Search

PDF file - 90K, Expression pattern of epithelial-mesenchymal transition markers in early and late passage SNUC cells. Expression pattern of epithelial markers (pan-keratin and E-cadherin) and mesenchymal markers (α-SMA and vimentin) in both early (at passage number 17 in MDA8788-6 and at passage number 15 in MDA8788-7) and late passage (at passage number 40) in the SNUC cells was analyzed by Western blotting. Both early and late passage of SNUC cells expressed only the epithelial markers and did not expressed mesenchymal markers.

PDF file - 88K, STR profile of the original specimen and MDA8788 cells

PDF file - 104K

Purpose: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer. Despite the use of multimodality treatment, the overall prognosis remains poor. To better understand the biologic features of SNUC and help develop new therapies for the disease, we established SNUC cell lines and characterized their biologic behaviors.Experimental Design: Cell lines were established from a patient with a T4N0M0 SNUC of the right maxillary sinus who was treated with surgical resection at our center. Tumor colonies were harvested and were sequentially replated onto larger plates. Two populations were developed and labeled MDA8788-6 and MDA8788-7. These cell lines were characterized with molecular, biomarker, functional, and histologic analyses.Results: Short tandem repeat genotyping revealed that the cell line is isogenic to the parental tumor, and cytogenetic analysis identified 12 chromosomal translocations. The SNUC cell lines do not form colonies in soft agar but are tumorigenic and nonmetastatic in an orthotopic mouse model of sinonasal cancer. Western blot analysis revealed that both MDA8788 cell lines express epithelial markers but do not express mesenchymal markers or the endocrine marker synaptophysin.Conclusions: This is the first report of the establishment of stable human-derived SNUC cell lines. The lines were highly tumorigenic and maintain the histologic and molecular features of the original tumor. These cell lines should serve as useful tools for the future study of SNUC biology and the development and testing of novel therapies for this deadly disease. Clin Cancer Res; 18(22); 6178–87. ©2012 AACR.

PDF file - 157K, Expression pattern of epithelial-mesenchymal transition markers in early and late passage SNUC cells. Expression pattern of epithelial markers (pan-keratin and E-cadherin) and mesenchymal markers (α-SMA and vimentin) in both early (at passage number 17 in MDA8788-6 and at passage number 15 in MDA8788-7) and late passage (at passage number 40) in the SNUC cells was analyzed by Western blotting. Both early and late passage of SNUC cells expressed only the epithelial markers and did not expressed mesenchymal markers.

PDF file - 79K, Cytogenetic analysis of the MDA8788-7 cell line. Representative G-banding of MDA8788-7 showed the same translocation in MDA8788-6; m1 t (1:17), m2 t (1:22), m3 t (1:15), m4 t (2:12), m5 t (4:15), m6 t (3:6), m7 t (8:19), m8 t (9:10), m9 t (9:16), m10 t (13:13), m11 t (14, 14) and m12 t (18:19).

PDF file - 169K, Tumorigenicity of MDA8788-7 cells. Tumorigenicity was examined by injecting cells into the flanks of the mice. (A) The cells injected into the flank without Matrigel formed in 75% of mice (6 of 8 mice). (B) By adding Matrigel, tumors grew much larger than the ones without adding Matrigel. (C) Average size of the tumors. (D) H& E staining from the tumor of the flank injection showed very similar appearance to the surgical specimen from the SNUC patient. The original magnifications x40 (left) and x200 (right).

PDF file - 133K, In vitro migration and invasion assays in MDA8788-6 cells. 4 x 104 cells were plated in insert wells or Matrigel-coated wells in the presence of 10% FBS. After 48 hours, OSC19 used as a positive control showed massive migration and invasion, whereas MDA8788-6 did not show any of them. The original magnification is x50.

PURPOSE: The incidence of sensorineural hearing loss (SNHL) after treatment with combination of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy in nasopharyngeal carcinoma (NPC) patients was evaluated, and relationships of SNHL with host factors, treatment-related factors, and radiation dosimetric parameters were investigated. METHODS: Fifty-one NPC patients treated with IMRT from 2004 to 2009 were analyzed. All patients received neoadjuvant, concurrent, or adjuvant use of cisplatin. Pure tone audiometry was performed during the follow-up period with a median time of 60 months, ranging from 28 to 84 months. Correlation of SNHL at low frequencies (pure tone average, 0.5-2 kHz) with a series of factors was analyzed. RESULTS: Among 102 ears, 12.7% had low-frequency SNHL and 42.2% had high-frequency (4 kHz) SNHL. The incidence of low-frequency SNHL was greater in patients with age > 40, with T-stage 4, or who received cumulative cisplatin dose (CCD) > 200 mg/m2 (P = .034, .011, and .003, respectively) and in ears with secretory otitis media (SOM) (P = .002). Several dosimetric parameters were found to be correlated with SNHL. Univariate analysis showed that the minimum radiation dose to 0.1 ml highest dose volume (D0.1 ml) of the cochlea was the best radiation-related predictive parameter. Multivariate analysis indicated that CCD, SOM, and D0.1 ml of cochlea (P = .035, .012, and .022, respectively) were the factors associated with SNHL. CONCLUSION: For NPC patients treated with IMRT and chemotherapy, the incidence of treatment-related SNHL was associated with CCD, D0.1 ml of cochlea, and SOM.

The female sex is traditionally considered a favorable prognostic factor for nasopharyngeal carcinoma (NPC). However, no particular study has reported this phenomenon. To explore the prognostic impact of gender on patients with NPC after definitive radiotherapy, we reviewed the clinical data of 2063 consecutive patients treated between 1st January 2000 and 31st December 2003 in the Sun Yat-sen University Cancer Center. The median follow-up for the whole series was 81 months. The female and male patients with early stage disease comprised 49.4% and 28.1% of the patient population, respectively. Both the 5-year overall survival (OS) and disease-specific survival (DSS) rates of female patients were significantly higher than those of male patients (OS: 79% vs. 69%, P < 0.001; DSS: 81% vs. 70%, P < 0.001). For patients with locoregionally advanced NPC, the 5-year OS and DSS rates of female vs. male patients were 74% vs. 63% (P < 0.001) and 76% vs. 64%, respectively (P < 0.001). A multivariate analysis showed that gender, age, and TNM stage were independent prognostic factors for the 5-year OS and DSS of NPC patients. The favorable prognosis of female patients is not only attributed to the early diagnosis and treatment but might also be attributed to some intrinsic factors of female patients.

BACKGROUND AND OBJECTIVE Early diagnosis of nasopharyngeal carcinoma (NPC) is difficult due to the insufficient specificity of the conventional examination method. This study was to investigate potential and consistent biomarkers for NPC, particularly for early detection of NPC. METHODS A proteomic pattern was identified in a training set (134 NPC patients and 73 control individuals) using the surface-enhanced laser desorption and ionization-mass spectrometry (SELDI-MS), and used to screen the test set (44 NPC patients and 25 control individuals) to determine the screening accuracy. To confirm the accuracy, it was used to test another group of 52 NPC patients and 32 healthy individuals at 6 months later. RESULTS Eight proteomic biomarkers with top-scored peak mass/charge ratios (m/z) of 8605 Da, 5320 Da, 5355 Da, 5380 Da, 5336 Da, 2791 Da, 7154 Da, and 9366 Da were selected as the potential biomarkers of NPC with a sensitivity of 90.9% (40/44) and a specificity of 92.0% (23/25). The performance was better than the current diagnostic method by using the Epstein-Barr virus (EBV) capsid antigen IgA antibodies (VCA/IgA). Similar sensitivity (88.5%) and specificity (90.6%) were achieved in another group of 84 samples. CONCLUSION SELDI-MS profiling might be a potential tool to identify patients with NPC, particularly at early clinical stages.

Purpose: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer. Despite the use of multimodality treatment, the overall prognosis remains poor. To better understand the biologic features of SNUC and help develop new therapies for the disease, we established SNUC cell lines and characterized their biologic behaviors. Experimental Design: Cell lines were established from a patient with a T4N0M0 SNUC of the right maxillary sinus who was treated with surgical resection at our center. Tumor colonies were harvested and were sequentially replated onto larger plates. Two populations were developed and labeled MDA8788-6 and MDA8788-7. These cell lines were characterized with molecular, biomarker, functional, and histologic analyses. Results: Short tandem repeat genotyping revealed that the cell line is isogenic to the parental tumor, and cytogenetic analysis identified 12 chromosomal translocations. The SNUC cell lines do not form colonies in soft agar but are tumorigenic and nonmetastatic in an orthotopic mouse model of sinonasal cancer. Western blot analysis revealed that both MDA8788 cell lines express epithelial markers but do not express mesenchymal markers or the endocrine marker synaptophysin. Conclusions: This is the first report of the establishment of stable human-derived SNUC cell lines. The lines were highly tumorigenic and maintain the histologic and molecular features of the original tumor. These cell lines should serve as useful tools for the future study of SNUC biology and the development and testing of novel therapies for this deadly disease. Clin Cancer Res; 18(22); 6178–87. ©2012 AACR.

Background Concurrent chemoradiotherapy (CCRT) has been shown to improve outcomes for stage III–IV nasopharyngeal carcinoma (NPC) patients compared with radiotherapy (RT) alone, but the effectiveness of the combined therapy for stage II NPC patients is unknown. Methods Patients with Chinese 1992 stage II NPC were randomly assigned to receive either RT alone (n = 114) or CCRT (n = 116). The CCRT patients were given concurrent cisplatin (30 mg/m 2 on day 1) weekly during RT. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), distant metastasis-free survival, and locoregional relapse-free survival. All patients were analyzed by the intent-to-treat principle. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) and in multivariable analyses to test the independent statistical significance of treatment intervention. Toxic effects and the response to treatment were analyzed using the x 2 test. All statistical tests were two-sided. Results With a median follow-up of 60 months, adding chemotherapy statistically significantly improved the 5-year OS rate (94.5% vs 85.8%; HR of death = 0.30, 95% CI = 0.12 to 0.76; P = .007), PFS (87.9% vs 77.8%; HR of progression = 0.45, 95% CI = 0.23 to 0.88; P = .017), and distant metastasis-free survival (94.8% vs 83.9%; HR of distant relapse = 0.27, 95% CI = 0.10 to 0.74; P = .007); however, there was no statistically significant difference in the 5-year locoregional relapse-free survival rate (93.0% vs 91.1%; HR of locoregional relapse = 0.61, 95% CI = 0.25 to 1.51; P = .29). Multivariable analysis showed that the number of chemotherapy cycles was the only independent factor that was associated with OS, PFS, and distant control in stage II NPC. The CCRT arm experienced statistically significantly more acute toxic effects (P = .001), although the rate of late toxic effects did not increase statistically significantly. Conclusion Concurrent chemotherapy and radiotherapy is associated with a considerable survival benefit for patients with

Background and Objective: Induction chemotherapy and radiotherapy or concurrent chemoradiotherapy are the most two effective treatments for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). This study was to compare the efficacy of induction-concurrent chemoradiotherapy versus induction chemotherapy and radiotherapy for patients with locoregionally advanced NPC. Methods: From August 2002 to April 2005, 408 patients were randomly divided into the induction-concurrent chemoradiotherapy (IC/CCRT) group and the induction chemotherapy and radiotherapy (IC/RT) group. Patients in both groups received the same induction chemotherapy, including two cycles of floxuridine (FuDR) plus carboplatin (FuDR 750mg/m^2, d1-5; carboplatin AUC=6). All the patients underwent radiotherapy one week after completing the induction chemotherapy. The patients in the IC/CCRT group also received carboplatin (AUC=6) on day 7, 28, and 49 during radiotherapy. Eight patients did not meet the inclusion criteria and were excluded. The remaining 400 cases were analyzed. Results: Grade Ⅲ/Ⅳ toxicity was found in 28.4% of the patients in the IC/CCRT group and 13.1% in the IC/RT group (P＜0.001). After a median follow up time of 3.9 years, the three-year overall survival was 75.9% and 83.4% (P=0.12) in the IC/CCRT and IC/RT groups, respectively. No significant differences in the failure-free survival rate, the locoregional control rate, and the distant control rate were found between the two groups. Conclusion: The IC/CCRT program does not improve the overall survival rate in patients with locoregionally advanced NPC compared with the IC/RT program.