NEDD4L inhibits cell viability, cell cycle progression, and glutamine metabolism in esophageal squamous cell carcinoma via ubiquitination of c-Myc.

Esophageal squamous cell carcinoma (ESCC) is a common subtype of esophageal cancer with high incidence. Surgery remains the main strategy for treatment of ESCC at early stage. However, the treatment outcome is unsatisfactory. Therefore, finding new therapeutics is of great importance. In the present study, we measured the level of NEDD4L, an ubiquitin protein ligase, in clinical samples and investigated the effects of NEDD4L on cell viability, cell cycle progression, and glutamine metabolism in TE14 cells determined by CCK-8 assay, flow cytometry and biochemical analysis, respectively. The results show that NEDD4L is significantly decreased in ESCC specimens, and its decreased expression is associated with a poor clinical outcome. Overexpression of NEDD4L significantly inhibits cell viability, cell cycle progression, and glutamine metabolism in TE14 cells. Mechanistic study indicates that NEDD4L regulates tumor progression through ubiquitination of c-Myc and modulation of glutamine metabolism. NEDD4L inhibits cell viability, cell cycle progression, and glutamine metabolism in ESCC by ubiquitination of c-Myc to decrease the expressions of GLS1 and SLC1A5. Our findings highlight the importance of NEDD4L/c-Myc signaling in ESCC.

Surgical approach of laryngofissure combined with epiglottis valley in treating locally-advanced pyriform sinus carcinoma. / å–‰è£‚å¼€è”åˆä¼šåŽŒè°·å ¥è·¯æ‰‹æœ¯æ²»ç–—å±€éƒ¨æ™šæœŸæ¢¨çŠ¶çªç™Œ.

OBJECTIVES: To evaluate feasibility and efficacy of surgical approach of laryngofissure combined with epiglottis valley in treating locally-advanced pyriform sinus carcinoma. METHODS: Clinical data of 216 patients with T3 and T4a pyriform sinus carcinoma, who came from the Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University between January 2013 and December 2019, were retrospectively analyzed. Three different types of surgery were used in these patients. Seventy-three patients were performed by approach of laryngofissure combined with epiglottis valley for partial laryngopharyngectomy (Group I); 75 patients were performed by approach of lateral pharynx for piriform fossa resection (Group II); 68 patients were performed by total laryngopharyngectomy (Group III). All patients were treated with radiotherapy and followed up regularly after operation. Kaplan-Meier regression model was used to analyze the overall survival rate. EAT-10 swallowing scale was utilized to evaluate the postoperative swallowing function, while the rate of tracheal tube extubation and the incidence of postoperative complications in each group were compared. RESULTS: There were 76.7% patients with T3 stage in Group I, 100% patients with T3 stage in Group II, and 64.7% patients with T4a stage in Group III. There was significant difference between them (P<0.01). Clinical stage IV patients in the Group I, Group II, and Group III were 74.0%, 54.7%, and 89.7%, respectively, with significant difference (P<0.01). The 3-year overall survival (OS) rate in Group I, Group II, and Group III were 69.9%, 53.3%, and 58.8%, respectively. Patients in the Group I had a better survival outcome than that in the Group II (P<0.05). The median score of EAT-10 swallowing scale was 12.0 in the Group I, 8.0 in Group II, and 5.0 in Group III, with significant difference (P<0.01). There was no significant difference in the rate of tracheal tube extubation and the incidence of complication among the 3 groups (both P>0.05). CONCLUSIONS: Surgical approach of laryngofissure combined with epiglottis valley in the treating locally-advanced piriform sinus carcinoma presents favorable outcome in terms of survival rate and laryngeal function preservation, which deserves to be promoted.

The genomic architectures of tumour-adjacent tissues, plasma and saliva reveal evolutionary underpinnings of relapse in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is characterised by a dismal prognosis; nonetheless, limited studies have unveiled the mechanisms underlying HNSCC relapse. METHODS: Next-generation sequencing was performed to identify the somatic mutations in 188 matched samples, including primary tumours, tumour-adjacent tissues (TATs), pre- and post-operative plasma, saliva and peripheral blood lymphocytes (PBLs) from 27 patients. The evolutionary relationship between TATs and tumours were analysed. The dynamic changes of tumour- and TAT-specific mutations in liquid biopsies were monitored together with survival analysis. RESULTS: Alterations were detected in 27 out of 27 and 19 out of 26 tumours and TATs, respectively. TP53 was the most prevalently mutated gene in TATs. Some TATs shared mutations with primary tumours, while some other TATs were evolutionarily unrelated to tumours. Notably, TP53 mutations in TATs are stringently associated with premalignant transformation and are indicative of worse survival (hazard ratio = 14.01). TAT-specific mutations were also detected in pre- and/or post-operative liquid biopsies and were indicative of disease relapse. CONCLUSIONS: TATs might undergo the processes of premalignant transformation, tumorigenesis and eventually relapse by either inheriting tumorigenic mutations from ancestral clones where the tumour originated or gaining private mutations independent of primary tumours. Detection of tumour- and/or TAT-specific genetic alterations in post-operative biopsies shows profound potential in prognostic use.

Endoscopic frontal recess anatomy directed by the drainage pathways using the connecting plates as landmarks.

PURPOSE: To investigate the anatomical features of frontal recess (FR) drainage, and the classification of FR cells and frontal sinus (FS). METHODS: Fifty sides from 30 adult cadaver heads were examined. FR cells and FS along the drainage pathways were dissected under 0° and 70° endoscopic views using unique connecting structures between the uncinate process and the ethmoid bulla as landmarks. RESULTS: Connecting plates between the uncinate process and the ethmoid bulla were discovered and termed medial suprainfundibular plate (MSIP), which were observed on each cadaver head, and lateral suprainfundibular plate (LSIP) on 92% (46/50) sides. Separated by MSIP, two drainage pathways were identified and named medial pathways of the FR (MPFR) medial to the MSIP and the lateral pathways of the FR (LPFR) in the lateral side. Different drainage pathways of the FS were confirmed, in which drained into the MPFR in 37 and into the LPFR in 13 of the cadaver sides. CONCLUSIONS: MSIP is the critical landmark for the recognition of MPFR, LPFR, and the classification of FR cells. The FR resection along LPFR and MPFR facilitated excellent exposure of FS.

Down-Regulation of MiR-181c-5p Promotes Epithelial-to-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma via Targeting SERPINE1.

Laryngeal squamous cell carcinoma (LSCC) arises from the squamous epithelium of the larynx and is associated with a high incidence of cervical lymph node metastasis. MicroRNAs (miRNAs) play a crucial role in the epigenetic regulation of cellular biological processes, including cancer metastasis. However, the molecular mechanisms of specific miRNAs responsible for LSCC metastasis and their clinical significance have yet to be fully elucidated. In this study, LSCC cohort datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were downloaded and examined by comprehensive bioinformatics analysis, which revealed that upregulation of mRNA SERPINE1 and downregulation of miR-181c-5p were associated with unfavorable overall survival. Our analysis showed that SERPINE1 expression negatively correlated with the expression level of miR-181c-5p in our LSCC patient samples. Silencing of miR-181c-5p expression promoted cell migration and invasion in cell lines, whereas the overexpression of miR-181c-5p suppressed cell migration and epithelial-to-mesenchymal transition (EMT) through the downregulation of SERPINE1. Further analysis showed that the enhancement effect on EMT and metastasis induced by silencing miR-181c-5p could be rescued through knockdown of SERPINE1 expression in vitro. Collectively, our findings indicated that miR-181c-5p acted as an EMT suppressor miRNA by downregulation of SERPINE1 in LSCC and offers novel strategies for the prevention of metastasis in LSCC.

Targeted Inhibitory Effect of Nasopharyngeal Carcinoma Cells by Hre2.Grp78 Chimeric Promoter Regulating Fusion Gene TK/VP3.

OBJECTIVE: To construct plasmids with Hre2.Grp78 chimeric promoter regulating fusion gene TK/VP3 and elaborate the effects of overexpressed TK/VP3 on nasopharyngeal carcinoma cells. METHODS: Four plasmids were constructed, including pcDNA3.1-CMV-TK/VP3, pcDNA3.1-Hre2.TK/VP3, pcDNA3.1-Grp78.TK/VP3, and pcDNA3.1-Hre2.Grp78.TK/VP3. The human nasopharyngeal carcinoma cell line HNE1 cells were transfected with the 4 plasmids, respectively. Cell viabilities were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis was conducted using flow cytometry analysis. The expression of TK, VP3, Grp78, and hypoxia-inducible factor 1α and apoptosis-related proteins was determined by real-time quantitative polymerase chain reaction and Western blotting. RESULTS: The recombinant plasmids that could steadily overexpress TK and VP3 were successfully constructed. Expression of TK and VP3 in cells transfected with pcDNA3.1-Hre2.TK/VP3 and pcDNA3.1-Grp78.TK/VP3 was significantly higher than pcDNA3.1-CMV-TK/VP3, and expression in cells transfected with pcDNA3.1-Hre2.Grp78.TK/VP3 was the highest. Under glucose deprivation or hypoxia condition, Grp78 or hypoxia-inducible factor 1α was overexpressed so that expression of TK and VP3 was significantly upregulated, which could further inhibit cell proliferation and enhance cell apoptosis. CONCLUSION: We successfully constructed 4 plasmids with Hre2.Grp78 chimeric promoter regulating fusion gene TK/VP3, which could significantly inhibit the proliferation as well as enhance the apoptosis of nasopharyngeal carcinoma cells under glucose deprivation or hypoxia condition.

Alcohol consumption, tobacco smoking, betel quid chewing and oral health associations with hypopharyngeal cancer among men in Central South China: a case-control study.

BACKGROUND: Hypopharyngeal cancer has relatively high incidence rates in China, especially in high-risk areas. However, data on the role of major risk factors in these areas of China are still limited. METHODS: We have evaluated the roles of alcohol, tobacco and betel quid consumption, and oral health, based on 278 hypopharyngeal cancer cases and 693 controls from two centers in Central South China. The odds ratio (OR) and 95% confidence interval (CI) values were estimated using logistic regression. RESULTS: We found that alcohol drinkers had a risk of hypopharyngeal cancer that was up to seven times higher than that for those who had never drunk. A very strong effect of traditional liquor as compared to other alcohol types was observed, with the OR reaching 11.26 (CI 6.53-19.41) for this cancer. Tobacco smokers were up to four times more likely to develop hypopharyngeal cancer than never smokers. The OR for betel quid chewing was 1.86 (CI 1.26-2.75) as compared to never users. Poor oral hygiene had a risk of hypopharyngeal cancer that was two times higher than that for normal oral hygiene. CONCLUSION: In this study, we have shown for what is believed to be the first time the association of increased hypopharyngeal cancer incidence with alcohol, tobacco, betel quid and oral hygiene in China. Alcohol may play a larger role for hypopharyngeal cancer in this population than in populations in other areas.

Metformin Suppresses Hypopharyngeal Cancer Growth by Epigenetically Silencing Long Non-coding RNA SNHG7 in FaDu Cells.

Local recurrence after therapy remains a challenging problem for hypopharyngeal cancer (HPC) due to the chemotherapy resistance. Metformin is associated with reduced cancer risk through promoting global DNA methylation in cancer cells by controlling S-adenosylhomocysteine (SAHH) activity. However, the mechanisms by which metformin inhibits HPC remain elusive. In this study, we aim to investigate the role of metformin in HPC and illustrate the mechanism by which metformin regulates long non-coding RNAs (lncRNAs) expression. CCK-8 and annexin-V/PI double staining were performed to analyze the cell viability and apoptosis. LncRNA microarray analysis, QPCR, methylation specific PCR, Western blot and RNA Immunoprecipitation were performed to analyze the molecular mechanism, Here, we report that metformin inhibits FaDu cell proliferation in time- and dose-dependent manner by suppressing lncRNA SNHG7. Further investigations revealed that SNHG7 interacted with SAHH and metformin decreased SNHG7 expression by activating SAHH activity. Increased SAHH activity resulted in upregulating DNMT1 expression, leading to hypermethylation of SNHG7 promotor. In addition, upregulation of SNHG7 was associated with advanced stage. The patients with high SNHG7 have lower overall survival than that of with low SNHG7. Interestingly, SNHG7 levels were higher in taxol resistant patients than in taxol sensitive patients. Metformin sensitizes FaDu cells to taxol and irradiation through decreasing SNHG7. In conclusion, our recent study demonstrates that metformin inhibits FaDu cell proliferation by decreasing SNHG7 expression via SAHH-mediated DNA methylation. These findings indicate that combined metformin with paclitaxel or irradiation would be a novel therapeutic strategy to overcome resistance and prevent recurrence in HPC.

Crocin inhibits RANKL­induced osteoclastogenesis by regulating JNK and NF­κB signaling pathways.

Receptor activator of nuclear factor­κB ligand (RANKL), a member of the tumor necrosis factor receptor-ligand family, is a crucial factor involved in osteoclast differentiation. Crocin, a pharmacologically active component of Crocus sativus L., has been reported to attenuate ovariectomy­induced osteoporosis in rats. However, the molecular mechanism underlying the effect of crocin on osteoclast formation remains to be determined. The present study aimed to investigate the effect of crocin on RANKL­induced osteoclastogenesis and its underlying molecular mechanism. Results demonstrated that crocin decreased osteoclastogenesis in bone marrow­derived macrophages (BMMs). In addition, the expression levels of osteoclast marker proteins were downregulated by crocin. Mechanistically, crocin inhibited RANKL­induced activation of nuclear factor­κB (NF­κB) by suppressing inhibitor of κBα degradation and preventing NF­κB p65 subunit nuclear translocation, and by activating c­Jun N­terminal kinase (JNK) in BMMs. In summary, the results of the present study suggested that crocin downregulates osteoclast differentiation via inhibition of JNK and NF­κB signaling pathways. Thus, crocin may be a potential therapeutic agent for the treatment of osteoclast­associated diseases, including osteoporosis.

Annexin A2 is an independent prognostic biomarker for evaluating the malignant progression of laryngeal cancer.

Due to the lack of a definite diagnosis, a frequent recurrence rate and resistance to chemotherapy or radiotherapy, the clinical outcome for patients with advanced laryngeal cancer has not improved over the last decade. Annexin A2 is associated with the invasion and metastasis of cancer cells. In the present study, it was demonstrated using differential proteomics analysis that Annexin A2 is highly expressed in laryngeal carcinoma tissues and this was confirmed using immunohistochemistry, which demonstrated that the expression of Annexin A2 in laryngeal carcinoma tissues was significantly higher than in healthy adjacent tissue. In addition, its potential predictive value in the prognosis of patients with laryngeal carcinoma was evaluated. The results demonstrated that Annexin A2 expression was significantly associated with tumor size, lymph node metastasis, distant metastasis and clinical stage. In addition, higher Annexin A2 expression was associated with a poor prognosis of patients with laryngeal cancer. Thus, the results of the present study indicate that Annexin A2 expression is an independent prognostic biomarker for evaluating the malignant progression of laryngeal cancer.

Whole-exome sequencing reveals novel mutations and epigenetic regulation in hypopharyngeal carcinoma.

Hypopharyngeal cancer (HPC) frequently presents at an advanced stage, resulting in poor prognosis. Although combined surgical therapy and chemoradiotherapy have improved the survival for patients with HPC over the past 3 decades, the mortality rate in late-stage diagnosis of HPC is unsatisfactory. In this study, we performed whole-exome sequencing (WES) of 23 hypopharyngeal tumor and paired adjacent normal tissue to identify novel candidate driver genes associated with hypopharyngeal carcinoma. We identified several copy number variants (CNVs) and 15 somatic mutation genes that were associated with hypopharyngeal carcinoma. Mutations in nine new genes (PRB4, NSD1, REC8, ZNF772, ZNF69, EI24, CYFIP2, NEFH, KRTAP4-5) were also indentified. PRB4 and NSD1 expression were significantly upregulated in hypopharyngeal carcinoma, which was confirmed in an independent cohort using IHC. There was a positive relationship between PRB4 and NSD1. Downregulation of PRB4 by siRNA could inhibit cell growth, colony formation and cell invasion. Notably, we here demonstrate that NSD1 could bind to the promoter regions of PRB4 and activate promoter activity by reducing the binding of H3K27me2 and increasing the binding of H3K36me2 on PRB4 promoter. In summary, we pinpoint the predominant mutations in hypopharyngeal carcinoma by WES, highlighting the substantial genetic alterations contributing to hypopharyngeal carcinoma tumorigenesis. We also indentify a novel epigenetically regulatory between PRB4 and NSD1 that contribute to hypopharyngeal carcinoma tumorigenesis. They may become potential prognostic biomarkers and therapeutic target for hypopharyngeal carcinoma treatment.

Chemoradiotherapy enhanced the efficacy of radiotherapy in nasopharyngeal carcinoma patients: a network meta-analysis.

OBJECT: A Bayesian network meta-analysis (NMA) was conducted to estimate the overall survival (OS) and complete response (CR) performance in nasopharyngeal carcinoma (NPC) patients who have been given the treatment of radiotherapy, concurrent chemoradiotherapy (C), adjuvant chemotherapy (A), neoadjuvant chemotherapy (N), concurrent chemoradiotherapy with adjuvant chemotherapy (C+A), concurrent chemoradiotherapy with neoadjuvant chemotherapy (C+N) and neoadjuvant chemotherapy with adjuvant chemotherapy (N+A). METHODS: Literature search was conducted in electronic databases. Hazard ratios (HRs) accompanied their 95% confidence intervals (95%CIs) or 95% credible intervals (95%CrIs) were applied to measure the relative survival benefit between two comparators. Meanwhile odd ratios (ORs) with their 95% CIs or CrIs were given to present CR data from individual studies. RESULTS: Totally 52 qualified studies with 10,081 patients were included in this NMA. In conventional meta-analysis (MA), patients with N+C exhibited an average increase of 9% in the 3-year OS in relation to those with C+A. As for the NMA results, five therapies were associated with a significantly reduced HR when compared with the control group when concerning 5-year OS. C, C+A and N+A also presented a decreased HR compared with A. There was continuity among 1-year, 3-year and 5-year OS status. Cluster analysis suggested that the three chemoradiotherapy appeared to be divided into the most compete group which is located in the upper right corner of the cluster plot. CONCLUSION: In view of survival rate and complete response, the NMA results revealed that C, C+A and C+N showed excellent efficacy. As a result, these 3 therapies were supposed to be considered as the first-line treatment according to this NMA.

Downregulation of Calcium-Binding Protein S100A9 Inhibits Hypopharyngeal Cancer Cell Proliferation and Invasion Ability Through Inactivation of NF-κB Signaling.

Hypopharyngeal cancer (HPC) frequently presents at an advanced stage and displays early submucosal spread, resulting in a poor prognosis. It is among the worst of all cancers in the head and neck subsites. Therefore, detection of HPC at an earlier stage would be beneficial to patients. In this study, we used differential in-gel electrophoresis (DIGE) and two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomics analysis to identify the potential biomarkers for HPC. Among the differential proteins identified, calcium-binding protein S100A9 was overexpressed in HPC tissues compared with normal adjacent tissues, and S100A9 expression in metastatic tissues and advanced tumor tissues was higher than in nonmetastatic tissues and early tumor tissues. S100A9 expression was further confirmed in a large additional cohort. Our data showed that a higher S100A9 level was associated with a poor prognosis for HPC patients, and this may be an independent factor for predicting their prognosis. In addition, S100A9 protein expression was upregulated in human HPC cell lines compared with normal oral cavity epithelia. Knockdown of S100A9 induced significant inhibition of cell growth and their invasive ability. Mechanically, we found that downregulation of S100A9 significantly reduced the expression of NF-κB, phosphorylation of NF-κB and Bcl-2, as well as the expression of MMP7 and MMP2. Restoration of NF-κB expression sufficiently reversed the inhibitory effects on cell proliferation and invasion induced by S100A9 downregulation in vitro and in vivo. In conclusion, for the first time, we have identified S100A9 as an independent prognostic factor for HPC. Inhibiting S100A9 expression would be a potential novel diagnostic biomarker and therapeutic target for HPC treatment.

[Clinical analysis of severe complications induced by esophageal foreign bodies].

OBJECTIVE: To investigate the clinical characteristics and treatment strategies of severe complications induced by esophageal foreign bodies. METHODS: The clinical data of 44 patients with severe complications of esophageal foreign bodies treated from July 2004 to July 2014 were retrospectively analyzed. The type of complications was recorded. RESULTS: The ratio of severe complications in patients with esophageal foreign bodies was 9.05% (44/486). The most common type of foreign body was animal bone, with a total of 34 cases (77.3%); Onset of the disease were 2-40 days, mostly above 6 days, accounting for 61.4%. Severe complications of esophageal foreign bodies included 16 cases (36.3%) of simple esophageal perforation or combined with esophageal regional inflammation, 14 cases (31.8%) of cervical abscess, 7 cases (15.9%) of abscess around esophagus, 3 cases (6.8%) of mediastinal abscess, one case (2.3%) of cervical subcutaneous emphysema, one case of tracheoesophageal fistula, one case (2.3%) of aortic fracture, and one case (2.3%) of subclavian artery pseudoaneurysm. Among the 44 patients with severe complications, 40 patients (90.9%) were cured and 3 patients (6.8%) died. One case didn't receieve treatment. CONCLUSIONS: Occurrence of the severe complications induced by esophageal foreign bodies is closely related to the type of foreign bodies and time before presentation. Early diagnosis and prompt treatments for esophageal foreign bodies are crucial for preventing of severe complications.

[Combined middle meatus and expand prelacrimal recess-maxillary ainus approach for orbital fracture treatment].

OBJECTIVE: To study surgical techniques and clinical applications of the intranasal endoscopic combined middle meatus and expand prelacrimal recess-maxillary ainus approach for orbital fracture treatment. METHOD: A retrospective clinical analysis of 3 patients whose admitted for orbital floor fractures or medial wall fractures operated by the intranasal endoscopic middle meatus with expand prelacrimal recess-maxillary ainus approach surgical treatment was studied, and the treatment effects and the postoperative complications were analyzed. RESULT: All patients had been followed up for 6 to 12 months. All cases of diplopia symptom were disappeared, enophthalmos were totally corrected, no cases of complication were found. CONCLUSION: Endonasal endoscopic combined middle meatus and expand prelacrimal recess-maxillary ainus approach for orbital fracture treatment have great and clear view. This approach with less tissue damage and high therapeutic effect makes the cost lower than other methods and complications will be decreased as well, it has a great advantage in the orbital fracture treatment.

[Construction of nasopharyngeal carcinoma CNE-2 cell lines expressing stable fusion suicide gene CD/UPRT. UL49].

OBJECTIVE: To construct nasopharyngeal carcinoma CNE-2 cell lines expressing stable fusion suicide gene CD/UPRT. UL49. METHOD: The plasmids of pcDNA3.1 (-)E6. BARF1p. CD/UPRT. UL49 was transfected into CNE-2 cells through lipofectamine, and the transfected CNE-2 cells were selected by G418 and prodrugs for getting the cells expressing fusion CD/UPRT. UL49 gene. The protein produced by the suicide gene was tested by Western-blotting in CNE-2 cells. RESULT: Suicide genes were expressed stably in CNE-2 cells. CONCLUSION: We constructed nasopharyngeal carcinoma cell lines CNE-2 expressing stable suicide gene through lipofectamine.

[Imaging classification for horizontal segment of uncinate process and its guiding significance in functional endoscopic sinus surgery].

OBJECTIVE: To explore a new method for horizontal segment of uncinate process classification from image of nasal sinus. METHODS: On the level of horizontal segment of uncinate process of nasal sinus high resolution CT (HRCT) coronal scan. A vertical line and a parallel line were drawn started from the fornix top of the inferior meatus and orbital floor. The uncinate process which suited in the 'Cross' regional was divided into four types by these lines. These were: intra-superior, intra-inferior and extra-superior, extra-inferior. According to this method, 119 patients with chronic sinusitis which were divided into these four types by the imaging classification for horizontal segment of uncinate process operated by functional endoscopic sinus surgery, and the treatment effects and the postoperative complications were analyzed. RESULTS: These 119 chronic sinusitis patients (238 sides uncinated process) were divided into four types by the imaging classification for uncinated process. The amount of intra-superior types was 66.0% (157/238), the amount of intra-inferior types was 16.8% (40/238), the amount of extra-superior types was 13.9% (33/238), and the amount of extra-inferior types was 3.4% (8/238). Functional endoscopic sinus surgery was performed according to this classification. All maxillary sinus natural ostium were found. Two cases occured orbital board damage (one was intra-superior, the other was extra-inferior). CONCLUSION: The imaging classification for horizontal segment of uncinate process demonstrates a guiding significance for us to predict the difficulty of the operation and prevent the complications.

[Resection of parapharyngeal neoplasms via styloid diaphragm approach].

OBJECTIVE: To evaluate the surgical technique and efficacy of the resection of parapharyngeal space neoplasm via styloid diaphragm approach. METHODS: Thirty-three cases underwent the resection of parapharyngeal space tumors via styloid diaphragm approach from Jan 2005 to Jan 2011 were reviewed. Of the cases, 28 were with benign tumors treated by surgery alone, and 5 were malignant tumors treated by surgery plus postoperative radical radiotherapy. RESULTS: The parapharyngeal neoplasms in all cases were completely resected via styloid diaphragm approach. The postoperative follow-up ranged from 13 months to 7 years (median = 4.6 years). No tumor recurrence was found in 30 cases, but 3 cases experienced tumor recurrence, including 1 chondrosarcoma (3 years after surgery and chemoradiotherapy), 1 chordoma and 1 adenoid cystic carcinoma (5 years after surgery and radiotherapy). Severe postoperative complications were not observed, but 2 cases showed mild mouth askew and fully recovered after 3 months, and 1 case was complicated with hoarseness and cough symptoms that disappeared after heteropathy. CONCLUSION: Resection of parapharyngeal neoplasms via styloid diaphragm approach is an ideal surgical technique, with well-exposed surgical field, less tissue injury, and less postoperative complication.

ARC is highly expressed in nasopharyngeal carcinoma and confers X-radiation and cisplatin resistance.

Apoptosis repressor with caspase recruitment domain (ARC), an inhibitor of apoptosis, is primarily expressed in terminally differentiated tissues. Recent studies have revealed that ARC is highly expressed in a variety of human cancer cell lines and epithelial-derived cancers, which suggests that ARC plays an important role in the process of carcinogenesis. However, whether ARC is involved in the development of nasopharyngeal carcinoma (NPC) and the various roles it plays in NPC remain unclear. In the present study, we examined the expression of ARC in NPC cell lines and NPC tissues and the relationship between its subcellular expression and clinicopathological grade; moreover, we explored the effect of this protein on radiation resistance and chemoresistance in NPC cells. We found that cytoplasmic ARC was expressed at high levels in NPC tissues, at moderate levels in severe atypical hyperplasia and at low levels in benign nasopharyngeal tissues. High expression of cytoplasmic and nuclear ARC was correlated with advanced local invasion. However, only a small amount of nuclear ARC was expressed in NPC in contrast to cytoplasmic ARC. We also found that attenuation of ARC expression by miRNA resulted in decreased X-radiation and cisplatin resistance in NPC CNE-2 cells. In contrast, overexpression of ARC resulted in increased X-radiation and cisplatin resistance in NPC 6-10B cells. Furthermore, we demonstrated that ARC appears to be critical for blocking the activation of casapse-8 and casapse-2 in NPC cells subjected to X-radiation or cisplatin. These results suggest that high expression of ARC plays an important role in the pathogenesis of NPC and leads to X-radiation and cisplatin resistance in NPC.

[Early genetic diagnosis in patients with HHT induced severe nosebleed].

OBJECTIVE: To study the early gene diagnosis of hereditary hemorrhagic telangiectasia (HHT) induced severe nosebleed. METHOD: Clinical features of 23 family members in two HHT pedigrees were examined. Genomic DNA was extracted from peripheral blood samples. PCR amplification was conducted to screen ENG and ACVRL-1 genes with their specific primers. Direct sequencing was performed to detect the mutation. Mutation analysis was carried out to evaluate its significance. RESULT: A heterozygous c. 263A > G mutation was identified in exon 3 of ACVRL-1 in 6 out of 11 members in NMG-1 pedigree. In GD-2 pedigree, 5 of 11 members carried c. 199C > G mutation. Mutation detection rate was 100% in subjects with nosebleed history and 25% in family members without epistaxis. CONCLUSION: Gene diagnosis characterized by high sensitivity and specificity is of great practi-cal significance and early genetic screening should be a clinical routine test for HHT induced severe nosebleed.