histological grade (extent of differentiation), and alcohol and smoking history were evaluated. Of the tumour tissues obtained, 35 (87.5%) were located in the glottic area and five (12.5%) in the supraglottic area. All patients were male and aged between 35 and 71 years; 12 (30.0%) presented with lymph node metastases, 24 (60.0%) had cancer classified as T1 or T2, and 16 (40.0%) as high clinical stage (T3 or T4). The pattern of HIF-1α protein localization in tumour tissues, when present, was mixed nuclear/cyto plasmic, with positive HIF-1α expression in 27 patients (67.5%). Differences in HIF-1α levels in samples from different tumour stages and in those with lymph node-positive versus lymph node-negative cancers were statistically significant.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Findings in Mucosa-Associated Lymphoid Tissue Lymphoma of the Larynx: A Case Report and Literature Review

Laryngeal mucosa-associated lymphoid tissue (MALT) lymphoma is rare, with only 25 cases reported in the literature. This report presents a case of laryngeal MALT lymphoma in a 35-year-old female with a 6-year history of progressively worsening hoarseness. MALT lymphoma was diagnosed based on biopsy and immunohistochemical analysis. The patient received two cycles of cyclo-phosphamide + epirubicin + vincristine + prednisone (CHOP) chemo therapy, which was ineffective. 18F-fluoro deoxy glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) showed 18F-FDG accumulation in the larynx only and identified stage IE lymphoma. CHOP chemotherapy was terminated and the patient was treated with radiotherapy. After 3 months (total radiation dose 27 Gy), 18F-FDG PET/CT scan showed that the laryngeal lesion was in complete remission. A review of the literature on the MEDLINE®/PubMed® databases regarding laryngeal MALT lymphoma and the use of PET/CT found that radiotherapy is the firstline treatment for stage I and II MALT lymphoma.

Anaplastic lymphoma kinase expression and prognosis in inflammatory myofibroblastic tumours of the maxillary sinus.

Inflammatory myofibroblastic tumours (IMT) of the nasal cavity and nasal sinus are rare and, although over 50 cases have been reported in the English-language literature, their precise aetiology and biological behaviour have not been elucidated. Recent studies suggest that anaplastic lymphoma kinase (ALK)-positive tumours have a very low risk of metastasis, but ALK reactivity does not appear to correlate with recurrence. Between March 2002 and December 2008, we encountered three cases of maxillary sinus IMT and investigated them to determine the clinicopathological course, prognosis and immunohistochemical expression of ALK. Two of the patients died < 13 months after the initial diagnosis and the third had multiple recurrences. All three cases were immunohistochemically negative for ALK expression. IMT of the sino-nasal tract is rare and may undergo malignant transformation in a minority of cases. The three cases manifested progressive extension with bone destruction and multiple recurrences, and two cases had a fatal outcome and one case had high recurrence.

Roles of glucose transporter-1 and the phosphatidylinositol 3‑kinase/protein kinase B pathway in cancer radioresistance

The mechanisms underlying cancer radioresistance remain unclear. Several studies have found that increased glucose transporter‑1 (GLUT‑1) expression is associated with radioresistance. Recently, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway was reported to be involved in the control of GLUT‑1 trafficking and activity. Activation of the PI3K/Akt pathway may itself be associated with cancer radioresistance. Thus, increasing attention has been devoted to the effects of modifying the expression of GLUT‑1 and the PI3K/Akt pathway on the increase in the radiosensitivity of cancer cells. This review discusses the importance of the association between elevated expression of GLUT‑1 and activation of the PI3K/Akt pathway in the development of radioresistance in cancer.

Expression of Glucose Transporter-1, Hypoxia-Inducible Factor-1α, Phosphatidylinositol 3-Kinase and Protein Kinase B (Akt) in Relation to [18F]Fluorodeoxyglucose Uptake in Nasopharyngeal Diffuse Large B-Cell Lymphoma: A Case Report and Literature Review

This report presents a case of nasopharyngeal diffuse large B-cell lymphoma and a literature review concerning the use of [18F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). A 37-year old man was admitted to hospital complaining of nasal secretions with minor epistaxis and a 20-year history of snoring. Nasal endoscopy found diffuse swelling in the nasopharynx and a biopsy was performed. Prior to chemotherapy, FDG-PET/CT showed soft-tissue diffuse thickening and FDG accumulation in the nasopharynx and bilateral cervical lymph nodes; FDG did not accumulate elsewhere. After four cycles of chemotherapy (rituximab, cyclo-phosphamide, doxorubicin, vincristine) and prednisone treatment, FDG-PET/CT showed that FDG still accumulated in the nasopharynx and bilateral cervical lymph nodes, therefore radiotherapy was initiated. At 1 year, FDG-PET/CT showed no FDG accumulation. Immunohistochemical analysis revealed that the tumour was positive for phosphorylated protein kinase B (Akt), suggesting that FDG uptake may be associated with factors activated by the phosphatidylinositol 3-kinase/Akt signalling pathway.