Combined Analysis of the Aberrant Epigenetic Alteration of Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most fatal malignancies due to its high morbidity and mortality. DNA methylation exerts a vital part in the development of PDAC. However, a mechanistic role of mutual interactions between DNA methylation and mRNA as epigenetic regulators on transcriptomic alterations and its correlation with clinical outcomes such as survival have remained largely uncovered in cancer. Therefore, elucidation of aberrant epigenetic alteration in the development of PDAC is an urgent problem to be solved. In this work, we conduct an integrative epigenetic analysis of PDAC to identify aberrant DNA methylation-driven cancer genes during the occurrence of cancer. METHODS: DNA methylation matrix and mRNA profile were obtained from the TCGA database. The integration of methylation and gene expression datasets was analyzed using an R package MethylMix. The genes with hypomethylation/hypermethylation were further validated in the Kaplan-Meier analysis. The correlation analysis of gene expression and aberrant DNA methylation was also conducted. We performed a pathway analysis on aberrant DNG methylation genes identified by MethylMix criteria using ConsensusPathDB. RESULTS: 188 patients with both methylation data and mRNA data were considered eligible. A mixture model was constructed, and differential methylation genes in normal and tumor groups using the Wilcoxon rank test was performed. With the inclusion criteria, 95 differential methylation genes were detected. Among these genes, 74 hypermethylation and 21 hypomethylation genes were found. The pathway analysis revealed an increase in hypermethylation of genes involved in ATP-sensitive potassium channels, Robo4, and VEGF signaling pathways crosstalk, and generic transcription pathway. CONCLUSION: Integrated analysis of the aberrant epigenetic alteration in pancreatic ductal adenocarcinoma indicated that differentially methylated genes could play a vital role in the occurrence of PDAC by bioinformatics analysis. The present work can help clinicians to elaborate on the function of differentially methylated expressed genes and pathways in PDAC. CDO1, GJD2, ID4, NOL4, PAX6, TRIM58, and ZNF382 might act as aberrantly DNA-methylated biomarkers for early screening and therapy of PDAC in the future.

Lovastatin Inhibits Cancer Stem Cells and Sensitizes to Chemo- and Photodynamic Therapy in Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignancy occurring at high incidence in Southeast Asia and southern China. In spite of the good response to radio- and chemo-therapy at the early stage, resistance and recurrence develop in NPC patients in the advanced setting. Cancer stem cells (CSCs) play an important role in drug resistance and cancer recurrence. Here we report that lovastatin, a natural compound and a lipophilic statin that has already been used in the clinic to treat hypercholesterolemia, inhibited the CSC properties and induced apoptosis and cell cycle arrest in sphere-forming cells derived from the 5-8F and 6-10B NPC cell lines. Furthermore, lovastatin conferred enhanced sensitivity to the chemotherapeutic and photodynamic agents in NPC CSCs. Together our findings suggest that targeting CSCs by lovastatin in combination with routine chemotherapeutic drugs or photodynamic therapy might be a promising approach to the treatment of NPC.

Reduction of internal carotid artery intima-media thickness in patients with moderate-to-severe obstructive sleep apnea syndrome after nasal surgery and uvulopalatopharyngoplasty.

CONCLUSION: Multi-level surgeries for the nasal cavity and palate can reduce the severity of obstructive sleep apnea with major narrowing above the retropalatal airway and reduce the carotid intima-media thickness, which can provide cardiovascular benefits to patients. OBJECTIVE: To evaluate the outcomes of moderate-to-severe obstructive sleep apnea syndrome by surgeries and the change of internal carotid artery intima-media thickness after surgeries. SUBJECTS AND METHODS: Sixty-four patients with obstructive sleep apnea, narrowing at the nasal cavity, and retropalatal airways were enrolled in this study. Fifty-two patients underwent nasal surgery and modified uvulopalatopharyngoplasty. Twelve patients who refused surgeries and continuous positive airway pressure treatment received only conservative treatment. All patients were evaluated within 1 month before and 6 months after treatment using polysomnography, upper airway endoscopy, and B mode ultrasound. RESULTS: The success rate was 61.5% (32/52 patients) in the surgery group. There were significant differences between the surgery group and non-surgery group 6 months after treatment in the apnea hypopnea index, minimum and mean oxygen saturation, blood pressure, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and internal Carotid intima-media thickness. The changes in the oxygen saturation and the apnea hypopnea index showed significant correlations with the changes in the intima-media thickness.

[Bilateral versus unilateral sudden sensorineural hearing loss].

OBJECTIVE: To analyze the clinical characteristics and treatment effect between bilateral (bi-) and unilateral (uni-) sudden sensorineural hearing loss (SSNHL). METHOD: Four hundred and eighty cases of SSNHL were retrospective study, which were divided into two groups of bi-SSNHL (n = 40) and uni-SSNHL (n = 440). Clinical characteristics and treatment effects were compared of the two groups. RESULT: The incidence rate of bi-SSNHL was 8.3 percent and uni-SSNHL was 91.7 percent of all patients with SSNHL. Bi-SSNHL occurs more commonly in patients of old age, diabetes mellitus, and lipid panes abnormalities compared to uni-SSNHL. Twenty-eight ears in the bi-SSNHL group showed hearing recovery (35%), compared with 56.4 percent of patients with uni-SSNHL. CONCLUSION: Bi-SSNHL and uni-SSNHL may have a completely different clinical characteristics and treatment effect, that implies a different pathophysiology and prognosis. Recognition their different clinical characteristics and treatment effect between bilateral and unilateral SSNHL can help in counseling and managing the patients and correctly evaluate the prognosis.

[Clinical investigation of different routes of administration of dexamethasone on sudden deafness].

OBJECTIVE: To investigate the therapeutic effects of conventional treatment with different routes of administration of dexamethasone on sudden deafness. METHOD: Eighty-four patients with sudden deafness were included in this prospective randomized study. Twenty one patients (group 1) were treated with taking dexamethasone orally combined with conventional methods. Another 21 patients (group 2) were treated with intravenous dexamethasone injection combined with conventional methods. Group 3 (21 patients) were treated with intratympanic dexamethasone injection by the way of external ear combined with conventional methods. The other 21 patients (group 4) were treated with intratympanic dexamethasone injection by the way of pharyngotympanic tube combined with conventional methods. The hearing gains at 0.5, 1.0, 2.0, 4.0 kHz and the mean values were compared among four groups. RESULTS: The average hearing gains of 1, 2, 3 and 4 group was 21.3 dB, 27.5 dB, 43.2 dB and 48.1 dB respectively. Group 3 and group 4 had statistical difference compared with group 1 and group 2 in the average hearing gains. There was no obviously statistical difference between group 1 and group 2 and between group 3 and group 4. In patients with PTA < or = 70 dB, the average hearing gains at 0.5, 1.0, 2.0, 4.0 kHz had no obvious difference (P > 0.05) among four groups. However, in patients with PTA > 70 dB, there was statistical difference between group 1, 2 and group 3, 4 (P < 0.05), the hearing gains of group 3. 4 were apparently higher than that of group 1, 2. However, there was no significant difference of hearing gains between group 1 and group 2 (P > 0.05) and between group 3 and group 4 (P > 0.05). CONCLUSION: The conventional drug treatment with taking dexamethasone orally or intravenous dexamethasone injection had no obvious effect on sudden deafness with PTA > 70 dB, but the conventional drug treatment with intratympanic dexamethasone injection is a useful treatment for sudden deafness. Comparison with whole body administration, intratympanic dexamethasone injection is more convenient to use in clinic, and with less prohibitions and complications. Patients with PTA > 70 dB should take intratympanic dexamethasone injection in early days.

[To investigate the relation of sudden deafness with hearing loss level and auditory threshold].

OBJECTIVE: To investigate the relation of sudden deafness with hearing loss level and auditory threshold. METHOD: A retrospective analysis was performed in 92 cases(97 years) of sudden deafness patients. RESULT: In this group,the best hearing loss prognosis was the ascend type and the back type the total effective rate was both 100.0%. The second was the slow descend type. The total effective rate of this type was 70.0% (7/10). the total effective rate of full deaf is 66.7% (14/21), the sudden descend type is poor, the effective rate was 50% (4/8). although the full deaf groups total effective rate was high than sudden descend type, without one ear completely recovering, and only one ear from sudden descend type was completely cured. After treatment, there were 6 ears of fall deaf in full deaf group. There was one case rised 65 dBHL and one case rised 50 dBHL from the 21 cases full deaf sufferer. In this deaf level group, the light level and the middle level was one ear respectively. Although the total effective rate of this group was the highest, all the cases were not completely recovered. After treatment, the hearing rise 17 dBHL and 19 dBHL respectively. After chi2 text (chi2 = 1.459, P > 0.05), the total effective rate of the more heavier, heavy, and the heaviest to full deaf was no significant difference but after chi2 text (chi2 = 10.09, P < 0.01), the full recover rate was significant difference. The more heavier level group's full recover rate was the highest 38.5% (10/26).the second was heavy level group ,the full recover rate is 33.3% (12/36), the worst level to full deaf group was the lowest: 6.0% (2/33). CONCLUSION: It was considered that the deafness level was no obvious relation to the total effective rate, but there was significant difference in fully recover rate. The different auditory threshold figure of the sudden deafness was closely related to the hearings prognosis.