FAP is a prognostic marker, but not a viable therapeutic target for clinical translation in HNSCC.

PURPOSE: PD-1 targeted immunotherapy has imparted a survival benefit to advanced head and neck squamous cell carcinoma (HNSCC), but less than 20% patients produce a durable response to this therapy. Here we aimed to investigate the potential biomarkers for predicting the clinical outcome and resistance to PD-1 targeted immunotherapy in HNSCC patients, and to examine the involvement of FAP+ cancer-associated fibroblasts (CAFs). METHODS: Bioinformatics methods were applied to analyze multiple datasets and explore the role of PD-1 and FAP in HNSCC. Immunohistochemistry was used to detect the expression of FAP protein. Fap gene knockout mice (Fap-/-) and L929 cells with different levels of Fap overexpression (L929-Fap-Low/High) were established to demonstrate the role of FAP+ CAFs in tumor development and immune checkpoint blockade (ICB) resistance. RESULTS: The expression level of PD-1 gene was positively correlated with better overall survival and therapeutic response to PD-1 blockade in HNSCC, but not all tumors with high expression of both PD-1 and PD-L1 were responsive. Moreover, FAP gene was overexpressed in pan-cancer tissues, and could serve as a prognostic biomarker for several cancers, including HNSCC. However, FAP protein was undetectable in mouse MTCQ1 tumors and barely expressed in human HNSCC tumors. Furthermore, FAP+ CAFs did not promote tumor growth or enhance the resistance to PD-1 inhibitor treatment. CONCLUSION: Although FAP+ CAFs have attracted increasing attention for their role in cancer, the feasibility and efficacy of FAP-targeting therapies for HNSCC remain doubtful.

Comparative study of optical coherence tomograph and histological images of eustachian tube nasopharyngeal region and adjacent structures in vivo and ex-vivo miniature pigs.

OBJECTIVES: Optical Coherence Tomograph (OCT) imaging technology can be used to examine, in vivo, the human ET. At present, it is impossible to achieve the OCT scanning vivo and ex vivo in the same individual human body, or study the consistency between OCT images and histological images of the eustachian tube nasopharyngeal region and adjacent structures. The aim of this study was to determine the consistency between OCT images and histological sections in vivo and ex vivo in miniature pigs. METHODS: OCT imaging was performed on five adult miniature pigs in vivo and ex vivo. The images of the eustachian tube OCT (ET-OCT), nasopharynx OCT (NP-OCT) and histological cross sections were further studied. RESULTS: All five miniature pigs achieved the OCT scan successfully, acquiring ET-OCT and NP-OCT images in vivo and ex vivo on both sides. The acquired ET OCT images closely matched the histological images, revealing details of the cartilage, submucosa, glands, and mucosa. The lower segment of the ET wall mucosa had an abundance of glands and submucosal tissues, with more low-signal areas appearing in the ex vivo images. The NP-OCT images of the nasopharynx matched the details of the mucosa and submucosal tissues. The ex-vivo OCT images showed thicker mucosa and more scattered slightly lower signal areas compared to the vivo OCT images. CONCLUSIONS: ET-OCT images and NP-OCT images matched the histological structure of eustachian tube nasopharyngeal region structures in miniature pigs both in vivo and ex vivo. OCT images may be sensitive to changes in edema and ischemia status. There is a great potential for morphological assessment of inflammation, edema, injure, mucus gland status.

Tumor size rather than the thyroid invasion affects the prognosis of parathyroid carcinoma without lymph node or distant metastasis.

PURPOSE: This study aimed to explore the prognostic value of thyroid invasion of parathyroid carcinoma without lymph node or distant metastasis. METHODS: Two hundred and nine cases of parathyroid carcinoma from the SEER (1989-2014) were eligible for this study. A Chi-squared test, t test, X-tile, Kaplan-Meier curves, and multivariate Cox proportional hazard regression were used for analysis. RESULTS: Thyroid invasion, sex, race, age, radiation, and surgery were not significantly associated with cancer-specific survival by multivariate analysis. However, tumor size ≥ 4 cm was significantly associated with worse cancer-specific survival (P < 0.001). CONCLUSION: Thyroid invasion, which was the criterion for T1 and T2 staging criteria of parathyroid carcinoma according to the AJCC, did not affect the prognosis of patients with parathyroid carcinoma without local lymph node or distant metastasis. Our study indicates that a tumor size ≥ 4 cm may be an appropriate indicator of T1 and T2 cancer staging.

Autoimmune thyroiditis in patients with sudden sensorineural hearing loss.

Objective: This study aims to evaluate the association between autoimmune thyroiditis and Sudden Sensorineural Hearing Loss (SSNHL). Methods: Hundred and five patients with SSNHL were enrolled. Audiometric tests, serum thyroid autoantibodies (TPOAb, TgAb) were studied. Based on the thyroid autoantibody results, patients were divided into two groups: thyroid autoantibody-positive and negative. The relationship between thyroid autoimmunity and audiological characteristics was analyzed. Results: Twenty-six patients (24.8%) of the SSNHL had thyroid autoantibody elevated. The pure tone average (PTA) of patients with and without thyroid autoantibody is 60 ± 38.51 and 54.99 ± 33.87 dBHL, respectively. The PTA was significantly improved in both groups after treatment (p < 0.001), but the hearing gains were similar in both groups (p = 0.205). Hearing loss of 2000-8000 Hz was worse than 125-1000 Hz among thyroid autoantibody-positive patients (p < 0.05), but the hearing improvement of both groups have no significant difference. The hearing improvement of 125-1000 Hz is significantly better than 2000-8000 Hz among patients with thyroid autoantibody negative (p < 0.05). Conclusions: We speculate that a potential association between thyroid autoimmunity and SSNHL. Thyroid autoimmunity may be a pathogenesis factor of SSNHL and associated with more severe hearing loss of high-frequency hearing.

Pan-cancer analysis of GALNTs expression identifies a prognostic of GALNTs feature in low grade glioma.

Polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), a group of isoenzymes that initiate mucin-type O-glycosylation, have been shown to mediate tumor growth and metastasis in various cancer types. However, data on the clinical significance and features of GalNAc-Ts remain scant. Here, we used Oncomine and The Cancer Genome Atlas (TCGA) databases to analyze the transcription and survival effect of GALNTs (N-acetylgalactosaminyltransferase genes) in pan-cancer. The data showed that the GALNTs were aberrantly expressed in various human cancers and significantly associated with patients' clinical outcomes. The expression of 13 GALNTs were correlated with prognosis in brain low grade glioma (LGG) patients. In addition, based on the expression profiles of GALNT family genes in TCGA-LGG dataset, we identified 2 molecular subtypes (cluster1/2) by consensus clustering and analyzed tumor heterogeneity. Our results demonstrated that cluster 2 group was associated with poor prognosis, CD8+ T cells, macrophages and DCs infiltration, up-regulated expression of immune checkpoints, and higher tumor immune dysfunction and exclusion score, indicating that GalNAc-Ts might contribute to tumor immune escape. Furthermore, we employed LASSO regression and time-dependent ROC analysis to construct a GALNTs-related prognostic signature with the TCGA-LGG dataset, and then validated the signature using 2 external cohorts. Taken together, our study successfully developed a novel prognostic biomarker for LGG and provides a basis for personalized immunotherapy in brain cancer.

This study successfully developed a novel prognostic biomarker for LGG and provides a basis for personalized immunotherapy in brain cancer.

Risk Factors of Anastomotic Leakage After Esophagectomy With Intrathoracic Anastomosis.

Purpose: Anastomotic leakage is one of the most common complications of esophagectomy, it serves as one of the main causes of postoperative death of esophageal cancer. It is of clinical significance to try to discover the risk factors that cause anastomotic leakage. Methods: This retrospective study was conducted on 1,257 consecutive esophageal cancer patients who underwent esophagectomy with intrathoracic anastomosis from January 2010 to December 2015 at a high volume cancer center. Multivariate Logistic Regression analysis, Spearman rank correlation analysis, Mann-Whitney U test and Kruskal-Wallis test were performed to identify the risk factors to the occurrence of anastomotic leakage and the length of hospital stay. Results: Intrathoracic anastomotic leakage occurred in 98 patients (7.8%). Older patients were more likely to develop anastomotic leakage. Patients with diabetes had a higher leakage rate. Intrathoracic anastomotic leakage, old age as well as comorbidities were associated with longer hospital stay. Conclusion: Our study suggested that old age and diabetes were risk factors to intrathoracic anastomotic leakage. In-hospital stay would be lengthened by intrathoracic anastomotic leakage, old age and comorbidities.

Role of primary tumor resection in patients with metastatic medullary thyroid cancer who have unresectable distant metastases.

BACKGROUND: Whether patients with medullary thyroid carcinoma (MTC) who have unresectable synchronous distant metastases should undergo primary surgical resection (PTR) remains controversial. This study aimed to identify predictive factors associated with the survival of such patients. METHODS: We conducted a retrospective study of patients with MTC who were registered in the Surveillance, Epidemiology, and End Results registry. The overall and cancer-specific mortality rates were assessed using risk-adjusted Cox proportional hazards regression modeling and stratified propensity score matching. RESULTS: One hundred and eight matched patients were assessed. Patients in the PTR group had lower overall mortality than did those in the non-PTR group. The 1-, 3-, and 5-year overall and cancer-specific survival rates in the PTR group were significantly higher. CONCLUSIONS: PTR appears to be the most appropriate intervention for patients with good performance status. Such patients are likely to benefit from surgery and to experience long-term stable disease.

The deubiquitinating enzyme ATXN3 promotes the progression of anaplastic thyroid carcinoma by stabilizing EIF5A2.

Ataxin-3 (ATXN3) is a ubiquitous deubiquitinating enzyme that plays an essential role in the carcinogenesis of numerous tumors and stabilizes the expression of substrates by deubiquitination. However, the functional role of ATXN3 in anaplastic thyroid carcinoma (ATC) remains unknown. In this research, we report that ATXN3 was overexpressed in ATC compared to that in paracancerous samples. Moreover, various gain/loss functional assays were performed to indicate that ATXN3 overexpression enhanced ATC cell proliferation and metastasis. We also found that ATXN3 and eukaryotic translation initiation factor 5A2 (EIF5A2) protein levels in ATC tissues are positively correlated, and ATXN3 promotes the proliferation and metastasis of ATC cells through EIF5A2. Mechanistically, ATXN3 promotes EIF5A2 expression by directly binding to EIF5A2 to reduce its ubiquitination and degradation. Therefore, for the first time, we clarified the role of ATXN3 in the carcinogenesis of ATC cells, which provides novel insights into potential therapeutic targets for ATC progression.

Overexpression of long non-coding RNA LINC00982 suppresses cell proliferation and tumor growth of papillary thyroid carcinoma through PI3K-ATK signaling pathway.

Long non-coding RNAs (lncRNAs) have been widely reported that involved in human cancers, including papillary thyroid carcinoma (PTC). The present study aims to investigate the biological role of LINC00982 in PTC. The mRNA expression of LINC00982 in human PTC tissues was detected using qPCR. Moreover, Kaplan-Meier method was performed to analyze the internal relevance between LINC00982 expression and overall survival (OS) rate of patients with PTC. In addition, gain- and loss-of-functions assays were performed to detect the effects of LINC00982 on the cell proliferation and migration in PTC cells. Furthermore, western blot assay was used to measure the alteration expression levels of apoptosis relative proteins and the relative protein involved phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Finally, a xenograft model was used to analyze the antitumor role of LINC00982 in vivo Here, we found that LINC00982 was decreased in human PTC tissues. Patients with decreased LINC00982 expression levels had a reduced OS (P=0.0019) compared with those with high LINC00982 expression levels. Overexpression of LINC00982 suppressed the proliferation and migration of BHT101 and B-CPAP cells and promoted cell apoptosis. Knockdown of LINC00982 promoted the proliferation and migration of BHT101 and B-CPAP cells and induced cell apoptosis. Moreover, in vivo assay showed that overexpression of LINC00982 could suppress the growth of PTC. Finally, LINC00982 could regulate the activity of PI3K/AKT signaling pathway in vitro and in vivo Taken together, our findings demonstrated that overexpression of LINC00982 could suppress cell proliferation and induce cell apoptosis by regulating PI3K/AKT signaling pathway in PTC.

Construction and preliminary identification of a prokaryotic expression single-chain antibody fragments library against Streptococcus pneumoniae from antibody-producing cells in human tonsil.

Tonsillitis is the inflammation of the tonsils due to infection, many patients ultimately have to undergo tonsillectomy. In order to improve the accuracy of diagnosis and even create a new treatment for tonsillitis, we constructed a prokaryotic expression single-chain antibody fragment library against Streptococcus pneumoniae with immunoglobulin heavy chain variable region (VH), κ light chain (Vκ), and λ light chain (Vλ) genes by using human tonsil tissue. Plasmid DNA sequencing showed that single-chain antibodies were complete and constructed correctly. The binding activity of recombinant clones was detected by enzyme-linked immunosorbent assay (ELISA), results showed that the binding activity and specificity of anti-S. pneumoniae single-chain fragment variable (scfv) is proved to be successful. The single-chain antibody may be an attractive strategy for tonsillitis etiologic diagnosis and therapy.

Treatment and Prognosis of Anaplastic Thyroid Carcinoma: A Clinical Study of 50 Cases.

INTRODUCTION: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the most aggressive human cancers. The optimal multimodal therapy policy of ATC is still debated, and a standardized treatment strategy remains to be established. This study aimed to evaluate the management aspect and prognosis of ATC. MATERIALS AND METHODS: The data were analyzed retrospectively for 50 patients with ATC to evaluate the clinical characters, management and factors influencing survival. Survival analysis was performed by Kaplan-Merier method and log-rank test, and multivariate analysis was performed using Cox proportional hazard model. RESULTS: The 1-year and 2-year overall survival rates (OS) were 48.0% and 26.0% respectively in all patients, with the 2-year OS of 40.0% and 31.0% and 6.3% for stage IVA, IVB and IVC respectively (P <0.05). In stage IVA and IVB patients, combined surgery with radiotherapy improved overall survival, and the 2-year OS were 50.0% and 35.7% respectively in the group with combined surgery with radiotherapy and the group with surgery with only (P <0.05). Postoperative radiotherapy improved local control rate in stage IVA and IVB patients (P <0.05). However, surgery, radiotherapy or chemotherapy could not improve the survival of stage IVC patients. Multivariate analysis showed that distant metastases, surgery, radiotherapy and tumor residue could predict the prognosis. CONCLUSION: Combined surgery and radiotherapy could improve overall survival in stage IVA and IVB patients. Patients with ATC have a bad prognosis. Distant metastases, surgery, radiotherapy and tumor residue are the most important factors affecting the prognosis.

Sam68 reduces cisplatin-induced apoptosis in tongue carcinoma.

BACKGROUND: Resistance to anticancer agents is a major obstacle for successful chemotherapy in tongue squamous cancer. Sam68 is an oncogenic-related protein in oral tongue squamous cell carcinoma functions as a signaling molecule mediating apoptosis, whose over-expression is associated with the clinicopathologic characteristics and prognosis of patients. The present study was to examine the effect of Sam68 on chemotherapeutics-induced apoptosis in oral tongue squamous cell carcinoma, and its clinical significance in oral tongue squamous cell carcinoma progression. METHODS: The effect of Sam68 on apoptosis induced by cisplatin was examined both in vitro and in vivo, using Annexin V staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays. Real-time PCR and Western blotting analysis were used to detect mRNA and protein expression levels. RESULTS: Upregulation of Sam68 significantly inhibited cisplatin-induced apoptosis in oral tongue squamous cell carcinoma cells, associated with induction of anti-apoptotic proteins caspase-9, caspase-3, and PARP. In contrast, Silencing Sam68 expression significantly enhanced the sensitivity of oral tongue squamous cell carcinoma cells to apoptosis induced by cisplatin both in vitro and in vivo. CONCLUSIONS: The current study suggests that Sam68 could enhance the anti-apoptosis activity of oral tongue squamous cell carcinoma cells. Sam68 is a potential pharmacologic target for the treatment of oral tongue squamous cell carcinoma and inhibition of Sam68 expression might represent a novel strategy to sensitize oral tongue squamous cell carcinoma to chemotherapy.

Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy.

BACKGROUND: The Mre11-Rad50-Nbs1 (MRN) complex is well known for its crucial role in initiating DNA double strand breaks (DSBs) repair pathways to resistant irradiation (IR) injury and thus facilitating radioresistance which severely reduces radiocurability of nasopharyngeal cancer (NPC). Targeting native cellular MRN function would sensitize NPC cells to IR. METHODS: A recombinant adenovirus containing a mutant Rad50 gene (Ad-RAD50) expressing Rad50 zinc hook domain but lacking the ATPase domain and the Mre11 interaction domain was constructed to disrupt native cellular MRN functions. The effects of Ad-RAD50 on the MRN functions were assessed in NPC cells lines using western blot, co-immunoprecipitation and confocal microscopy analyses. The increased radiosensitivity of transient Ad-RAD50 to IR was examined in NPC cells, including MTT assay, colony formation. The molecular mechanisms of radiosensitization were confirmed by neutral comet assay and western bolts. Nude mice subcutaneous injection, tumor growth curve and TUNEL assay were used to evaluate tumor regression and apoptosis in vivo. RESULTS: Rad50 is remarkably upregulated in NPC cells after IR, implying the critical role of Rad50 in MRN functions. The transient expression of this mutant Rad50 decreased the levels of native cellular Rad50, Mre11 and Nbs1, weakened the interactions among these proteins, abrogated the G2/M arrest induced by DSBs and reduced the DNA repair ability in NPC cells. A combination of IR and mutant RAD50 therapy produced significant tumor cytotoxicity in vitro, with a corresponding increase in DNA damage, prevented proliferation and cell viability. Furthermore, Ad-RAD50 sensitized NPC cells to IR by causing dramatic tumor regression and inducing apoptosis in vivo. CONCLUSION: Our findings define a novel therapeutic approach to NPC radiosensitization via targeted native cellular Rad50 disruption.

Cancer-associated fibroblasts provide a suitable microenvironment for tumor development and progression in oral tongue squamous cancer.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is still associated with a poor prognosis due to local recurrence and metastasis. Cancer-associated fibroblasts (CAFs) play an important role in the complex processes of cancer stroma interaction and tumorigenesis. This study aims to determine the role of CAFs in the development and progression of OTSCC. METHODS: Immunohistochemistry was performed to evaluate the frequency and distribution of CAFs in 178 paraffin specimens from patients with OTSCC. Immunofluorescence, a cell proliferation assay, flow cytometry, migration and invasion assays and western blot analysis were used to study the effects of CAFs and the corresponding conditioned medium (CM) on the proliferation and invasion of OTSCC cell lines. RESULTS: Statistical analysis showed a strong correlation between the frequency and distribution of CAFs and the clinicopathological characteristics of patients with cN0 OTSCC, including pathological stage (P = 0.001), T classification (P = 0.001), and N classification (P = 0.009). Survival analysis demonstrated a negative correlation of the frequency and distribution of CAFs with the overall survival and disease-free survival of patients with cN0 tongue squamous cell cancer (P = 0.009, 0.002, respectively); Cox regression analysis showed that the presence of CAFs (relative risk: 2.113, CI 1.461-3.015, P = 0.023) is an independent prognostic factor. A functional study demonstrated that CAFs and CM from CAFs could promote the growth, proliferation, mobility, invasion and even Epithelial Mesenchymal Transition (EMT) of OTSCC cells compared with NFs and CM from NFs. CONCLUSIONS: CAFs were an independent prognostic factor for patients with OTSCC. Compared with NFs, CAFs and their CM have the ability to promote the growth, proliferation, metastasis and even EMT of OTSCC cells.

Acute spontaneous neck haematoma in children: a rare entity.

BACKGROUND: Acute spontaneous neck haematoma is rare in children. This rare type of hematoma occurs abruptly without any preceding trauma or iatrogenic damage, making it very difficult to determine the cause precisely. We report here the first two cases of acute spontaneous neck haematoma presenting with neck swelling, and discuss in this article the diagnosis and treatment strategy in our patients. CASE PRESENTATION: We report a 19-month-old girl and a 30 month-old boy with neck swelling for 10 days. There was no history of trauma, cough, excessive muscular strain or iatrogenic injury, and both patients were not on any anticoagulants or antiplatelet drugs. On initial examination, the swelling was tender, firm and not mobile on palpation. A definite diagnosis was made by hematoma puncture. Both of the haematoma resolved spontaneously in two weeks without any complications or sequelae. CONCLUSIONS: Acute spontaneous neck hematoma in children is a rare disorder without any etiology or precipitating factors. The difficulty in making an early diagnosis is mainly due to the nonspecific presenting symptoms. Conservative management and follow-up is recommended as a choice of treatment.

The Role of Tracheostomy in Anaplastic Thyroid Carcinoma.

Even though management of thyroid cancer is generally standardized and has an overall excellent long-term outcome, anaplastic thyroid cancer (ATC) continues to be a major diagnostic and therapeutic challenge. ATC is an uncommon thyroid malignancy with a poor prognosis. American Thyroid Association guidelines acknowledge the complexity of airway management in these patients. We studied the literature with the aim of providing guidance in airway management in ATC. Tracheotomy can facilitate completion of palliative treatment in those patients with ATC and stridor. Given the short life expectancy of these patients, a balanced decision must be made regarding the role and timing of tracheotomy.

[Effects of lentivirus-mediated epidermal growth factor-like domain 7 silencing on proliferation and invasion of human laryngeal carcinoma Hep-2 cells].

OBJECTIVE: To explore the effects of epidermal growth factor-like domain 7 (EGFL7) gene silencing on the proliferation and invasion ablity of laryngeal carcinoma cells. METHODS: A lentiviral vector expressing EGFL7 shRNA was constructed and transfected into human laryngeal carcinoma Hep-2 cells. The expressions of EGFL7 mRNA and protein were detected by Real-time PCR and Western blot, respectively. Cell proliferation was evaluated by CCK-8 assay, cell cycle and apoptosis were tested by flow cytometry, and cell invasion was detected by transwell invasion assay. RESULTS: The relative expression level s of EGFL7 mRNA and protein in EGFL7-SuRNA group were svgnificantly lower than control group (P < 0.001). Western blot analysis proved that the relative expression of EGFL7 protein in NC group, Lenti-NC group and Lenti-EGFL7 group was (0.39 ± 0.12),(0.36 ± 0.14) and (0.07 ± 0.04), respectively. EGFL7 expression in Lenri-EGFL7 group was significantly inhibited than NC group (P < 0.001), which confirmed that the recombinant lentivirus was successfully transfected into Hep-2 cells. The proliferation of Hep-2 cells was significantly inhibited after transfection (P < 0.01). Compared with the NC group and Lenti-NC group, the proportion of cells in S phase was significantly increased in Lenti-EGFL7 group (P < 0.01), and the proportion in G1 phase was significantly decreased (P < 0.05). Cell apoptosis assay showed that the apoptotic rate in Lenti-EGFL7 group (66.2 ± 1.28) % was significantly increased in NC group (6.09 ± 3.28) % and Lenti-NC group (9.86 ± 2.13) %. In Transwell invision assay, the mean number of cells coming through the Metrigel in Lenti-EGFL7 group was significantly decreased than in the NC group and Lenti-NC group (P < 0.01). CONCLUSION: The proliferation and invasion ablity of laryngeal carcinoma Hep-2 cells can be inhibited by siRNA mediated EGFL7 gene silencing.

[Effects of tetrandrine on enhancing radiosensitivity of human nasopharyngeal carcinoma cells].

OBJECTIVE: To study the effect and mechanism of tetrandrine (Tet) on enhancing radiosensitivity of human nasopharyngeal carcinoma cell lines in vitro. METHODS: CNE1 and CNE2 were exposed to radiation with or without Tet, the DNA damage of the cells were evaluated by neutral comet electrophoresis, and cell cycle and apoptosis were analyzed by flow cytometry. RESULTS: The mean tail movements (TM) of CNE1 treated with radiation or radiation plus Tet were (7.13 ± 3.70) (X(-) ± s) and (13.61 ± 5.45), respectively (t = 2.784, P < 0.05), and TM of CNE2 treated with radiation or radiation plus Tet were (11.52 ± 4.04) and (18.85 ± 6.18), respectively (t = 3.089, P < 0.05). With the exposure to radiation or radiation plus Tet, the percentages of CNE1 in G2 phases were (42.62 ± 2.07)% and (17.02 ± 1.87)%, respectively (t = 23.173, P < 0.01), and the percentages of CNE2 in G2 phases were (34.82 ± 2.74)% and (19.64 ± 4.82)%, respectively(t = 16.500, P < 0.01). There was no significant difference in the apoptosis rates between the cells treated with radiation or radiation plus Tet regardless of CNE1 (17.24 ± 0.99)% vs (19.11 ± 1.24)%, and CNE2 (16.68 ± 0.27)% vs (18.51 ± 2.41)% (P > 0.05). CONCLUSIONS: Tet can enhance radiosensitivity of human nasopharyngeal carcinoma cell lines. The mechanism could be related to abrogation of radiation-induced G2/M arrest and reduction of double-strand break repair capacity.

Prognostic significance of Flotillin1 expression in clinically N0 tongue squamous cell cancer.

PURPOSE: The present study aimed to investigate the clinical and prognostic significance of Flotillin1 (FLOT1) in clinically N0 tongue squamous cell cancer (cN0 TSCC). METHODS: Real-time PCR and Western blotting analyses were carried out to examine FLOT1 expression in four tongue squamous cell cancer cell lines, primary cultured normal tongue epithelial cells, and eight matched pairs of oral tongue cancer samples and adjacent non-cancerous tissue samples from the same patient. Immunohistochemistry was performed to examine FLOT1 protein expression in paraffin-embedded tissues from 181 cN0 TSCC patients. Statistical analyses evaluated the diagnostic value and the associations of FLOT1 expression with clinical parameters. RESULTS: FLOT1 mRNA and protein levels were upregulated in tongue squamous cell cancer cell lines and cancerous tissues compared with that in TEC and adjacent non-cancerous tissue samples. The level of FLOT1 protein was positively correlated with clinical stage (P = 0.001), T classification (P = 0.009), N classification (P = 0.001) and recurrence (P = 0.018). Patients with higher FLOT1 expression had shorter overall survival times. CONCLUSION: Our results suggest that overexpression of FLOT1 can be found in patients with higher pathological stage, T classification, N classification or recurrence. FLOT1 expression is associated with cN0 TSCC progression and may be valuable for the prognostic evaluation of cN0 TSCC.

Galectin-3 accelerates the progression of oral tongue squamous cell carcinoma via a Wnt/ß-catenin-dependent pathway.

The purpose of this study was to elucidate the clinicopathological significance and mechanism of action of galectin-3 in oral tongue squamous cell carcinoma (OTSCC). Here, the expression of galectin-3 was quantified in OTSCC (n = 68) and paired OTSCC and normal surrounding tissues (n = 10) using immunohistochemical staining. Tca8113 OTSCC cells were transfected with a plasmid expressing galectin-3 cDNA or siRNA against galectin-3. Cell proliferation, migration and invasion were measured using the MTT assay, Matrigel-coated Transwell migration assay and wound healing assay. The effect of galectin-3 on the Wnt/ß-catenin signaling pathway and epithelial mesenchymal transition (EMT) were investigated using a plasmid expressing the Wnt antagonist dickkopf 1 (DKK1) and Western blotting. Galectin-3 was expressed at significantly higher levels in OTSCC than the normal adjacent tissues; galectin-3 expression correlated strongly with pathological stage, pathological grade and lymph node invasion in OTSCC. Overexpression of galectin-3 promoted Tca8113 cell proliferation, migration and invasion, upregulated Wnt protein expression, activated ß-catenin and induced the EMT; knockdown of galectin-3 had the opposite effects. Co-transfection of Tca8113 cells overexpressing galectin-3 with the Wnt antagonist DKK1 reduced the ability of galectin-3 to increase cell proliferation, migration and invasion, reduced upregulation of Wnt, inhibited ß-catenin activation and abrogated the EMT, demonstrating that the Wnt/ß-catenin signaling pathway mediated the effects of galectin-3. Galectin-3 plays an important role in the progression of OTSCC via activation of the Wnt/ß-catenin signaling pathway.