Oral Malignant Acanthosis Nigricans: An Early Diagnostic Sign for Ovarian Carcinoma: A Case Report.

Acanthosis nigricans (AN) is a dermatological condition characterised by the symmetrical development of velvety, hyperpigmented plaques predominantly in intertriginous areas such as the axillae, neck, inframammary regions, and groin. The malignant variant of AN is frequently associated with internal malignancies, particularly gastric adenocarcinoma, accounting for 55-61% of cases. Patients exhibiting characteristic skin lesions are commonly initially evaluated in dermatology departments. This case report details a rare instance of a patient diagnosed with malignant acanthosis nigricans, presenting with only a mild form of florid oral papillomatosis concomitant with ovarian carcinoma. The early identification and management of these subtle clinical manifestations enabled timely intervention for the tumor, resulting in patient survival. There are few reported cases of malignant acanthosis nigricans associated with ovarian cancer. Oral medicine specialists should be cognisant of conditions manifesting as extensive oral papillary hyperplasia, and the possibility of an underlying malignant disease should be considered, particularly in cases of elderly-onset AN presenting exclusively with oral lesions.

Inter-relationships of galectin-3 and NLR family pyrin domain containing 3 inflammasomes with oral lichen planus: a preliminary cross-sectional in vitro study.

BACKGROUND: The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome has been reported to be highly expressed in oral lesions with the potential for malignant development such as oral lichen planus (OLP). And the NLRP3 inflammasome can be activated by galectin-3 (Gal-3) in immune-mediated chronic inflammatory diseases. This study aimed to explore the inter-relationships among Gal-3, NLRP3 inflammasome, and OLP. METHODS: A cross-sectional analysis of oral biopsy specimens from 30 patients with Erosive OLP and 30 healthy controls was performed. Immunohistochemical staining was used to evaluate the expression of Gal-3 and NLRP3 inflammasome. Two-sample t-test and Pearson correlation test were applied to analyze the data. RESULTS: Erosive OLP patients had significantly higher Gal-3 levels compared with controls (p < 0.0001). A similar pattern emerged for NLRP3 inflammasome. In the overall sample, a positive correlation was observed between Gal-3 and NLRP3 (r = 0.92, p < 0.01). CONCLUSIONS: Patients with Erosive OLP lesions showed increased protein expression levels of Gal-3. A positive correlation was observed between Gal-3 and NLRP3 inflammasome.

HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway.

Laryngeal squamous cell carcinoma (LSCC) is an aggressive and lethal malignant neoplasm with extremely poor prognoses. Accumulating evidence has indicated that preferentially expressed antigen in melanoma (PRAME) is correlated with several kinds of cancers. However, there is little direct evidence to substantiate the biological function of PRAME in LSCC. The purpose of the current study is to explore the oncogenic role of PRAME in LSCC. PRAME expression was analyzed in 57 pairs of LSCC tumor tissue samples through quantitative real-time PCR, and the correlation between PRAME and clinicopathological features was analyzed. The result indicated that PRAME was overexpressed in the LSCC patients and correlated with the TNM staging and lymphatic metastasis. The biological functions and molecular mechanism of PRAME in LSCC progression were investigated through in vitro and in vivo assays. Functional studies confirmed that PRAME facilitated the proliferation, invasion, migration, and epithelial-mesenchymal transition of LSCC cells, and PRAME also promoted tumor growth in vivo. HDAC5 was identified as an upstream regulator that can affect the expression of PRAME. Moreover, PRAME played the role at least partially by activating PI3K/AKT/mTOR pathways. The above findings elucidate that PRAME may be a valuable oncogene target, contributing to the diagnosis and therapy of LSCC.

Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6.

Long noncoding RNAs (lncRNAs) have an effect on the occurrence and progression of a considerable number of diseases, especially cancer. Existing research has suggested that MAGI2 antisense RNA 3 (MAGI2-AS3) takes on a critical significance in the development of hepatocellular carcinoma and lung cancer. However, the functions of MAGI2-AS3 in laryngeal squamous cell carcinoma (LSCC) remain unclear. In this study, MAGI2-AS3 expression level in LSCC tissue and cell lines was detected, and the effect of MAGI2-AS3 overexpressed on LSCC phenotypes and the possible influence mechanisms were examined. MAGI2-AS3 was downregulated in the tissues of LSCC patients versus non-tumor tissues, and it was correlated with advanced TNM (tumor, node, metastasis) stage and lymph node metastases, as indicated by the results of this study. MAGI2-AS3 inhibited the proliferation, migration, and invasion of LSCC cells in vitro and in vivo. Furthermore, the hypermethylation level of the MAGI2-AS3 promoter region was indicated by bisulfite genomic sequencing and methylation-specific polymerase chain reaction, such that MAGI2-AS3 expression was downregulated. Besides, MAGI2-AS3 promoter hypermethylation was regulated by DNA methyltransferase 1 (DNMT1), and MAGI2-AS3 expression was reversed by 5-Aza-2'-deoxycytidine (5-Aza). Moreover, the result of the RNA pull-down experiment suggested that 38 proteins were enriched in the MAGI2-AS3 group versus the control group in TU177 cells. To be specific, SPT6 (ie, a conserved protein) was enriched by fold change >10. SPT6 knockdown reduced the antitumor effect of MAGI2-AS3 in TU177 and AMC-HN-8 cells. Meanwhile, SPT6 overexpression inhibited the proliferation, metastasis, and invasion of TU177 and AMC-HN-8 cells. As revealed by the above findings, DNMT1-regulated MAGI2-AS3 promoter hypermethylation led to downregulated MAGI2-AS3 expression, such that the presence and progression of LSCC were inhibited in an SPT6 binding-dependent manner.

Interleukin-6 released by oral lichen planus myofibroblasts promotes angiogenesis.

Oral lichen planus (OLP), defined as a potential for malignant transformation, is a chronic inflammatory disease in which abnormal angiogenesis serves a role in the malignant changes of the disease. OLP-associated fibroblasts (OLP-MFs), derived from the stroma of OLP tissues, are characterized by the presence of myofibroblasts and contribute to the secretion of pro-inflammatory cytokines, which may be involved in the molecular pathogenesis of OLP. However, the associated mechanisms of angiogenesis in OLP remain unknown. The present study aimed to verify the expression of intercellular adhesion molecular 1, vascular cell adhesion molecule 1, VEGF and CD34 in OLP, and to investigate whether IL-6 secreted by OLP-MFs promoted OLP angiogenesis and the effect of its corresponding antibody inhibition. The results of the experiments demonstrated that inflammation was present and OLP upregulated the secretion of IL-6 by OLP stromal fibroblasts, thereby enhancing OLP angiogenesis. Anti-IL-6 receptor antibody inhibited OLP-stroma IL-6 signaling and suppressed OLP angiogenesis. The antibody inhibited the inflammatory response by inhibiting the secretion of inflammatory factors, including IL-6, to suppress angiogenesis and reduce disease progression, thus indicating that this could be a potential target to develop a treatment for OLP.

Identification of MSC-AS1, a novel lncRNA for the diagnosis of laryngeal cancer.

PURPOSE: Our study was aimed to identify potential lncRNAs related to laryngeal cancer (LC) and explore their potential regulatory mechanisms. METHODS: RNA sequencing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to identify differentially expressed genes (DEGs). Receiver operating characteristic (ROC) curve analysis was performed to analyze the sensitivity and specificity of differentially expressed lncRNAs (DElncRNAs) as biomarkers. Weighted gene co-expression network analysis (WGCNA) was applied to identify co-expressed DElncRNAs and differentially expressed mRNAs (DEmRNAs) associated with clinical indicators. We performed functional enrichment analysis on target genes and constructed a lncRNA-miRNA-mRNA ceRNA network. The expression of lncRNA and mRNAs in ceRNA network were validated via RT-qPCR. RESULTS: By differential expression analyzing TCGA and GEO data, 6 up-regulated DElncRNAs were consistently identified, and their predictive performance were suggested to be considerable via ROC curve. 1998 DEmRNAs and 6 lncRNAs were involved in the construction of WGCNA network, in which the MEblue module was positively correlated with clinical stage. Functional enrichment analysis of this module suggested that the functions of DEmRNAs were closely involved in PI3K/Akt pathway. A ceRNA network composed of MSC-AS1, miR-429, COL4A1 and ITGAV was constructed. It was verified by RT-qPCR that the lncRNA and mRNAs in the ceRNA network were highly expressed in multiple LC tissues. CONCLUSIONS: This study identified lncRNA MSC-AS1 as a potential biomarker of LC. Besides, we constructed a ceRNA network, which provides a basis for the research of ceRNA in LC.

lncRNA RASSF8­AS1 suppresses the progression of laryngeal squamous cell carcinoma via targeting the miR­664b­3p/TLE1 axis.

Long non­coding (lnc)RNAs have been found to play a crucial role in tumor progression. The present study aimed to investigate the association between lncRNA RASSF8­AS1 and laryngeal squamous cell carcinoma (LSCC) and the underlying mechanisms. Reverse transcription­quantitative PCR was used to measure the mRNA expression level of RASSF8­AS1, microRNA(miR)­664b­3p and transducin­like enhancer of split 1 (TLE1) in LSCC. The associations between RASSF8­AS1 and miR­664b­3p, and between miR­664b­3p and TLE1 were investigated using a dual luciferase reporter assay, while the former was further verified using an RNA immunoprecipitation (RIP) assay. The association between RASSF8­AS1 and miR­664b­3p on cell biological functions was investigated in vitro using MTS, colony formation and Transwell assays. The RASSF8­AS1 mRNA expression level was decreased in LSCC cell lines and carcinoma tissues, while overexpression of RASSF8­AS1 reduced the migration, invasion and proliferation abilities of LSCC cells. Furthermore, luciferase and RIP assays confirmed that RASSF8­AS1 was a competitive endogenous (ce)RNA by sponging miR­664b­3p to activate TLE1. miR­664b­3p was negatively modulated by RASSF8­AS1; however, TLE1 was positively regulated by RASSF8­AS1. Functionally, RASSF8­AS1 acted as a ceRNA to upregulate TLE1 by sponging miR­664b­3p. In conclusion, the RASSF8­AS1/miR­664b­3p/TLE1 axis acts by suppressing LSCC progression and may provide a novel insight for the molecular mechanism of LSCC.

Aberrant DNA hypermethylation-silenced LINC00886 gene accelerates malignant progression of laryngeal carcinoma.

BACKGROUND: Long noncoding RNAs (lncRNAs) play crucial role in formation and progression of tumors. DNA methylation has become increasingly recognized as a frequent event of epigenetic alterations and one of the primary mechanisms of gene inactivation. The research aims to investigate the biofunction of a novel lncRNA in LSCC. METHODS: qRT-PCR, BGS, and MSP methods were employed to measure the relative expression level and methylation status of LINC00886. Additionally, we examined the effects of LINC00886 on cells proliferation and invasion using LINC00886 over-expression. Nude mouse xenograft models were conducted to assess LINC00886 effects on LSCC growth in vivo. High-throughput sequencing technology and Western blot assay were carried out to have an in-depth study of the downstream target genes and signaling pathways in which LINC00886 may participate. RESULTS: The remarkable downregulation of LINC00886 was observed in tumor tissues and laryngeal cancer cell lines. The significant decrease of LINC00886 was correlated with pathological grade in LSCC tissues. The expression level of LINC00886 in laryngeal cancer cell lines was significantly reversed by 5-Aza-dC. The occurrence of aberrant methylation events in the LINC00886 TSS was more responsible for the down-expression of LINC00886. Over-expression of LINC00886 dramatically mitigated cell proliferation, migration, and invasion in vitro as well as suppressed tumor growth in vivo. LINC00886 may be associated with VEGFA/PI3K/AKT signaling pathways and epithelial-mesenchymal transition (EMT) process. CONCLUSIONS: We provide the first evidence of the involvement of LINC00886 in laryngeal carcinoma, which was downregulated due to methylation of the promoter region and served as tumor suppressor genes. LINC00886 is expected to become a novel biomarker in laryngeal carcinoma.

Aberrant methylation-mediated downregulation of lncRNA SSTR5-AS1 promotes progression and metastasis of laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is among the most common malignant tumors with poor prognosis. Accumulating evidences have identified the important roles of long noncoding RNAs (lncRNAs) in the initiation and progression of various cancer types; however, the global lncRNAs expression profile for metastatic LSCC is limited. RESULTS: In the present study, we screen expression profiles of lncRNAs in advanced LSCC patients with paired tumor tissues and corresponding normal tissues by microarrays. We identify numerous differentially expressed transcripts, and after the necessary verification of the transcripts expression in expanded samples, we experimentally validate the expression patterns of the remarkable low expressed gene, SSTR5, and its antisense lncRNA, SSTR5-AS1. Downregulation of SSTR5 is detected in LSCC tissues and laryngeal carcinoma cells. Aberrant DNA hypermethylation of the CpG sites clustered in the exon 1 and accumulation of inactive histone modifications at SSTR5 promoter region may be epigenetic mechanisms for its inactivation in LSCC. SSTR5-AS1 may play antitumor role in LSCC and may be regulated by the hypermethylation of the same CpG sites with SSTR5. SSTR5-AS1 inhibits laryngeal carcinoma cells proliferation, migration, and invasion. SSTR5-AS1 increases the enrichment of MLL3 and H3K4me3 at the promoter region of SSTR5 by interacting with MLL3 and further induces the transcription of SSTR5. Furthermore, SSTR5-AS1 interacts with and recruits TET1 to its target gene E-cadherin to activate its expression. CONCLUSION: These findings suggest that the identified lncRNAs and mRNAs may be potential biomarkers in metastatic LSCC, and SSTR5-AS1 may act as a tumor suppressor as well as a potential biomarker for antitumor therapy.

TGF-ß-induced long non-coding RNA MIR155HG promotes the progression and EMT of laryngeal squamous cell carcinoma by regulating the miR-155-5p/SOX10 axis.

Non­coding RNAs, particularly long non­coding RNAs (lncRNAs), play important roles in tumorigenesis. The miR­155 host gene (MIR155HG) lncRNA has been found to play a crucial role in tumor progression. However, the role of MIR155HG in laryngeal squamous cell carcinoma (LSCC) remains unclear. Thus, the aim of the present study was to explore the roles and underlying molecular mechanisms of action of MIR155HG and miR­155­5p in LSCC, in an effort to provide novel approaches for the antitumor therapy for LSCC. In the present study, the expression levels of miR­155­5p and MIR155HG were detected by reverse tran-scription­quantitative polymerase chain reaction. In addition, the biological functions of MIR155HG and miR­155­5p on LSCC were evaluated in vitro by MTS assay, colony formation assay and Transwell assays, and in vivo by tumorigenesis assays. It was revealed that MIR155HG and miR­155­5p were significantly upregulated in LSCC tissues, and were associated with the TNM stage, pathological differentiation and lymph node metastasis. Moreover, the knockdown of MIR155HG and miR­155­5p inhibited the proliferation, migration and invasion of LSCC cells, whereas their overexpression exerted the opposite effects in vitro and MIR155HG overexpression promoted tumorigenesis in vivo. Furthermore, MIR155HG downregulation reduced the expression level of miR­155­5p. The inhibitory effect of MIR155HG knockdown on malignant behavior was abrogated by miR­155­5p overexpression. Bioinformatics analysis and luciferase reporter assay confirmed that miR­155­5p contributed to the progression of LSCC by directly binding to the 3' untranslated region of SRY­related­HMG­box 10 (SOX10). In addition, MIR155HG and miR­155­5p were upregulated by the induction of transforming growth factor­ß (TGF­ß) and promoted the expression of mesenchymal markers synergistically. On the whole, the findings of the present study indicate a novel role of MIR155HG in the TGF­ß­induced EMT of LSCC cells by regulating EMT markers through the miR­155/SOX10 axis. The MIR155HG/miR­155­5p/SOX10 axis plays an important role in promoting the progression of LSCC and may thus serve as a potential therapeutic target for LSCC treatment.

Aberrant methylation and downregulation of ZNF667-AS1 and ZNF667 promote the malignant progression of laryngeal squamous cell carcinoma.

BACKGROUND: Dysregulated long noncoding RNAs (lncRNAs) are involved in the development of tumor. Aberrant methylation is one of the most frequent epigenetic alterations that regulate the expression of genes. The aim of this study was to determine the expression and methylation status of ZNF667-AS1 and ZNF667, elucidate their biological function in the development of LSCC, and identify a cis-regulation of ZNF667-AS1 to ZNF667. METHODS: The expression and methylation status of ZNF667-AS1 and ZNF667 in laryngeal cancer cell lines and LSCC samples were tested respectively. The function of two laryngeal cancer cell lines with overexpression of ZNF667-AS1 or ZNF667 was detected. The regulation between ZNF667-AS1 and ZNF667 was determined. RESULTS: Significant downregulation of ZNF667-AS1 was detected in laryngeal cancer cell lines and LSCC tumor tissues. The reduced expression of ZNF667-AS1 was associated with moderate/poor pathological differentiation of LSCC tumor tissues. Aberrant hypermethylation of the CpG sites of ZNF667-AS1, closing to the transcriptional start site (TSS), was more critical for gene silencing, and associated with moderate/poor pathological differentiation. In vitro hypermethylation of promoter region closing to TSS of ZNF667-AS1 decreased the luciferase reporter activity. Overexpression of ZNF667-AS1 reduced the proliferation, migration, and invasion ability of AMC-HN-8 and TU177 cells. The sense strand, ZNF667, was positively correlated with ZNF667-AS1 in expression and function. Overexpression of ZNF667-AS1 led to increased expression of ZNF667 in mRNA and protein level. ZNF667-AS1 and ZNF667 may be associated with epithelial-mesenchymal transition (EMT) process. CONCLUSIONS: ZNF667-AS1 and ZNF667 are both down-regulated by hypermethylation, and they serve as tumor suppressor genes in LSCC. ZNF667-AS1 regulates the expression of ZNF667 in cis.

Expression profile analysis identifies the long non-coding RNA landscape and the potential carcinogenic functions of LINC00668 in laryngeal squamous cell carcinoma.

In order to explore the differentially expressed long non-coding RNAs (lncRNAs) in laryngeal squamous cell carcinoma (LSCC), the GSE84957 lncRNA expression profile was included in the present study through data mining in the National Center for Biotechnology Information/Gene Expression Omnibus (NCBI/GEO). Then, the differentially expressed genes (DEGs) of LSCC (1646 lncRNAs and 2713 mRNAs, fold change ≥ 2, P ≤ 0.05) were identified from the GSE84957 dataset using bioinformatics analysis. Of the 10 selected differentially expressed lncRNAs, the expression of 7 lncRNAs were verified by qRT-PCR method. Then, LINC00668, a potential carcinogenic lncRNA, was screened out by narrowing down the screening criteria (fold change ≥ 4, P ≤ 0.01). Furthermore, correlation analysis demonstrated that expression levels of LINC00668 were associated with age, pathological differentiation degree, T stage, clinical stage and cervical lymph node metastasis. Moreover, a series of bioinformatics tools and in vitro experiments proved that knockdown of LINC00668 inhibited the proliferation, migration and invasion ability of LSCC cells. The present study identified the lncRNAs landscape of LSCC through data mining and bioinformatics analysis, and verified oncogenic LINC00668, which may play important roles in promoting LSCC cells proliferation, migration and invasion.

Screening and clinical significance of tumor markers in head and neck squamous cell carcinoma through bioinformatics analysis.

In order to identify potential diagnostic and prognostic biomarkers, and treatment targets for head and neck squamous cell carcinoma (HNSCC), the present study obtained the gene expression profiles in HNSCC through public data mining, and core genes were identified using a series of bioinformatics analysis methods and databases. A total of nine hub genes (SPP1, ITGA6, TMPRSS11D, MMP1, LAMC2, FAT1, ACTA1, SERPINE1 and CEACAM1) were identified to be significantly correlated with HNSCC. Furthermore, overall survival analysis demonstrated that the expression values of hub genes were associated with overall survival in HNSCC. Furthermore, certain of the identified genes, including, TMPRSS11D, ACTA1 and CEACAM1, have not been thoroughly investigated in HNSCC previously. Taken together, the nine hub genes obtained by screening in the present study may serve as potential tumor markers and important prognostic indicators for HNSCC.

Oral lichen-planus-associated fibroblasts acquire myofibroblast characteristics and secrete pro-inflammatory cytokines in response to Porphyromonas gingivalis lipopolysaccharide stimulation.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease in which comprehensive inflammation-related cytokines are involved. These cytokines are commonly produced by immune cells and specific nonimmune cells including keratinocytes, endothelial cells and fibroblasts. This raises the question of whether fibroblasts in OLP lesions contribute to the inflammatory process upon inflammatory simulation. METHODS: Primary cultured Oral lichen-planus-associated fibroblasts (OLP AFs, n = 5) and normal buccal mucosal fibroblasts (NFs, n = 5) were examined by immunohistochemistry, Western blotting and reverse transcription-polymerase chain reactions (RT-PCR). Various inflammatory mediators were evaluated with a multiplex assay. Differences among groups were assessed using a Student's test or repeated measures one-way ANOVA, as appropriate. RESULTS: OLP AFs express significantly higher levels of α-smooth muscle actin (α-SMA) than NFs, indicating the presence of myofibroblasts. Myofibroblasts secrete Interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) in response to Porphyromonas gingivalis lipopolysaccharide (pg. LPS). CONCLUSION: OLP AFs demonstrated α-SMA expression and secreted pro-inflammatory cytokines in response to pg. LPS stimulation.

A systems biology approach identifies effective tumor-stroma common targets for oral squamous cell carcinoma.

The complex interactions between cancer cells and their surrounding stromal microenvironment play important roles in tumor initiation and progression and represent viable targets for therapeutic intervention. Here, we propose a concept of common target perturbation (CTP). CTP acts simultaneously on the same target in both the tumor and its stroma that generates a bilateral disruption for potentially improved cancer therapy. To employ this concept, we designed a systems biology strategy by combining experiment and computation to identify potential common target. Through progressive cycles of identification, TGF-ß receptor III (TßRIII) is found as an epithelial-mesenchymal common target in oral squamous cell carcinoma. Simultaneous perturbation of TßRIII in the oral cancerous epithelial cells and their adjacent carcinoma-associated fibroblasts effectively inhibits tumor growth in vivo, and shows superiority to the unilateral perturbation of TßRIII in either cell type alone. This study indicates the strong potential to identify therapeutic targets by considering cancer cells and their adjacent stroma simultaneously. The CTP concept combined with our common target discovery strategy provides a framework for future targeted cancer combinatorial therapies.

Yes-associated protein expression in head and neck squamous cell carcinoma nodal metastasis.

INTRODUCTION: Yes-associated protein (YAP) is considered an oncogene found amplified in multiple tumors, including head and neck squamous cell carcinoma (HNSCC). However, the role for YAP expression in HNSCC is not understood. Based on the central role of YAP in the hippo pathway, we tested if YAP was associated with the stage of HNSCC progression and metastatic potential. METHODS: To determine the expression of YAP in human benign and HNSCC tissue specimens, immunohistochemical analyses were performed in whole tissue samples and tissue microarrays. The expression of YAP in tissues of microarray was first associated with clinic-pathologic factors and results verified in samples from whole tissue sections. To investigate the role of YAP and p63 in regulating HNSCC epithelial to mesenchymal transition, epithelial and mesenchymal markers were assayed in Fadu and SCC-25 cells, HNSCC cells with endogenously elevated YAP expression and siRNA-mediated expression knockdown. RESULTS: Analysis of human HNSCC tissues suggested YAP expression was elevated in tumors compared to benign tissues and specifically localized at the tumor invasive front (p value < 0.05). But, indexed YAP expression was lower with greater tumor grade (p value  =  0.02). In contrast, p63 expression was primarily elevated in high-grade tumors. Interestingly, both YAP and p63 was strongly expressed at the tumor invasive front and in metastatic HNSCC. Strikingly, we demonstrated YAP expression in the primary HNSCC tumor was associated with nodal metastasis in univariate analysis (p value  =  0.02). However, the knockdown of YAP in Fadu and SCC-25 cell lines was not associated with changes in epithelial to mesenchymal transdifferentiation or p63 expression. CONCLUSION: Together, YAP expression, in combination with p63 can facilitate identification of HNSCC tumors from hyperplastic and benign tissues and the metastatic function of YAP in HNSCC may not be a result of epithelia to mesenchymal transdifferentiation.

Downregulation of TGF-beta receptor types II and III in oral squamous cell carcinoma and oral carcinoma-associated fibroblasts.

BACKGROUND: The purpose of this study was to assess the expression levels for TßRI, TßRII, and TßRIII in epithelial layers of oral premalignant lesions (oral leukoplakia, OLK) and oral squamous cell carcinoma (OSCC), as well as in oral carcinoma-associated fibroblasts (CAFs), with the final goal of exploring the roles of various types of TßRs in carcinogenesis of oral mucosa. METHODS: Normal oral tissues, OLK, and OSCC were obtained from 138 previously untreated patients. Seven primary human oral CAF lines and six primary normal fibroblast (NF) lines were established successfully via cell culture. The three receptors were detected using immunohistochemical (IHC), quantitative RT-PCR, and Western blot approaches. RESULTS: IHC signals for TßRII and TßRIII in the epithelial layer decreased in tissue samples with increasing disease aggressiveness (P < 0.05); no expression differences were observed for TßRI, in OLK and OSCC (P > 0.05); and TßRII and TßRIII were significantly downregulated in CAFs compared with NFs, at the mRNA and protein levels (P < 0.05). Exogenous expression of TGF-ß1 led to a remarkable decrease in the expression of TßRII and TßRIII in CAFs (P < 0.05). CONCLUSION: This study provides the first evidence that the loss of TßRII and TßRIII expression in oral epithelium and stroma is a common event in OSCC. The restoration of the expression of TßRII and TßRIII in oral cancerous tissues may represent a novel strategy for the treatment of oral carcinoma.

Lycopene: features and potential significance in the oral cancer and precancerous lesions.

Data from epidemiological studies have indicated that diets rich in fruits and vegetables are likely to benefit many aspects of the prevention of oral malignancy. Lycopene is a red-coloured carotenoid predominantly accumulated in tomatoes as well as other fruits and vegetables. It has been claimed to alleviate chronic diseases such as cancers and cardiovascular disease. Hence, the aim of this review is to summarize the features and its potential significance of lycopene in the development, prevention and treatment of oral premalignant lesions and oral cancer. Studies showed that lycopene might have beneficial effects in the management of some premalignant lesions in the oral cavity including oral submucous fibrosis and oral leukoplakia and may be an adjunct in the prevention and therapy of oral cancer. However, more mechanistic studies and randomized controlled trials of large sample size are necessary to further confirm these effects and to eventually make lycopene to be used in the community prevention and clinically routine management of these diseases.

Evaluation of penicillin G potassium troches in the treatment of minor recurrent aphthous ulceration in a Chinese cohort: a randomized, double-blinded, placebo and no-treatment-controlled, multicenter clinical trial.

OBJECTIVE: The aim of this study was to explore the effectiveness and safety of topical application of 50 mg penicillin G potassium troches in the treatment of minor recurrent aphthous ulcerations (MiRAU) in a Chinese cohort. MATERIAL AND METHODS: A randomized, double-blinded, placebo and no-treatment-controlled, multicenter clinical trial was performed. Troches were consecutively applied 4 times per day for 4 days. The size and pain level of ulcers were measured and recorded on days 0, 3, 4, 5, and 6. RESULTS: A total of 258 subjects with minor recurrent aphthous ulcerations (86 subjects in penicillin G potassium group, 88 subjects in placebo control group, and 84 subjects in no-treatment control group) fulfilled the study. Penicillin G potassium significantly reduced ulcer size (P < .00001 for days 3, 4, 5, and 6) and alleviated ulcer pain (P < .00001 for days 3, 4, 5, and 6). No severe adverse reactions were observed. Only 4 subjects experienced mild adverse reaction. CONCLUSIONS: Penicillin G potassium troches are effective in reducing ulcer size and alleviating ulcer pain of the patients in the treatment of a single episode of MiRAU in this Chinese cohort. Few adverse effects were observed with this therapeutic approach.