• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4621-4625
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• 2013

The purpose of this study was to construct a protein-protein interaction (PPI) network related to oral squamous cell carcinoma (OSCC). Each protein was ranked and those most associated with OSCC were mined within the network. First, OSCC-related genes were retrieved from the Online Mendelian Inheritance in Man (OMIM) database. Then they were mapped to their protein identifiers and a seed set of proteins was built. The seed proteins were expanded using the nearest neighbor expansion method to construct a PPI network through the Online Predicated Human Interaction Database (OPHID). The network was verified to be statistically significant, the score of each protein was evaluated by algorithm, then the OSCC-related proteins were ranked. 38 OSCC related seed proteins were expanded to 750 protein pairs. A protein-protein interaction nerwork was then constructed and the 30 top-ranked proteins listed. The four highest-scoring seed proteins were SMAD4, CTNNB1, HRAS, NOTCH1, and four non-seed proteins P53, EP300, SMAD3, SRC were mined using the nearest neighbor expansion method. The methods shown here may facilitate the discovery of important OSCC proteins and guide medical researchers in further pertinent studies.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2955-2958
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• 2013

Background: Mast cells can influence tumor progression via different pathways and increased mast cell density has been demonstrated in oral squamous cell carcinoma (OSCC). It has been shown that the serum tryptase level is elevated with some malignant tumours and may thus be a useful parameter. However, there are no data available about OSCC. The main aim of this study was the evaluation of mast cell tryptase (MCT) level in OSCC patient serum. Materials and Methods: In this cross-sectional, analytic study, the circulating levels of MCT were assessed in sera of 55 OSCC patients and 34 healthy individuals with ELISA technique. Results: The serum MCT level in OSCC patients was 12-14 ng/ml, which was not significantly higher than the healthy control group. While the serum level of MCT was higher with larger tumours, there was no apparent correlation with clinico-pathological features such as patient age, gender, tumor location, stage, nodal status, distant metastasis, histological grade and smoking. Conclusions: Our findings showed that despite the results obtained from studies of other malignant tumors, serum level of MCT in OSCC patients could not be a credited as a reliable indicator of the presence or progression of tumours.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1073-1075
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• 2013

Background: In normal cells, activated epidermal growth factor receptor (EGFR) molecules are subjected to ubiquitination-mediated proteasome degradation pathway by c-Cbl, an ubiquitin ligase that checks uncontrolled proliferation. Hence expression of wild type c-Cbl molecule is essential to keep this degradation machinery in a functional state. Loss of expression or function of c-Cbl may consequently lead to sustained activation of EGFR and promote carcinogenesis, loss of function mutations in the c-Cbl gene already being reported in lung and hematopoietic cancers. However, the genetic status of c-Cbl in oral squamous cell carcinoma (OSCC) is not known. Hence in the present study we investigated the genomic DNA isolated from OSCC tissue biopsy samples for mutations in the RING finger domain coding region of c-Cbl gene, which has also been reported to be most frequently mutated in other cancers. Materials and Methods: Total genomic DNA isolated from thirty two post surgical OSCC tissue samples were amplified using primers flanking the exon 8 of c-Cbl gene that codes for the RING finger domain. The PCR amplicons were then resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations. Results: The sequencing data of the thirty two OSCC samples did not identify mutations in the RING finger domain coding region of c-Cbl gene. Conclusions: To the best of our knowledge, this is the first time that the genetic status of c-Cbl gene in OSCC samples has been investigated. The present data indicates that genetic alteration of RING finger domain coding region of c-Cbl gene is relatively infrequent in OSCC samples.

• International Journal of Oral Biology
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• v.41 no.1
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• pp.1-8
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• 2016

OSCC is currently the most common malignancy of the head and neck, affecting tens of thousands of patients per year worldwide. Natural flavonoids from plants are potential sources for novel anti-cancer drugs. Icariin is the active ingredient of flavonol glycoside, which is derived from the medical plant Herba Epimedii. A metabolite of icariin, icariside II exhibits a variety of pharmacological actions, including anti-rheumatic, anti-depressant, cardiovascular protective, and immunomodulatory functions. However, the exact mechanism causing the apoptosis-inducing effect of icariside II in OSCC is still not fully understood. In the present study, we assessed the anti-cancer effect of icariside II in OSCC cell lines by measuring its effect on cell viability, cell proliferation, and mitochondria membrane potential (MMP). Icariside II treatment of OSCC cells resulted in a dose- and time-dependent decrease in cell viability. Hoechst staining indicated apoptosis in icariside II-treated HSC cells. Icariside II inhibited cell proliferation and induced apoptosis in HSC cells, with significant increases in all present parameters in HSC-4 cells. The results clearly suggested that icariside II induced apoptosis via activation of intrinsic pathways and caspase cascades in HSC-4 cell lines. The collective findings of the study suggested that Icariside II is a potential treatment for OSCC; in addition, the data could provide a basis for the development of a novel anti-cancer strategy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.1
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• pp.71-82
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• 2008

Survivin is a member of the inhibitors of apoptosis (IAP) family that have been known to inhibit activated caspases in apoptosis. In contrast to most IAP family members, survivin mRNA is expressed during fetal development, is not found in normal adult tissues and is overexpressed again in the cancer. Though survivin expression has been documented in most human cancers, little is known about its expression in OSCC and its potential value as a predictor of cancer survival. The purpose of this study was to investigate survivin expression in OSCC and to evaluate its value as a prognostic marker. We evaluated survivin expressions in cancer lines and OSCC samples and investigated the relationships between survivin expressions and clini-co-pathological parameters including stage, differentiation, proliferation, lymph node metastasis, blood vessel density, and gelatinolytic activity. With immunohistochemistry, we analyzed survivin expression in 38 OSCCs. Patients' clinico-pathological parameters and their survival rate were analyzed to reveal their correlations with Survivin expressions. We cultured oral cancer cell lines and evaluated the correlation between gelatinolytic activities and survivin expressions of them. Survivin protein was observed both in nuclei and cytoplasm of tumor specimens while little or not observed in normal gingival mucosal tissues. Additionally, survivin expressions were correlated with lymph node metastasis, tumor proliferation and survival rate. Survivin expression was observed in 100% of 38 samples of OSCC and its expression levels are statistically associated with the proliferative activity of the tumors, lymph node metastasis and the survival of the patients. Based on these results, survivin is commonly expressed in OSCC and may thus provide valuable prognostic information related with lymph node metastasis, proliferation and survival rate as well as a potential therapeutic target in OSCC.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.45 no.2
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• pp.83-90
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• 2019

Objectives: This study evaluated the predictive factors for survival of patients with oral squamous cell carcinoma (OSCC) and investigated the overall and disease-specific survival (DSS) outcomes. Materials and Methods: A total of 67 consecutive patients who underwent surgery for OSCC from January 2006 to November 2014 were included in this study. Patients were classified according to age, sex, pTNM stages, primary sites, smoking and alcohol drinking habits, depth of invasion, perineural and lymphovascular invasion, cell differentiation and postoperative radiotherapy. Kaplan-Meier methods were used to estimate the survival categorized by patient groups. Cox regression methods were used to investigate the main independent predictors of survival. Results: Nineteen patients died of OSCC during follow-up periods. Another five patients died of other diseases including lung adenocarcinoma (n=1), cerebral infarction (n=1), general weakness (n=2), and pneumonia (n=1). The tongue (n=16) was the most common site for primary origin, followed by buccal mucosa (n=15), mandibular gingiva (n=15), maxillary gingiva (n=9), floor of mouth (n=9), retromolar trigone (n=2), and palate (n=1). Eleven patients had pTNM stage I disease, followed by stage II (n=22) and stage IV (n=34). No patients had pTNM stage III disease in this study. The overall survival of all patients was 64.2% and the DSS was 71.6%. DSS of patients with stage I and II disease was 100%. Stepwise Cox regression showed the two predictors for DSS were pTNM stage (P<0.0001, odds ratio=19.633) and presence of metastatic lymph nodes (P=0.0004, odds ratio=0.1039). Conclusion: OSCC has been associated with poor prognosis; however, there were improved survival outcomes compared with past studies. Advanced-stage disease and presence of metastatic lymph nodes were associated with poorer survival compared with early-stage OSCC and absence of neck node metastasis. Stage I and II OSCC were associated with excellent survival results in this study.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8377-8382
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• 2014

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. Methods: In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1-oxide induced OSCC. Results: Results showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Conclusion: Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.

• Korean Journal of Pharmacognosy
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• v.48 no.3
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• pp.213-218
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• 2017

In order to search for anticancer agent as therapy of oral squamous cell carcinoma (OSCC) and malignant pleural mesothelioma (MPM) from Korean traditional prescriptions, we selected 58 traditional prescriptions based on a review of the Korean traditional medicine books. Among the selected traditional prescriptions, only water extracts of paedoksan (敗毒散) showed relatively good cytotoxicity at the concentration of $50{\mu}g/ml$. Additionally, we evaluated cytotoxicity for various paedoksans and each herbal ingredient in paedoksans. The root of Anthriscus sylvestris exhibited more cytotoxic effect than any other ingredients in paedoksans. Bioactivity-guided fractionation of the MC layer of Anthriscus sylvestris led to the isolation of deoxypodophyllotoxin (DPT). DPT exhibited dose-dependently significant cytotoxicity against OSCC and MPM cell with nM range. Therefore, DPT from A. sylvestris might be a potential candidate as an effective anticancer therapeutic agent for OSCC and MPM.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8957-8961
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• 2014

Background: Promoter hypermethylation leads to altered gene functions and may result in malignant cellular transformation. Thus, identification of biomarkers for hypermethylated genes could be useful for diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC). Objectives: To screen hypermethylated genes with a microarray approach and to validate selected hypermethylated genes with the methylation-specific polymerase chain reaction (MSPCR). Materials and Methods: Genome-wide analysis of normal oral mucosa and OSCC tissues was conducted using the Illumina methylation microarray. The specified differential genes were selected and hypermethylation status was further verified with an independent cohort sample of OSCC samples. Candidate genes were screened using microarray assay and run by MSPCR analysis. Results: TP73, PIK3R5, and CELSR3 demonstrated high percentages of differential hypermethylation status. Conclusions: Our microarray screening and MSPCR approaches revealed that the signature candidates of differentially hypermethylated genes may possibly become potential biomarkers which would be useful for diagnostic, prognostic and therapeutic targets of OSCC in the near future.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2273-2278
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• 2014

Purpose: The purpose of our study was to explore the molecular mechanisms in the process of oral squamous cells carcinoma (OSCC) development. Method: We downloaded the affymetrix microarray data GSE31853 and identified differentially expressed genes (DEGs) between OSCC and normal tissues. Then Gene Ontology (GO) and Protein-Protein interaction (PPI) networks analysis was conducted to investigate the DEGs at the function level. Results: A total 372 DEGs with logFCI >1 and P value < 0.05 were obtained, including NNMT, BAX, MMP9 and VEGF. The enriched GO terms mainly were associated with the nucleoplasm, response to DNA damage stimuli and DNA repair. PPI network analysis indicated that GMNN and TSPO were significant hub proteins and steroid biosynthesis and synthesis and degradation of ketone bodies were significantly dysregulated pathways. Conclusion: It is concluded that the genes and pathways identified in our work may play critical roles in OSCC development. Our data provides a comprehensive perspective to understand mechanisms underlying OSCC and the significant genes (proteins) and pathways may be targets for therapy in the future.