Prevention Of Oral Squamous Cell Carcinoma Research Articles

Genomic DNA Copy Number Aberrations, Histological Diagnosis, Oral Subsite and Aneuploidy in OPMDs/OSCCs.

Oral potentially malignant disorders (OPMDs) characterized by the presence of dysplasia and DNA copy number aberrations (CNAs), may reflect chromosomal instability (CIN) and predispose to oral squamous cell carcinoma (OSCC). Early detection of OPMDs with such characteristics may play a crucial role in OSCC prevention. The aim of this study was to explore the relationship between CNAs, histological diagnosis, oral subsite and aneuploidy in OPMDs/OSCCs. Samples from OPMDs and OSCCs were processed by high-resolution DNA flow cytometry (hr DNA-FCM) to determine the relative nuclear DNA content. Additionally, CNAs were obtained for a subset of these samples by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. Our study shows that: i) aneuploidy, global genomic imbalance (measured as the total number of CNAs) and specific focal CNAs occur early in the development of oral cancer and become more frequent at later stages; ii) OPMDs limited to tongue (TNG) mucosa display a higher frequency of aneuploidy compared to OPMDs confined to buccal mucosa (BM) as measured by DNA-FCM; iii) TNG OPMDs/OSCCs show peculiar features of CIN compared to BM OPMDs/OSCCs given the preferential association with total broad and specific focal CNA gains. Follow-up studies are warranted to establish whether the presence of DNA aneuploidy and specific focal or broad CNAs may predict cancer development in non-dysplastic OPMDs.

Alphitolic acid, an anti-inflammatory triterpene, induces apoptosis and autophagy in oral squamous cell carcinoma cells, in part, through a p53-dependent pathway

The antitumour mechanism of alphitolic acid (ALA), an anti-inflammatory triterpene, in oral squamous cell carcinoma (OSCC) cells was investigated. ALA suppressed the proliferation of SCC4 and SCC2095 OSCC cells with IC50 values of 12 and 15 µM, respectively, via apoptotic induction. Mechanistically, this drug effect on apoptosis was, in part, associated with its ability to block Akt–NF-κB signalling. Moreover, ALA induced autophagy, as evidenced by increased expression of the autophagy biomarkers Beclin 1, Atg7, and LC3B-II, and autophagosome formation. This autophagy induction played a protective role as autophagy inhibitors enhanced cellular susceptibility to ALA-induced apoptosis. Also noteworthy is the involvement of p53 in ALA-mediated cytotoxicity. ALA increased p53 phosphorylation/expression, accompanied by parallel decreases in the expression of the oncogenic E3 ligase MDM2, and shRNA-mediated knockdown of p53 partially rescued ALA-mediated cytotoxicity. Together, these findings suggest the translational value of ALA as an ingredient in functional food/dietary supplement for OSCC prevention.

Immunohistochemical expression of TLR4 and TLR9 in various grades of oral epithelial dysplasia and squamous cell carcinoma, and their roles in tumor progression: a pilot study

Toll-like receptors (TLRs) play an essential role in the activation of innate immunity. TLRs are expressed in B-lymphocytes, monocytes, dendritic cells and epithelial cells. We examined the immunohistochemical expressions of TLR4 and TLR9 in various grades of oral epithelial dysplasia (OED), oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM) to determine the association between TLR4 and TLR9 in the progression of lesions from dysplasia to carcinoma. Expressions of TLR4 and TLR9 were assessed using immunohistochemistry (IHC) on paraffin embedded tissue blocks of various grades of OED (28 cases), OSCC (27 cases) and NOM (10 cases). Expression of TLR4 was high in all grades of OED and OSCC. Expression of TLR9 was high in well differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinomas, and moderate to low in poorly differentiated squamous cell carcinomas. Although expression was high in case of TLR4, it was not statistically significant. Expression of TLR9 was statistically significant. In OED, expression of TLR9 was less than that of TLR4. Our results indicated that the pattern of expression of TLR4 and TLR9 increased significantly from mild to severe dysplasia compared to controls. Expression of TLR4 and TLR9 reflects progression of OED to OSCC, which suggests that TLR may play a role in tumorigenesis and that it could be used as a target for OSCC prevention and therapy in the future.

Therapeutic and Preventive Effects of an Epidermal Growth Factor Receptor Inhibitor on Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is the sixth most common human neoplasm worldwide. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is highly expressed in human OSCC and is a target for cancer therapy and prevention. This study investigated the therapeutic and preventive effects of an inhibitor of EGFR (PD153035) on OSCC. The effects of PD153035 were examined in human cancer cell lines in vitro, in an athymic nude mouse xenograft model in vivo, and in the 7,12-dimethyl benz[a]anthracene (DMBA)-induced hamster cheek pouch tumour model in vivo. PD153035 significantly inhibited cell growth, delayed cell cycle progression and induced apoptosis in human OSCC cells in vitro. In vivo, PD153035 inhibited xenograft tumour growth in nude mice in a dose-dependent manner and prevented the development of OSCC at the postinitiation stage in the DMBA-induced hamster cheek pouch tumour model. PD153035 inhibited the DMBA-induced increases in cell proliferation and in levels of phosphorylated EGFR and phosphorylated signal transducer and activator of transcription 3 (STAT3) protein in the hamster cheek pouch. Inhibitors of EGFR, such as PD153035, have potential value in the treatment and prevention of OSCC.

P142. The evaluation of hinokitiol in oral squamous cell carcinoma prevention

P142. The evaluation of hinokitiol in oral squamous cell carcinoma prevention

Increased expression of Toll-like receptor-9 has close relation with tumour cell proliferation in oral squamous cell carcinoma

ObjectiveToll-like receptor-9 (TLR-9), a new member of the interleukin-1 receptor superfamily, was recently found to have a high level of expression in many carcinoma specimens. The objective of this study was to examine the TLR-9 expression and its role in tumour cell proliferation in oral squamous cell carcinoma. Materials and methodsWestern blot and immunohistochemistry were used to detect TLR-9 protein in oral squamous cell carcinoma (OSCC) Tca-8113 cell lines and clinical specimens (n=60). The relationship between TLR-9 expression and clinicopathologic features was analysed. Cell proliferation and inflammatory chemokines secretion were tested by MTT and ELISA methods respectively. ResultsResults showed that TLR-9 expression level was higher in OSCC tissues than in paired adjacent normal tissues (P<0.01), and the expression level of TLR-9 was significantly associated with tumour size (P=0.001), tumour clinical stage (P=0.003) and Ki-67 expression (P<0.01). In vitro results also suggested that stimulation of Tca-8113 cells with TLR-9 agonist CpG-ODN could significantly increase tumour cell proliferation as well as subsequent IL-1α and IL-6 secretions (P<0.01), which could be partially inhibited by usage of anti-TLR-9 protein. ConclusionsIt was therefore hypothesized that increased expression of TLR-9 may be of great value in assessing the development of OSCC, and could be used as a new target for OSCC prevention and therapy in future.

Positive Correlations of Oct-4 and Nanog in Oral Cancer Stem-Like Cells and High-Grade Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC), like many solid tumors, contains a heterogeneous population of cancer cells. Recent data suggest that a rare subpopulation of cancer cells, termed cancer stem cells (CSC), is capable of initiating, maintaining, and expanding the growth of tumor. Identification and characterization of CSC from OSCC facilitates the monitoring, therapy, or prevention of OSCC. We enriched oral cancer stem-like cells (OC-SLC) through sphere formation by cultivating OSCC cells from established OSCC cell lines or primary cultures of OSCC patients within defined serum-free medium. Differential expression profile of stemness genes between enriched OC-SLC and parental OSCC was elucidated. Furthermore, immunohistochemical staining of stemness markers on OSCC patient tissues was examined to evaluate the association between stemness genes and prognosis of OSCC. Enriched OC-SLC highly expressed the stem/progenitor cell markers and ABC transporter gene (Oct-4, Nanog, CD117, Nestin, CD133, and ABCG2) and also displayed induced differentiation abilities and enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Elevated expression of CD133 was shown in the enriched OC-SLC from OSCC patients' tumors. Positive correlations of Oct-4, Nanog, or CD133 expression on tumor stage were shown on 52 OSCC patient tissues. Kaplan-Meier analyses exhibited that Nanog/Oct-4/CD133 triple-positive patients predicted the worst survival prognosis of OSCC patients. We enriched a subpopulation of cancer stem-like cell from OSCC by sphere formation. The enriched OC-SLC possesses the characteristics of both stem cells and malignant tumors. Additionally, expression of stemness markers (Nanog/Oct-4/CD133) contradicts the survival prognosis of OSCC patients.