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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

LncRNAs are reported to be involved in tumor proliferation, invasion and metastasis, and are considered as potential biomarkers and therapeutic targets for human cancer, including head and neck cancer. In this study, we screened the differentially low-expressed linc01513 by bioinformatic to detect its expression and biological effect on nasopharyngeal carcinoma (NPC). MTT was used to evaluate the effect of linc01513 on the proliferation of NPC cells. Wound healing assay was used to determine the cells migration ability. The matrix transwell was used to further detect the role of linc01513 in cell invasion. Western blot was used to detect the expression of epithelial-mesenchymal transformation (EMT)-induced transcription factors E-cadherin, vimentin and Slug. The results showed that silence of linc01513 could promoted the proliferation, migration and invasion of NPC cells. The in vivo experiment showed that overexpression of linc01513 could inhibit the volume and weight of xenograft tumors. Database prediction, RNA pull-down and RIP experiments suggested that linc01513 may play an anti-tumor effect by inhibiting PTBP1 protein level. It is suggested that linc01513 directly binds to PTBP1 protein and mediates the EMT process and malignant biological behavior of NPC cells, which provides a new molecular marker for the prognosis and treatment of NPC.

To investigate the role of CT radiomics for preoperative prediction of lymph node metastasis (LNM) in laryngeal squamous cell carcinoma (LSCC).LSCC patients who received open surgery and lymphadenectomy were enrolled and randomized into primary and validation cohorts at a ratio of 7:3 (325 vs. 139). In the primary cohort, we extracted radiomics features from whole intratumoral regions on venous-phase CT images and constructed a radiomics signature by least absolute shrinkage and selection operator (LASSO) regression. A radiomics model incorporating the radiomic signature and independent clinical factors was established via multivariable logistic regression and presented as a nomogram. Nomogram performance was compared with a clinical model and traditional CT report with respect to its discrimination and clinical usefulness. The radiomics nomogram was internally tested in an independent validation cohort.The radiomics signature, composed of 9 stable features, was associated with LNM in both the primary and validation cohorts (both p.001). A radiomics model incorporating independent predictors of LNM (the radiomics signature, tumor subsite, and CT report) showed significantly better discrimination of nodal status than either the clinical model or the CT report in the primary cohort (AUC 0.91 vs. 0.84 vs. 0.68) and validation cohort (AUC 0.89 vs. 0.83 vs. 0.70). Decision curve analysis confirmed that the radiomics nomogram was superior to the clinical model and traditional CT report.The CT-based radiomics nomogram may improve preoperative identification of nodal status and help in clinical decision-making in LSCC.• The radiomics model showed favorable performance for predicting LN metastasis in LSCC patients. • The radiomics model may help in clinical decision-making and define patient subsets benefiting most from neck treatment.

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.

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.

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.

Purpose. In the clinical management of hypopharyngeal squamous cell carcinoma (HSCC), preoperative identification of early recurrence (≤2 years) after curative resection is essential. Thus, we aimed to develop a CT-based radiomic signature to predict early recurrence in HSCC patients preoperatively. Methods. In total, 167 HSCC patients who underwent partial surgery were enrolled in this retrospective study and divided into two groups, i.e., the training cohort (n=133) and the validation cohort (n=34). Each individual was followed up for at least for 2 years. Radiomic features were extracted from CT images, and the radiomic signature was built with the least absolute shrinkage and selection operator (LASSO) logistic regression (LR) model. The associations of preoperative clinical factors with early recurrence were evaluated. A radiomic signature-combined model was built, and the area under the curve (AUC) was used to explore their performance in discriminating early recurrence. Results. Among the 1415 features, 335 of them were selected using the variance threshold method. Then, the SelectKBest method was further used for the selection of 31 candidate features. Finally, 11 out of 31 optimal features were identified with the LASSO algorithm. In the LR classifier, the AUCs of the training and validation sets in discriminating early recurrence were 0.83 (95% CI: 0.76-0.90) (sensitivity 0.8 and specificity 0.83) and 0.83 (95% CI: 0.67-0.99) (sensitivity 0.69 and specificity 0.71), respectively. Conclusions. Using the radiomic signature, we developed a radiomic signature to preoperatively predict early recurrence in patients with HSCC, which may serve as a potential noninvasive tool to guide personalized treatment.

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.

Background. The accurate prediction of prognosis is key to prompt therapy adjustment. The purpose of our study was to investigate the efficacy of diffusion kurtosis imaging (DKI) in predicting progression-free survival (PFS) and overall survival (OS) in osteosarcoma patients with preoperative chemotherapy. Methods. Thirty patients who underwent DKI before and after chemotherapy, followed by tumor resection, were retrospectively enrolled. The patients were grouped into good responders (GRs) and poor responders (PRs). The Kaplan-Meier and log-rank test were used for survival analysis. The association between the DKI parameters and OS and PFS was performed by univariate and multivariate Cox proportional hazards models. Results. Significantly worse OS and PFS were associated with a lower mean diffusivity (MD) after chemotherapy (HR, 5.8; 95% CI, 1.5-23.1; P=0.012 and HR, 3.5; 95% CI, 1.2-10.1: P=0.028, respectively) and a higher mean kurtosis (MK) after chemotherapy (HR, 0.3; 95% CI, 0.1-0.9; P=0.041 and HR, 0.3; 95% CI, 0.1-0.8; P=0.049, respectively). Likewise, shorter OS and PFS were also significantly associated with a change rate in MD (CR MD) of less than 13.53% (HR, 8.6; 95% CI, 1.8-41.8; P=0.007 and HR, 2.9; 95% CI, 1.0-8.2; P=0.045, respectively). Compared to GRs, PRs had an approximately 9- and 4-fold increased risk of death (HR, 9.4; 95% CI, 1.2-75; P=0.034) and progression (HR, 4.2; 95% CI, 1.2-15; P=0.026), respectively. Conclusions. DKI has a potential to be a prognostic tool in osteosarcoma. Low MK and high MD after chemotherapy or high CR MD indicates favorite outcome, while prospective studies with large sample sizes are warranted.

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.

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

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.

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.

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.

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.

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

Background: Notch1 expression has been reported to be associated with chemotherapy resistance and poor prognosis, but the role of Notch1 in head and neck squamous cell carcinoma (HNSCC) sensitivity to anticancer drugs remains unclear. The aim of this study was to evaluate HNSCC sensitivity to paclitaxel and cisplatin in vitro and the chemotherapeutic response of HNSCC to these two drugs in vivo. Methods: We used immunohistochemistry to assess Notch1 expression in fresh HNSCC samples treated by PF (cisplatin+5- fluorouracil) and TPF (paclitaxel + cisplatin+5- fluorouracil). We also assessed the sensitivity of two HNSCC cell lines to the Notch1 inhibitor of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). The overall and progression-free survival were assessed. Results: High Notch1 expression was significantly associated with paclitaxel resistance (P

A novel halogen- and formaldehyde-free flame retardant named Neo-FR was synthesized and applied to cellulosic fabrics. The chemical structure of the flame retardant was characterized by Fourier-transform infrared spectroscopy (FTIR). The flame retardant performance was evaluated by Limiting oxygen index (LOI) and vertical flammability tests. The results indicated that the flame retardant had excellent flame retardancy and durability for cellulosic fabrics. The surface morphology of treated fibre and fibre char residue were observed through scanning electron microscope (SEM). The SEM graphs demonstrated that the Neo-FR system played intumescent flame retarding mechanism on cotton fibre. The thermal property of the flame retardant treated cotton fabric was investigated through thermal gravimetric analysis (TGA). The results indicated that char residue of the treated fabrics was about 36.5%, which was much higher than that of untreated fabric. The mechanical properties such as tensile strength and elongation of the cotton samples treated with Neo-FR system were much less affected than those treated by a commercial durable flame retardant agent (Pyrovatex CP New). The laundering test results show that the Neo-FR system is a durable flame retardant for cellulosic fabrics.

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

Background FAS/FASL promoter variants are considered in altering transcriptional activity of those genes and consequently alter regulation of cell death. However, no studies have investigated whether tumor sites contribute to the association between FAS/FASL polymorphisms and risk for second primary malignancy (SPM). Method In this study, FAS670 A > G, FAS1377 G > A, FASL124 A > G, and FASL844C > T polymorphisms were genotyped in 752 OPC and 777 non-OPC patients. Both univariate and multivariable cox proportional hazard models were used to assess the associations. Results The univariate and multivariable analyses showed that patients with index OPC and FASL844 CT/TT genotype had significantly increased risk of SPM (cHR, 2.5; 95 % CI, 1.1–5.8, P = 0.043 and aHR, 2.7; 95 % CI, 1.2–6.0, P = 0.032) compared with those with FASL844 CC genotype as the reference group, while index non-OPC patients with FAS670 AG/GG and FasL844 CT/TT genotypes had significantly increased risk of SPM (cHR, 2.2 and 1.8; 95 % CI, 1.2–5.7 and 1.1–3.2; and P = 0.04 and 0.041, respectively and aHR, 2.4 and 1.7; 95 % CI, 1.1–5.1 and 1.0-3.0; and P = 0.043 and 0.049, respectively) compared with their corresponding AA and CC genotypes . Moreover, patients carrying more FAS/FASL variants significantly increased risk of SPM among index non-OPC patients. The stratified analysis showed that smoking status differently modified the associations between FAS/FASL polymorphisms and risk of SPM among index non-OPC from OPC patients. Conclusion These results suggested that FAS/FASL polymorphisms might significantly modify SPM risk among patients with SCCHN in a tumor site-specific manner.

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.

The increasing incidence of oral squamous cell carcinoma (OSCC) in young adults has been associated with sexually transmitted infections of human papillomavirus (HPV), particularly HPV16. Given the roles of p53 in tumor suppression and of HPV E6 and MDM2 oncoproteins in p53 degradation, we evaluated HPV16 L1 seropositivity and MDM2 promoter variants to examine their possible associations with OSCC risk in a case-control study of 325 patients and 335 cancer-free matched controls. Compared with individuals having MDM2-rs2279744 GT or GG genotypes and HPV16 L1 seronegativity, the TT genotype and HPV16 L1 seronegativity were found to be associated with an odds ratio (OR) of 1.25 [95% confidence interval (CI), 1.06–2.19] for OSCC risk, and GT/GG and HPV16 L1 seropositivity were associated with an OR of 2.81 (95% CI, 1.67–4.74). For those with both the TT genotype and HPV16 L1 seropositivity, the associated OR was 5.57 (95% CI, 2.93–10.6). Similar results were observed for the MDM2-rs937283 polymorphism. Moreover, there was a borderline significant or significant interaction between the individual or combined MDM2 genotypes of the two polymorphisms and HPV16 L1 seropositivity (Pint = 0.060 for MDM2-rs2279744, Pint = 0.009 for MDM2-rs937283, and Pint = 0.005 for the combined MDM2 genotypes) on risk of OSCC. Notably, that effect modification was particularly pronounced in never smokers and never drinkers, and for oropharyngeal as opposed to oral cavity cancer. Taken together, our results indicate that the risk of OSCC associated with HPV16 L1 seropositivity is modified by MDM2 promoter polymorphisms. Cancer Res; 70(18); 7199–208. ©2010 AACR.

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.

To analyze the clinical characters, surgical treatments and prognosis of differentiated thyroid carcinoma (DTC) with laryngeal or tracheal invasion.Forty-six cases including 33 papillary and 13 follicular were retrospectively reviewed. Thirty-four cases with tracheal invasion received conservative resection (17), window resection (11) and sleeve resection (6). One case with subglottic invasion was performed subglottic partial laryngectomy. Eleven cases with trachea-laryngeal invasion received total laryngectomy(4), 3 shave technique and 4 preservative laryngectomy.Complications included infections and hypocalcaemia, 15 patients got permanent fistula. 5-year survival rate in cases of tracheal shave resection was 88.2%, while 63.6% in those of window resection and 83.3% in those of sleeve resection. Survival rate within 5 years of patients received preservative laryngectomy was 62. 5%. Conclusion: With meticulous preoperative examination and positive surgical treatment, both survival rate and quality of life could be improved in patients of DTC with laryngeal or tracheal invasion.

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.

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.