Xiao-Lin Zhu

DJ-1: a novel independent prognostic marker for survival in glottic squamous cell carcinoma.

DJ‐1 is frequently overexpressed in a large variety of solid tumors, but the DJ‐1 expression in laryngeal squamous cell cancer and its clinical/prognostic significance is unclear. We aimed to evaluate DJ‐1 protein expression in glottic squamous cell carcinoma (GSCC) and to correlate this with clinicopathological data including patient survival. The expression of DJ‐1 in GSCCs (60) and adjacent normal tissue (44) was assessed by immunohistochemistry and western blot analysis. In addition, the role of DJ‐1 was investigated in tumorigenesis by transfecting DJ1‐specific siRNA into laryngeal squamous cell carcinoma (LSCC) Hep‐2 cells. Our data showed that positive expression of DJ‐1 was found in 85% of GSCCs. In univariate survival analysis of the GSCC cohorts, a highly significant association between DJ‐1 expression with shortened patient overall survival (5‐year survival rate 92.9%vs 66.6%; P = 0.001; log rank test) was demonstrated. In multivariate analyses, DJ‐1, tumor grading, and pT status were significant prognostic parameters for shortened patient overall survival. Furthermore, siRNA targeting DJ‐1 can effectively inhibit DJ‐1 expression, resulting in enhanced apoptosis and less proliferation of Hep‐2 cells. We concluded that DJ‐1 overexpression might be a novel independent molecular marker for poor prognosis (shortened overall survival) of patients with GSCC.

Biological characteristics of CD133+ cells in nasopharyngeal carcinoma

Cancer stem cells are regarded as the cause of tumour formation and recurrence in nasopharyngeal carcinoma (NPC). However, ideal surface markers for stem cells in NPC remain unidentified. In the present study, we investigated the expression of CD133, Nanog and Sox2 in the nasopharyngeal carcinoma cell line CNE2 and primarily cultured NPC cells using immunofluorescence or flow cytometry. A cell population with a CD133+ phenotype was enriched using magnetic-activated cell sorting technology. We demonstrated that CD133+ cells exhibited a strong potential for self-renewal, proliferation and differentiation and a greater potential for in vivo tumour formation in nude mice compared to CD133− cells, although the percentage of CD133+ cells was small. However, the specific marker antigens Nanog and Sox2 were simultaneously expressed in normal cancer stem cells. Our results showed that CD133 can serve as a specific surface marker for nasopharyngeal cancer stem cells.

Smartphone Application WeChat for Clinical Follow-up of Discharged Patients with Head and Neck Tumors: A Randomized Controlled Trial

Background:Nowadays, social media tools such as short message service, Twitter, video, and web-based systems are more and more used in clinical follow-up, making clinical follow-up much more time- and cost-effective than ever before. However, as the most popular social media in China, little is known about the utility of smartphone WeChat application in follow-up. In this study, we aimed to investigate the feasibility and superiority of WeChat application in clinical follow-up. Methods:A total of 108 patients diagnosed with head and neck tumor were randomized to WeChat follow-up (WFU) group or telephone follow-up (TFU) group for 6-month follow-up. The follow-ups were delivered by WeChat or telephone at 2 weeks, 1, 2, 3, and 6 months to the patients after being discharged. The study measurements were time consumption for follow-up delivery, total economic cost, lost-to-follow-up rate, and overall satisfaction for the follow-up method. Results:Time consumption in WFU group for each patient (23.36 ± 6.16 min) was significantly shorter than that in TFU group (42.89 ± 7.15 min) (P < 0.001); total economic cost in WFU group (RMB 90 Yuan) was much lower than that in TFU group (RMB 196 Yuan). Lost-to-follow-up rate in the WFU group was 7.02% (4/57) compared with TFU group, 9.80% (5/51), while no significance was observed (95% confidence interval [CI]: 0.176–2.740; P = 0.732). The overall satisfaction rate in WFU group was 94.34% (50/53) compared with 80.43% (37/46) in TFU group (95% CI: 0.057–0.067; P = 0.034). Conclusions:The smartphone WeChat application was found to be a viable option for follow-up in discharged patients with head and neck tumors. WFU was time-effective, cost-effective, and convenient in communication. This doctor-led follow-up model has the potential to establish a good physician-patient relationship by enhancing dynamic communications and providing individual health instructions. Trial Registration:Chinese Clinical Trial Registry, ChiCTR-IOR-15007498; http://www.chictr.org.cn/ showproj.aspx?proj=12613.

Tumorigenesis role and clinical significance of DJ-1, a negative regulator of PTEN, in supraglottic squamous cell carcinoma

BackgroundDJ-1 can induce the tumor cell proliferation and invasion via down-regulating PTEN in many malignant tumors, and correlated to prognostic significance. However, the tumorigenesis role and clinical significance of DJ-1 in supraglottic squamous cell carcinoma (SSCC) is unclear. We aimed to evaluate the DJ-1 the relationship between DJ-1 and clinicopathological data including patient survival.MethodsThe expression of DJ-1 and PTEN in SSCCs (52) and adjacent non-cancerous tissues (42) was assessed by immunohistochemistry (IHC), and the relationship between DJ-1 and clinicopathological data was analyzed.ResultsDJ-1 was detected mainly in SSCCs (88.5%) and less frequently in adjacent non-cancerous tissues (21.0%). PTEN expression was detected in 46.2% of SSCCs and in 90.5% of adjacent non-cancerous tissues. DJ-1 expression was linked to nodal status (P = 0.009), a highly significant association of DJ-1 expression with shortened patient overall survival (5-year survival rate 88.0% versus 53.9%; P = 0.007; log rank test) was demonstrated.ConclusionsOur data suggested that DJ-1 over-expression was linked to nodal status, and might be an independent prognostic marker for patients with SSCC.

Blockade of MCP-1/CCR4 signaling-induced recruitment of activated regulatory cells evokes an antitumor immune response in head and neck squamous cell carcinoma

FoxP3+ regulatory T (Treg) cells have diverse functions in the suppression of antitumor immunity. We show that FoxP3hiCD45RA−CD4+ Treg cells [activated Treg (aTreg) cells] are the predominant cell population among tumor-infiltrating FoxP3+ T cells, and that high aTreg cell-infiltrating content is associated with reduced survival in patients with head and neck squamous cell carcinoma (HNSCC). In vitro studies have demonstrated that aTreg cells can suppress tumor-associated antigen (TAA) effector T cell immune responses in HNSCC. Moreover, C-C chemokine receptor 4 (CCR4) was specifically expressed by aTreg cells in the peripheral blood of HNSCC patients. Using a RayBiotech human chemokine antibody array, we showed that monocyte chemoattractant protein-1 (MCP-1), an endogenous CCR4-binding ligand, was specifically upregulated in the HNSCC microenvironment compared to the other four CCR4-binding ligands. Blocking MCP-1/CCR4 signaling-induced aTreg cell recruitment using a CCR4 antagonist evoked antitumor immunity in mice, and lead to inhibition of tumor growth and prolonged survival. Therefore, blocking aTreg cell trafficking in tumors using CCR4-binding agents may be an effective immunotherapy for HNSCC.

Inhibition of GSK 3β Activity Is Associated with Excessive EZH2 Expression and Enhanced Tumour Invasion in Nasopharyngeal Carcinoma

Background Enhancer of zeste homolog 2 (EZH2) has been shown to contribute to tumour development and/or progression. However, the signalling pathway underlying the regulation of EZH2 in nasopharyngeal carcinoma (NPC) remains unclear. Since EZH2 contains the putative Glycogen synthase kinase 3 beta (GSK3β) phosphorylation motif ADHWDSKNVSCKNC (591) and may act as a possible substrate of GSK-3β, it is possible that inactivation of GSK3β may lead to excessive EZH2 expression in NPC. Method We first examined the expression of EZH2 and phosphorylated GSK3β (p-GSK3β) by immunohistochemical staining in NPC samples. Then, we evaluated the interaction of GSK3β and EZH2 using immunoprecipitation and immune blot. Moreover, we determined the effect of inhibition of GSK3β activity on EZH2 expression and tumor invasiveness in NPC cell lines in vitro. Finally, we evaluated the invasive properties of NPC cells after knocking down EZH2 expression with EZH2 siRNA. Results We found that expression of EZH2 correlated with phosphorylated GSK3β (p-GSK3β) at Ser 9 (an inactivated form of GSK3β) in human nasopharyngeal carcinoma (NPC) samples. We also provided evidence that GSK3β is able to interact with EZH2 using immunoprecipitation and immune blot. Furthermore, we found that inhibition of GSK3β activity can lead to upregulation of EZH2 in NPC cell lines in vitro, with enhanced local invasiveness. By knocking down EZH2 expression with EZH2 siRNA, we found that these invasive properties were EZH2 dependent. Conclusion Our findings indicate that GSK3β inactivation may account for EZH2 overexpression and subsequent tumour progression, and this mechanism might be a potential target for NPC therapy.

Clinical analysis of the cranial complications of endoscopic sinus surgery

Abstract Conclusions: The most frequently affected sites of cranial complications of endoscopic sinus surgery (ESS) are the boundary between the anterior and posterior ethmoid roof, the frontal recess, and the cribriform plate. Being aware of cranial complications in time and provision of appropriate treatment may minimize the serious consequences. Objectives: To investigate the reasons for cranial complications secondary to ESS and to find optimal prevention of cranial complications of ESS. Methods: The cranial complications of 19 patients were retrospectively reviewed. Eight patients underwent surgery in our hospital and the others underwent surgery in eight other hospitals, and were then transferred to our hospital for further examination and management of their complications. Results: The type of cranial complications involved defects of the skull base (n = 19), cerebrospinal fluid leak (n = 14), frontal lobe injury (n = 3), subarachnoid hemorrhage (n = 1), meningitis (n = 2), and concomitant pneumocephalus (n = 3). In 10 cases, the boundary between the anterior and posterior ethmoid roof was damaged. The frontal recess was involved in five cases and the cribriform plate was damaged in three patients. All of the complications resolved completely after treatment.

Middle Frontal Horizontal Partial Laryngectomy (MFHPL): A Treatment for Stage T1b Squamous Cell Carcinoma of the Glottic Larynx Involving Anterior Vocal Commissure

Objective The therapeutic effect of middle frontal horizontal partial laryngectomy (MFHPL) in treating stage T1b squamous cell carcinoma of the glottic larynx involving anterior vocal commissure (AVC) was compared with that of the anterior frontolateral vertical partial laryngectomy (AFVPL). The feasibility and practical significance of MFHPL in clinical application was discussed in the present study. Methods From January 1996 to January 2010, a total of 65 patients diagnosed with stage T1bN0M0 glottic laryngeal cancer were treated with MFHPL or AFVPL. The postoperative complications, glottic reconstruction, recurrence rate, voice quality and survival rates were evaluated and compared between two treatments. Results AFVPL and MFHPL were performed in 34 and 31 patients, respectively. Flexible fiberoptic laryngoscopy revealed that in the MFHPL-treated patients the reconstructed glottis was spacious and symmetric. In contrast, AFVPL treatment resulted in irregular glottic area with poor symmetry and tubular glottis. The incidence of postoperative laryngeal stenosis significantly differed between the MFHPL- and AFVPL-treated groups (P = 0.025). No significant difference was detected in the 3- and 5-year overall- or tumor-free survival rates between two treatments. The Voice Handicap Index (VHI) and maximum phonation time (MPT) after surgery were 51.0±12.99 and 12.42±3.44 sec in the AFVPL-treated group; while in the MFHPL-treated patients they were 31.81±7.48 and 7.65±1.98 sec, respectively. Both differences in VHI (P = 0.012) and MPT (P = 0.024) were significant between two treatments. Conclusions MFHPL was comparable to AFVPL with respect to postoperative complications, recurrence rate and survival rates, but possessed advantages over AFVPL in terms of the incidence of laryngeal stenosis and voice quality. Our study indicated that MFHPL has a potential value in clinical practice of treating stage T1b squamous cell carcinoma of the glottic larynx involving AVC.

Expression of mismatch repair gene PMS2 in nasopharyngeal carcinoma and regulation by glycogen synthase kinase-3β in vivo and in vitro

OBJECTIVE To evaluate the expression of mismatch repair gene PMS2 in human nasopharyngeal carcinoma (NPC) tissues and evaluate the effect of glycogen synthase kinase (GSK)-3β on PMS2 production in vivo and in vitro. METHODS The expression of PMS2 and inactivated phosphorylated GSK-3β(s9) was examined by immunohistochemical staining in 25 NPC tissues and the relation was determined by correlation analysis. The effect of GSK-3β transfection in CNE-2 cells on PMS2 production as well as cell apoptosis and chemosensitization were evaluated using small interference RNA (siRNA), immunoblotting and flow cytometric analysis in vitro. RESULTS The expression of inactivated phosphorylated GSK-3β(s9) was found to negative correlated with PMS2 in vivo. And transfected GSK-3β was found to be able to enhance PMS2 production, and increase cell apoptosis in CNE-2 cells in combination with cisplatin administration in vitro. CONCLUSION Inactivation of GSK-3β might be important for NPC tumorgenesis through negatively regulating PMS2 production, and enhanced PMS2 production by GSK-3β is beneficial for understanding the NPC tumorgenesis and developing potential strategy for future therapy.

Combined Effect of Rapamycin and Cisplatin on Survival of Hep-2 Cells In Vitro

The cytotoxic effects and mechanism of action of cisplatin and the mTOR inhibitor rapamycin on Hep-2 laryngeal cancer cells were investigated. Hep-2 cells were cultured in the presence of different concentrations of rapamycin, cisplatin, or the two combined. Inhibition of cell growth, apoptosis, and AKT, mTOR, S6K, and ERCC1 protein levels were assessed. All combinations of rapamycin and cisplatin resulted in synergistic inhibition of cell growth (as indicated by q values determined using Jins formula > 1.15). Rapamycin inhibited Hep-2 cell growth, induced G1 arrest, and when combined with cisplatin, enhanced apoptosis. p-mTOR and S6K expressions were significantly downregulated by rapamycin. ERCC1 expression was significantly upregulated with cisplatin treatment. Combined cisplatin and rapamycin treatment resulted in significant downregulated p-mTOR and S6K expression, but no change in ERCC1 expression. Rapamycin and cisplatin act in a synergistic manner, increasing the cytotoxic effect on Hep-2 cells. Rapamycin may facilitate increased Hep-2 cell apoptosis with cisplatin via inhibiting downstream expression of proteins in the AKT-mTOR signaling pathway.