Entity

Time filter

Source Type


Chuang H.-C.,Kaohsiung Chang Gung Head and Neck Oncology Group | Chen C.-H.,Chang Gung University | Huang C.-C.,Kaohsiung Chang Gung Head and Neck Oncology Group | Fang F.-M.,Kaohsiung Chang Gung Head and Neck Oncology Group | And 2 more authors.
Experimental and Therapeutic Medicine | Year: 2011

The functions of telomeric repeat-binding factor 1 (TRF1) and 2 (TRF2) in oral carcinogenesis are largely unexplored. This study examined the relationship between the expression of TRF1 and TRF2 and clinicopathological variables and survival in oral cavity squamous cell carcinoma (OCSCC). Western blotting and immunohistochemistry were used to evaluate the protein expression of TRF1 and TRF2 in paired OCSCC patient specimens. Expression of TRF1 and TRF2 was assessed by immunohistochemistry in 256 OCSCC patients who underwent tumor resection without previous radiotherapy. The results were analyzed using Fisher's exact test. Protein expression of TRF1 and TRF2 was significantly lower in the OCSCC than in the adjacent non-tumor tissue. Reduced TRF1 and TRF2 levels in 256 patients, as revealed by immunohistochemistry, were significantly associated with aggressive clinicopathological features, such as advanced tumor stage (p<0.001) and advanced tumor node metastasis stage (p<0.001). According to Kaplan-Meier analysis, reduced TRF1 expression was significantly correlated with an unfavorable cumulative 5-year overall survival rate (p<0.001). In conclusion, decreased expression of TRF1 was significantly associated with tumor progression and poor prognosis in OCSCCpatients.


Chien C.-Y.,Chang Gung University | Chien C.-Y.,Kaohsiung Chang Gung Head and Neck Oncology Group | Tsai H.-T.,Chang Gung University | Tsai H.-T.,Kaohsiung Chang Gung Head and Neck Oncology Group | And 14 more authors.
Oncotarget | Year: 2014

The clinical significances, cellular effects, and molecular mechanisms by which Aurora-A mediate its invasive effects in HNSCC are still unclear. Here, we found that Aurora-A expression is significantly higher in tumor tissues on 14-microarray of HNSCC in Oncomine-databases. The activity of Aurora-A was not only found in HNSCC specimens, but also significantly correlated with advanced-T-classification, positive-N-classification, TNM-stage and the poor 5-year survival rate. HNSCC-microarray profile showed that osteopontin and Aurora-A exhibited positive correlation. Stimulation of HNC cells with osteopontin results in an increase in Aurora-A expression where localized at the centrosome. Functionally, Aurora-A had the abilities to stimulate cell motility in HNC cells through increase ERK1/2 activity under osteopontin stimulation. Conversely, depletion of Aurora-A expression by siRNAs suppressed ERK1/2 activity as well as inhibition of cell invasiveness. Treatment with anti-CD44 antibodies in HNC cells not only caused a decrease of mRNA/protein of Aurora-A and ERK1/2 activity upon osteopontin stimulation, but also affected the abilities of Aurora-A-elicited cell motility. Finally, immunohistochemical/Western-blotting analysis of human aggressive HNSCC specimens showed a significant positively correlation between osteopontin-Aurora-A and ERK1/2. These findings suggest that Aurora-A is not only an important prognostic factor but also a new therapeutic target in the osteopontin/CD44/ERK pathway for HNSCC treatment.


Lin Y.-T.,Chang Gung University | Lin Y.-T.,Kaohsiung Chang Gung Head and Neck Oncology Group | Chuang H.-C.,Chang Gung University | Chuang H.-C.,Kaohsiung Chang Gung Head and Neck Oncology Group | And 10 more authors.
BMC Cancer | Year: 2012

Background: Hypoxic tumors are refractory to radiation and chemotherapy. High expression of biomarkers related to hypoxia in head and neck cancer is associated with a poorer prognosis. The present study aimed to evaluate the clinicopathological significance of erythropoietin receptor (EPOR) expression in oral squamous cell carcinoma (OSCC).Methods: The study included 256 patients who underwent primary surgical resection between October 1996 and August 2005 for treatment of OSCC without previous radiotherapy and/or chemotherapy. Clinicopathological information including gender, age, T classification, N classification, and TNM stage was obtained from clinical records and pathology reports. The mRNA and protein expression levels of EPOR in OSCC specimens were evaluated by Q-RT-PCR, Western blotting and immunohistochemistry assays.Results: We found that EPOR were overexpressed in OSCC tissues. The study included 17 women and 239 men with an average age of 50.9 years (range, 26-87 years). The mean follow-up period was 67 months (range, 2-171 months). High EPOR expression was significantly correlated with advanced T classification (p < 0.001), advanced TNM stage (p < 0.001), and positive N classification (p = 0.001). Furthermore, the univariate analysis revealed that patients with high tumor EPOR expression had a lower 5-year overall survival rate (p = 0.0011) and 5-year disease-specific survival rate (p = 0.0017) than patients who had low tumor levels of EPOR. However, the multivariate analysis using Cox's regression model revealed that only the T and N classifications were independent prognostic factors for the 5-year overall survival and 5-year disease-specific survival rates.Conclusions: High EPOR expression in OSCC is associated with an aggressive tumor behavior and poorer prognosis in the univariate analysis among patients with OSCC. Thus, EPOR expression may serve as a treatment target for OSCC in the future. © 2012 Lin et al.; licensee BioMed Central Ltd.


Lin Y.-T.,Chang Gung University | Lin Y.-T.,Kaohsiung Chang Gung Head and Neck Oncology Group | Chien C.-Y.,Chang Gung University | Chien C.-Y.,Kaohsiung Chang Gung Head and Neck Oncology Group | And 13 more authors.
Laryngoscope | Year: 2015

Objectives/Hypothesis Perineural invasion (PNI), lymphovascular invasion (LVI), and extracapsular spread (ECS) of lymph nodes are adverse histopathologic factors among patients with oral cancer. We analyzed the clinical impact of the combination of PNI, LVI, and ECS among patients with oral cancer. Study Design Retrospective analysis of patients with oral cancer that was treated primarily with surgery with at least 5 years of follow-up data in a tertiary referral center. Methods In total, 554 patients diagnosed with oral cavity squamous cell carcinoma who underwent operations consecutively between 2006 and 2008 in our hospital were enrolled. Clinical characteristics, 5-year survival rates, and local/regional control rates were analyzed. Results There were 41 females and 513 males. Patients with PNI, LVI, or ECS presented pathologically had 5-year overall survival rates of 58.4%, 50.4%, and 31.4%, respectively. Patients with both ECS and PNI or both ECS and LVI presented had 5-year overall survival rates of 31.5% and 22.2%, respectively. Patients presenting with triple-positive status (PNI, LVI, and ECS) had only a 20.0% 5-year overall survival rate. The 5-year local/regional control rate for patients with both ECS and PNI or both ECS and LVI was 26% and 44.4%, respectively; for all three factors, it was 26.7%. Conclusion Patients with triple-positive status (PNI, LVI, ECS), ECS and PNI, or ECS and LVI experienced very low 5-year local/regional control rates, 5-year overall, and disease-specific survival rates. Novel interventions are necessary to improve these clinical outcomes. Level of Evidence 4. Laryngoscope, 125:E300-E305, 2015 © 2015 The American Laryngological, Rhinological and Otological Society, Inc.


Hwang C.-F.,Chang Gung University | Hwang C.-F.,Kaohsiung Chang Gung Head and Neck Oncology Group | Chien C.-Y.,Chang Gung University | Chien C.-Y.,Kaohsiung Chang Gung Head and Neck Oncology Group | And 13 more authors.
Journal of Pathology | Year: 2010

Nasopharyngeal carcinoma (NPC) is known for its highly metastatic character. Recent advances in diagnosis and treatment have not improved the high mortality rate that is attributable to early metastasis. Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear. We demonstrate comprehensively that fibulin-3 is down-regulated in NPC. Loss of fibulin-3 expression is significantly correlated with advanced tumour and lymph node-metastasis stages, and indicates a poor 5-year survival rate. Functionally, fibulin-3 has the ability to suppress cell migration and invasion in NPC cancer cells by decreasing the activity of phospho-AKT. Conversely, its depletion by fibulin-3-mediated siRNAs may elevate phospho-AKT activity and significantly enhance the ability of NPC cancer cells to migrate and invade. Consistent with this negative association between fibulin-3 and phospho-AKT, their expression levels are inversely correlated in NPC specimens by immunohistochemical analysis. Thus, lower fibulin-3 expression is an important indicator of poor survival. It may also contribute to the development of new therapeutic strategies to block the PI3K/AKT pathway in NPC cancer cells. © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Discover hidden collaborations