The limitation of markers for chronic oral diseases such as oral lichen planus (OLP) and burning mouth syndrome (BMS) is a diagnostic challenge for clinicians. The pathogenesis of OLP and BMS is not yet fully understood. Therefore, diagnoses are mainly based on the observation of clinical features and history, rather than established markers. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are used to determine the state of inflammation; however, these markers have some limitations. Recently, a new inflammatory marker, pentraxin-3 (PTX3), has been identified in other systemic inflammatory diseases. PTX3 is a member of the pentraxin family and is classified as a long pentraxin. PTX3 is found in various human tissues, whereas the classical short pentraxin, CRP, is secreted only in the liver. PTX3 is a marker of autoimmune diseases and periodontitis. However, there are no studies on PTX3 in OLP and BMS; therefore, we sought to determine if PTX3 can be a diagnostic marker for OLP and BMS. PTX3 was found to be correlated with other inflammatory markers, suggesting its diagnostic value for inflammatory oral diseases. We also found that the PTX3 levels were lower in patients with OLP and BMS. ESR levels were elevated in the OLP and BMS groups, but CRP levels were not. Despite these associations, no correlation was found between PTX3 expression and other known clinical features of OLP and BMS. We suggest that PTX3 plays a role in the immunological and neurological pathways involved in the complex pathogenesis of OLP and BMS.

Hypoxia is one of the most common features of cancer. It is also associated with cancer progression and the acquisition of aggressiveness, which includes invasion and metastasis. Oral squamous cell carcinoma accounts for 90% of all oral cancers, and its 5-year survival rate is about 50%. Despite various attempts and trials, its prognosis has not improved. Among numerous adverse prognostic factors, hypoxia is suspected as one of the most important factors, as it increases the aggressiveness of oral cancer cells. We attempted to observe the effect of hypoxia on the expression of epithelial-mesenchymal transition markers in oral cancer cells. We analyzed and compared both the mRNA and protein expression levels of epithelial-mesenchymal markers using qRT-PCR and western blotting in both normoxic and hypoxic YD10B oral squamous cell carcinoma cells. Eighty-six genes were analyzed through real-time PCR using commercial microarray plates, performed in triplicate. Among the 86 genes, the expression of 24 were increased (≥ 2 fold) by hypoxia, while that of three genes was decreased (≥ 2 fold). Hypoxia significantly affects epithelial-mesenchymal transition-related genes. Further studies on the regulation of these genes may help to develop more efficient therapeutic modalities for oral cancer and to improve prognosis of oral cancer patients.

Recently chronic inflammation is focused on the association with cancer progression and acquisition of aggressive biologic behaviors, such as invasion, metastasis, and resistance to chemotherapeutic reagents. Due to the close vicinity within oral cavity, oral cancer may be intimately associated with chronic periodontitis. The present study was done to observe the effect of chronic periodontitis on oral cancer cells by utilizing P. gingivalis infection, a major pathogen in chronic periodontitis. We analyzed and compared the mRNA expression levels of epithelial-mesenchymal transition (EMT) markers in non-infected and P. gingivalis-infected oral cancer cells. Eighty-six genes, which are well known as EMT markers, were analyzed using commercially available EMT microarray plates, performed in triplicate. Among the 86 genes, the expression of 26 was increased (≥ 2 fold) by P. gingivalis, whereas that of 7 genes was decreased (≥ 2 fold). Our study suggests that P. gingivalis infection evokes significant changes in EMT-related genes. Further observations on molecular mechanisms underlying these changes may help to clarify the role of chronic periodontitis on cancer progression and to develop more efficient preventive and therapeutic modalities for oral cancer. (182 words)

Porphyromonas gingivalis is a gram-negative bacteria of rod shape, and grown in an anerobic condition. It colonizes in subgingival crevice and is known as a major pathogen causing chronic periodontitis. It possesses an invasive property and replicative potential within various cell types, presumably playing an important role in modulating biological behaviors of oral cancer. However, the pathophysiology of P. gingivalis in the malignant transformation of oral cancer has not been fully understood. In this study, we aimed to investigate molecular changes of oral squamous cell carcinoma cells induced by repetitive P. gingivalis infection that clinically resembles chronic periodontitis.

Recently, the importance of inflammation in carcinogenesis has been recognized and studied extensively. As a result, a clear correlation between inflammation and carcinogenesis has been well established in some types of cancers. Despite a high prevalence of chronic periodontitis, one of the most common inflammatory diseases in the general population, there are only a few reports on the role of chronic periodontitis in oral cancer progression. In this study, we aimed to investigate genetic changes in oral cancer cells induced by repetitive Porphryomonas gingivalis infections to mimic chronic periodontitis in a clinical setting. Cells of oral squamous cell carcinoma (OSCC), the most common type of oral cancer, and P. gingivalis 381 were used for the present study. ID1 and ID3 were mRNAs of higher expression in the P. gingivalis-infected group compared to the uninfected control. These mRNAs have been regarded as important modulators participating in cancer progression. Future studies will provide an insight into the roles of the molecules we identified in oral cancer progression. Outcomes from these studies will also shed light on the significance of chronic periodontitis induced by bacterial pathogen, such as P. gingivalis, in progression of oral cancer and relevant molecular mechanisms underlying altered cancer cell behaviors.

Chronic inflammation is widely considered to predispose individuals to cancer. Microorganisms facilitate recruitment and activation of inflammatory cells and thus allow release of inflammatory mediators. These molecules can then promote accumulation of mutations, leading to tumor development in the host. Porphyromonas gingivalis, a pathogen causing chronic periodontitis, is detected in oral squamous cell carcinoma (OSCC) tissues. Considering a strong link between chronic inflammation and tumor development, functional consequences of P. gingivalis infection may include malignant transformation of the host cells. In this study, we monitored transcriptional changes induced by invasion of P. gingivalis in OSCC cells using microarrays. Our preliminary results suggest changes in a wide range of genes involved in inflammation, apoptosis and autophagy, tumor progression, and carcinogenesis. Further studies on molecular mechanisms underlying these changes will lay a useful foundation to elucidate the role of microorganism-related inflammation and for the development of preventive and therapeutic agents for oral cancer.

Cancer cells are often found in an ischemic condition due to the rapid outgrowth of their vascular supply, and these cells are expected to develop an increased potential for local invasive growth. Since the first steps are characterized by increased motility and invasiveness, expression of molecules involved in cellular adhesion to extracellular matrix (ECM) is increased in the process of cancer cell invasion and metastasis. In this work we explored the molecular characteristics and its regulatory mechanism of hypoxic oral squamous cell carcinoma (OSCC) cells. Our experiment identified that hypoxia increases α5 integrin protein levels through phosphoinositide 3-kinase (PI3K)/Akt pathway in OSCC cells.

In t his study, we tried to identify the key elements that respond to EGCG t reatment and its role in cell survival 0 1' apop tosis by EGCG. focusing on Akt pathway and Raf-MEK-ERK pathways. Cells were serum starved for 16 h and then treated with (-) -epiga llocatechin-3-gallate. To cletermine which pathway is related to effects of EGCG on cell s, the levels of phosphorylated Akt(pAkt) and Erk (pErk) were a nalyzed by immunoblotting. A549 cell s showed the increase of pAkt in response to EGCG‘ whereas Hela cells exhi bited no difference in the levels of pAkt by EGCG treatment Phos phorylation of Akt over initial basal levels became evident a fter 1 h of EGCG treatment and peaked at 3 h pErk was also increased by EGCG in Hela cells as well as in A549 cells To determine th e effect of EGCG on growth of cells‘ A549 cells were treated wi th vari 。u s concentrations of EGCG (from 10 μ M to 300 μ M) for 3 h. Cell growth was examined by MTI assay. The resulting growth curves of A549 cell s showed that EGCG promotecl cell prolifera tion in a close-dependent manner at early phase. When cells were t rea ted with EGCG for 24 h. pAkt and pErk expressions were significantly i띠1ibited ， even at 10 μ M B-raf ex pression was also clecreased in a close-dependent manner. In teresti ngly. the presence of serum weakened t his inhibitory effect of EGCG on the ex pression of survival facto rs. Our study inrucates that EGCG stimulates cell survival of A549 cells through thc PI3K/AKT pathway. though it fina lly be haves like a suppressive agent on cell su rvival

Disruption of cell - matrix attachment results in a loss of prosurvival signals and culminates in programmed cell death, referred to as anoikis , Apoptosis signal- regulating kinase 1(ASKl)/MKK5 is a ubiquitously expressed enzyme that acti vates c-Jun N-terminal kinase/stress-activated protein kinase JNK/SAPK and p38 pathways by direct site specific Ser/Thr phosphoryl ation of their respective MKKs-MKK4/MKK7 for JNK and MKK3/MKK6 for p38 kinases, The kinase activity of ASKl is stimulated by a variety of death signals, including TNF, Fas ligation, reactive oxygen species, and antineoplastic agents , The aim of this study was to investigate the relative importance of ASKl in anOlkls 1n the present study cells which lost their adhesion showed higher rate of cell death in compared to cells which maintained anchorage. 1nterestingly the res ult showed that suspended cells expressing ASK1 were more susceptible to anoikis than suspended cells having no ASK1 1n addition, cellu lar attachment seems to have significant effect on ASKl activity and p38 MAPK protein rather than serum stimulation