Xing-Mei Luo

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.

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.

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.

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.

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.

CD34-Positive Expression in Benign Nasal Glomus Tumour: Two Case Reports and a Literature Review

Nasal glomus tumours are extremely rare neoplasms with poorly understood histogenesis, but which are clinically recognized as benign. The neoplastic cells of glomus tumours resemble normal glomus cells and are arranged around a varying number of thin-walled, sometimes branching, capillaries. CD34 is known to be a marker of tumour progenitor cells. In this report, two cases of benign nasal glomus tumour are presented. The tumours were excised completely via endoscopic endonasal surgery under local anaesthesia. During surgery, there was little bleeding and the post-surgical course for both patients was uneventful. Tumour cells from both cases were positive for α-smooth muscle actin, actin, vimentin and CD34 protein. Thus, CD34 positivity against a background of other immunohistochemical markers is helpful in the differential diagnosis of glomus tumours.

Etiology analysis and computed tomography imaging of a tonsillar inflammatory myofibroblastic tumor: report of an immunocompetent patient and brief review

ObjectivesThe etiology of Inflammatory myofibroblastic tumor(IMT) is contentious. In this study, we used computed tomography (CT) to examine tonsillar IMT and further analyzed the etiology of this entity.MethodologyWe presented CT features of left tonsillar IMT and reviewed the English-language literature published between 1984 and 2011.ResultsTo our knowledge, there are only six published cases of tonsillar IMT including the present case. Two patients were asymptomatic at initial presentation. Two patients were taking immunosuppressants, and one was pregnant and in an immunomodulated state. CT of our patient revealed a 2.6 × 1.8 cm irregular soft tissue mass between the left tonsil and the base of the tongue. It did not invade surrounding structures and was not enhanced on contrast-enhanced imaging.ConclusionsTonsillar IMT may be a benign tumor. We suggest that preoperative recognition of tonsillar IMT by CT may be important to avoid unnecessary expanded surgery.

Calponin Expression in Laryngeal Myoepithelial Carcinoma and Its Prognostic Implications: A Case Report and Literature Review:

A case report of laryngeal myoepithelial carcinoma (MEC) is presented and the literature concerning prognostic factors in MEC is reviewed. A 61-year old man was admitted to hospital with hoarseness and progressive dyspnoea. On examination, both vocal cords were fixed in the midline with a glottic fissure of only 3 mm. No tumour was seen, but the subglottis was not completely visible. A computed tomography scan showed a soft mass below the right vocal cord obstructing two-thirds of the larynx. On suspension laryngoscopy, a dull mass (1.5 × 1.5 cm) was seen below the right vocal cord, which was malignant on frozen biopsy. A total laryngectomy was performed and the patient received radiotherapy. He died of recurrence 25 months later. The tumour was positive for cytokeratin 14, S-100 protein and calponin. MEC of the larynx is extremely rare. The clinical behaviour of MEC is variable and prognostic factors have been poorly analysed. Calponin expression may be a prognostic factor, but other factors also affect the outcome in MEC.