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Objective: To evaluate the clinical benefits of liquid platelet-rich fibrin (PRF) in patients with temporomandibular joint (TMJ) pain and dysfunction., Methods: Forty-eight TMJs in 37 patients with painful internal derangement (ID) (Wilkes' I-V) were included. Patients were injected with 1.5-2cc of PRF within the superior joint space at 2-week intervals. Pain and subjective dysfunction were recorded using a visual analog scale. Statistical analyses were done using the ANOVA test., Results: Thirty-three of 48 TMJs (69%) showed significant reduction in pain at 8 weeks, and at 3, 6, and 12 months (Responders). Fifteen of 48 TMJs (31%) did not improve (Non-responders). The best Responders to liquid PRF injections were ID stages Wilkes' IV (78.5%) and V (100%), compared to Wilkes' I (0%), II (47%), and III (33%). A non-significant, but notable decrease in dysfunction was found., Conclusion: Preliminary findings support that liquid PRF exhibits long-term analgesic effects in most patients with painful TMJ ID.

Lung squamous cell carcinoma (LSCC) is the most common histological type of primary lung cancer. In this study, we had tested the biological role of TRIM29 in LSCC cells. TRIM29 abundance, the relationships between TRIM29 and E-cadherin and autophagy degradation related proteins in clinical tissues and six cell lines were studied with quantitative real-time PCR test (qRT-PCR) and western blot. TRIM29 overexpression treated HTB-182 cells and knockdown treated NCL-H1915 cells was used for studying cell proliferation, colony formation, migration, invasion, and the expression of epithelial mesenchymal transformation (EMT) associated biomarkers. The relationships between TRIM29 and BECN1 were investigated with western blot. TRIM29 was profoundly overexpressed in LSCC tissues and cells compared with human normal bronchial epithelial cells (HNBE). High TRIM29 expression was closely related to overall survival (OS). TRIM29 overexpression and knockdown affected LSCC activity and the expression of EMT associated biomarkers. TRIM29 can regulate the degradation of E-cadherin and autophagy of LSCC through BECN1 gene, and promote autophagy in HTB-182 and NCL-H1915 cells. Our results revealed that TRIM29 could promote the proliferation, migration, and invasion of LSCC via E-cadherin autophagy degradation. The results are useful for further study in LSCC.

Background: Laryngeal squamous cell carcinoma (LSCC) is the most common histologic subtype of laryngeal cancer characterized by a poor prognosis. Determining gene expression changes in LSCC should improve our understanding of putative risk factors and provide potential targets for therapy., Objectives: To assess differential gene expression between LSCC tissue and paired normal laryngeal tissue, and to provide gene targets for future studies of this type of laryngeal cancer., Materials and Methods: Three paired-sample groups (tumor and normal tissue) from patients with laryngeal squamous cell carcinoma were analyzed by RNA sequencing (RNA-seq)., Results: The six cDNA libraries generated raw reads ranging from 15,195,586 to 21,443,488 counts. Changes in gene expression levels were determined in 40,205 of these counts, with 18,466 deferentially expressed genes in all three groups. Compared to normal tissue, the expression levels of MMP1 and MMP2 increased significantly in tumor tissue of patients with laryngeal squamous cell carcinoma., Conclusions: Whole transcriptome sequencing revealed that MMP1 and MMP2 are highly expressed in LSCC. These genes may be useful both as biomarkers for LSCC diagnosis and as targets for therapy, as well as for increasing our understanding of LSCC tumorigenesis., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Increasing evidence has suggested that microRNAs (miRNAs) play critical roles in the initiation and development of cancers. Here, we found that miR-140-5p was significantly downregulated in both laryngeal squamous cell carcinoma (LSCC) tissues and cell lines. Decreased expression of miR-140-5p was significantly associated with the metastasis of LSCC. Overexpression of miR-140-5p inhibited proliferation and induced apoptosis of LSCC cells. Mechanistically, the fibroblast growth factor 9 (FGF9) was identified as the target of miR-140-5p. miR-140-5p bound the 3'-untranslated region (3'-UTR) of FGF9 and suppressed the expression of FGF9 in LSCC cells. Additionally, the level of FGF9 was upregulated in LSCC tissues and negatively correlated with the expression of miR-140-5p. Restoration of FGF9 attenuated the suppressive role of miR-140-5p in regulating the growth of LSCC cells. Collectively, these results indicated that the tumor suppressive function of miR-140-5p in LSCC was partially exercised by modulating the expression of FGF9.

Lung squamous cell carcinoma (LSCC) is a prevalent form of lung cancer exhibiting distinctive histological and genetic characteristics. Chromosome 3q26 copy number gain (CNG) is a genetic hallmark of LSCC present in >90% of tumors. We report that 3q26 CNGs occur early in LSCC tumorigenesis, persist during tumor progression, and drive coordinate overexpression of PRKCI , SOX2 , and ECT2. Overexpression of PRKCI , SOX2 , and ECT2 in the context of Trp53 loss is sufficient to transform mouse lung basal stem cells into tumors with histological and genomic features of LSCC. Functionally, PRKCI and SOX2 collaborate to activate an extensive transcriptional program that enforces a lineage-restricted LSCC phenotype, whereas PRKCI and ECT2 collaborate to promote oncogenic growth. Gene signatures indicative of PKCι-SOX2 and PKCι-ECT2 signaling activity are enriched in the classical subtype of human LSCC and predict distinct therapeutic vulnerabilities. Thus, the PRKCI , SOX2 , and ECT2 oncogenes represent a multigenic driver of LSCC. • 3q26 CNG and TP53 mutation associate with progression of carcinoma in situ to LSCC • PRKCI , SOX2 , and ECT2 overexpression transforms Trp53 −/− mouse lung basal stem cells • Active PKCι-SOX2 and PKCι-ECT2 signaling is required for LBSC transformation • A PKCι-SOX2 molecular signature suggests unique therapeutic vulnerabilities in LSCC Liu et al. report that three oncogenes, PRKCI , SOX2 , and ECT2 , which are coordinately amplified and overexpressed in lung squamous cell carcinoma (LSCC), can transform Trp53 −/− mouse lung basal stem cells into tumors with histological and genomic features of LSCC and drive oncogenic signaling necessary to maintain a LSCC phenotype. [ABSTRACT FROM AUTHOR]

Platelet-rich fibrin (PRF) is a blood concentrate derived from venous blood that is processed without anticoagulants by a one-step centrifugation process. This three-dimensional scaffold contains inflammatory cells and plasma proteins entrapped in a fibrin matrix. Liquid-PRF was developed based on the previously described low-speed centrifuge concept (LSCC), which allowed the introduction of a liquid-PRF formulation of fibrinogen and thrombin prior to its conversion to fibrin. Liquid-PRF was introduced to meet the clinical demand for combination with biomaterials in a clinically applicable and easy-to-use way. The aim of the present study was to evaluate, ex vivo, the interaction of the liquid-PRF constituents with five different collagen biomaterials by histological analyses. The results first demonstrated that large variability existed between the biomaterials investigated. Liquid-PRF was able to completely invade Mucograft® (MG; Geistlich Biomaterials, Wolhusen, Switzerland) and to partly invade Bio-Gide® (BG; Geistlich Biomaterials, Wolhusen, Switzerland) and Mucoderm® (MD; Botiss Biomaterials, Berlin, Germany), and Collprotect® (CP; Botiss Biomaterials, Berlin, Germany) showed only a superficial interaction. The BEGO® collagen membrane (BCM; BEGO Implant Systems) appeared to be completely free of liquid-PRF. These results were confirmed by the different cellular penetration and liquid-PRF absorption coefficient (PAC) values of the evaluated membranes. The present study demonstrates a system for loading biomaterials with a complex autologous cell system (liquid-PRF) in a relatively short period of time and in a clinically relevant manner. The combination of biomaterials with liquid-PRF may be clinically utilized to enhance the bioactivity of collagen-based biomaterials and may act as a biomaterial-based growth factor delivery system. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have been reported to play critical roles in tumorigenesis. However, the roles of circRNAs in laryngeal squamous cell carcinoma (LSCC) are still largely unknown. In our present study, we identified a novel circRNA hsa_circ_0042666, which was poorly expressed in LSCC. Low hsa_circ_0042666 expression was closely associated with advanced tumor stage, lymph-node metastasis, and poor overall survival. In vitro function assays, we showed that hsa_circ_0042666 dramatically reduced LSCC cells proliferation and invasion in vitro. In mechanism, our data indicated that hsa_circ_0042666 could competitively bind to miR-223 as a miRNA sponge to regulate TGFBR3 expression in LSCC progression. Altogether, these findings elucidated that hsa_circ_0042666 regulated LSCC cells proliferation and invasion by miR-223/TGFBR3 axis, which might provide a therapeutic strategy for the treatment of LSCC. [ABSTRACT FROM AUTHOR]

Secreted protein acidic and rich in cysteine (SPARC) plays a crucial role in the malignant progression of a number of human cancers. However, the roles of SPARC in lung squamous cell carcinoma (LSCC) remain elusive. In this present study, we first detected SPARC expression and investigated the relationship between SPARC expression and the clinicopathological attributes of LSCC patients. Then we constructed SPARC-overexpression model in LSCC cell line to explore the characteristics of SPARC in LSCC development both in vitro and in vivo. The data demonstrated a remarkably higher level of SPARC in LSCC tissues than in corresponding non-cancerous tissues and elevated SPARC expression was significantly correlated with poor outcome in LSCC patients. Moreover, a serial of phenotypic experiments indicated that SPARC overexpression substantially facilitated the growth and inhibited the apoptosis in LSCC cells and xenografts. Taken together, our results suggest that SPARC is a novel prognostic marker for LSCC prognosis and SPARC significantly promotes LSCC tumorigenesis. Targeting SPARC may provide a novel therapeutic strategy for LSCC management. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to uncover a regulatory network comprised of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in laryngeal squamous cell carcinoma (LSCC), to explore its underlying mechanisms and development, and to identify key genetic biomarkers for the prognosis of LSCC., Methods: Here, we compared mRNA, lncRNA, and miRNA expression profiles between 111 LSCC and 12 adjacent normal tissues using RNA sequencing (RNA-Seq) data from the Cancer Genome Atlas (TCGA) database. Based on the interaction information obtained from miRcode, TargetScan, miRTarBase, and miRDB, a lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was constructed using differentially expressed lncRNAs (DElncRNA), miRNAs (DEmiRNA), and mRNAs (DEmRNA). By assessing the functional enrichment of DEmRNAs in this network, the potential underlying mechanisms were explored. In addition, Kaplan-Meier survival analysis was used to assess genetic biomarkers related to the prognosis of LSCC patients., Results: Upon comparing LSCC and control tissues, 1640 DElncRNAs, 75 DEmiRNAs, and 3217 DEmRNAs were identified. Based on the prediction between lncRNA-miRNA and miRNA-mRNA relationships, we constructed a ceRNA network comprised of 93 lncRNAs, nine miRNAs, and nine mRNAs. This network predicted that two lncRNAs (AC016773.1 and C00299), two mRNAs (DIO1 and STC2), and two miRNAs (hsa-mir-137 and hsa-mir-210) were significant biomarkers of LSCC prognosis according to thorough topological and survival analyses (P < .05)., Conclusion: Through a ceRNA network analysis, our study identifies new lncRNAs, miRNAs, and mRNAs, which can be used as potential biomarkers of LSCC and as therapeutic targets for treating LSCC, thus laying a foundation for future clinical studies., (© 2019 Wiley Periodicals, Inc.)

Laryngeal squamous cell cancer (LSCC) is a highly aggressive malignancy in the head and neck region. Recent studies have shown that long noncoding RNAs (lncRNAs) are novel transcripts that play an important role in the progression of LSCC. However, the overall pathophysiological regulation of lncRNAs to LSCC is largely unknown. The present study aimed to determine the clinical significances of lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) and to identify its potential roles in LSCC. Quantitative real-time PCR (qRT-PCR) showed that FTH1P3 expression was significantly up-regulated in LSCC tissues than that in non-neoplastic tissues. High FTH1P3 expression was positively correlated with the poor differentiation, high T classification, positive lymph node metastasis, and advanced clinical stage. Overall survival analysis showed that high levels of FTH1P3 predicted a poor prognosis in LSCC patients. Moreover, elevated expression of FTH1P3 was found to increase LSCC cell proliferation, migration and invasion, and to inhibit cell apoptosis, Conversely, knockdown of FTH1P3 suppressed LSCC cell proliferation, migration and invasion, and induced cell apoptosis. In addition, overexpression of FTH1P3 resulted in an increase in cells in S phase and a decrease in cells in G0/G1 phase, whereas inhibition of FTH1P3 did the opposite effects. Taken together, these results suggested that increased expression of FTH1P3 predicts a poor prognosis and promotes aggressive phenotypes of LSCC by regulating cell proliferation, migration, invasion, apoptosis, and cell cycle, indicating FTH1P3 may serve as a promising therapeutic biomarker for the treatment of LSCC., (© 2019 The Author(s).)

Background: Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with laryngeal squamous cell carcinoma (LSCC) are not well understood. In the present study, we attempted to provide novel basis for targeted therapy for LSCC from the aspect of circRNA-microRNA (miRNA)-mRNA interaction. Methods: We investigated the expression of circRNAs in three paired LSCC tissues and adjacent non-tumor tissues by microarray analysis. Differentially expressed circRNAs were identified between LSCC tissues and non-cancerous matched tissues, including 527 up-regulated circRNAs and 414 down-regulated circRNAs. We focused on hsa&#95;circ&#95;0059354, which is located on chromosome 20 and derived from RASSF2, and thus we named it circRASSF2. Results: circRASSF2 was found to be significantly up-regulated in LSCC tissues and LSCC cell lines compared with paired adjacent non-tumorous tissues and normal cells. Moreover, knockdown of circRASSF2 significantly inhibited cell proliferation and migration in vitro , which was blocked by miR-302b-3p inhibitor. Bioinformatics analysis predicted that there is a circRASSF2/miR-302b-3p/ insulin-like growth factor 1 receptor (IGF-1R) axis in LSCC progression. Dual-luciferase reporter system validated the direct interaction of circRASSF2, miR-302b-3p, and IGF-1R. Western blot verified that inhibition of circRASSF2 decreased IGF-1R expression. Furthermore, silencing circRASSF2 suppressed LSCC growth in vivo Importantly, we demonstrated that circRASSF2 was up-regulated in serum exosomes from LSCC patients. Altogether, silencing circRASSF2 suppresses progression of LSCC by interacting with miR-302b-3p and decreasing inhibiting IGF-1R expression. Conclusion: In conclusion, these data suggest that circRASSF2 is a central component linking circRNAs to progression of LSCC via an miR-302b-3p/IGF-1R axis., (© 2019 The Author(s).)

Background: To investigate the effect of DACH1 over-expression on proliferation and invasion of laryngeal squamous cell carcinoma (LSCC). Methods: The 120 cases of LSCC tumors and 114 adjacent non-neoplastic tissues were collected to detect the expression of DACH1 by immunohistochemistry. The changes of DACH1 expression from each group were assessed and correlated to the clinical parameters of the patients. Plasmid-DACH1 was transfected into Hep-2 cells to up-regulate the expression of DACH1C. Real-time PCR, Western blot, CCK8 and transwell assay were used to verify the cell proliferation and invasion after plasmid-DACH1 transfection. Results: The results indicated that DACH1 was downregulated in LSCC tissues as compared to corresponding adjacent non-neoplastic tissues. Decreased expression of DACH1 was found in the tumors upraglottic tumor, lymph node metastases, T3–4 stage and advanced clinical stage. In Hep-2 cells, transfection with plasmid-DACH1 could suppress cell proliferation, invasion and induce G1 phase extension in cell cycle. Conclusions: DACH1 may act as a tumor suppressor gene and could be a potential target for therapeutic intervention of LSCC. [ABSTRACT FROM AUTHOR]

Background: Laryngeal Squamous Cell Carcinoma (LSCC) is a malignant epithelial tumor with poor prognosis and its incidence rate increased recently. rLj-RGD3, a recombinant protein cloned from the buccal gland of Lampetra japonica, contains three RGD motifs that could bind to integrins on the tumor cells., Methods: MTT assay was used to detect the inhibitory rate of viability. Giemsa's staining assay was used to observe the morphological changes of cells. Hoechst 33258 and TUNEL staining assay, DNA ladder assay were used to examine the apoptotic. Western blot assay was applied to detect the change of the integrin signal pathway. Wound-healing assay, migration, and invasion assay were used to detect the mobility of Hep2 cells. H&E staining assay was used to show the arrangement of the Hep2 cells in the solid tumor tissues., Results: In the present study, rLj-RGD3 was shown to inhibit the viability of LSCC Hep2 cells in vitro by inducing apoptosis with an IC50 of 1.23µM. Western blot showed that the apoptosis of Hep2 cells induced by rLj- RGD3 was dependent on the integrin-FAK-Akt pathway. Wound healing, transwells, and western blot assays in vitro showed that rLj-RGD3 suppressed the migration and invasion of Hep2 cells by integrin-FAKpaxillin/ PLC pathway which could also affect the cytoskeleton arrangement in Hep2 cells. In in vivo studies, rLj-RGD3 inhibited the growth, tumor volume, and weight, as well as disturbed the tissue structure of the solid tumors in xenograft models of BALB/c nude mice without reducing their body weights., Conclusion: These results suggested that rLj-RGD3 is an effective and safe suppressor on the growth and metastasis of LSCC Hep2 cells from both in vitro and in vivo experiments. rLj-RGD3 might be expected to become a novel anti-tumor drug to treat LSCC patients in the near future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Impact Statement: This study evaluated for the first time the composition and bioactivity of platelet-rich fibrin (PRF) produced from small animal blood by reducing the initial blood volume needed for the preparation of PRF from 10 to 3 mL. The results showed that different preparation protocols of PRF produced using 3 mL of animal blood exhibit the same composition, properties, and bioactivity as PRF prepared using 10 mL human blood.

Background: Non-small cell lung carcinomas (NSCLCs), mainly adenocarcinoma (AC) and squamous cell carcinoma (LSCC), account for about 80% of all lung cancer cases. One of the proteins involved in NSCLC progression may be special AT-rich binding protein 1 (SATB1), a potent transcriptional regulator, able to control the expression of whole sets of genes simultaneously. SATB1 has been found to be associated with aggressive phenotype and poor prognosis in numerous malignancies, including breast, colon, ovary and prostate cancer. However, its role in NSCLC is still not fully understood. The aim of this study was to investigate the expression of SATB1 protein and mRNA in NSCLC and non-malignant lung tissue (NMLT) samples, as well as to determine possible relationships of SATB1 expression with both the expression of Ki-67 and the clinicopathological data of the patients., Materials and Methods: The study was performed on 277 NSCLC (158 AC, 119 LSCC) and 20 NMLT samples., Results: We observed increased SATB1 immunoreactivity in NSCLC when compared to NMLT, and in LSCC when compared to AC cases. We also noted that an elevated SATB1 immunoreactivity was associated with a poor degree of AC differentiation, whereas in LSCC, an inverse relationship was observed. Our analyses revealed that the expression of SATB1 positively correlated with Ki-67 index in NSCLC and LSCC, but not in AC cases. Finally, we found that high SATB1 expression was associated with a better overall survival of patients with NSCLC., Conclusion: SATB1 plays diverse roles in different NSCLC subtypes, and its expression may have a prognostic significance for patients with these tumours., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The aim of this study was to investigate the association between piezo type mechanosensitive ion channel component 2 ( PIEZO2 )-promoter methylation with and its clinical value for laryngeal squamous cell carcinoma (LSCC). Quantitative methylation-specific polymerase chain reaction technology was applied to measure PIEZO2 promoter methylation levels from 99 LSCC patients. Inclusive in the analysis were 133 (117 LSSC and 16 normal) samples from The Cancer Genome Atlas (TCGA). Our results showed significantly higher levels of PIEZO2 promoter methylation in LSCC than normal tissues (our cohort: P = 2.94E-21; TCGA cohort: P = 1.07E-19). In addition, PIEZO2 methylation was significantly associated with gender, differentiation, tumor (T) stage, lymph node metastasis, and clinical stage. The areas under the receiver characteristic curves (AUCs) based on our cohort and TCGA cohort were 0.917 and 0.978, respectively. Meanwhile, our study confirmed that PIEZO2 promoter hypermethylation could independently predict a poorer overall survival of LSCC patients (hazard ratio = 6.671; 95% confidence interval = 2.087-21.324). In conclusion, our study revealed that PIEZO2 promoter hypermethylation was a risk factor and might be involved in progression and metastasis, as well as serve as a potential clinical biomarker of LSCC., Competing Interests: None., (IJCEP Copyright © 2017.)

Background: P38MAPK has been investigated as a tumor-related signaling molecule because of its apparent association with tumorigenesis. This study aimed to investigate P38MAPK expression and its role in lung squamous carcinoma (LSCC)., Methods: The expression of P38MAPK and phosphorylated P38 (P-P38) in LSCC tissues and cells was examined by Western blot, real-time PCR, and immunohistochemistry. The influence of P38MAPK inhibitor SB203580 on the proliferation of LSCC cells was detected by MTT and flow cytometry., Results: The expression of P-P38 in LSCC tissues and cells was lower than that in cancer-adjacent normal tissues and normal bronchial epithelial cells (P<0.05). In addition, the expression of P-P38 was downregulated in LSCC tissues of poor differentiation, stages III and IV, and with lymph node metastasis compared with the LSCC tissues of well differentiation, stages I and II, and without lymph node metastasis (P<0.05). Moreover, the cell proliferation of LSCC SK-MES-1 cells treated by P38MAPK inhibitor SB203580 significantly increased in a concentration-dependent manner compared with that of SK-MES-1 cells without SB203580 (P<0.05). The inhibition of P38MAPK promoted the transition of the S phase to the G2 phase., Conclusions: P-P38 was poorly expressed in LSCC tissues and cells. Its low expression was correlated with low-grade differentiation, lymph node metastasis, and advanced stage of LSCC. Inhibition of P38MAPK expression could significantly increase the proliferation of LSCC cells by promoting the transition of the S phase to the G2 phase., Competing Interests: None.

N-myc downstream-regulated gene 3 (NDRG3), which belongs to the NDRG family, is believed to play important roles in human cancer. In this present study, one-step quantitative reverse transcription-polymerase chain reaction (qPCR) and western blotting tests with 10 fresh-frozen laryngeal squamous cell carcinoma (LSCC) samples and immunohistochemistry (IHC) analysis in 109 LSCC cases were performed to investigate the relationship between NDRG3 expression and the clinicopathological characteristics of LSCC. Results demonstrated that NDRG3 mRNA and protein expression levels were statistically higher in LSCC tissues than that in non-cancerous tissues (all p<0.05). IHC data showed that the NDRG3 protein expression was remarkably correlated with lymph node metastasis (p=0.043). Univariate and multivariate survival analysis implied that high NDRG3 expression (p=0.004), lymph node metastasis (p=0.044) and TNM stage (p=0.020) were independently associated with the unfavourable overall survival of patients with LSCC. The above findings suggested that NDRG3 may be identified as a novel biomarker predicting the prognosis of LSCC., (Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Lysosome-associated membrane protein-1 (LAMP1) has been suggested to play complicated roles in cancer development and metastasis. The aim of this study was to explore the expression of LAMP1 in laryngeal squamous cell carcinoma (LSCC) and investigate the relationship between LAMP1 expression and clinicopathological characteristics in LSCC patients. One-step quantitative reverse transcription PCR (qPCR) tests (20 fresh LSCC and non-cancerous tissue samples) and immunohistochemistry (IHC) analyses (137 paraffin-embedded LSCC and non-cancerous tissue samples) were performed to evaluate the LAMP1 expression in both mRNA and protein levels. Results showed that the expression of LAMP1 in LSCC tissues was significantly higher than that in non-cancerous tissues. Furthermore, the expression level of LAMP1 protein was statistically associated with lymph node metastasis and TNM stage. Results of Kaplan-Meier survival and Cox regression analyses revealed that LSCC patients with high LAMP1 cytoplasmic expression (p=0.044), high cytoplasmic+low mesenchymal expression of LAMP1 (H+L) (p=0.015) and histopathological grade (p=0.014) encountered poor overall survival. The data implied that high LAMP1 expression is associated with unfavourable prognosis in LSCC patients, and LAMP1 may be identified as a novel prognostic biomarker., (Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Eg5 is identified as a microtubule-dependent motor protein and has been suggested to play important role in cancer development. The aim of this study was to detect the expression of Eg5 and its clinicopathological characteristics in patients with laryngeal squamous cell carcinoma. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) test with 20 fresh-frozen LSCC samples and immunohistochemistry (IHC) analysis in 137 LSCC cases were performed to investigate the relationship between Eg5 expression and the clinicopathological characteristics of LSCC. The Eg5 mRNA and protein levels were significantly higher in LSCC tissues compared with corresponding non-cancerous tissues (p < 0.05). Eg5 protein expression was significantly correlated to lymph node metastasis (p = 0.021) and TNM stage (p = 0.030). Kaplan-Meier survival and multivariate analysis with Cox regression model indicated that high Eg5 expression (p = 0.031) and TNM stage (p = 0.011) were independent factors to predict unfavourable prognosis for patients with LSCC. The data suggested that Eg5 may be identified as a novel prognostic biomarker and targeting Eg5 seems to be a novel strategy for LSCC treatment., (Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Sex-determining region Y (SRY)-box protein 1 (SOX 1) has been reported to have the inhibiting effects on various cancer cells; however, the expression and effect of SOX 1 on laryngeal squamous cell carcinoma (LSCC) have not been determined. Therefore, the aim of this study was to assess the anti-proliferation and metastatic effects of SOX 1 and its related mechanisms on LSCC. According to our present study, first, we found that overexpression of SOX 1 could significantly inhibit proliferation and promote apoptosis in Tu212 cells. Additionally, overexpression of SOX 1 suppressed the migration and invasion potential of Tu212 cells via regulating Wnt/β-catenin pathway. Finally, we demonstrated for the first time that overexpression of SOX 1 could downregulate the expression of SOX 2, and co-expression of SOX 1 and SOX 2 could reverse the anti-tumor effect of SOX 1. In conclusion, our studies suggested that SOX 1 suppressed cell growth and invasion in Tu212 cells by inhibiting Wnt/β-catenin pathway, and the anti-tumor effect of SOX 1 could be weakened by SOX 2, which may be a potential molecular basis for clinical treatment of LSCC.

Background: To evaluate the association of MMP11 and P14(ARF) expression in laryngeal squamous cell carcinoma (LSCC) with clinical pathological characteristics and survival., Methods: The mRNA and protein levels for both genes were determined in 65 LSCC patients. A log-rank test and Cox models were used to compare survival among different groups., Results: The mRNA expressions of MMP11 and P14(ARF) were significantly different between LSCC and their corresponding adjacent tissues (All P < 0.001). The expressions of MMP11 and P14(ARF) were correlated with several clinical characteristics (All P < 0.05). Patients with low MMP11 and high P14(ARF) expression had significantly better survival compared with those with high MMP11 and low P14(ARF) expression, respectively (All P < 0.05). The patients with surgery only had significantly better survival than those with chemoradiotherapy (log rank: P = 0.016), particularly in patients with low MMP11 and high P14(ARF) expression (log rank: P = 0.006). Furthermore, multivariable analysis showed that patients with low MMP11 and high P14(ARF) expression alone had a significantly reduced risk of death compared with those with high MMP11 and low P14(ARF) expression. The reduced risk for overall death was pronounced for patients with low and high expression of both genes (HR, 0.2; 95% CI, 0.1-0.5) compared with any other co-expression status of both genes, particularly for patients with surgery only (HR, 0.1; 95% CI, 0.0-0.9)., Conclusion: These results suggest that altered expression of MMP11 and P14(ARF) in tumors may individually, or in combination, predict poor prognosis of LSCC, particularly for patients with surgery only.

Background: The expression of P21 and TBX2 in laryngeal squamous cell carcinoma (LSCC) and their corresponding adjacent normal laryngeal tissues, as well as their association with clinical pathological features and survival remain unclear., Method: we used the RT-PCR and immunohistochemistry to detect their mRNA and protein levels in 75 LSCC patients. We also use log-rank test and Cox models to compare survival among different groups., Results: The mRNA expression level of TBX2 was up-regulated, while P21 was down-regulated in LSCC compared with their matched adjacent laryngeal tissues (All P < 0.001). The expression of P21 was correlated with tumor stage, lymph node metastasis and smoking; and TBX2 expression was associated with lymph node metastasis, differentiation degree and smoking (All P < 0.05). Patients with high TBX2 and low P21 expression had significantly worse survival than those with low TBX2 and high P21 expression, respectively (All P < 0.05). A significant correlation between expression of TBX2 and P21 (Pearson, P < 0.05) was observed. Furthermore, multivariable analysis showed that patients with low TBX2 and high P21 expression alone had a significantly reduced risk for overall death compared with those with low TBX2 and high P21 expression. The risk for overall death was even lower for patients with both low and high expression of both genes than any other co-expression status of both genes (HR, 0.1; 95% CI, 0.0-0.9)., Conclusion: These results suggest that abnormal expression of P21 and TBX2 in tumors may jointly, or individually, predict poor prognosis of LSCC.

Objectives: Metastasis is the most significant prognostic factor for laryngeal carcinoma which necessitates the identification of molecular alterations associated with metastasis. The identification of such molecular alterations will not only prove useful in treatment but also provide insight into mechanisms of cancer metastasis. The studies conducted so far have not specifically focused on metastasis or invasion pathways. Therefore we investigated the expression profiles with a pathway focused approach., Materials and Methods: Total RNA was extracted from 36 laryngeal tumors and paired cancer free tissue. Expression levels of 88 genes were determined using a PCR array system following cDNA synthesis. Obtained data was used for the calculation of altered expression levels, facilitating relevant algorithms. Significant alterations were determined according to their p-value obtained by Student's t-test., Results: Sixteen genes have shown altered expression when compared with adjacent cancer-free tissue. 2 of these 16 genes have shown differential expression in tumors with neck metastasis in respect to non-metastatic tumors., Conclusion: We found that TGFB1, TIMP1, c-Myc, SPARC, COL4A2 and SOX4 show altered expression in laryngeal tumors. c-Myc and SOX4 expression is decreased as laryngeal tumors switch to metastatic phenotype., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The tissue inhibitor of metalloproteinase-1 (TIMP-1) is an endogenous inhibitor of matrix metalloproteinases and potential biomarker of various types of human cancers. However, the association between TIMP-1 expression and the clinical features of laryngeal squamous cell carcinoma (LSCC) is barely investigated. In this study, one-step quantitative reverse transcription-polymerase chain reaction and immunohistochemical staining with tissue microarrays were employed to evaluate the relationship between TIMP-1 expression and the clinicopathological characteristics of LSCC. Results showed that the TIMP-1 mRNA and protein expression levels were significantly higher in LSCC than in the corresponding non-cancerous tissues (p<0.05). TIMP-1 protein expression in LSCC was associated with tumor differentiation (p=0.012) and overall survival (p=0.043). Kaplan-Meier method and Cox multi-factor analysis suggested that high TIMP-1 expression (p=0.008) and positive lymph node metastasis (p=0.029) were significantly associated with the poor survival of patients with LSCC. These data indicated that TIMP-1 may be identified as a prognostic marker of LSCC.

MiRNAs are small, noncoding RNA molecules that act as posttranscriptional regulators of gene expression and function as important regulators in cancer-related processes. The miR-19a is overexpressed in various cancers and has been causally related to cellular proliferation and growth. To determine whether miR-19a plays a role in laryngeal squamous cell carcinoma (LSCC), we used quantitative real time PCR to detect miR-19a expression in LSCC tissues. We found that miR-19a is overexpressed in LSCC and correlated with neck nodal metastasis, poor differentiation and advanced stage. Statistical analysis suggests that higher level of miR-19a was associated with reduced overall survival. In vitro functional study showed that inhibition of miR-19a by antisense oligonucleotides (ASO) led to apoptosis and reduction of cell proliferation in LSCC cells. Furthermore, growth of LSCC xenograft tumors was significantly suppressed by repeated injection of ASO-miR-19a lentivirus. The TUNEL stain and transmission electron microscopy also detected increased apoptotic cells in ASO-miR-19a treated LSCC xenografts. In addition, both realtime PCR and western blot showed ASO-miR-19a can upregulate TIMP-2 expression and this suggests miR-19a is related with TIMP-2 pathway in LSCC cells. Taken together, these data suggest that miR-19a plays an oncogenic role in the progression of LSCC, and may serve as a biomarker or therapeutic target for patients with LSCC.

The vibration velocity of the lateral semicircular canal and the cochlear promontory was measured on 16 subjects with a unilateral middle ear common cavity, using a laser Doppler vibrometer, when the stimulation was by bone conduction (BC). Four stimulation positions were used: three ipsilateral positions and one contralateral position. Masked BC pure tone thresholds were measured with the stimulation at the same four positions. Valid vibration data were obtained at frequencies between 0.3 and 5.0 kHz. Large intersubject variation of the results was found with both methods. The difference in cochlear velocity with BC stimulation at the four positions varied as a function of frequency while the tone thresholds showed a tendency of lower thresholds with stimulation at positions close to the cochlea. The correlation between the vibration velocities of the two measuring sites of the otic capsule was high. Also, relative median data showed similar trends for both vibration and threshold measurements. However, due to the high variability for both vibration and perceptual data, low correlation between the two methods was found at the individual level. The results from this study indicated that human hearing perception from BC sound can be estimated from the measure of cochlear vibrations of the otic capsule. It also showed that vibration measurements of the cochlea in cadaver heads are similar to that measured in live humans., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Pervasive transcription occurs in the human genome to generate thousands of RNA transcripts, and accumulating evidence suggested that the RNA molecules, without protein coding ability, have important roles in diverse biological functions. Long non-coding RNA (lncRNA), with size larger than 200 nt, is a new class of the non-coding RNA that contributes to cancer development and progression. Roles for several lncRNAs in cancers have been characterized and strategies targeting them have inhibitory effects to malignant cells in vitro and in vivo. These findings point to the potential of lncRNAs as prospective novel therapeutic targets in cancers. Recent advance in biological drugs, led by nucleic acid drugs (i.e. siRNAs, antisense oligonucleotides), suggest directions for the development of cancer therapies targeting lncRNAs. Here, we discuss the characteristics of lncRNAs regarding their synthesis, stability and functional role in cells, and emphasize their unique properties that determine their molecular functions. We then discuss the association of lncRNAs with cancers, and illustrate the anticancer effects induced upon modulating the level and function of lncRNAs. We also revisit established methods for targeting RNA molecules and discuss new agents and strategies to attenuate lncRNAs in cancer., (Copyright © 2013 Elsevier Ltd. All rights reserved.)