Key Laboratory of Otolaryngology

Jinan, China

Key Laboratory of Otolaryngology

Jinan, China

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Sun Y.,University of Houston | Sun Y.,Qingdao University | Yu W.,University of Houston | Yu W.,Peking University | And 9 more authors.
BMC Cancer | Year: 2016

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. © 2016 Sun et al.


Liu J.,Shandong University | Liu J.,Key Laboratory of Otolaryngology | Cao X.-L.,Hangzhou First Peoples Hospital | Zhang Z.,Shandong University | And 8 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2011

Purpose: Several research groups have investigated the influence of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphism on head and neck cancer (HNC) susceptibility. However, the results remain inconclusive and controversial. We therefore conducted the present meta-analysis. Methods: Relevant studies were identified through a search of PubMed databases until July 2011 and selected on the basis of established inclusion criteria for publications. Results: A total of 8 case-control studies on the association of hOGG1 Ser326Cys polymorphism with HNC risk were included in the present meta-analysis. Overall significant associations were observed (G allele vs. C allele: OR=1.49, 95%CI=1.08-2.05, P<0.01 for heterogeneity; GG vs.CC: OR=2.30, 95%CI=1.05-5.05, P<0.01 for heterogeneity; CG vs. CC: OR=1.40, 95%CI=1.03-1.90, P<0.01 for heterogeneity; dominant model (GG+CG vs. CC): OR=1.52, 95%CI=1.06-2.16, P<0.01 for heterogeneity; recessive model (GG vs. CG+CC): OR=2.04, 95%CI=1.05-3.96, P=0.01 for heterogeneity) after excluding the studies that were not in agreement with HWE. On performance of a subgroup meta-analysis by ethnicity, significant associations were found (G allele vs. C allele: OR=1.40, 95%CI=1.001-1.95, P<0.01 for heterogeneity; GG vs.CC: OR=2.30, 95%CI=1.05-5.05, P<0.01 for heterogeneity; recessive model (GG vs. CG+CC): OR=2.04, 95%CI=1.05-3.96, P=0.01 for heterogeneity) in Caucasian populations after excluding one study not in agreement with HWE. Conclusions: Our results suggested that the G allele might be associated with an increased risk of HNC in Caucasian populations.


Chen W.,Shandong University | Chen W.,Key Laboratory of Otolaryngology | Xia T.,Shandong University | Xia T.,Key Laboratory of Otolaryngology | And 7 more authors.
Oncotarget | Year: 2016

The brain microenvironment has emerged as an important component in malignant progression of human glioma. However, astrocytes, the most abundant glial cells in the glioma microenvironment, have as yet a poorly defined role in the development of this disease, particularly with regard to invasion. Here, we co-cultured human astrocytes with human glioma cell lines, U251 and A172, in an in vitro transwell system in order to ascertain their influence on migration and invasion of gliomas. mRNA and protein expression assays were subsequently used to identify candidate proteins mediating this activity. Astrocytes significantly increased migration and invasion of both U251 and A172 cells in migration and invasion (plus matrigel) assays. Membrane type 1 matrix metalloproteinase (MMP14) originating from glioma cells was identified in qRT-PCR as the most highly up-regulated member of the MMP family of genes (~ 3 fold, p < 0.05) in this system. A cytokine array and ELISA were used to identify interleukin-6 (IL-6) as a highly increased factor in media collected from astrocytes, especially under co-culture conditions. IL-6 was also the key cytokine inducing cytomembrane MMP14 expression, the active form of MMP14, in glioma cells. Knockdown of MMP14 with siRNA led to decreased migration and invasion. Taken together, our results indicated that cytomembrane MMP14 was induced by IL-6 secreted from astrocytes, thereby enhancing the migration and invasion of glioma cells through activation of MMP2. Therefore, this IL-6 and MMP14 axis between astrocytes and glioma cells may become a potential target for treatment of glioma patients.


Lei D.,University of Texas M. D. Anderson Cancer Center | Lei D.,Shandong University | Lei D.,Key Laboratory of Otolaryngology | Sturgis E.M.,University of Texas M. D. Anderson Cancer Center | And 5 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2010

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. ©2010 AACR.


Gao Y.,Memorial University of Newfoundland | Liu D.,University of Toronto | Liu D.,Shandong University | Liu D.,Key Laboratory of Otolaryngology
European Archives of Oto-Rhino-Laryngology | Year: 2016

The main objective of the meta-analysis was to investigate whether intratympanic steroid injections in combination with systemic steroids would provide an additional advantage over systemic steroid therapy (SST) alone in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). The results will provide a meaningful suggestion in clinical therapy of ISSNHL. The electronic database search was based on the database in OVID Medline, Embase and PubMed up to December 15, 2015 with the goal of identifying all available observational studies examining the effects of combination therapy and SST in ISSNHL patients. Observational studies that compared the pure tone average (PTA) improvement and recovery rate between combination therapy and SST group in ISSNHL patients were selected. Finally we have identified eight eligible studies that focused on comparing the combination therapy and SST in ISSNHL from designated researches. In the PTA improvement group, seven studies have been analyzed to compare the pooled mean differences between two therapy modalities and subgroups based on initial hearing loss and treatment delay. In the recovery rate group, six studies were calculated for pooled risk ratios and subgroup analysis was also conducted. Through our meta-analysis, we have reached the conclusion that combination therapy exhibited better outcomes in PTA improvement than SST alone, especially in severe-profound initial hearing loss cases. Combination therapy also showed advantages in recovery rate. Whether time of treatment delay would influence the PTA improvement and recovery rate requires further researches. © 2016 Springer-Verlag Berlin Heidelberg


Summary Our aim of the study was to investigate the precise relationship of repair cross-complementation group 1 (ERCC1) expression and the survival as well as objective response rate to cisplatin-based concurrent chemoradiotherapy (CCRT) and a meta-analysis was conducted to analysis ERCC1's prognostic roles in head and neck cancer. A search based on published articles in PubMed, Embase and CKNI database (up to Oct 15, 2014) to find eligible studies meeting eligibility criteria and then a meta-analysis was conducted to assess the outcomes in head and neck squamous cell carcinomas (HNSCC) patients with different ERCC1 expression. The principle outcomes were hazard ratio (HR) for survival analysis and relative risks (RR) for objective response. Fixed or random model was used for calculation according to the heterogeneity. The results showed that 9 studies involving 568 patients met the inclusion criteria. Low/negative expression of ERCC1 was associated with longer overall survival (OS) and profession-free survival (PFS) after receiving cisplatin-based CCRT therapy (HR 0.38; 95% confidence interval (CI) 0.21-0.63; P < 0.001 and HR 0.37; 95%CI 0.21-0.63; P < 0.001). And there was no significant difference discovered in objective response rate between low/negative and high/positive ERCC1 expression (RR 1.19; 95%CI 1.00-1.43; P = 0.06). Evidence of modest heterogeneity was found between ERCC1 expression and OS (I2 = 48.8%, P < 0.05) and subgroup analysis was performed based on ethnicity, variable methods and primary tumor location. The conclusion is that ERCC1 might be the one of adverse prognostic factors affecting the survival time and objective response to cisplatin-based chemoradiotherap due to its drug-resistance characteristics. © 2015 Elsevier Ltd.


Song P.-L.,Harbin Medical University | Song P.-L.,Capital Medical University | Li H.-J.,Harbin Medical University | Wang N.-Y.,Capital Medical University | Wang N.-Y.,Key Laboratory of Otolaryngology
Chinese Medical Journal | Year: 2011

Background Many factors interfering with a listener attempting to grasp speech in noisy environments. The spatial hearing by which speech and noise can be spatially separated may play a crucial role in speech recognition in the presence of competing noise. This study aimed to assess whether, and to what degree, spatial hearing benefit speech recognition in young normal-hearing participants in both quiet and noisy environments. Methods Twenty-eight young participants were tested by Mandarin Hearing In Noise Test (MHINT) in quiet and noisy environments. The assessment method used was characterized by modifications of speech and noise configurations, as well as by changes of speech presentation mode. The benefit of spatial hearing was measured by speech recognition threshold (SRT) variation between speech condition 1 (SC1) and speech condition 2 (SC2). Results There was no significant difference found in the SRT between SC1 and SC2 in quiet. SRT in SC1 was about 4.2 dB lower than that in SC2, both in speech-shaped and four-babble noise conditions. SRTs measured in both SC1 and SC2 were lower in the speech-shaped noise condition than in the four-babble noise condition. Conclusion Spatial hearing in young normal-hearing participants contribute to speech recognition in noisy environments, but provide no benefit to speech recognition in quiet environments, which may be due to the offset of auditory extrinsic redundancy against the lack of spatial hearing.


Wang Z.,University of Houston | Wang Z.,Tongji University | Sturgis E.M.,University of Houston | Zhang F.,University of Houston | And 10 more authors.
Molecular Cancer | Year: 2012

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 p27109 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. © 2012 Wang et al; licensee BioMed Central Ltd.


Liu J.,Shandong University | Liu J.,Key Laboratory of Otolaryngology | Lei D.-P.,Shandong University | Lei D.-P.,Key Laboratory of Otolaryngology | And 7 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2011

Purpose: The purpose of this study was to examine the expression of mir-21 and phosphatase and tensin homologue (PTEN) in laryngeal squamous cell carcinomas (LSCCs) and hypopharyngeal squamous cell carcinomas (HSCCs), and assess correlations between the two as well as with clinical characteristics of patients. Methods: The expression of mir-21 in tumor and adjacent non-tumor tissues was investigated by real-time RT-PCR. Immunohistochemistry (IHC) was carried out to analyze PTEN protein levels. Results: Mir-21 was up-regulated in LSCCs and HSCCs compared to adjacent non-tumor tissues (P < 0.05), and the up-regulated expression of mir-21 was associated with clinical stage (P = 0.001), T classification (P = 0.007), pathologic differentiation (P = 0.025), and lymph node positivity (P = 0.002). In contrast, PTEN IHC staining was notably weaker in tumor tissues than in matched non-tumor tissues (P < 0.05), and the down-regulated expression of PTEN was correlated with tumor staging (P = 0.025), the extent of tumor (P = 0.017), and lymph node positivity (P = 0.040). Furthermore, the level of mir-21 was reversely correlated with PTEN expression (P = 0.006). Conclusion: mir-21 and PTEN might play important roles in the progression of LSCC and HSCC, the two fcators demonstrating a negative correlation.


Guan X.,University of Texas M. D. Anderson Cancer Center | Guan X.,Nanjing University | Sturgis E.M.,University of Texas M. D. Anderson Cancer Center | Lei D.,University of Texas M. D. Anderson Cancer Center | And 6 more authors.
Clinical Cancer Research | Year: 2010

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. ©2010 AACR.

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