Folate-Functionalized Lipid Nanoemulsion to Deliver Chemo-Radiotherapeutics Together for the Effective Treatment of Nasopharyngeal Carcinoma.

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

Subtotal facial nerve decompression in preventing further recurrence and promoting facial nerve recovery of severe idiopathic recurrent facial palsy.

The objective of the study is to document the role of subtotal facial nerve decompression in preventing further recurrence and promoting facial nerve recovery of severe idiopathic recurrent facial palsy. Twenty-two cases with idiopathic recurrent facial palsy, which had over 95% degeneration of facial nerve on electroneurography, were included in the study, among which 12 accepting subtotal facial nerve decompression were involved in surgery group, and 10 who refused surgery and received prednisolone were classified into control group. The recurrence of facial palsy and facial nerve recovery was compared. The patients were followed up for 5.3 years (range 3-8 years) and 5.2 years (range 3-7 years) in surgery group and control group, respectively. Further recurrence of facial palsy occurred in none of 12 patients (0%) in surgery group in contrast to 4 of 10 cases (40%) in control group, with statistical difference (p < 0.05). 11 of 12 cases (91.7%) in surgery group recovered to Grade I or Grade II compared to 3 of 10 cases (30.0%) in control group, with significant difference (p < 0.05). Subtotal facial nerve decompression is effective to prevent further recurrence of facial palsy and promote facial nerve recovery of severe idiopathic recurrent facial palsy.

Decreased calcium-activated potassium channels by hypoxia causes abnormal firing in the spontaneous firing medial vestibular nuclei neurons.

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

Extracellular acidic pH-activated, outward rectifying chloride currents can be regulated by reactive oxygen species in human THP-1 monocytes.

Extracellular acidic pH-activated chloride channels (ICl,acid) have been found in a variety of mammalian cells. In the present study, the expression and regulation of ICl,acid were investigated in THP-1 cells. Patch clamp recordings demonstrated that an extracellular acidic solution induced an outward rectified current, which could be blocked by the Cl(-) channel blocker. The currents exhibited time-dependent facilitation and inactivation. The relative anion permeability of this current followed the sequence Cl(-)>Br(-)>I(-)>gluconate. NADPH oxidase inhibitors did not decrease pH 4.4-induced currents. However, reactive oxygen species (ROS) scavengers and mitochondrial inhibitors inhibited pH 4.4-induced currents. Fluorescence imaging of intracellular ROS and mitochondrial activity confirmed these findings. We conclude that ICl,acid occurs in human THP-1 cells and that ICl,acid may be regulated by intracellular ROS mainly originating from mitochondria.

Down-regulation of EMP1 is associated with epithelial hyperplasia and metaplasia in nasal polyps.

AIMS: The aim of this study was to assess protein and mRNA expression of epithelial membrane protein 1 (EMP1) in the nasal mucosa of patients with nasal polyps (NP), and to determine what changes occur in response to glucocorticosteroid (GC) treatment. METHODS AND RESULTS: NP tissue was obtained from 55 patients, 18 of whom were treated with nasal GCs (i.e. these 18 patients had NP biopsies taken before and after treatment). Biopsies of inferior turbinate mucosa from 30 healthy subjects were used as controls. Quantitative PCR and immunohistochemistry were performed to determine the expression levels of EMP1. EMP1 mRNA expression was significantly lower (2.77-fold) in tissues from NP patients before GC treatment when compared to controls, but was increased in these patients after GC treatment. EMP1 staining in nasal epithelium co-localized with both basal (p63(+)) and differentiated (CK18(+)) epithelial cells. Their immunoreactivity was significantly greater in controls than NP patients. EMP1 mRNA levels were lower in the epithelium with severe hyperplasia (1.79-fold) or with metaplasia (1.85-fold) as compared to those with mild to moderate hyperplasia or non-metaplastic epithelium, respectively. Positive correlations between EMP1 and other epithelial cell-related gene (e.g. JUN, PTGS2, AREG etc.) mRNAs were observed. CONCLUSIONS: EMP1 could be a biomarker for aberrant epithelial remodelling and metaplasia in chronic inflammatory upper airway mucosa (e.g. NP).

XPA A23G polymorphism and susceptibility to cancer: a meta-analysis.

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

Anesthesiologist's knowledge and attitudes about obstructive sleep apnea: a survey study.

OBJECTIVE: The objectives of this study were to measure the anesthesiologists' knowledge and attitudes about OSA and assess the need for additional educational programs focusing on OSA. METHODS: The Obstructive Sleep Apnea Knowledge and Attitude Questionnaire (OSAKA) developed by Helena Metal was translated into Chinese and distributed to anesthesiologists from Shandong Province. Anesthesiologists completed the OSAKA questionnaire containing sections regarding knowledge (18 items) and attitudes about OSA (5 items). RESULTS: A total of 321 questionnaires were completed. The mean total knowledge score was 11.21, with the scores ranging from 2 to 17. The total correct score ratio was 62%. The knowledge score positively corrected with the participants' job titles and attitude scores. None of the dependent variables, such as sex, age, education, and working in a different hospital level, affected the score. CONCLUSION: The study shows that anesthesiologists lack adequate knowledge about OSA. The total correct score ratio was 62%; when they managed an OSA patient, the positive attitude score is mostly below 50%. They have low confidence about OSA patients. It is necessary to develop special training programs on OSA regularly for anesthesiologists after graduation.

Association between Health-Related Physical Fitness and Risk of Dyslipidemia in University Staff: A Cross-Sectional Study and a ROC Curve Analysis.

BACKGROUND: This study aimed to assess the relationship between dyslipidemia (DL) risk and health-related physical fitness (HPF) and evaluated the prognostic value of HPF for risk of DL. METHODS: A total of 776 university staff members were recruited, of which 407 were females, and 369 males. Blood samples and HPF tests were collected from all participants after 12 h fasting. RESULTS: The prevalence of DL was 41.77% and 51.49% in female and male university staff members, respectively, and there was no significant difference between genders (χ2 = 2.687, p = 0.101). According to the logistic regression analysis, age, male sex, GLU, hypertension, BMI, BF, WHtR, and LAP were significant risk factors for DL (p < 0.05), VCI and, SAR were significant protective factors for DL (p < 0.05), and SMI, GS, and VG were not significantly associated with the risk of DL. The area under the receiver-operating characteristic (ROC) curve (AUC) analysis indicated that, LAP (AUC: 0.730, 95CI%: 0.697-0.762), WHtR (AUC: 0.626, 95CI%: 0.590-0.660), and BMI (AUC: 0.599, 95CI%: 0.563-0.634) are valid predictors of DL, and LAP and WHtR perform better than BMI (Z = 8.074, p < 0.001) in predicting DL in male and female university staff members. CONCLUSION: The risk of DL is significantly related to body composition, cardiorespiratory fitness, and flexibility. LAP and WHtR perform better than BMI in predicting risk of DL in male and female university staff members.

[Determination of isoguanosine in Semen Crotonis Tiglii by high-performance liquid chromatography].

OBJECTIVE: To develop a high-performance liquid chromatographic method for the determination of isoguanosine in Semen Crotonis Tiglii. METHODS: The determination was done by using reverse-phase high-performance liquid chromatography with a Hedera ODS-2 column (4.6 mm x 250 mm, 5 microm). Elution was employed with the mobile phase of acetonitrile-methanol-water (1:4:95) at flow rate of 1.0 mL/min. The detection wavelength was set at 292 nm and the column temperature was 25 degrees centigrade. Injection volume was 10 microL. RESULTS: The linear range of isoguanosine was from 0.161 to 0.967 mg. The correlation coefficient of the calibration curves was 0.999 8. The average recovery rate was 98.78% with relative standard deviation of 0.02%. CONCLUSION: The results show that the method is simple, accurate, and repeatable, and it is suitable for quality control of Semen Crotonis Tiglii.

Suppression of survivin expression by short hairpin RNA induces apoptosis in human laryngeal carcinoma cells.

PURPOSE: The aim of this study was to evaluate the suppression effect of survivin shRNA on the expression of the survivin gene in the human laryngeal cancer cell line Hep-2. PROCEDURES: 60 cases of laryngeal squamous-cell carcinoma (LSCC) and 10 cases of normal laryngeal mucosa were examined using immunohistochemistry to determine whether the expression of survivin correlated with tumorigenesis. Three plasmid vectors of short hairpin RNA (shRNA) specific for survivin were designed and generated. Western blot and real-time PCR analysis of survivin expression in Hep-2 cells was performed 48 h after transfection. The growth curve was used to determine the cell proliferation. Propidium iodide (PI) single staining was applied to detect the cell cycle. The apoptosis of the cells was analyzed by flow cytometry with the FITC-annexin-V/PI double staining and PI single staining. RESULTS: 68.33% (41 out of 60) of tumors were positive for survivin expression and significantly associated with lymph node metastasis and advanced stage. In contrast, no expression of survivin in normal mucosa was detected. Transfection of Hep-2 cells with survivin shRNA significantly inhibited survivin expression at both the mRNA and the protein level in Hep-2 cells. Downregulation of survivin resulted in increasing the apoptosis index, but the results showed no obvious influence on cell cycle. CONCLUSIONS: This study demonstrates that survivin shRNA effectively inhibits survivin gene expression in Hep-2 cells leading to growth suppression and apoptotic induction in Hep-2 cells.

[Surgical management and preservation of laryngeal function for senile patients with advanced laryngeal carcinoma].

OBJECTIVE: To explore the methods of surgical treatment and preservation of laryngeal function in senile patients with advanced laryngeal carcinoma. METHODS: A retrospective data review of 87 advanced laryngeal carcinoma patients aged over 65 years was carried out. Of these 87 patients treated by different modes of surgery, 48 had supraglottic cancer, 35 glottic cancer and 4 subglottic cancer. The surgery modes consisted of major partial laryngectomy in 36 patients, subtotal partial laryngectomy with laryngoplasty in 21 and total laryngectomy in 30. All patients received postoperative radiotherapy to a dose of 50-60 Gy. Kaplan-Meier method was used to analyze the survival. RESULTS: The overall 3- and 5-year survival rate was 73.2% and 67.4%, respectively. The ultimate rate of larynx preservation was 65.5%. Of 57 patients with partial laryngectomy, 46 were decannulated with a decannulation rate of 80.7%. Yet, in all patients, the nasal feeding tube was removed and food intake per os was resumed. All patients who underwent partial laryngectomy regained their phonation function. CONCLUSION: It is safe and effective to treat and preserve laryngeal function surgically in the senile patients with advanced laryngeal carcinoma. The key points to achieve this are selection of proper patient, renovation of surgical procedure and improvement of surgical skill.

Aberrant methylation and expression of DAPk1 in human hypopharyngeal squamous cell carcinoma.

CONCLUSION: 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. OBJECTIVES: This study aimed to investigate the methylation and expression of DAPk1, a tumor suppressor gene, in HSCC, and explore its clinical significance. METHODS: 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. RESULTS: 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, p < 0.001). 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).

Chloroquine-enhanced efficacy of cisplatin in the treatment of hypopharyngeal carcinoma in xenograft mice.

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

[Surgical treatment of tonsillar cancer].

OBJECTIVE: To study the surgical treatment of tonsillar cancer. METHODS: Twenty-four patients with tonsillar cancer were treated with surgery and postoperative radiotherapy. The choice of surgical procedure was decided on the condition of the lesion. The tumor was resected through the transoral approach, mandibular swing approach, mandibular resection approach or hyoid approach. Surgical defect was repaired by pectoralis major myocutaneous flap, sternohyoid myofascial flap, tongue flap or soft palate flap. RESULTS: The 3- and 5-year survival rates were 76.0% and 60.8%. Function of chewing, deglutition, respiration and speech was restored well. CONCLUSION: Method of total resection of the tonsillar carcinoma through the optimum approach is best chosen according to the condition of the lesion, while preserving the oropharyngeal function. When combined with postoperative radiotherapy, the survival rate and quality of life of patients can be improved.

[Substitution of esophagus with stomach or colon without thoracotomy in the treatment of cervical esophageal carcinoma with laryngeal function preserved].

OBJECTIVE: To study the feasibility and effect of substituting esophagus with stomach or colon without thoracotomy in the treatment of cervical esophageal carcinoma with laryngeal function preserved. METHODS: Twenty-four patients with cervical esophageal carcinoma were retrospectively reviewed. The esophagus was resected and substituted with 19 gastric pull-up and 5 colon interposition. Nineteen patients received radiotherapy postoperatively (dose 50 - 70 Gy). RESULTS: Twenty two patients were follow up over 3 years. The 3- and 5-year survival rates for T2 were 3 and 1, for T3, T4 8 and 3, respectively. The laryngeal function preservation rate was 77% (17/24) and the decannulation rate was 75% (12/16). The complication rate was 29%. CONCLUSION: Surgical resection of cervical esophageal carcinoma with removal of the extraesophageal invaded tissues while preserving the laryngeal function is possible. The continuity of the esophagus is restored by stomach transposition and colon interposition. Combined with radiotherapy, the survival rate and life quality of the patient might be improved.

Reduced growth and proliferation dynamics of nasal epithelial stem/progenitor cells in nasal polyps in vitro.

Basal cells in nasal epithelium have stemness/progenitor characters and play essential roles in the epithelial remodeling in nasal polyps (NP). We investigate whether the human nasal epithelial stem/progenitor cells (hNESPCs) from patients with NP are inherently distinct from those obtained from healthy controls. Epithelial basal cells were isolated and cultured for four passages from NP tissues and control nasal mucosa. hNESPCs from controls were stained positively with stem cell marker p63 and KRT5 and presented a consistent high Ki67 expression level over four passages. In contrast, hNESPCs from NP patients showed: i). a reduced growth and proliferation rate at each passage by evaluating colony-forming efficiency and doubling time; ii). a lower percentage of Ki67(+) cells among p63(+) cells in the colonies in late passages, which was also confirmed by immunostaining in the NP tissues. Thus reduced growth/proliferation dynamics in hNESPCs from NP could be an important pathological phenomenon in NP development.

Aberrant expression of Beclin-1 and LC3 correlates with poor prognosis of human hypopharyngeal squamous cell carcinoma.

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<0.0001). Furthermore, 41.5% (34/82) of HSCC specimens exhibited high LC3 immunoreactivity (adjacent non-cancerous tissues, 74.1%, 40/54; P=0.0002). Beclin-1 and LC3-II mRNA transcript levels were significantly lower in HSCCs than in paired non-cancerous tissues (P<0.0001, P=0.0001, respectively). Similarly, western blotting assays showed that beclin-1 and LC3-II were markedly decreased in HSCCs (P=0.02, P=0.004, respectively). A positive correlation was observed between the mRNA transcript levels of beclin-1 and LC3-II in HSCCs (r=0.51, P<0.0001; 95%CI: 0.273 to 0.689). Beclin-1 and LC3 expression were significantly correlated with T categories, differentiation and lymph node metastasis. Negative beclin-1 immunoreactivity and low LC3 expression were associated with poorer overall survival in HSCC patients (P<0.0001, P=0.0145, respectively). Multivariate analysis revealed that beclin-1 was an independent prognositic factor for overall survival. CONCLUSION: Beclin-1 and LC3-II are downregulated in HSCCs and their aberrant expression correlates with poor prognosis of HSCCs.

The Expression of SIRT1 and DBC1 in Laryngeal and Hypopharyngeal Carcinomas.

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

[Surgical treatment of advanced laryngeal cancer with preservation of laryngeal function].

OBJECTIVE: To explore the surgical methods for advanced laryngeal cancer and long term effects of laryngectomy. METHODS: Two hundred and thirty-eight cases of laryngeal cancer at different stages, including 103 cases with supraglottic cancer, 118 cases with glottic cancer, 3 cases with subglottic cancer, and 14 cases with recurrent cancer, underwent different kinds of operation from 2000 to 2010. The TNM classifications were as follows: T3 168 cases, T4 70 cases. Stage III 145 cases, Stage IV 93 cases. N0 134 cases,N1 64 cases,N2 38 cases, and N3 2 cases. The effects of operation, especially with the preservation of laryngeal function, was analyzed. The disease-free survival rate was calculated by Kaplan-Meier methods. RESULTS: Partial laryngectomy was performed on 142 of the 238 cases (59.7%). Total laryngectomy was performed on 96 cases. In 142 patients who received partial laryngectomy with preservation of laryngeal function, the trachea cannula was extracted in 90 patients, with the decannulation rate as 63.4%. The nasal feeding tube was removed and peroral feeding was recovered in all patients. The patients undergoing partial laryngectomy succeeded in phonation. The 3 years and 5 years disease-free survival rates in all patients were 81.4% and 59.5%. The 3 years and 5 years disease-free survival rate of partial laryngectomy were 82.9% and 64.3%. The 3 years and 5 years disease-free survival rates in total laryngectomy were 79.2% and 52.4%. There was no significantly different between the two groups (χ(2) = 2.478, P = 0.115). CONCLUSION: For the advanced laryngeal cancer, it is possible to preserve the laryngeal function without compromising the remote survival rate by detailed pre-operational estimation, properly selected operation and skilled surgical practice.

Role of centromere protein H and Ki67 in relapse-free survival of patients after primary surgery for hypopharyngeal cancer.

PURPOSE: Centromere protein H (CENP-H) and Ki67 are overexpressed in some malignancies, but whether they are predictors of survival after primary resection for hypopharyngeal squamous cell carcinoma (HSCC) remains unknown. METHODS: We assessed immunohistochemical expression of CENP-H and Ki67 in 112 HSCC specimens collected between March 2003 and March 2005 for analysis by clinical characteristics. The Kaplan-Meier method was used to analyze relapse-free survival and logistic multivariate regression to determine risk factors of relapse-free survival. Cholecystokinin octapeptide assays and flow cytometry were used to examine cell proliferation and apoptosis after siRNA inhibition of CENP-H in HSCC cells. RESULTS: Overall, 50 (44.6%) HSCC specimens showed upregulated CENP-H expression and 69 (61.6%) upregulated Ki67. An increased CENP-H protein level was associated with advanced cancer stage and alcohol history (P=0.012 and P=0.048, respectively) but an increased Ki67 protein level only with advanced cancer stage (P=0.021). Increased CENP-H or Ki67 were associated with short relapse-free survival (P<0.001 or P=0.009, respectively) and were independent predictors of relapse-free survival (P=0.001 and P=0.018, respectively). siRNA knockdown of CENP-H mRNA inhibited cell proliferation and promoted cancer cell apoptosis in vitro. CONCLUSIONS: Upregulated CENP-H and Ki67 levels are significantly associated with short relapse-free survival in HSCC. These factors may be predictors of a relapsing phenotype in HSSC cases.