Masayuki Motohashi

Producing Capabilities of Interferon-gamma and Interleukin-10 in Peripheral Blood from Oral Squamous Cell Carcinoma Patients

In order to evaluate the Th1 and Th2 responses of Oral Squamous Cell Carcinoma (OSCC) patients, we investigated the cytokine producing capability of peripheral blood (PB), and compared it with clinicopathological appearances of OSCC patients. The production of a Th1-type cytokine, interferon (IFN)-γ, from lipopolysaccharide (LPS)-stimulated PB correlated positively with the frequency of lymph node metastasis. We also investigated the production of a Th2-type cytokine, IL-10, however, no significant correlation was observed with the clinicopathological appearances. Our results suggested that the IFN-γ producing capability was specifically regulated and dependent on the regional metastatic potencies of OSCCs.

Passage of a Sialolith

An otherwise healthy 77-year-old woman presented with a 6-month history of dull pain on the right side of the tongue. Intraoral examination revealed a visible sialolith emerging from Whartons duct, with marked redness and swelling of the right sublingual caruncle.

Comprehensive Study of Oral Squamous Cell Carcinoma Patients Using Blood Samples and Gene Expression Profiles

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy which shows a variable degree of malignant behavior. To identify molecular signatures and establish a new diagnostic model for oral malignancies, we have identified marker genes representing pre-malignant and malignant phenotypes of oral mucosal lesions. The expression of marker genes was examined by quantitative reverse transcription-PCR. Then, we created discriminatory predictor models using Fisher’s linear discriminant analysis and leave-one-out cross validation. These models were applicable for the diagnoses of pre-malignant leukoplakias (LPs), and of invasion status for advanced OSCCs. The clinical course of various cancers is also influenced by host immune response. Our preliminary data using flow cytometric analysis demonstrate that the percentage of CD4+CD57+ T cells in peripheral blood lymphocyte was higher in the high grade OSCCs than that in the low grade ones. Furthermore, lipopolysaccharides (LPS)-induced ex-vivo production of Interferon (IFN)-γ from peripheral blood cells was highest in stage I patients and gradually decreased during the course of OSCC progression up to stage III. These decreased levels in the early stages were inversely correlated with tumor size. In this review, we propose that the usage of the immunological status of OSCC patients combined with the molecular signatures of tumor tissues could provide valuable indices for diagnosis of oral malignancies.

Gene expression analyses associated with malignant phenotypes of metastatic sub-clones derived from a mouse oral squamous cell carcinoma Sq-1979 cell line

To elucidate the genetic events that occur during the development of OSCC, the present study established a model of oral malignancy using a mouse oral squamous cell carcinoma (OSCC) Sq-1979 cell line. Sq-1979 cells were implanted into syngeneic C3H mice. Subsequently, 233 cells and metastatic sub-clones (L cells) from primary OSCC, as well as the metastasized lymph node tissues of Sq-1979-implanted mice were established. Compared with parental Sq-1979 and 233 cells, the majority of L cells exhibited a higher proliferation rate and transplantability, and conferred a lower survival rate on the implanted mice. To investigate the genetic background of L cells, preferentially expressed genes in L cells were identified by cDNA microarray and reverse transcription-polymerase chain reaction analyses. The expression of FYN-binding protein (Fyb), solute carrier family 16 member 13 (Slc16a13), keratin 7, transmembrane portion 173 and Slc44a3 mRNAs was significantly elevated in L cells compared with that in Sq1979 and 233 cells. The mRNA expression was also evaluated in human OSCC and leukoplakia (LP) tissues. Among the 5 aforementioned mRNAs, the expression of FYB and SLC16A13 was significantly higher in OSCC than in LP tissues. Furthermore, the expression of SLC16A13 mRNA was significantly elevated in highly invasive OSCCs, which were classified as grades 3 and 4 by the Yamamoto-Kohama (YK) classification of invasion, compared with those in lower grades (YK-1 and -2). The model proposed in the present study could thus describe essential marker genes for the diagnosis of oral malignancies.