Yanhong Ma

Genomic methylation profiling combined with gene expression microarray reveals the aberrant methylation mechanism involved in nasopharyngeal carcinoma taxol resistance.

Taxol is a first-line chemoagent used for treatment of nasopharyngeal carcinoma (NPC). A major obstacle to achieving successful treatment is the development of cellular taxol drug resistance. Aberrant DNA methylation has been recognized to be associated with the transcriptional inactivation of genes related to cancer drug resistance development. To identify the mechanism of DNA methylation involved in NPC taxol resistance, we applied a genome-wide DNA methylation microarray assay to reveal methylation alteration in taxol-resistant NPC cell lines (CNE-1/taxol, 5–8F/taxol, HNE-2/taxol) established previously in our laboratory. Combining with gene expression microarray, we identified drug resistance-associated genes in taxol-resistant cell lines. We also investigated the coeffect of taxol and the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-dC) to confirm the involvement of DNA methylation. The methylation profiling revealed differential patterns between the drug-sensitive and -resistant cell lines. As a result, taxol-resistant cell lines were detected to be globally hypermethylated. Forty-eight differentially methylated genes (30 hypermethylated and 18 hypomethylated) were further identified commonly in the three taxol-resistant cell lines. Six of them (DLC1, CHFR, ABCC5, PEG10, ERBB2, and GSTP1) were independently confirmed to contribute to taxol resistance by both methylation-specific PCR and quantitative real-time PCR. Finally, we conclude that DNA methylation is closely correlated with taxol drug resistance in NPC cells. Combined analysis of DNA methylation and gene expression may enable the discovery of new therapeutic targets and prognostic biomarkers of cancers. Furthermore, DNA methylation inhibitors can reverse chemoresistance and prevent the development of acquired drug resistance.

Therapeutic effectiveness of endoscopic vidian neurectomy for the treatment of vasomotor rhinitis.

Abstract Conclusion: Our results indicate that vidian neurectomy may be recommended as an effective method for the treatment of vasomotor rhinitis (VMR). Objective: The aim of this work was to study the feasibility and effectiveness of vidian neurectomy treatment under the nasal endoscope for VMR. Methods: The study included 45 patients with VMR. They were all assigned to functional endoscopic surgery with vidian neurectomy. Results: The obtained data showed that, using the rhinoconjunctivitis quality of life questionnaire, vidian neurectomy treatment relieved the symptoms of VMR in 82.2% of the patients. Vidian neurectomy also led to the reduction of expression of several cytokines, including vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P, interleukin (IL)-4, and IL-5.

Analysis of prognostic factors of endoscopic optic nerve decompression in traumatic blindness

Abstract Conclusions: Hemorrhage within the ethmoid and/or sphenoid sinus and an interval between the time of injury and the time of operation exceeding 3 days are the risk factors for the visual prognosis of traumatic blindness. Objectives: To investigate the therapeutic efficacy of endoscopic optic nerve decompression in the treatment of traumatic blindness and to evaluate the relevant prognostic factors. Methods: Eighty-five cases of traumatic blindness were analyzed retrospectively. Univariate analysis and multiple logistic regression were performed to evaluate potential prognostic factors. Results: The overall rate of vision acuity improvement was 44.7% (38 of 85). Univariate analysis indicated that hemorrhage within the ethmoid and/or sphenoid sinus was significantly associated with unrecovered visual acuity. However, multiple logistic regression analysis identified that an interval between the time of injury and the time of operation exceeding 3 days, and hemorrhage within the ethmoid and/or sphenoid sinus were significantly correlated with the efficacy of treatment of traumatic blindness.

Univariate and multivariate analyses for postoperative bleeding after nasal endoscopic surgery

Abstract Conclusions: Our study suggested that the major risk factors for postoperative bleeding after nasal endoscopic surgery (NES) included hypertension, long-term non-steroidal anti-inflammatory drugs (NSAIDs), and previous nasal surgery. The use of preoperative corticosteroids is a valuable measure for reducing postoperative bleeding after NES. Objectives: To explore risk factors for postoperative bleeding after NES and find effective measures to reduce or prevent the condition. Methods: A total of 641 patients who underwent NES were analyzed retrospectively. Univariate analysis and logistic regression were performed to find potential risk factors. Results: The incidence of postoperative bleeding after NES was 8.4%. Multivariate logistic regression analysis revealed that the occurrence of postoperative bleeding after NES was positively associated with hypertension, long-term NSAIDs, previous NES, and modified submucosal septoplasty, but negatively associated with the use of preoperative corticosteroids.

Inhibition of α folate receptor resulting in a reversal of taxol resistance in nasopharyngeal carcinoma.

Objective. To further determine the role of FOLR1 in taxol resistance of nasopharyngeal carcinoma (NPC) and whether inhibition of FOLR1 expression reverses the taxol-resistant phenotype. Study Design. Correlation study between gene expression and cancer cell survival. Setting. University hospital. Subjects and Methods. Three taxol-resistant sub–cell lines with a different resistant index were established from the parental CNE-1 NPC cell line. The correlation between FOLR1 expression and taxol sensitivity was statistically analyzed. Inhibition of FOLR1 expression was carried out by RNA interference and by a FOLR1-specific monoclonal antibody, and taxol sensitivity was examined by colony formation assays. FOLR1 expression was also examined in 72 NPC patient specimens by immunohistochemistry. Results. The levels of FOLR1 expression were positively and significantly correlated with a taxol resistance phenotype (P < .05). Inhibition of FOLR1 expression resulted in a significantly increased sensitivity of taxol to taxol-resistant NPC cells (P < .05). An increase of FOLR1 expression by gene transfection caused a taxol-resistant phenotype in parental NPC cells. The level of FOLR1 expression was found to be related to clinical stage in NPC tissue samples. Conclusion. These results suggest that FOLR1 plays an important role in taxol resistance of NPC cells.

Increased Expression of Cullin 3 in Nasopharyngeal Carcinoma and Knockdown Inhibits Proliferation and Invasion

This study aimed to investigate the clinical significance of cullin 3 expression in nasopharyngeal carcinoma (NPC), as well as to explore the regulatory mechanism of cullin 3 underlying the growth and metastasis of NPC cells. Our findings showed that the expression levels of cullin 3 were significantly increased in both NPC tissues and cell lines. A strong positive correlation was found between cullin 3 expression and the Ki-67-based proliferation index in NPC tissues. Moreover, cullin 3 overexpression was correlated with local relapse and distant metastasis in NPC patients. In vitro experiments showed that knockdown of cullin 3 caused a significant reduction in the proliferation of NPC cells, probably by inducing cell cycle arrest. In addition, downregulation of cullin 3 inhibited colony formation and the migratory and invasive capacities of NPC cells. The expression levels of PCNA and epithelial-to-mesenchymal transition (EMT)-related proteins were also meditated by cullin 3 in NPC cells. Based on these findings, we demonstrated that cullin 3 plays a promoting role in the malignant progression of NPC and suggest that the cullin 3-based ubiquitin proteasome pathway may be used as a promising therapeutic target for NPC.