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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

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.

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.

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) 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 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

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.

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.

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).

To summarize and analyze the clinical features, diagnosis methods, surgical approaches and treatment outcomes of patients with primary parapharyngeal space tumors.A retrospective review of 91 cases with primary parapharyngeal space tumors treated from January 1999 to December 2011 was performed. All patients underwent preoperative enhanced CT scan and postoperative histopathologic examination. Intraoperative frozen section biopsies were performed in 36 of 91 cases. The surgical approaches included trans-cervical approach in 73 cases, trans-parotid approach in 5 cases, trans-oral approach in 5 cases, and mandibulotomy in 8 cases.The postoperative pathological diagnoses consisted of 29 variants, including 20 for benign tumors and 9 for malignant tumors. Of the 80 cases with benign tumors, 6 cases were lost to follow-up and 74 cases were followed up for 31-84 months with no recurrence. Eleven cases with malignant tumor were followed up for 8-51 months (median 29 months), of them 7 cases died and 1 case was lost to follow-up. The post-operative complications included Horner syndrome in 3 cases, hoarseness in 2 cases, hypoglossal nerve palsy in 1 case, accessory nerve palsy in 1 case, upper airway obstruction in 1 case, and internal carotid artery cavernous sinus fistula in 1 case.Parapharyngeal space tumors are rare, with atypical clinical manifestation, and have pathological types of diversification. CT or MRI is helpful to evaluate the tumor size, location and possible sources, and to make operation scheme. Surgery is the first choice for parapharyngeal space tumors. Trans-cervical approach can be applied to most tumors. Parapharyngeal benign tumors have good prognosis, but malignant tumors have poor prognosis.

BACKGROUND: Surgical treatment of pleomorphic adenoma of the parotid gland remains a subject of major debate. The investigators compared postoperative complications and surgical parameters between modified partial superficial parotidectomy and conventional superficial parotidectomy. METHODS: Clinical records of 129 patients were reviewed and analyzed for clinical characteristics. RESULTS: Compared with the conventional superficial parotidectomy group, the modified partial superficial parotidectomy group had significantly lower rates of auricular numbness, Frey’s syndrome, and obvious facial asymmetry (all P values ,.05). The distance between the primary tumor capsule and satellite nodules ranged from .06 to 8.48 mm, and the greatest distance between the primary tumor capsule and satellite nodules was observed in tumors .4 cm. Furthermore, satellite nodules were more common in tumors . 4c m than in tumors, 2c m or tumors between 2a nd 4c m (allP values ,.05). CONCLUSIONS: Modified partial superficial parotidectomy compares favorably surgically and clinically with conventional superficial parotidectomy in certain patients.

Background Cell cycle deregulation is common in human cancer, and alterations of p27 and p21, two critical cell cycle regulators, have been implicated in the development of many human malignancies. Therefore, we hypothesize that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms modifies risk of second primary malignancy (SPM) in patients with index squamous cell carcinoma of head and neck (SCCHN). Methods A cohort of 1,292 patients with index SCCHN was recruited between May 1995 and January 2007 at the M.D. Anderson Cancer Center and followed for SPM occurrence. Patients were genotyped for the three polymorphisms. A log-rank test and Cox proportional hazards models were used to compare SPM-free survival and SPM risk. Results We found that patients with p27 109 TG/GG, p21 98 CA/AA and p21 70 CT/TT variant genotypes had a worse SPM-free survival and an increased SPM risk than those with the corresponding p27 109 TT, p21 98 CC, and p21 70 CC common genotypes, respectively. After combining the three polymorphisms, there was a trend for significantly increased SPM risk with increasing number of the variant genotypes (P trend = 0.0002). Moreover, patients with the variant genotypes had an approximately 2.4-fold significantly increased risk for SPM compared with those with no variant genotypes (HR, 2.4, 95% CI, 1.6-3.6). Conclusions These results suggest that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms increases risk of SPM in patients with index SCCHN.

To investigate the effects of caveolin-1 (CAV1) on the growth of hypopharyngeal squamous cell carcinoma (HSCC) FaDu cells in vitro and in vivo.A CAV1-RNAi-lentivirus construct was transfected into FaDu cells and expression of caveolin-1 was tested by RT-PCR and western blotting analysis. Cell apoptosis was analyzed by transferase-medisated dUTP nick-end labeling (TUNEL) assay. Tumor inhibition effects were investigated by injecting rCAV1-RNAi-lentivirus construct into tumors created with FaDu cells in the HSCC mouse model, with the empty-vector lentivirus as a control. CAV1 expression in xenografts was tested by RT-PCR and immunohistochemistry.RT-PCR and western blot analysis demonstrated successful construction of the CAV1-RNAi-lentivirus construct producing small hairpin RNA. The average weights and volumes of tumor in mice treated with CAV1-RNAi-lentivirus were lower than in mice with control treatment (P0.05). RT-PCR revealed weak positive expression of CAV1 in CAV1-construct-treated xenografts and immunohistochemistry confirmed lower CAV1 expression than in controls.(P0.05). In addition, downregulation of CAV1 increased cell apoptosis in vitro.The growth of HSCCs could be inhibited by recombinant CAV1-RNAi-lentivirus in vitro and in vivo.

Background: Single-nucleotide polymorphisms in the promoter region of the FAS and FASLG may alter the transcriptional activity of these genes. We therefore investigated the association between the FAS and FASLG polymorphisms and risk for second primary malignancy (SPM) after index squamous cell carcinoma of the head and neck (SCCHN). Methods: We used log-rank test and Cox proportional hazard models to assess the association of the four single-nucleotide polymorphisms (FAS -1377 G > A, FAS -670 A > G, FASLG -844 C > T, and FASLG -124 A > G) with the SPM-free survival and SPM risk among 1,286 incident SCCHN patients. Results: Compared with patients having the FAS -670 AA or the FASLG -844 CC genotypes, the patients having variant genotypes of FAS -670 AG/GG or FASLG -844 CT/TT genotypes had significantly increased risk for SPM, respectively. A trend for significantly increased SPM risk with increasing number of risk genotypes of the four polymorphisms was observed in a dose-response manner. Moreover, the patients with three or four combined risk genotypes had an ∼1.8- or 2.5-fold increased risk for developing SPM compared with patients with zero or one risk genotypes, respectively. Conclusions: Our results suggest a modestly increased risk for SPM after index SCCHN with FAS -670 A > G and FASLG -844 C > T polymorphisms and an even greater risk for SPM with multiple combined FAS and FASLG risk genotypes. Impact: The FAS and FASLG polymorphisms may serve as a susceptible marker for SCCHN patients at high SPM risk. Cancer Epidemiol Biomarkers Prev; 19(6); 1484–91. ©2010 AACR.

Purpose: Transforming growth factor-β1 (TGF-β1) plays an important role in inflammation and immune responses, which control the human papillomavirus (HPV) clearance and escape of immune surveillance, and may contribute to genetic susceptibility to HPV16 infection. Experimental Design: In this case series study, we analyzed the HPV16 status in tumor specimens and genotyped three TGF-β1 polymorphisms using genomic DNA from the blood of 200 squamous cell carcinoma of the oropharynx (SCCOP) cases. We calculated odds ratio (OR) and 95% confidence intervals (95% CI) in univariate and multivariable logistic regression models to examine the association between the TGF-β1 polymorphisms and HPV16 status in SCCOP. Results: Compared with those with the common homozygous genotype, the TGF-β1 T869C variant genotypes were significantly associated with HPV16-positive tumor status among patients with SCCOP (OR, 1.97; 95% CI, 1.03-3.76), but no significant association was observed for the TGF-β1 C509T or G915C polymorphism. When all variant genotypes were combined, however, SCCOP patients carrying genotypes with any of these TGF-β1 variants were more than twice as likely to have an HPV16-positive tumor (OR, 2.28; 95% CI, 1.16-4.50) as patients with no variant genotypes. The stratified analysis showed that those under 54 years of age, non-Hispanic white patients, never smokers, and never drinkers with any variant TGF-β1 genotypes were also more likely to have HPV16-positive tumors. Conclusions: TGF-β1 polymorphisms may serve as a susceptibility marker for tumor HPV16 status among SCCOP patients, particularly those who were never smokers and never drinkers. Large studies are needed to validate our findings. Clin Cancer Res; 16(5); 1416–22

p21 plays an important role in modulating cell cycle control, inducing apoptosis, and inhibiting cell growth, subsequently affecting cancer risk. We investigated the association between two putatively functional single-nucleotide polymorphisms (SNPs) of p21 (p21 C98A and p21 C70T) among 1282 patients diagnosed with incident squamous cell carcinoma of the head and neck (SCCHN) and risk of second primary malignancy (SPM) in an ongoing molecular epidemiology study. We used Log-rank test and Cox proportional hazard models to assess the association of these two SNPs with SPM-free survival and SPM risk. We found that patients with either p21 variant genotypes of the two polymorphisms had a significantly reduced SPM-free survival compared with patients with either p21 wild-type homozygous genotypes (Log-rank test, P = 0.0016). Compared with patients having the p21 98 CC and p21 70 CC genotypes, the patients having p21 98 CA/AA and p21 70 CT/TT variant genotypes had a significantly greater risk of developing SPM, respectively, [hazard ratio (HR) = 1.80, 95 % CI = 1.14―2.82 for p21 C98A and HR = 1.82, 95% confidence interval (CI) = 1.16―2.85 for p21 C70T]. Moreover, after combining the variant genotypes of two SNPs, patients with variant genotypes had a significantly moderately increased risk for SPM compared with patients with no variant genotypes (HR = 2.00, 95% CI = 1.26―3.00), and the risk was particularly pronounced in several subgroups. Our results support an increased risk of SPM after index SCCHN with both p21 polymorphisms individually and in combination.

To analyze the mutation and abnormal expression of the FHIT gene in human hypopharyngeal carcinoma.Matched normal and cancerous tissues from 24 patients with hypopharyngeal squamous cell carcinoma were obtained immediately after surgery. Total RNA was extracted, the FHIT gene was detected by nested RT-PCR and DNA sequencing technology.Normal sized FHIT transcript was detected in 23 of the 24 cases of normal matched tissues. Aberrant FHIT transcripts were found in 9/24 (37.5%) cases in hypopharyngeal carcinoma. Aberrant FHIT transcripts rate of well-differentiated, moderately differentiated and poorly differentiated squamous cell carcinoma, was 28.6% (2/7), 50.0% (4/8) and 33.3% (3/9), respectively. There the carcinoma with FHIT aberrant transcripts was neither corresponding to histological grade (P0.05) nor to lymphatic metastasis. The sequence analyses of the two aberrant cDNAs revealed absence of exon 8 and exon 7-9. All initial deletion were in conjunction of exons.High deletion rate of the FHIT gene in Chinese hypopharyngeal squamous cell carcinoma suggested the FHIT gene, a candidate tumor suppressor gene at 3p14.2, plays an important role in the tumor carcinogenesis, development and progression of the tumor, and thus may become a new prognostic marker in hypopharyngeal carcinoma.

Background CyclinD1 and p16 are involved in the regulation of G1 checkpoint and may play an important role in the tumorgenesis of laryngeal squamous cell carcinoma (LSCC). Previous studies have examined the level of expression of cyclinD1 or p16 in LSCC but no such information is available for their relation and their correlation with lymph node metastasis in Chinese patients. Patients and methods A total of 58 patients underwent surgical resection of laryngeal tumours in the Department of Otolaryngology, Qilu Hospital Shandong University between January 2001 and December 2002. All pathologic specimens were available for immunohistochemical study using antibodies against cyclinD1 and p16. Results Compared with normal epithelium, expression of CyclinD1 in the LSCC was significantly higher (62.1% vs. 10.0%, P

To study the expressions of Cyclin D1 and p16 proteins in hypopharyngeal squamous cell carcinoma and their clinical significance.Immunohistochemical technology (P-V) was applied to detect the expression of Cyclin D1 and p16 in 36 cases of hypopharyngeal squamous cell carcinoma and 10 cases of normal epithelium.(1) The expression of cyclin D1 in the tumorous cell was significantly higher than that in normal epithelium (P0.05). The expression of p16 in the tumorous cell was significantly lower than that in normal epithelium (P0.05); (2) The positive rate of Cyclin D1 was significantly correlated with clinical stage and cervical lymph node metastases (P0.05). The positive rate of p16 was correlated with cervical lymph node metastases (P0.05). The positive rates of Cyclin D1 and p16 were not correlated with the gender, age, tumor size, primary lesion and cell differentiation (P0.05); (3) There was correlation between the expression of Cyclin D1 and the expression of p16 (r(s) = -0.420, P0.05).The over-expression of Cyclin D1 and the under-expression of p16 may play a significant role in the occurrence incidence and development of hypopharyngeal squamous cell carcinoma, and may be important indicators for cervical lymph node metastases.

To investigate the effect and clinical value of multiple plane operations in treating severe OSAHS.The clinical data of 28 patients with severe OSAHS were retrospectively analyzed. All the patients were performed two planes of operations or more as below: submucous nasal septum resection, nasal sinus endoscopy, adenoidectomy, uvulopalatopharyngoplasty (UPPP), tongue base incision, hyoid suspension, tongue base Coblation etc. Operations were finished in the same term or by stages. All patients underwent polysomnography(PSG) examination before operation, and 6-month and 1-year after surgical treatment separately.No severe complication occurred, the 6-month, 1-year responders are 100% and 89.29% respectively. Both AHI and LSaO2 changed obviously (P0.01).Most OSAHS have multi-level obstructions in upper airway caliber, such as nasal, nasopharyngeal, velo-pharyngeal and tongue-pharyngeal obstruction. Multiple plane operations which based on idiographic obstruction sites can improve curative effect. Operation project should be established according to the conditions of upper airway and patients' intention.

To investigate the expression of fragile histidine triad gene protein (Fhit) and the possible relationship between Fhit and biological behaviors of hypopharyngeal carcinoma.The expression of Fhit protein in 66 cases with hypopharyngeal carcinoma were detected by rabbit antibody to human FHIT gene protein with SP immunohistochemical method. The relationship between historical grade and lymphatic metastasis were analysed.(1) The positive expression rate of Fhit was 42.42% (28/66) in hypopharyngeal carcinoma, and 83.33% (55/66) in normal hypopharyngeal tissue, respectively. There was a significant difference in the expression of Fhit between the cancer tissue and normal tissue (P0.01). (2) The positive expression of Fhit in well, moderate, poor differentiated hypopharyngeal carcinoma were 65.38% (17/26), 38.10% (8/21) and 26.32% (5/19), respectively. There are significant statistic difference among them each other (P0.01). (3) The positive expression of Fhit was 75.00% (12/16) in the group without lymph node metastasis, and 36.00% (18/50) with lymph node metastasis.The expression of Fhit in hypopharyngeal squamous cell carcinoma lower than normal tissue. The expression of Fhit significantly associated with historical grade and lymphatic metastasis in hypopharyngeal squamous cell carcinoma. It suggested that the expression of Fhit decreased may plays an important role in the development and progression of the tumor, and thus may become a new prognostic marker in hypopharyngeal carcinoma.

To assess the role of soluble intercellular adhesion molecule-1 (sICAM-1) in etiology of nasal polyps.Twenty-nine patients with nasal polyps and 20 healthy control cases were chosen. Their serum sICAM-1 was determined by a sandwich enzyme-linked immunosorbent assay (ELISA). All patients were treated by glucocorticoid, serum sICAM-1 was determined post-treatment again.(1) Serum levels of sICAM-1 in patients with nasal polyps were higher than that of control group: (2) Serum levels of sICAM-1 in patients were reduced after glucocorticoid treatment, the decrease of sICAM-1 was more apparent in evident-effect group than in effect group; (3) There was a close correlation between the decrease of polyp-size scores and the decrease of serum sICAM-1.The elevated expressions of sICAM-1 in patients with nasal polyps indicate its important role in eosinophil recruitment, which was considered as a representative hallmark for nasal polyps. The sICAM-1 is down-regulated by systemic and topical glucocorticoid treatment and the decrease of sICAM-1 is correlated with clinical effect. To take these lines of evidence together, anti-adhesion therapy may be effective for nasal polyps, serum sICAM-1 levels may be use to monitor the effect of steroid therapy in nasal polyps.

To explore the relationship between the expression of MDM2 and p27 in hypopharyngeal carcinoma and clinicopathological parameters and their clinical significance.The expression of MDM2 and p27 in 59 hypopharyngeal carcinoma were detected by S-P immunohistochemical technique.The high-expression rates of MDM2 and p27 were 66.1% and 33.9%, respectively, and the low-expression rates of them were 33.9% and 66.1%, respectively. The expression of MDM2 was unrelated to p27 (P0.05). The lymph node metastasis in high-expression group of MDM2 was significantly higher than that in low-expression group (P0.01). The expression rate of p27 was significantly different among the four T groups and degree of differentiation, respectively (P0.05). The survival rate was significantly higher in high-expression rate group of MDM2 than that in low-expression rate group (P0.01), while the survival rate was significantly lower in high-expression rate group of p27 than that in low-expression rate group (P0.05).The expression of MDM2 and p27 may be involved in carcinogenesis and progression in hypopharyngeal carcinoma. Combined detecting of MDM2 and p27 may predict its prognosis better in hypopharyngeal carcinoma.

To improve the curative effects of laryngotracheal stenosis.Seventy patients treated for laryngotracheal stenosis on the different pathologic condition of the larynx and trachea were retrospectively reviewed. Different operative reconstruction methods were used accordingly.Among 70 patients, 65 (92.9) patients succeed in decannulation. The average course of usage of stent was 14.8 days, the average course from operation to decannulation was 82.0 days.The choice of surgical procedure must be decided on the pathologic conditions of the larynx and trachea. Eliminating the defect of the mucosa and reconstructing a wide enough airway was the key to improve the curative effect.

To explore the surgery way for T1, T2 glottic carcinoma.Small partial laryngectomy were performed to 112 patients with T1, T2 (T1 N0 M0, T2 N0 M0) glottic carcinoma. The surgery method, effect and treatment advantage was summarized and compared with laser therapy and radiotherapy, the dynamic follow-up of arytaenoidea cartilage movement, glottidis rimae conformation and voice change was analyzed. The preoperative and postoperative voice quality was compared with the software of Dr. speech system for windows.All incisions were healed one stage in 6 or 7 days, the mean time in hospital is 9.76 days; all patients took food with mouth after 2 or 3 days, all trachea cannula was removed successfully during in hospital, the mean time with cannula is 7.32 days and the rate of removing cannula 100%. Arytaenoidea cartilago movement of 47 cases 1 week after surgery weakened and gradually improved, glottidis rimae conformation is close to be normal after 2 months. There is no significant difference of Shimmer and NNE between preoperative and postoperative 1 week (P0.05), but there is a significant difference between preoperative and postoperative 2 months, half a year, and also is between postoperative 1 week and 2 months, half a year (P0.01). All 76 cases survive during 3 years' follow-up, 35 of 36 cases in 5 years' follow-up survive (1 case died without definite cause), and there is 2 cases for recurrence.Small partial laryngectomy can provide large operative view, resect the tumor completely, make diet and speech recover in shorter time and improve the voice quality, so the surgery is available.

To study effective treatment of stomal recurrence.Thirty-one patients with stomal recurrence underwent surgical management. Twelve of them considered to have the probability of metastasis to regional lymphnodes underwent modified radical neck dissection. Twenty-five cases(I and II type) received complete tumor excision, but for III and IV type, only 50% (3/6) of the patients gained complete tumor excision. The surgical defects were repaired by pectoralis major myocutaneous flap in all the patients.In 13 cases of type I, 7 cases had followed up for 3 years, 4 cases died, while in 12 cases of type II, 8 cases had followed up for 3 years, 5 cases died. Survival remains poor for III or IV type. Most of them died within 3 years after operation. The complication rate of pharyngeal fistula and pneumatothorax was 12.9% and 9.7%, respectively.The overall prognosis of stomal recurrence is dismal. A proper surgical treatment in some cases will prolong the lifetime and improve their quality of life.

To observe the appliance value of uni-pedicled sternohyoid myofascial flap in laryngeal function reconstruction after partial laryngectomy.Forty patients who underwent partial laryngectomy from 1981 to 1999 were summarized(male 36 cases, female 4 cases). Among them 19 were supraglottic carcinomas (T2N0 6, T2N2 1, T3N0 2, T3N1 1, T3N2 2, T4N0 4, T4N1 1, T4N2 2), 19 cases were glottic carcinomas(T2N0 6, T3N0 11, T3N2 2), 2 cases were subglottic carcinomas(T2N0 1, T3N0 1). The choice of surgical procedure was decided on the pathologic conditions of the larynx, the laryngeal function was reconstructed using uni-pedicled sternohyoid myofascial flap.Thirty-three cases were decannulated and recovered with laryngeal functions. The decannulation rate was 82.50%. All the patients rehabilitated deglutition in 10 to 20 days after surgery. None presented complication of aspiration. The 3-year survival rate was 86.58% and 5-year survival rate was 72.49%.The uni-pedicled sternohyoid myofascial flaps are appropriate for reconstruction of surgical defect in laryngeal carcinomas.

To investigate clinical prognosis and the one-stage methods of reconstruction for advanced thyroid carcinoma while larynx and cervical trachea involved.One-stage resection and laryngotracheal reconstruction were performed in 18 advanced thyroid carcinomas. Among them, total laryngectomy were performed in 3 cases and partial laryngectomy in the other 4 larynx-involved cases. Cervical trachea involvement were found in all 18 cases. Besides 8 shave-off of tumor, area of trachea invaded by carcinoma were removed in other 10 cases. The methods applied for the tracheal reconstruction were 1 simple suture, 3 tracheal anastomosis, 2 pedicled sternocleidomastoid myoperiosteous flap, 3 insular myocutaneous pectoralis major flap and 1 cervical flap.One patient died of cancer reoccurrence while in the hospitalization. Except for 3 cases with total laryngectomy, larynx preservation were done in 14 cases and tracheal cannula were pulled out in 8, blocked in 2 and kept carrying in 4 cases.One stage reconstruction of larynx and cervical trachea involved by advanced thyroid carcinoma is feasible and practical. Curative rate, survival time and life quality all can be improved.

To explore new methods of preservative surgery for T4 glottic cancer and to evaluate their long term results.22 cases with T4 glottic cancer were treated surgically from 1982 to 1998. The lesions and involved cartilage and extrinsic laryngeal tissues were removed entirely, the sternohyoid myofascial flap, platysma myocutaneous flap, platysma myofascial flap, thyroid perichondral flap and hypopharyngeal mucosa flap were utilized to restore the defects of larynx, while the epiglottis or lamina of cricoid cartilage were reserved for laryngeal function restruction.The 3- and 5-year survival rates were 86.4% and 75.0% in all cases. 68.2% had laryngeal functions(voice, respiration and deglutition) restored and 31.8% partially restored(voice and deglutition).Despite the fact that the T4 glottic cancer usually involved with cartilage and extrinsic laryngeal tissues, preservative surgery can be carried out for the carefully selected cases with the lesions entirely removed.

To assess the possible relation between the MspI polymorphism of Cytochrome P4501A1(CYP1A1) gene and the susceptibility to laryngeal cancer.The genotypes of CYP1A1 MspI site were detected using the methods of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 62 cases of laryngeal squamous carcinoma and 56 healthy controls. Genetic risk of CYP1A1 genotypes was analyzed by smoking index (SI, cigarettes smoked per day x years of smoking).Three genotypes of CYP1A1 MspI were classified into the predominant homozygotes (A), heterozygotes (B) and the rare homozygotes (C). The frequency of heterozygote B (58.1%) and genotype C (14.5%) in the patients with laryngeal cancer were higher than that of the controls (39.3%, 7.1%, P0.05), while their odds ratios were 2.89 (95% confidence interval, CI: 1.31-6.37) and 3.97 (95% CI: 1.10-14.28), respectively. The odds ratios of genotype C was 9 (95% CI: 1.60-50.74) in the high dose cigarette smoking group, but was 4.5 (95% CI: 0.64-31.61) in the low dose cigarette smoking group.With the carcinogenesis and development of laryngeal cancer, the polymorphism of CYP1A1 gene and smoking exposure together may play an important role. The individuals with genotype C are at especially high risk of laryngeal cancer, which grows with increasing cigarette consumption.

To assess the quality of life and relevant factors following laryngectomy.Quality of life was evaluated in 42 laryngeal cancer and hypopharyngeal cancer patients following laryngectomy and in 38 controls. The assessment included General Quality of Life Inventory, University of Washington Quality of Life Head and Neck Questionnaire and a study specific questionnaire.The laryngectomized patients reported significant lower scores of quality of life than the controls in many aspects of physical health, psychological health and social function dimensions. For patients, the most important dimension affecting quality of life was psychological condition, and the others were physical function, social function, and economic condition in turn; while for the controls, they were of opposite order. The significant factors affecting quality of life in patients following total laryngectomy were their concern about prognosis, disfigurement, decannulation, employment, speech and breathing conditions. The most important factor affecting psychological condition was physical function, while psychological condition was the most important factor affecting social function. Items ranked in the top five included those related to physical function, economic condition, psychological condition, social situation and social communication.More attention should be paid to research about quality of life. The quality of life of patients undergone laryngectomy is affected by many factors. Through the integration of psychological, clinical and social interventions, the quality of life of patients may have an overall improvement.

To study the feasibility, surgical technique and results of laryngeal function preservation in surgical treatment for medial wall pyriform sinus cancer.From 1992 to 1999, 31 patients with medial wall pyriform sinus cancer including stage I 1, II 4, III 14 and IV 12 lesions were treated. Partial resection of pyriform sinus and partial laryngectomy were performed, then, the remains of epiglottis and uni-pedicled sternohyoid myofascial flap were used to restore the defects of larynx. At last, the remaining hypopharyngeal mucosa was sutured to cover the wound of hypopharynx and for artificial rebuild-up. All patients received postoperative radiotherapy.The 3- and 5-year survival rates were 62.1% and 43.6% respectively, with 77.4% patients having laryngeal functions (voice, respiration and deglutition) completely restored and 32.6% partially restored (voice and deglutition).Conservative surgery so introduced is feasible for selected medial wall pyriform sinus cancer patients with the lesion completely resected.

To observe the application value of epiglottis in laryngeal reconstruction after partial laryngectomy.The data of 168 patients, 25 with supraglottic carcinoma (T1N0 2, T2N0 10, T2N1 1, T2N2 1, T3N0 7, T3N2 1, T4N0 2, and T4N2 1), 140 with glottic carcinoma (T1N0 36, T1N1 1, T2N0 52, T2N1 1, T2N2 1, T3N0 40, T3N2 2, T4N0 6, and T4N2 1), and 3 with subglottic carcinoma (T3N0 1, and T4N0 2), who underwent partial laryngectomy from 1982 to 1999 were summarized. The choice of surgical procedure was decided on the pathology of the larynx. Epiglottis was used in larynx reconstruction.Out of the 168 cases, 135 cases were decannulated with a decannulation rate of 80.36%, regained deglutation, recovered all laryngeal functions, and resumed normal diet. None presented complication of accidental aspiration. The 3-year and 5-year survival rates were 89.48% and 74.14% respectively.Epiglottis has many advantages in laryngeal reconstruction.

To explore the surgical methods for laryngeal cancer and long-term effects of larygectomy.625 cases of laryngeal cancer at different stages, including 182 cases of supraglottic cancer, 429 cases of glottic cancer, and 14 cases of subglottic cancer, underwent operation of different kinds from 1979 to 1999. Radiotherapy was given to those with poorly differentiated squamous carcinoma or with metastasis of cervical lymph nodes postoperatively. The effects of operation, especially that on the preservation of laryngeal function was analyzed.Partial laryngectomy was performed on 521 of the 625 cases (83.4%) and 203 of the 305 cases at stages III and IV (66.6%). The decannulation rate was 84.07% in the cases undergoing partial laryngectomy. The nasal feeding tube was removed and peroral feeding was recovered in all patients. All cases undergoing partial laryngectomy succeeded in phonation. The overall 3-year survival rate was 89.63% and the overall 5-year survival rate was 77.36%. For the cases with laryngeal cancer at stages III and IV, the 3-year survival rate among those undergoing partial laryngectomy was 84.9%, not significantly different from that among those cases undergoing total laryngectomy (87.7%, P0.05); the 5-year survival rate was 66.6% among those undergoing partial laryngectomy and was 69.7% among those undergoing totals laryngectomy (P0.05).The rate of partial laryngectomy is rather high in this group. It is possible to preserve the laryngeal function without compromising the remote survival rate. The prerequisite for the preservation of laryngeal function is to master and choose the proper renovation methods.

To investigate the relationship between polymorphism of N-acetyltransferase (NAT2) gene and genetic susceptibility to laryngeal carcinoma.A case-control study on 62 laryngeal carcinoma patients and 56 controls was conducted. NAT2 alleles were differentiated by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methods using originally created PCR primers and genomic DNA extracted from peripheral white blood cells. Genetic risk for NAT2 genotype was analyzed by smoking index (SI, cigarettes smoked per day x years of smoking).The frequency of NAT2 slow genotype was 80.6% in patients with laryngeal carcinoma and 60.7% in the controls, the difference of which was statistically significant (chi(2) = 5.70, P = 0.017). The odds ratios were 2.70 (95% CI 1.19 approximately 6.11). Among the individuals with NAT2 slow genotype at high level of cigarette smoking, there was a significantly higher risk of 5.64 (95% CI 1.77 approximately 17.92), while those at low level were considered the reference group (OR 1.38, 95% CI 0.42 approximately 4.52).NAT2 slow genotype increases the risk of susceptibility to laryngeal carcinoma. The combined effect of NAT2 slow genotype and exposure to smoking is observed during the development of laryngeal cancer.

To explore the surgical methods and evaluate the long-term result of laryngectomy in patients with supraglottic laryngeal cancer.182 patients with supraglottic laryngeal carcinoma underwent operation from 1979 to 1999, with stage I 11, stage II 45, stage III 49 and stage IV 77 lesions. The choice of surgical procedure was decided with the disease condition of the larynx. The surgical procedures proposed by TD Wang were adhered to as: minor partial laryngectomy 36, major partial laryngectomy 85, subtotal partial laryngectomy with laryngoplasty 22 and total laryngectomy 39.The ultimate rate of larynx preservation was 78.6% (143/182) with 69.8% (88/126) in stage III and IV diseases. The decannulation 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. They were 82.5% and 67.0% in similar advanced cases who were treated by total laryngectomy. The difference in the survival rates between these two groups was not statistically significant.It is suggested that preservation of the laryngeal function be possible for advanced supraglottic laryngeal carcinoma without compromising the remote survival rate. To improve the rate of larynx preservation, one should follow the surgical methods suggested.

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

Background Several long noncoding RNAs (lncRNAs) are involved in oncogenesis. Methods and Results Our microarray analysis showed that numerous lncRNAs are dysregulated in hypopharyngeal squamous cell carcinoma (HSCC) tumor tissues as compared with normal tissues. Among those lncRNAs, urothelial carcinoma-associated 1 (UCA1) has been found to have an oncogenic role in HSCC. We confirmed the upregulation of UCA1 in HSCC by assessing its expression levels in a cohort of 53 patient tumors and paired non-tumor samples. In addition, we found that high UCA1 expression was significantly associated with advanced T category, late clinical stage, greater lymphatic invasion, and worse prognosis. Furthermore, in vitro experiments demonstrated that UCA1 functioned as an oncogene by promoting the proliferation and invasion and preventing the apoptosis of HSCC cells. Conclusions Taken together, our findings for the first time identify the role of UCA1 as a tumor promoter and a pro-metastatic factor in HSCC, demonstrating that UCA1 is a potential prognostic biomarker and therapeutic target in HSCC.