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Background G protein‐coupled receptor 12 (GPR12) is an orphan receptor with no confirmed endogenous ligands. It plays important roles in both physiological and pathological conditions such as neurogenesis and neural inflammation. However, it remains unclear whether GPR12 regulates carcinogenesis and progression in head and neck squamous cell carcinoma (HNSCC), such as esophageal cancer (EC) and hypopharyngeal cancer (HC). Methods The Cancer Genome Atlas (TCGA) database was applied to explore the expression of GPR12. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to detect the expression of GPR12 in cancer tissues. Wound healing and transwell assays were carried out to verify the effect of GPR12 on cell migration. Flow cytometric analysis and caspase‐Glo 3/7 assay were carried out to verify the influence of GPR12 on cell apoptosis. Western blotting was used to measure the expression of proteins related to migration and apoptosis. Result The qRT‐PCR analyses showed that the expression of GPR12 decreased in EC and HC than that in their paired adjacent normal tissues. Wound healing assay and transwell assay demonstrated that GPR12 inhibited tumor cell migration. Flow cytometry analysis and Caspase‐Glo 3/7 Assay suggested that GPR12 promoted apoptosis. The mechanism of GPR12 may function via modulating caspase‐7, E‐cadherin, and α‐catenin in EC and HC cells. Conclusion In conclusion, GPR12 induced apoptosis by activating caspase‐7 and inhibited migration through epithelial‐to‐mesenchymal transition (EMT) in EC and HC. Our findings demonstrated that GPR12 as a potential tumor suppressor mediated cell migration and apoptosis in EC and HC., GPR12 induced apoptosis by activating caspase‐7 and inhibited migration through epithelial‐to‐mesenchymal transition (EMT) in EC and HC. Our findings demonstrated that GPR12 as a potential tumor suppressor mediated cell migration and apoptosis in EC and HC

Background Conservative surgery has proven advantageous in controlling hypopharyngeal squamous cell carcinoma (HSCC) and preserving speech and swallowing function in carefully selected patients, typically with early T-stages diseases. A variety of modified surgical procedures or techniques have been proposed. Methods In this study, we present a novel surgical approach for hypopharyngeal carcinoma resection utilizing the paraglottic space. Results The paraglottic space approach can help expose neoplasms under direct vision and save mucosa during surgery while sufficiently preserving laryngeal function, thus benefiting postoperative swallowing and reducing complications. A large cohort of 426 patients with HSCC underwent surgical treatment at our institution using this approach, demonstrating an overall survival (OS) rate of 52.3% and low incidences of postoperative complications. Conclusions This surgical approach can be applied in patients with the lesions that do not involve the paraglottic space.

Hypopharyngeal squamous cell carcinoma (HSCC) accounts 95% of hypopharyngeal cancer, which is characterized by high early metastasis rate and poor prognosis. It is reported that circular RNA is involved in the occurrence and development of cancer; however, the role of circRNA in hypopharyngeal cancer has little been investigated. We performed hypopharyngeal carcinoma circRNA microarray and qRT-PCR verification. The results showed circ_0058106 expression level was significantly upregulated in tumor tissues than in corresponding normal tissues. We found that circ_0058106 upregulation promoted proliferation, migration and invasion of HSCC cells, while knockdown of circ_0058106 inhibited proliferation, migration and invasion of HSCC cells both in vitro and in vivo. Bioinformatics predicted circ_0058106 may interact with miR-185-3p. We verified circ_0058106 directly bound miR-185-3p and downregulated miR-185-3p expression by using dual-luciferase reporter assay and qRT-PCR. Moreover, we proved circ_0058106 promoted HSCC cells tumorigenesis and EMT process by regulating Wnt2b/β-catenin/c-Myc pathway via miR-185-3p. In conclusion, our findings firstly confirmed the carcinogenic effect of circ_0058106 in promoting HSCC cells tumorigenesis, metastasis, invasion and EMT process by regulating Wnt2b/β-catenin/c-Myc pathway through sponging miR-185-3p, indicating that circ_0058106 may be a new therapeutic target and prognostic marker for HSCC.

Increasing number of circular RNAs (circRNAs) have been reported to play important role in gene regulation, carcinogenesis and pathogenesis in various cancers. However, the biological functions and underlying molecular mechanisms of circRNAs in hypopharyngeal squamous cell carcinoma (HSCC) remain elusive. Thus, secondary circRNA‐seq profiling was performed to identify the differentially expressed circRNAs between HSCC tissues and adjacent normal tissues, and the expression level of circMATR3 (derived from human gene matrin3 (MATR3), has_circRNA_0008922) was confirmed by qRT‐PCR. Proliferation of HSCC cells was detected by cell counting kit‐8 (CCK8) assay, apoptosis and the cell cycle were analysed by flow cytometry, and the migration and invasion of HSCC cells was determined by transwell assay. Bioinformatics analysis was conducted to predict possible pathways and potential miRNA targets of circMATR3. We found that circMATR3 was up‐regulated in HSCC tissues, and abundant circMATR3 expression was markedly correlated with late T classification, advanced clinical stage, greater lymph node metastasis, and poor prognosis. Furthermore, knock‐down of circMATR3 significantly inhibited proliferation, migration and invasion of HSCC cells, whereas silencing of circMATR3 induced cell apoptosis. Our analysis predicted that circMATR3 may participate in cancer‐related pathways by serving as miRNA sponges. In conclusion, our findings first identified the oncogenic roles of circMATR3 in promoting the progression of HSCC and demonstrated that circMATR3 may be a novel prognostic marker and therapeutic target for HSCC.

Since the prognosis of hypopharyngeal squamous cell carcinoma (HSCC) remains poor, identification of miRNA as a potential prognostic biomarker for HSCC may help improve personalized therapy. In the 2 cohorts with a total of 511 patients with HSCC (discovery: N = 372 and validation: N = 139) after post‐operative radiotherapy, we used miRNA microarray and qRT‐PCR to screen out the significant miRNAs which might predict survival. Associations of miRNAs and the signature score of these miRNAs with survival were performed by Kaplan‐Meier survival analysis and multivariate Cox hazard model. Among 9 candidate, miRNAs, miR‐200a‐3p, miR‐30b‐5p, miR‐3161, miR‐3605‐5p, miR‐378b and miR‐4451 were up‐regulated, while miR‐200c‐3p, miR‐429 and miR‐4701 were down‐regulated after validation. Moreover, the patients with high expression of miR‐200a‐3p, miR‐30b‐5p and miR‐4451 had significantly worse overall survival (OS) and disease‐specific survival (DSS) than did those with low expression (log‐rank P

The authors aimed to clarify the optimal treatment strategy and the indication of different treatments in managing advanced laryngeal squamous cell carcinoma (LSCC). A total of 9700 patients with advanced (T3-4aN0-3M0) LSCC who treated with (1) surgery alone, (2) surgery plus adjuvant radiation with or without chemotherapy (aCRT/RT), or (3) definitive CRT/RT was retrieved from the SEER database. The propensity score matching (PSM) was applied to balance confounding factors. Kaplan–Meier method and Cox proportional hazards regression were used to comparing the overall survival (OS) of patients. After optimal matching, 907 patients were screened from each treatment cohort. Kaplan–Meier and multivariate analyses presented that patients treated with surgery plus aCRT/CT had significantly longer OS than those treated with either surgery alone or CRT/RT, even after PSM. However, significant interactions were tested in treatment effects in stratified analyses of the primary subsite, T stage, N stage, and insurance status (PInteraction 0.05 for all). Besides, supraglottic tumors presented a poorer prognosis than glottic subsite. Current study suggests that surgery with aCRT/RT is the preferred initial therapy for patients with T4a tumors, whereas patients with T3 tumors could be treated with either surgery (followed by aCRT/RT if it presents N +) or definitive CRT/RT for achieving laryngeal preservation. More-intense treatment should be emphasized for advanced supraglottic cancer.

Hypopharyngeal cancer (HC) is the most common subset of head and neck cancers. These tumors often have an aggressive clinical outcome characterized by local invasion and regional nodal metastasis. Upregulated miRNAs might be useful as biomarkers for prognosis and molecular targets for these tumors. We determined tumor expression of candidate miRNAs using microarray in 8 HC patients and validated in 372 HC patients. We also used paired tumorous and mucosal tissue to verify the miRNA expression. Log-rank test and Cox model were used to evaluate the survival; and Harrell's C-index was used to compare concordance of Cox models. Our results indicated 7 miRNAs aberrantly expressed in HC. Three of these candidate miRNAs (miRNA-4415, miRNA-200a, and miRNA-30b) were selected for further qRT-PCR validation and all of them were frequently found upregulated in HC tumors; with miR-4451 being the most differentially expressed. Moreover, high expression of miR-4451 was positively correlated with advanced tumor stage and increased mortality risk (HR: 1.6, 95% CI: 1.2-2.3; adjusted HR: 1.5, adjusted 95% CI: 1.1-2.1). Finally, significantly higher expression of miR-4451 in tumors compared to in fresh adjacent normal tissues indicates an oncogenic role of miR-4451 in this tumor. Upregulated miR-4451 in HC samples were frequently found and is significantly associated with advanced stage and poor survival of HC, which may indicate an association of this miRNA with the carcinogenesis process in this tumor site; and they could serve as a prognostic biomarker as well as help develop potential new targets for therapy.

To evaluate clinical features, diagnosis, surgical management, and treatment of parapharyngeal space tumors in a single-center setting due to limited knowledge of diagnosis and treatment of parapharyngeal space.Clinical records of 103 patients were included for the analysis of such clinical characteristics.A total of 29 different types of tumors were diagnosed after operation: 20 benign and 9 malignant. With a follow-up of 31-84 months for 90 benign cases, 84 cases had no recurrence and 6 cases were lost to follow-up. In contrast, with an 8- to 51-month follow-up for 13 malignant cases, 11 patients died and 2 were lost to follow-up. Furthermore, for postoperative complications, 3 cases had Horner syndrome, 2 had hoarseness, 2 had facial nerve dysfunction, and each for other types.Surgery remains the first choice for the treatment of parapharyngeal space tumors, with the transcervical approach used for most tumors. Moreover, CT or MRI may assist in making decisions about operation schemes.

// Jieyu Zhou 1, 2, * , Shengda Cao 1, * , Wenming Li 1 , Dongmin Wei 1 , Zhentao Wang 2 , Guojun Li 3, 4 , Xinliang Pan 1 and Dapeng Lei 1 1 Department of Otorhinolaryngology, Qilu Hospital, Shandong University, Key Laboratory of Otolaryngology, NHFPC - Shandong University, Jinan, Shandong, 250012, P.R. China 2 Department of Otorhinolaryngology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200011, P.R. China 3 Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA 4 Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA * These authors contributed equally to this work Correspondence to: Xinliang Pan, email: panxinl915@126.com Dapeng Lei, email: leidapeng@sdu.edu.cn Keywords: hypopharyngeal squamous cell carcinoma, radioresistance, lncRNA, mRNA, microarray Received: December 05, 2016 Accepted: April 10, 2017 Published: April 21, 2017 ABSTRACT Radioresistance remains a major problem in the treatment of patients with hypopharyngeal squamous cell carcinoma (HSCC). Long noncoding RNAs (lncRNAs) have important roles in the development, invasion, and metastasis of various tumors, including HSCC, but little is known about the role of lncRNAs in cancer radioresistance. The aim of this study was to identify radioresistance-related lncRNAs and mRNAs in radioresistant (RS) hypopharyngeal cancer subclone RS-FaDu cells. In this study, we performed microarray analysis to find the differences in time-course lncRNA and mRNA expression profiles between RS-FaDu and parent FaDu cells after 4 Gy radiation therapy, whose reliability was confirmed by validation experiment. Among these consistently dysregulated lncRNAs, we found that some lncRNAs (e.g., TCONS_00018436) might control resistance of HSCC cells to radiation. Furthermore, our bioinformatics analyses from mRNA/lncRNA microarray data showed that certain lncRNAs or mRNAs potentially are involved in radioresistance of HSCC. Our results from this study laid the foundation for further investigating the roles of these lncRNAs and mRNAs as promising candidates in the occurrence and development of HSCC radioresistance.

Hypopharyngeal squamous cell carcinoma (HSCC) remains one of the most lethal malignancies in the head and neck. Long noncoding RNA (lncRNA) HOXA11-AS is proven to function as an oncogene and a therapeutic target in various tumors. Our previous study and others have demonstrated that HOXA11-AS is one of the most upregulated lncRNAs in HSCC. However, the role of HOXA11-AS in HSCC has not yet been identified. The current study demonstrated that the expression of HOXA11-AS was significantly upregulated in HSCC tumors and was positively associated with lymph node metastasis. Moreover, functional experiments revealed that HOXA11-AS knockdown suppressed the proliferation and migration potential in FaDu cells. Furthermore, luciferase reporter gene assay combined with cellular functional experiments demonstrated that HOXA11-AS functioned as a molecular sponge for miR-155, and inhibition of miR-155 attenuated the suppressive effect of HOXA11-AS knockdown on the aggressive phenotype in HSCC. This study identifies a tumor-promoting role of HOXA11-AS in HSCC and suggests HOXA11-AS might be a potential diagnostic and therapeutic target for HSCC.

Sweroside, as one of the main components of Swertia L. in Gentianaceae, has the effect of clearing heat and detoxifying. In previous studies, sweroside has been reported to have anti-inflammatory effect on LPS-induced inflammation by alleviating NF-κB signaling pathway. In this paper, we investigate the anti-inflammatory effects of sweroside by establishing LPS-induced acute lung injury (ALI) model in mice. Experimental results showed that sweroside could reduce the wet-to-dry ratio of the lung and inhibit MPO activity. In addition, it turned out that sweroside reduced pathological changes in lung tissue and the numbers of inflammatory cells. Moreover, sweroside significantly reduced the levels of inflammatory cytokines and down-regulated the NF-κB signaling pathway. And the results demonstrated that sweroside could increase the expression of SIRT1, and the protective effects of sweroside on LPS-induced ALI were reversed by SIRT1 inhibitor EX-527. In conclusion, sweroside can protect LPS-induced ALI mice through inhibiting inflammation.

Jianing Xu,1,2 Yuanwei Zang,3 Shengda Cao,1,2 Dapeng Lei,1,2 Xinliang Pan1,2 1Department of Otorhinolaryngology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 2NHC Key Laboratory of Otorhinolaryngology, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 3Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China Background: Hypopharyngeal squamous cell carcinoma (HSCC) is among the most lethal tumors encountered in the head and neck, and currently lacks satisfactory therapeutic targets. Platelet activating factor acetylhydrolase 1B3 (PAFAH1B3), a cancer-relevant metabolic driver, is reported to play a critical role in controlling tumorigenesis and aggressiveness in several types of cancers. However, the role of PAFAH1B3 in HSCC progression has not yet been identified. Methods: The expression pattern of PAFAH1B3 was examined using immunohistochemistry in 83 HSCC tumor tissues and 44 paired adjacent non-tumor samples. Univariate and multivariate analyses were conducted to explore its association with prognosis of HSCC. In vitro loss-of-function assays were performed to explore the impact of PAFAH1B3 knockdown on the biological phenotype of the human HSCC cell line, ie, FaDu cells. Results: PAFAH1B3 was overly expressed in the HSCC tumor tissues compared with the adjacent non-tumor samples. Moreover, high expression of PAFAH1B3 was positively correlated with cervical lymph node metastasis. PAFAH1B3 overexpression was associated with poor outcome in HSCC, but it was not an independent prognostic indicator. Furthermore, in vitro loss-of function experiments demonstrated that PAFAH1B3 knockdown suppressed cell proliferation by inducing apoptosis and disrupting cell cycle process, and the migratory and invasive capacities were also attenuated in the absence of PAFAH1B3. Conclusion: This study for the first time demonstrated the clinical value and the role of PAFAH1B3 in the biological function of HSCC. This work suggested that PAFAH1B3 might serve as a potential therapeutic target for HSCC patients. Keywords: hypopharyngeal squamous cell carcinoma, platelet activating factor acetylhydrolase 1B3, prognosis, cell proliferation, migration, invasion

Tumour-associated macrophages (TAMs) are the key components in the tumour microenvironment. TAMs have two major subtypes, M1 and M2. M1 macrophages are tumour inhibitory, while M2 macrophages are tumour promotive. Repolarising TAMs from M2 to M1 is a promising strategy in cancer treatment. M1 and M2 macrophages were generated from murine bone marrow-derived macrophages (BMDMs). We found that chloroquine (CQ), an autophagy inhibitor, was able to repolarise M2 macrophages to the anti-tumour M1 phenotype. The repolarised macrophages demonstrated higher phagocytotic activity towards Hep-2 laryngeal tumour cells and re-sensitised Hep-2 cells to cisplatin (CDDP) treatment in vitro. While CQ did not demonstrate cytotoxicity to Hep-2 cells in vitro, CQ treatment reduced Hep-2 laryngeal tumour growth in vivo and improved CDDP treatment outcomes. It seems that CQ-induced M2-to-M1 macrophage repolarisation played an important role in tumour growth inhibition, and the CQ/CDDP combined therapy might have clinical potential in laryngeal cancer treatment.

Objectives. We sought to identify the expression of CD68-tumor-associated macrophages (TAMs) and CD34-microvascular density (MVD) in laryngeal squamous cell carcinoma (LSCC), to study the relationship with clinical pathological parameters and to determine whether their expression is predictive of disease. Methods. Pathologically confirmed 45 LSCC tissue and 20 peritumoral non-tumor tissue were examined. Immunohistochemical studies were used to detect the expression of CD68-TAMs and CD34-MVD. Results. The positive expression rate of CD68 in LSCC tissue was 82% (37/45), which was higher than the 10% (2/20) expression rate of the peritumoral tissue (P

Objective To investigate the effect and mechanism of action of metformin on proliferation of a human hypopharyngeal carcinoma cell line (FaDu). Methods FaDu cells were treated with metformin (25–125 mmol/l). Cell proliferation was evaluated via CCK-8 assay. Real-time quantitative reverse transcription–polymerase chain reaction was used to evaluate microRNA (miR)-21-5p and PDCD4 (programmed cell death 4) expression. PDCD4 protein was quantified by Western blot. Results Metformin significantly inhibited FaDu cell proliferation in a dose- (25–100 mmol/l) and time-dependent manner (12 h–36 h), significantly downregulated miR-21-5p, and upregulated PDCD4 mRNA and protein expression. Conclusions Metformin significantly inhibited FaDu cell proliferation , possibly via downregulation of miR-21-5p and upregulation of PDCD4.

The present study aimed to identify the role of caveolin-1 (CAV1) in hypopharyngeal squamous cell carcinoma (HSCC) and identify its possible correlation with tumor clinical parameters. Expression of CAV1 was measured using immunohistochemical staining of 66 HSCC samples and 44 samples from morphologically normal tissues adjacent to the carcinomas. Expression of CAV1 in HSCC and paracancerous tissues were 71.2 and 9.5% respectively. Levels of CAV1 expression were significantly associated with tumor differentiation, tumor-node-metastasis stage and lymph nodes metastasis (P

Laryngeal cancer is an uncommon form of cancer. The tumor suppressor P16, known to be mutated or deleted in various types of human tumor, including laryngeal carcinoma, is involved in the formation and development of laryngeal carcinoma. It has been previously reported that the inactivation or loss of P16 is associated with the acquisition of malignant characteristics. The current study hypothesized that restoring wild‑type P16 activity into P16‑null malignant Hep2 cells may exert an antitumor effect. A recombinant adenovirus carrying the P16 gene (Ad‑P16) was used to infect and express high levels of P16 protein in P16‑null Hep2 cells. Cell proliferation and invasion assays and polymerase chain reaction were performed to evaluate the effects of the P16 gene on cell proliferation and the antitumor effect on Hep2 cells. The results demonstrated that the Hep2 cells infected with Ad‑P16 exhibited significantly reduced cell proliferation, invasion and tumor volume compared with untreated or control adenovirus cells. Furthermore, the expression of laryngeal carcinoma‑associated genes, EGFR, survivin and cyclin D1, were measured in Ad‑P16‑infected cells and were significantly reduced compared with control groups. The results of the current study demonstrate that restoring wild‑type P16 activity into P16-null Hep2 cells exerts an antitumor effect.

Hypopharyngeal squamous cell carcinoma (HSCC) is among the most lethal tumors encountered in the head and neck and frequently involves regional metastasis. However, the mechanism underlying the aggressiveness of HSCC remains elusive. S100A4 is a well-established metastasis-promoting regulator in a variety of malignancies, but its role in HSCC has not yet been identified. Our objectives were to explore the expression levels of S100A4 in HSCC tumors and its association with clinicopathological parameters and the clinical prognosis of HSCC and to confirm its role in the metastatic process of the HSCC FaDu cell line in vitro. We assessed the expression levels of S100A4 with immunohistochemistry (IHC) in HSCC tumors (n = 71) and adjacent normal tissues (n = 44). In vitro experiments were performed to explore the impact of S100A4 knockdown on biological phenotypes of human HSCC FaDu cell line, including migration, invasion, proliferation, apoptosis, and cell cycle. The expression of S100A4 was elevated in HSCC tumors compared with adjacent normal tissues and positively correlated with cervical lymph node metastasis in this HSCC patient cohort. In vitro experiments showed that S100A4 knockdown significantly impaired migration and invasion and increased the proportion of cells in G0/G1 phase with no change in proliferation or apoptosis in FaDu cells. Additionally, nuclear S100A4 expression proved to be an independent prognostic indicator in patients with HSCC. This study demonstrated for the first time that S100A4 expression is upregulated in HSCC tumors and that this upregulation is positively correlated with cervical lymph node metastasis of this malignancy. The metastasis-promoting role of S100A4 was further validated in the HSCC FaDu cell line, indicating that S100A4 is a potential therapeutic target for HSCC. Furthermore, this study suggests that nuclear S100A4 expression could be considered a prognostic biomarker for HSCC.

BACKGROUND The ability to precisely predict which intubations will be difficult during administration of anesthesia is an important part of preoperative preparation. This study's goal is to accurately identify patients who will be difficult to intubate using the number of tracheal rings observed preoperatively by fiberoptic laryngoscopy. METHODS We enrolled 994 adult patients in our study who required general anesthesia and orotracheal intubation for their elective surgeries. All patients received a Mallampati Test, a Wilson Risk-Sum Score, and fiberoptic laryngoscopy before operation. Each patient's age, Body Mass Index (BMI), and neck circumference was recorded preoperatively. Logistic regression analysis was applied to evaluate the association between the recorded risk factors and a potentially difficult intubation. The three preoperative assessments were compared using three parameters: positive predictive value, sensitivity, and specificity. RESULTS The risk factors which were determined to be predictive for difficult intubation were: BMI, neck circumference, Mallampati Test, Wilson Risk-Sum Score, and fiberoptic laryngoscopy (P

Long noncoding RNAs (lncRNAs) are associated with the development, progression, and prognosis of human cancers. However, the clinical significance and biological function of lncRNAs in hypopharyngeal squamous cell carcinoma (HSCC) remain largely unknown. We characterized the novel lncRNA AB209630 in vivo and in vitro. First, using qRT-PCR, we evaluated whether AB209630 levels differ between HSCC tissues/cell lines and adjacent normal tissues/cell lines. We then assessed whether AB209630 expression levels stimulate or inhibit proliferation, invasion, apoptosis, and metastasis in vitro. Finally, we investigated whether AB209630 levels in tumor tissues were associated with survival outcomes. Our results demonstrated that AB209630 levels were markedly lower in HSCC tissues and cells than in normal tissues and cells, and increased expression of AB209630 level significantly inhibited growth, metastasis, and invasion and stimulated apoptosis in vitro. In addition, patients with decreased expression of AB209630 had a significantly poorer prognosis than those with high AB209630 expression. These data suggest that increased expression of AB209630 might either stimulate or inhibit biological activities involved in HSCC development, indicating a potential application of AB209630 in future treatment for this disease. This study suggest that AB209630 functions as a tumor suppressor in HSCC, and its decreased expression may help predict a poor prognostic outcome of HSCC. Our future work will focus on the mechanisms of whether and how AB209630 as a tumor suppressor gene is involved in HSCC development.

The aims of the present study were to review the experience of different surgical reconstruction methods for hypopharyngeal squamous cell carcinoma (HSCC) and compared the survival of patients with and without laryngeal function (LF) preservation. The clinical characteristics of 580 patients were retrospectively obtained and analyzed. Survival curves were analyzed using the Kaplan‑Meier method for survival and Cox models for hazard ratios (HRs) with 95% confidence intervals (CIs). LF was preserved in 403 cases and not preserved in 177 cases. The 3‑ and 5‑year survival rates were 70.9 and 52.7%, respectively, in the LF preservation group and 48.4 and 30.5%, respectively, in the no LF preservation group. Compared with the patients without LF preservation, patients with LF preservation had a significantly reduced risk of overall death (HR=0.63, 95% CI: 0.50-0.80). LF preservation positively affects the prognosis of patients with HSCC.

Background/Aims: Researchers have shown that long noncoding RNAs are closely associated with the pathogenesis of laryngeal squamous cell carcinoma (LSCC). However, the role of the long noncoding RNA taurine-upregulated gene 1 (TUG1) in the pathogenesis of LSCC remains unclear, although it is recognized as an oncogenic regulator for several types of squamous cell carcinoma. Methods: qRT-PCR was performed to measure the expression of TUG1 in LSCC tissues and cell lines. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) was used to measure the effect of TUG1 on cell proliferation. Transwell assay and flow cytometry were employed to determine the effect of TUG1 on cell migration and invasion. Western-blot were performed to explore the relation of TUG1 and p53 mRNA. Results: Higher TUG1 expression in LSCC than in paired normal tumor-adjacent tissue specimens ( N = 64) was observed using quantitative real-time polymerase chain reaction. Also, high TUG1 expression was positively associated with advanced T category, worse lymph node metastasis and late clinical stage. Furthermore, in vitro experiments demonstrated that silencing of TUG1 markedly inhibited proliferation, cell-cycle progression, migration, and invasion of LSCC cells, whereas depletion of TUG1 led to increased apoptosis. Conclusion: These findings demonstrated that upregulated TUG1 expression exerted oncogenic effects by promoting proliferation, migration, and invasion, and inhibiting apoptosis in LSCC cells.

The E26 transformation-specific (ETS) family is one of the largest families of transcription factors. Upon activation by MAPK pathway, ETS participates in cell proliferation, differentiation, migration, apoptosis, and metastasis. However, the mechanism by which ETS is deregulated in cancer is unclear. In this study, the authors investigated the role of ETS factor, ETS2, in hypopharyngeal cancer pathogenesis in hypopharyngeal cancer tissues (N = 20) and corresponding non-neoplastic tissues (N = 20). The results showed that expression of ETS2 was increased in cancer tissues as compared with the expression in corresponding non-neoplastic tissues. Analysis of clinicopathological characteristics showed that increased level of ETS2 is associated with III-IV tumor node metastasis stage and lymph node metastasis. In addition, knockdown of ETS2 by siRNA in pharyngeal cancer cell line, FaDu, significantly decreased cell's vitality and colony-forming ability by inducing caspase-3-dependent apoptosis and cell cycle arrest. Furthermore, inhibition of ETS2 could abrogate the migration, invasion, and transforming growth factor-β-induced epithelial mesenchymal transition through the upregulation of E-cadherin, zona occludens protein-1, together with downregulation of vimentin and α-sooth muscle actin. These functions of ETS2 could be associated with the activation of MAPK/p38/ERK/JNK signals. Taken together, the authors opined that ETS2 functions as an oncogene and plays a key role in the progression of hypopharyngeal cancer.

Vertebrobasilar insufficiency (VBI) presents complex varied clinical symptoms, including vertigo and hearing loss. Little is known, however, about how Ca(2+)-activated K(+) channel attributes to the medial vestibular nucleus (MVN) neural activity in VBI. To address this issue, we performed whole-cell patch clamp and quantitative polymerase chain reaction (qPCR) to examine the effects of hypoxia on neural activity and the changes of the large conductance Ca(2+) activated K(+) channels (BKCa channels) in the MVN neurons in brain slices of male C57BL/6 mice. Brief hypoxic stimuli of the brain slices containing MVN were administrated by switching the normoxic artificial cerebrospinal fluid (ACSF) equilibrated with 21% O2/5% CO2 to hypoxic ACSF equilibrated with 5% O2/5% CO2 (balance N2). 3-min hypoxia caused a depolarization in the resting membrane potential (RM) in 8/11 non-spontaneous firing MVN neurons. 60/72 spontaneous firing MVN neurons showed a dramatic increase in firing frequency and a depolarization in the RM following brief hypoxia. The amplitude of the afterhyperpolarization (AHPA) was significantly decreased in both type A and type B spontaneous firing MVN neurons. Hypoxia-induced firing response was alleviated by pretreatment with NS1619, a selective BKCa activator. Furthermore, brief hypoxia caused a decrease in the amplitude of iberiotoxin-sensitive outward currents and mRNA level of BKCa in MVN neurons. These results suggest that BKCa channels protect against abnormal MVN neuronal activity induced by hypoxia, and might be a key target for treatment of vertigo and hearing loss in VBI.

This study compares clinical characteristics and survival between patients with and without laryngeal function (LF) preservation during surgical treatment for hypopharyngeal carcinoma. We retrospectively reviewed 485 cases of hypopharyngeal carcinoma treated at a single institution for analysis. There were 337 cases with and 148 cases without LF preservation after surgery. Preservation of LF was complete in 237 patients and partial in 100 patients. There were significant statistical differences between the preservation group and the group without preservation in T-stage (P

microRNAs, a family of small non-coding RNAs, involve in the pathogenesis of several types of cancers, including laryngeal squamous cell carcinoma (LSCC). MiR-370 is frequently aberrant expressed in various types of human cancer including LSCC. However, the role for miR-370 in LSCC remains elusive. Here, we demonstrate that miR-370 was down-regulated in human LSCC tissues. Furthermore, there was an inverse relationship between Forkhead Box ml (FoxM1), which was up-regulated and miR-370 expression in LSCC tissues. FoxM1 was subsequently predicted by bioinformatics and verified to be a target of miR-370 by Luciferase reporter assay. Restored expression of miR-370 in Hep2 cells significantly inhibited cell proliferation. In conclusion, our results suggest that miR-370 may function as a tumor suppressor in LSCC through downregulation of FoxM1, suggesting that miR-370 could serve as a novel potential maker for LSCC therapy.

Myeloid cell leukemia-1 (Mcl-1) plays an important role in survival, chemo- and radioresistance of head and neck squamous cell carcinoma (HNSCC). Cyclin-dependent kinase 9/cyclin T (CDK9) promotes excessive production of multiple pro-survival proteins including Mcl-1, leading to impaired apoptosis of cancer cells. As such, CDK9 is an emerging therapeutic target in cancer therapy. We herein report the first study of targeting CDK9 as a treatment strategy for hypopharyngeal squamous cell carcinoma (HSCC), an aggressive malignancy associated with one of the worst prognoses within HNSCC. We showed that mRNA levels of Mcl-1 were significantly higher in HSCC tumor tissues than in the adjacent non-tumor mucosae. In addition, the levels of Mcl-1 mRNA correlated with the tumor size and clinical stage of HSCC patients. CDKI-73, a potent CDK9 inhibitor, was capable of downregulating the expression of Mcl-1 in the HSCC cells by suppression of the CDK9 mediated phosphorylation of RNA polymerase II. CDKI-73 effectively induced apoptosis as a single agent and synergized anti-tumor activity of cisplatin in HSCC cells. Taken together, our study presents compelling evidence for developing CDK9 inhibitors, such as CDKI-73, as new therapeutic strategy for HSCC. Refereed/Peer-reviewed

Aim of the investigation was to develop folate-functionalized lipid nanoemulsion (LNE) comprising chemo-radiotherapeutics for targeted delivery to nasopharyngeal carcinoma (NPC). Soy lecithin nanoemulsion of doxorubicin (Dox) and yittrium-90 (90Y) was prepared by nanoprecipitation using ultrasonic homogenization technique followed by folic acid conjugation. Nanoemulsion (Dox-LNE) was characterized as positively charged (zeta potential), spherical shape (transmission electron microscopy) nano-droplets of uniform size distribution (polydispersity index). No significant variation in parameters such as particle size, zeta potential, and polydispersity index was observed when the stability of Dox-LNE was assessed during long-term storage at room temperature and at 8000 rpm, 121°C temperature, and 5000 time dilution in water. In vitro release of Dox from Dox-LNE was observed to be controlled for at least 48 h. Folate decoration over Dox-LNE surface (FD-Dox-LNE) and incorporation of 90Y in FD-Dox-LNE (FD-Dox + 90Y-LNE) changed droplet size up to 50 nm; however, surface charge of Dox-LNE did not change significantly. FD-Dox + 90Y-LNE inhibited growth of cancerous cell line like CNE1 (folate receptor rich) in vitro and alleviated tumor volume in NPC-induced nude mice significantly as compared to Dox + 90Y-LNE. Massive necrosis and hemorrhage of CNE1 cells were observed by FD-Dox + 90Y-LNE (89.9%); however, inhibition of growth of nasal epithelial cells (RPMI 2650; folate deficient) by FD-Dox + 90Y-LNE and Dox + 90Y-LNE was observed to be 21.5 and 43.65%, respectively. The investigation highlights the vast utility of folate-decorated lipid emulsion in delivering chemo-radiotherapeutics to the specific NPC site. FD-Dox + 90Y-LNE might offer a cost-effective, safe, efficacious, and clinically pertinent option to the available therapeutics.

Background Although epithelial stem/progenitor cells have been isolated from many parts of the human airway epithelium such as lung and trachea, there is limited information in regard to stem cells in nasal epithelium. The aim of this study was to determine if (1) human nasal epithelial stem/progenitor cells (hNESPCs) can be isolated and propagated in vitro and (2) allogeneic adult primary human fibroblasts can serve as a feeder layer for hNESPCs expansion under serum-free conditions. Methods Primary cells taken from inferior turbinate biopsy specimens (n = 3) were enzymically dissociated and plated on either allogeneic human fibroblasts or murine NIH 3T3 fibroblasts, in a chemical-defined medium supplemented with growth factors. Self-renewal, proliferation, and differentiation potential were compared. Results The optimized media were capable of supporting the undifferentiated growth and expansion of hNESPCs on both feeder cells. The doubling time and cloning efficiency of hNESPCs cultured on a human feeder layer were comparable with that cultured on 3T3 feeders. Significantly, the hNESPCs on both feeder layers could be cultured for four passages, and they can differentiate into ciliated columnar cells and goblet cells at the air–liquid interface, resembling the in vivo mucociliary airway epithelium. Conclusion Our results showed the feasibility of expanding hNESPCs for clinical purpose by using human feeder layer, avoiding components of animal source, while preserving their self-renewal and differentiation potential. This study represents an early step toward a better understanding of hNESPCs, and serum -free media plus human feeder potentially would be an ideal method for making clinical grade hNESPCs on a large scale.

Xeroderma pigmentosum group A (XPA) participates in modulating recognition of DNA damage during the DNA nucleotide excision repair process. The XPA A23G polymorphism has been investigated in case-control studies to evaluate the cancer risk attributed to the variant, but the results were conflicting. To clarify the effect of XPA A23G polymorphism in cancer risk, we conducted a meta-analysis that included 30 published case-control studies. Overall, no significant association of XPA A23G variant with cancer susceptibility was observed for any genetic model. However, significant association was observed for colorectal cancer (GG vs. AA: OR = 1.68, 95% CI = 1.15-2.44; dominant genetic model GG + AG vs. AA: OR = 1.54, 95% CI = 1.08-1.17), for breast cancer an increased but non-significant risk was found (GG vs. AA: OR = 1.27, 95% CI = 0.98-1.66; dominant genetic model GG + AG vs. AA: OR = 1.27, 95% CI = 0.99-1.63), and for head and neck cancer an increased risk was observed in recessive model (OR = 1.19, 95% CI = 1.02-1.38), whereas for lung cancer a significant reduced risk was observed (GG vs. AA: OR = 0.77, 95% CI = 0.66–0.90; dominant genetic model GG + AG vs. AA: OR = 0.76, 95% CI = 0.66-0.87), it’s noting that in Asian population the inverse association was more apparent. In addition, in Asian population for esophageal cancer a significant decreased risk was also found in dominant genetic model (OR = 0.55; 95% CI = 0.43-0.70) and for head and neck cancer an increased risk was observed in dominant genetic model (OR = 1.51, 95% CI = 1.03-2.23). The meta-analysis suggested that the XPA A23G G allele is a low-penetrant risk factor for cancer development.

Signal transducers and activators of transcription (STAT) are important in the development of laryngeal carcinomas and are potential novel molecular targets for therapy to improve survival of patients with this cancer. This study was designed to investigate the influence of the janus activated kinase (JAK)/STAT inhibitor AG490 on proliferation and apoptosis of Hep-2 human laryngeal cancer cells and whether there was any inhibition by AG490 of the JAK/STAT3 signalling pathway. AG490 inhibited cell proliferation in dose-and time-dependent manners and induced apoptosis in Hep-2 cells, with the number of apoptotic cells increasing with time. AG490 inhibited G1 to S cell cycle transition and induced G1 cell cycle arrest as well as significantly down-regulating STAT3, phosphorylated STAT3 and survivin in Hep-2 cells. This study showed that AG490 significantly inhibited proliferation and induced apoptosis of laryngeal carcinoma cells through down-regulation of STAT3 and survivin, suggesting a potential target for laryngeal carcinoma treatment.

Objective: There are controversies on management of carotid artery invasion in advanced head and neck cancer. En bloc resection has been considered a curative modality. In this study, we evaluated the feasibility of using expanded polytetrafluoroethylene (ePTFE) in reconstructing the common carotid artery in patients with carotid artery invasion requiring resection. Method: A retrospective study including 13 patients managed from 2002 to 2005. All patients underwent en bloc resection of the tumor and internal carotid artery then reconstructed with ePTFE. Results: All patients had en bloc resection of the tumor together with internal carotid artery and reconstruction with ePTFE. Some patients required wound coverage with myocutaneous flaps in eight patients and local flaps in five patients. Intraoperative shunting was used in all patients. Intraoperative heparin infusion and postoperative low dose aspirin were used to prevent thrombosis. One patient developed graft blowout and he was treated with ligation without hemiplegia. One patient had minor stroke. The follow-up period was 18.4 ± 8.6 months. No patient suffered from neurological deficit or graft occlusion. Disease survival was 61.5% in 1 year and 38.5% in 2 years. Overall survival was 18.3 months. Conclusion: En bloc resection and tumor together with carotid artery and ePTFE reconstruction is shown to be a feasible modality in treatment of advanced head and neck cancer with carotid artery invasion.

The aim of this study was to determine the expression of cellular FLICE-like inhibitory protein (cFLIP) in head and neck squamous cell carcinoma (HNSCC) and revealed its possible correlation to Fas protein and tumour clinical parameters.The expression of cFLIP was analysed in 58 HNSCC samples and 30 morphologically normal tissues adjacent to the carcinomas using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. Furthermore, its possible correlation to the expression of Fas protein and tumour clinicopathologic parameters were discussed.Cellular FLICE-like inhibitory protein was demonstrated to be up regulated in most HNSCC than in normal tissues by immunohistochemistry (p0.01). Although the mRNA levels of both isoforms of cFLIP, long form (cFLIP(L)) and short form (cFLIP(S)), in HNSCC were higher than those in normal tissues (p0.01), only cFLIP(L) protein could be detected by western blot. Furthermore, the expression of cFLIP(L) protein was significantly associated with tumour clinical stage (p0.01) and lymph node metastasis (p=0.01). Since all of the tumours with Fas immunostaining also express cFLIP protein, there was no significant correlation between them (p0.05).Overexpression of cFLIP(L) is a frequent event in HNSCC and HNSCC cells in vivo may need it to evade apoptosis mediated by Fas or other receptors, which might contribute to tumour development and progression.

Brain-derived neurotrophic factor (BDNF) is critical for sensory neuron survival and is necessary for vesicular glutamate transporter 3 (VGLUT3) expression. Whether the transcription factors Etv4 and Etv5 are involved in these BDNF-induced effects remains unclear. In the present study, primary cultured dorsal root ganglion (DRG) neurons were used to test the link between BDNF and transcription factors Etv4 and Etv5 on VGLUT3 expression and neurite outgrowth. BDNF promoted the mRNA and protein expression of Etv4 and Etv5 in DRG neurons. These effects were blocked by extracellular signal-regulated protein kinase 1/2 (ERK1/2) inhibitor PD98059 but not phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 or phospholipase C-γ (PLC-γ) inhibitor U73122. Etv4 siRNA and Etv5 siRNA effectively blocked the VGLUT3 expression and neurite elongation induced by BNDF. The overexpression of Etv4 or Etv5 potentiated the effects of BNDF-induced neurite elongation and growth-associated protein 43 (GAP-43), medium neurofilament (NF-M), and light neurofilament (NF-L) expression while these effects could be inhibited by Etv4 and Etv5 siRNA. These data imply that Etv4 and Etv5 are essential transcription factors in modulating BDNF/TrkB signaling-mediated VGLUT3 expression and neurite outgrowth. BDNF, through the ERK1/2 signaling pathway, activates Etv4 and Etv5 to initiate GAP-43 expression, promote neurofilament (NF) protein expression, induce neurite outgrowth, and mediate VGLUT3 expression for neuronal function improvement. The biological effects initiated by BDNF/TrkB signaling linked to E26 transformation-specific (ETS) transcription factors are important to elucidate neuronal differentiation, axonal regeneration, and repair in various pathological states.

The present study was undertaken to investigate the mechanisms of peroxisome proliferator activated receptor-gamma (PPAR-gamma) ligand-induced apoptosis on human myeloid leukemia K562 and HL-60 cell lines. The results revealed that both 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and troglitazone (TGZ) have significant anti-proliferation- and apoptosis-inducing effects on these two kinds of leukemia cells. Marked morphological changes of cell apoptosis including condensation of chromatin and nuclear fragmentation were observed clearly using Wright's and Hoechst 33258 staining. Reverse transcription-PCR and western blot analyses demonstrated that both survivin and bcl-2 expression were downregulated markedly, while bax expression was upregulated concurrently when apoptosis occurred. We therefore conclude that 15d-PGJ2 and TGZ have significant apoptosis effects on K562 and HL-60 cells in vitro, and that upregulation of bax as well as downregulation of survivin and bcl-2 expression may be the important apoptosis-inducing mechanisms. The results suggest that PPAR-gamma ligands may serve as potential therapeutic agents for both acute and chronic myeloid leukemia.

OBJECTIVE To explore the surgical methods and evaluate the long-term results of laryngectomy in patients with supraglottic laryngeal cancer. METHODS A total of 182 patients with supraglottic laryngeal carcinoma underwent an operation from 1979 to 1999. These cases comprised 11 in stage Ⅰ , 45 in stage Ⅱ , 49 in stage Ⅲ and 77 in stage Ⅳ. The choice of surgical procedure was decided based on the condition of the diseasedl arynx. The surgical procedures proposed by TD Wang were adhered to as follows: minor partial laryngectomy 36, major partial laryngectomy 85,subtotal partial laryngectomy with laryngoplasty 22 and total larygectomy 39. RESULTS The final rate of larynx preservation was 78.6% (143/182) and 69.8% (88/126) in patients with stage III and IV diseases. The extubation rate was 81.8% in cases with preservation of laryngeal function. The overall 3-and 5-year survival rates were 82.9% and 67.3%, with 76.88% and 57.4% in the advanced (stage III and IV) cases who survived with preserved laryngeal function, and 82.5% and 67.0% in similar advanced cases who were treated by total laryngectomy. The difference in the survival rates between these 2 groups was not statistically significant. CONCLUSION It is suggested that preservation of the laryngeal function is possible for advanced supraglottic laryngeal carcinoma without compromising the long-term survival rate. To improve the rate of larynx preservation, one should follow the surgical methods suggested.

Oridonin, an extract from the Chinese herb Rabdosia rubescens, is currently one of the most important traditional Chinese herbal medicines. We investigated the anti-proliferative effect of oridonin on the lung cancer cell line SPC-A-1 and its mechanism of action. Growth inhibition was measured using a microculture tetrazolium assay and apoptosis was measured by several standard methods. Western blot analysis measured the expression of bcl-2 and bax proteins. Oridonin (> 28 μmol/l) inhibited the growth of SPC-A-1 cells and induced apoptosis. Marked morphological changes indicative of apoptosis were observed, especially in cells treated with oridonin for 48–60 h. Western blot analysis revealed downregulation of bcl-2 and upregulation of bax proteins following treatment with oridonin for 48 h. We conclude that oridonin demonstrated anti-proliferative and apoptosis-inducing effects on SPC-A-1 cells in vitro, and that changes in bcl-2 and bax protein levels may play an important role in its mechanism of action.

Claudin-l and cyclin B1 are abnormally expressed in certain malignancies, but their expression in hypopharyngeal squamous cell carcinoma (HSCC) has not been reported thus far. Studying the expression levels of claudin-1 and cylin B1 in HSCC tissues and their association with clinical stage, pathological grade and prognosis in patients with HSCC may provide a theoretical basis and guide future research on HSCC targeted therapy. The protein expression levels of the above two biomarkers was immunohistochemically detected in 97 HSCC cases and 90 matched adjacent tissue samples. The correlation between the expression levels of claudin-1 and cylin B1 and the patients' clinical parameters was analyzed via Pearson's χ2 test, while survival analysis was performed using a log-rank test. The results of the current study revealed that claudin-1 and cyclin B1 were highly expressed in HSCC tissues, and the expression of claudin-1 was associated with tumor differentiation degree and lymph node metastasis, while cyclin B1 expression was associated with tumor differentiation degree. Furthermore, Kaplan-Meier analysis revealed that claudin-1 expression correlated with survival (P=0.003), and the expression levels of claudin-1 and cyclin B1 were observed to be positively correlated, in patients with HSCC. Cyclin B1 and claudin-1 exhibited an elevated expression in HSCC specimens, thus suggesting their use as tumor markers. Therefore, the joint detection of claudin-1 and cyclin B1 may aid to guide cancer therapy and to determine prognosis in HSCC. Furthermore, claudin-1 may be used as an HSCC-monitoring index, and may serve as a therapeutic target.

These findings indicate that in hypopharyngeal squamous cell carcinoma (HSCC), hypermethylation and down-regulation of death-associated protein kinase-1 (DAPk1) are common events, which are associated with a poor prognosis.This study aimed to investigate the methylation and expression of DAPk1, a tumor suppressor gene, in HSCC, and explore its clinical significance.The tumor and adjacent non-tumor tissues were collected from 53 patients with HSCC. The methylation status of DAPk1 was detected by methylation-specific polymerase chain reaction (MSP), and expression of DAPk1 was determined with real-time reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blot at mRNA or protein levels. Correlations between the findings and patients' clinicopathological parameters were further evaluated.The methylation ratio of DAPk1 in tumor tissues (60.38%) was significantly higher than that in the adjacent non-tumor tissues (26.42%) (p = 0.001), while DAPk1 expression in the tumors was down-regulated markedly (real-time RT-PCR, p = 0.002; immunohistochemistry, p = 0.006; Western blot, p0.001). DAPk1 methylation was negatively correlated with its mRNA expression (p = 0.002, r = -0.521). Both hypermethylation and down-regulation of DAPk1 were closely related to lymph node metastasis (p = 0.001 and 0.001, respectively), advanced TNM stage (p = 0.009 and 0.019, respectively), and low survival rates (p = 0.031 and 0.045, respectively).

Hypopharyngeal squamous cell carcinoma (HSCC) has the worst prognosis among head and neck cancers. Cisplatin (DDP)-based chemotherapy is an important part of multimodal treatments. However, resistance to DDP severely impairs the effectiveness of chemotherapy for HSCC. Chloroquine (CQ) has been reported to enhance the effectiveness of chemotherapy and radiotherapy in liver, pancreas, breast, prostate and colon tumors, but it is unclear whether CQ could increase the efficacy of DDP for treating HSCC. We inoculated BALB/c nude mice with a subcutaneous injection of human hypopharyngeal FaDu cells to generate our animal model. Mice were randomly divided into 4 groups and treated with vehicle control, CQ (60 mg/kg/day), DDP (5 mg/kg/6 days), or a combination of DDP and CQ. Tumor growth and survival of the mice were monitored. We found that CQ inhibited autophagy and increased DDP-induced apoptosis in the xenograft mouse model. CQ enhanced the efficacy of DDP, resulting in decreased tumor growth and prolonged survival of the mice. To test whether blocking autophagy enhanced the efficacy of DDP, FaDu cells were infected with lentiviral shRNA to Beclin-1 and inoculated into the flanks of nude mice. Inhibition of autophagy markedly enhanced the DDP-induced antitumor effect. Our study suggests that the addition of CQ to DDP-based chemotherapy could be a potential therapeutic strategy for treating HSCC, and the inhibition of autophagy may contribute to chemotherapy sensitization in HSCC.

The technique of endoscopy-assisted transoral approach (EATA) has improved greatly, which should provide a better alternative for parapharyngeal space (PPS) tumors. Here, we compared curative effects between the resection of parapharyngeal space (PPS) tumors by EATA and external approaches (EAs), including the transcervical, transparotid, and transmandibular approaches. Based on the tumors’ position and the relationship with adjacent structures, we selected 20 patients with parapharyngeal space tumor hospitalized in the Second People’s Hospital in Shenzhen from January 2008 to December 2013, which were divided into the observation group and the control group with patients’ informed consents. In the observation group, the tumors were removed solely by transoral approach under the guidance of endoscopes (EATA), while in the control group, the tumors were resected completely using an external approach (EA). We compared the total removal rate, the operation time, blood loss, postoperative pain, hospitalized time, complication rate, scar, and recurrence between the two groups. All the tumors were completely removed and patients were followed up for 6 months–5 years with no recurrence in either group. There was no significant difference regarding total removal rate, operation time, complication rate, and recurrence rate between the two groups (P > 0.05). However, significant differences were observed in blood loss, hospitalized time, and postoperative pain between the two groups (P

BACKGROUND The question of whether "recurrent" laryngeal carcinoma is truly a new tumour with a clonal origin that differs from that of the primary tumour has remained unanswered. The objective of this study was to determine whether recurrent tumours have the same genetic basis as primary tumours, as the answer to this question is important for the development of treatment strategies. MATERIALS AND METHODS Matched samples consisting of primary tumour, recurrent tumour and normal tissue were obtained from the same patient. A total of 37 patients with laryngeal cancer were examined for loss of heterozygosity (LOH) on the 3p, 5p, 7q, 8p, 9p, 13p, 17p and 18q chromosomal arms using PCR to amplify microsatellite markers. All patients were routinely followed up and 5-year survival rates were calculated using directly calculating method and Kaplan-Meier's method. RESULTS A total of 28 out of 37 (75.6%) patients showed LOH at a minimum of one locus, and 19 out of 37 (51.3%) patients showed LOH at two loci. Primary and recurrent tumours in each patient showed identical allelic loss patterns and incidence rates. Patients without LOH had a longer average time to recurrence than patients with LOH (P

To investigate the clinical pathological features of aspirated tracheobronchial foreign body (FB) cases in children under the age of 3 years and to improve the level of diagnosis and treatment.A retrospective study was conducted examining 316 children under the age of 3 years who had been treated for tracheobronchial FB in Shenzhen children's hospital between January 2004 and December 2008. We analyzed the patients for gender, age, FB localization, treatment history, the history of foreign body aspiration (FBA), the type of foreign body and the cause of death. In addition, each patient was analyzed for FB-related complication, the results of bronchoscopic removal and the presence of foreign bodies in the airways.Fifty-two infants under the age of one year (median age=10m, group A), 199 children between the ages of 1 and 2 years (median age=17 m, group B) and 65 children between the ages of 2 and 3 years (median age=30m, group C) were included in this study. There were 38 (73.1%) patients with a confirmed history of FBA in group A, a higher percentage than that observed in group B (55.8%) or group C (53.8%) (P0.05). Earthnuts were the most common cause of FB (171 cases, 54.1%). Melon seeds (including sunflower seeds, watermelon seeds and pumpkin seeds) were the second most common cause of FB (62 cases, 19.6%). Animal sources (including 16 pig bones, 8 fish bones, 7 chicken bones and 4 other animal-based foods) comprised 11.1% (35 cases) of FB cases and were the third most common cause of FB. The percentage of animal-based FBs observed in group A was higher than in groups B and C (P0.01). Five inorganic FBs (a pushpin, a rubber band, a screw, a small stone and a plastic toy) were also observed and were the least common type of FB. There were no significant differences in the distribution of FBs between the left (41.8%) and right (40.5%) bronchia. There is no difference in the distribution of FBs among the three groups either. The data show that the youngest cohort of patients (0-1 years) is the most likely to be sent to the hospital to receive treatment within 24h of aspiration (50%) (P0.01). Five patients (1.58%) died as the result of FBA.FBAs of animal-derived FBs (especially animal bones) are very common in infants in southern China. Children between the ages of 1 and 2 years are most likely to suffer from FBA. FBA in children under the age of 3 years carries significant hazards, including morbidity and mortality. Asphyxia and/or cardiopulmonary arrest is prone to occur shortly after FBA in infants, but these events can occur days later in older children after FBA because of delays in the diagnosis and/or treatment of this condition.

To the Editor: Ossifying fibroma is a benign but rare fibro-osseous tumor in the craniofacial region. Complete resection is the only way to treat it. Here, we reported one case of maxillary juvenile ossifying fibroma operated with intranasal endoscopic prelacrimal recess approach in which nasolacrimal duct (NLD) and inferior turbinate (IT) were spared. A 9-year-old girl presented left facial asymmetry for 2 months and was hospitalized in the Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital in June 2013. A paranasal sinus computed tomography (CT) scan showed a lesion in left maxillary sinus (MS). No nasal obstruction, rhinorrhea, decreased vision, proptosis or epistaxis was ever complained. No abnormal finding was noted in and out of her nose during the physical examination and nasal endoscopy. Imaging study revealed that the left MS expanded to 2.4 cm × 2.8 cm × 3.0 cm. Soft tissue density was present inside the sinus surrounded with a clear boundary and intact bone wall [Figure ​[Figure1a1a and ​and1b].1b]. Tumor resection was performed with intranasal endoscopic prelacrimal recess approach under general anesthesia. First, we chiseled off the anterior bony portion of the medial wall of the MS to expose the NLD posteriorly and mucosa of MS interiorly. The sinus was filled with a solid, encapsulated and sand like mass, about 2.4 cm × 2.8 cm × 3.0 cm in size. Surrounding bone walls appeared as stalactite, and the surface was rough. Second, the tumor was removed completely. On the 2nd day after operation, the nasal packing was taken away, and the postoperative CT scan was carried out at the same time [Figure ​[Figure1c1c and ​and1d].1d]. Pathological finding was ossifying fibroma [Figure 2]. During the 6 months follow-up, there was no recurrence or complications. Figure 1 Preoperative paranasal sinus computed tomography (CT) in coronal position (a) and horizontal position (b) showed ossifying fibroma in left maxillary sinus (triangles). Postoperative paranasal sinus CT in coronal position (c) and horizontal position (d) ... Figure 2 Pathological finding showed ossifying fibroma (HE, original magnification ×200). For ossifying fibroma, early surgery is necessary to achieve a complete tumor resection. There are many procedures available depending on the involvements of lesion,[1,2] such as midfacial desgloving approach, Denker or modified Dener operation, Caldwell-Luc operation, medial maxillectomy, etc.[3] In all the above procedures, IT and/or NLD is to be sacrificed, and dry nose, epiphora or facial numbness may occur after operation. To improve the quality of life, Zhou et al.[4] introduced intranasal endoscopic prelacrimal recess approach to treating such disease. Without ablation of IT and NLD, the function of the nasal cavity and lacrimal aperture are preserved. Meanwhile, hospital stay can be shortened. This was first reported to use this approach to remove ossifying fibroma in MS. The surgery went smoothly and follow-up results showed no postoperative complications. In short, juvenile ossifying fibroma of MS may be the potential indications for prelacrima recess approach.

The tumor's grade, rather than the tumor's location, was related to the opportunity of preserving laryngeal functions in patients with pyriform sinus cancer. The survival rate decreased significantly with the increase of tumor grade or node grade. Preservation of laryngeal functions is a safe and promising method without compromising the survival rate of patients with pyriform sinus cancer.Surgical resection of pyriform sinus carcinoma has a profound influence on the preservation of laryngeal functions. The purpose of this study was to assess the safety and efficacy of the surgical treatment of pyriform sinus carcinoma in the preservation of laryngeal functions without compromising the survival rate.Two hundred and thirty patients with pyriform sinus cancer had been operated from March 1978 to December 2002. Of them, 158 cases had been operated with the preservation of laryngeal functions and 72 cases had been undergone total laryngectomy. In addition, 216 cases had received adjuvant postoperative radiotherapy. All cases were followed up for 6-12 months (mean 51 ± 26) after surgery. The survival rate was calculated on the basis of Kaplan-Meier analysis, and the factors that influenced the survival rate of patients with and without preservation of laryngeal functions were analyzed with the log-rank test.Laryngeal functions were preserved completely (speech, respiration, and deglutition) in 70.9% (112/158) cases, and partially (speech and deglutition) in 29.1% (46/158) cases. The 3- and 5-year survival rates were 75.4% and 59.0%, respectively, for the group with laryngeal function preservation, and 58.6% and 41.5%, respectively, for the group without preservation. There was no statistically significant difference in the survival rate between the two groups within the follow-up period (p0.05). Increase in the tumor grade resulted in a proportional decrease of patients with preservation of laryngeal function (p0.05). Increase in the tumor grade (p0.05) or node grade (p0.05) also led to significant decrease in the survival rate. The location of the primary lesions (the lateral wall or medial wall of the pyriform sinus) showed no significant influence on either the opportunity for preserving laryngeal functions (p0.05) or survival rate of patients (p0.05).

Background Beclin-1, a key regulator of autophagy. Microtubule-associated protein 1 light chain 3 (LC3), is involved in autophagsome formation during autophagy. The autophagic genes beclin-1 and LC3 paly an important role in the development and progression of tumor. This study was designed to investigate the expression of beclin-1 and LC3 and to clarify their clinical significance in hypopharyngeal squamous cell carcinoma (HSCC). Methods Eighty-two surgical hypopharyngeal squamous cell carcinoma specimens and fifty-four adjacent non-cancerous mucosal epithelial tissues were obtained. Beclin-1 and LC3-II expression was examined by immunohistochemistry, real-time RT-PCR and Western blotting assays. Correlations with patient clinical characteristics and overall survival were evaluated. Results Beclin-1 was positively expressed in 42.7% (35/82) of HSCC specimens (adjacent non-cancerous tissues, 79.6%, 43/54; P

RATIONALE AND OBJECTIVESirtuin 1 (SIRT1) plays an important role in tumorigenesis and is increased in many human tumors. DBC1 is a negative regulator of SIRT1 via promotion of p53-mediated apoptosis. It is necessary to investigate the expression of SIRT1 and DBC1 in laryngeal and hypopharyngeal squamous cell carcinomas (LSCC and HSCC) and its correlation with available clinical parameters.METHODSThe mRNA levels of SIRT1 and DBC1 were measured in 54 paired LSCC or HSCC tumors and corresponding adjacent noncancerous mucosae using quantitative RT-PCR (qRT-PCR). The protein levels of SIRT1 and DBC1 were also evaluated in 120 cases of patients with LSCC or HSCC using immunohistochemical staining. The correlation between SIRT1 and DBC1 expression and clinical parameters was analyzed with Pearson chi-square test.RESULTSqRT-PCR assay showed that, compared with the paired adjacent noncancerous mucosae, SIRT1 mRNA was significantly decreased in tumors. The immunohistochemical results indicated that the SIRT1 protein was also downregulated in tumors compared with noncancerous mucosae. Moreover, decreased SIRT1 was significantly correlated with the tumor clinical stage and lymph node metastasis. Additionally, DBC1 mRNA was significantly increased in tumors compared with noncancerous mucosae. The immunohistochemical results indicated that the DBC1 protein was downregulated in tumors, which is inconsistent with the results obtained by qRT-PCR. Finally, decreased DBC1 protein was significantly correlated with tumor differentiation, lymph node metastasis, and p53 expression.CONCLUSIONSSIRT1 and DBC1 might be involved in the pathophysiology of laryngeal and hypopharyngeal squamous cell carcinomas and are associated with lymph node metastasis and p53 positive staining in LSCCs and HSCCs.