Guolin Tan

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.

Sinus Balloon Catheter Dilation in Pediatric Chronic Rhinosinusitis Resistant to Medical Therapy

IMPORTANCE Sinus balloon catheter dilation (SBCD) has been used for chronic rhinosinusitis (CRS). It is necessary to evaluate its effect on children with CRS. OBJECTIVE To evaluate the efficacy of SBCD on pediatric CRS in China. DESIGN, SETTING, AND PARTICIPANTS A prospective case-control study was conducted from October 1, 2012, to May 31, 2013, in an academic tertiary referral hospital. Participants included a total of 79 patients, aged 7 to 12 years, with CRS resistant to medical therapy. INTERVENTIONS Medical or SBCD treatment of pediatric CRS. MAIN OUTCOMES AND MEASURES Age, sex, and results of computed tomographic scan, SBCD (case group) or conservative treatment (control group), sinonasal-5 questionnaire (SN-5), and visual analog scale (VAS) were analyzed and compared. RESULTS Data from 79 of 96 patients who had complete follow-up documents were statistically analyzed (42 boys; 37 girls; mean [SD] age, 9.3 [1.7] years). Compared with the preoperative scores, the SN-5 and VAS scores in children with CRS who underwent SBCD with or without adenoidectomy were significantly lower at 3 months (2.5 vs 4.3 for SN-5; P < .001; 3.1 vs 5.2 for VAS; P < .001) and at 1 year (2.9 vs 4.3 for SN-5; P = .001; 3.1 vs 5.2 for VAS; P < .001). Both SN-5 and VAS scores in the control group were significantly decreased at 3 months (3.1 vs 4.2 for SN-5; P = .001; 3.9 vs 5.1 for VAS; P < .001) but not significantly changed at 12 months (3.8 vs 4.2 for SN-5; P = .01; 4.9 vs 5.1 for VAS; P = .54). The SN-5 and VAS scores in the SBCD group were significantly lower than those for controls at 3 months (2.5 vs 3.1 for SN-5; P = .003; 3.1 vs 3.9 for VAS; P = .01) and at 1 year after surgery (2.9 vs 3.8 for SN-5; P < .001; 3.1 vs 4.9 for VAS; P < .001). By the 12-month SN-5 score evaluation, the rates of marked, moderate, and mild improvement were significantly better in the SBCD group (52% [22 of 42], 26% [11 of 42], and 14% [6 of 42], respectively) than in the control group (14% [5 of 37], 19% [7 of 37], and 11% [4 of 37], respectively) (P < .05 for all comparisons). CONCLUSIONS AND RELEVANCE The SBCD procedure is a safe and effective technique for pediatric CRS resistant to medical therapy.

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.

Blockage of SSRP1/Ets-1/Pim-3 signalling enhances chemosensitivity of nasopharyngeal carcinoma to docetaxel in vitro.

Nasopharyngeal carcinoma (NPC) is a rare cancer in most parts of the world, but is prevalent in South China area. Besides, therapeutic outcome is still unsatisfactory for patients with refractory and relapsed NPC, even though receiving a second line of docetaxel-based chemotherapy. These reasons require a better understanding of mechanisms underlying the carcinogenesis, malignancy and chemoresistance. In the basis of our previous finding of SSRP1 over-expression in NPC cell lines, this study continuously discovered up-regulated Ets-1, phosphor-Ets-1 and Pim-3 in NPC tissues with immunohistochemistry assay and revealed a close correlation of these up-regulated proteins with NPC proliferation and invasion. Using gene-silencing technology followed by western blot and immunocytochemistry detections, SSRP1 was found to facilitate the translocation of phosphor-Ets-1 from cytoplasm to cell nucleus, but have marginal effect on Ets-1 expression and phosphorylation. Pim-3 was positively regulated by Ets-1. In NPC HNE-1 cells, all SSRP1, Ets-1 and Pim-3 knockdown diminished the cell proliferation, enhanced the apoptosis, as well as inhibited the autophagy, invasion and clonogenicity in the presence or absence of docetaxel at IC25. Exposure of HNE-1 cells to docetaxel (IC25) alone had modest effect on cell proliferation and autophagy, and was not as effective as docetaxel treatment after knockdown of SSRP1, Ets-1 or Pim-3 on induction of the apoptosis and on inhibition of the invasion and clonogenicity. Our data indicate that SSRP1/Ets-1/Pim-3 signalling is tightly associated with the proliferation, apoptosis, autophagy, invasion and clonogenicity of NPC cells, and blockage of this signalling facilitates chemosensitivity of the cells to docetaxel.

Endoscopic endonasal transsphenoidal approach for sellar tumors beyond the sellar turcica

Abstract Conclusions: The endoscopic endonasal transsphenoidal approach can be a choice for sellar tumors beyond the sellar turcica, but it is necessary to make the choice carefully because of the severe surgical risks. Objectives: To summarize our experience of removal of sellar tumors beyond the sellar turcica via the endoscopic endonasal transsphenoidal approach and to evaluate the surgical efficacy and complications. Methods: Between January 2007 and January 2012, 30 patients with sellar tumors beyond the sellar turcica underwent surgery using the endoscopic endonasal transsphenoidal approach. Results: Postoperative pathological examination demonstrated that pituitary adenoma occurred in 22 patients, craniopharyngioma in 5, and meningioma in 3. Total removal was achieved in 21 patients (70.0%) and subtotal removal was achieved in 8 patients (26.7%). After the surgery, cerebrospinal fluid leakage occurred in 3 patients, temporary diabetes insipidus occurred in 25 patients and persistent diabetes insipidus in 4 patients, intracranial infection occurred in 1 patient, frontal subdural effusion occurred in 1 patient, sinusitis occurred in 2 patients, epistaxis occurred in 3 patients, and 1 patient with a huge pituitary adenoma died of hypothalamic failure related to the operation.

Endoscopic transsphenoidal resection of sellar tumors with conchal sphenoid sinus: A report of two cases

A conchal non-pneumatized sphenoid sinus was previously considered to be a contraindication to the endoscopic transsphenoidal route to the sella due to its small sellar floor and poor anatomical landmarks, such as the optic nerve canal, opticocarotid recess and internal carotid arteries canal. The present study aimed to investigate the methodology and characteristics of the endoscopic transsphenoidal resection of sellar tumors with a conchal sphenoid sinus. Two patients with sellar tumor patients and non-pneumatized sphenoid sinuses received endoscopic transsphenoidal surgery. The two conchal sphenoid sinuses were accessed safely, total resection was achieved and no serious complications occurred. Therefore, the presence of a conchal non-pneumatized sphenoid is not an absolute contraindication for employing the endoscopic transsphenoidal route in the resection of sellar tumors; a positive outcome may be achieved, in particular when the surgery is performed by an experienced otolaryngologist.

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.