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The mammalian target of rapamycin (mTOR) has recently emerged as a promising target for therapeutic anti-cancer interventions in several human tumors. In present study, we investigated the expression of mTOR, and subsequently examined its relationship with clinicopathological factors and the anti-tumor effect of everolimus (also known as RAD001) in oral squamous cell carcinoma (OSCC). The expression of phosphorylated mTOR (p-mTOR) was immunohistochemically evaluated in specimens obtained from 70 OSCC patients who underwent radical surgery. The relationships between the expression of p-mTOR and clinicopathological factors and survival were determined. We also investigated the effect of everolimus on the OSCC cell lines, SAS, HSC-2, HSC-3, HSC-4, OSC-20, SCC25 and Ca9-22 by the MTT assay. We further evaluated whether mTOR contributed to cell functions by blocking its activity with everolimus, and confirmed the direct target by the Matrigel invasion assay, wound healing assay and Western blotting. p-mTOR was overexpressed in 37 tumors (52.8 %), and correlated with the T classification, N classification, and survival rate (P < 0.05). The treatment with everolimus significantly inhibited cell growth, and significantly reduced the expression of p-mTOR, downstream signaling proteins, and hypoxic related proteins as well as invasion and migration potentials (P < 0.05). The results of the present study suggest that everolimus may represent an attractive approach for the future treatment of OSCC., identifier:Pathology & Oncology Research, 21(3), pp.765-773; 2015

Intramuscular lipoma (IML) is an uncommon tumor in the oral cavity, and characterized by infiltrating adipose tissue and muscle atrophy. Although oral IMLs are almost always solitary, we reported a rare case of IML of the tongue complicated with diffuse lipomatosis of the forearm. A 58-year-old woman was referred to our department with a painless swelling of the left tongue that had been present for 6 months. Clinical examination revealed a 35mm×30mm×20mm well-defined, elastic soft mass in the anterior left region of the tongue border. The lesion was removed under general anesthesia via the left margin of the tongue. No signs of recurrence have been observed 15 months after surgery., identifier:Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 24(4), pp.237-240; 2012

British Journal of Oral and Maxillofacial Surgery, 50(3), pp.e43-e44; 2012

Amelanotic melanoma of the oral mucosa is extremely rare. We describe herein our experience of amelanotic melanoma arising in the mandibular mucosa. An 85-year-old woman was referred to our clinic with swelling of the left lower gingival mucosa. The histopathological diagnosis was amelanotic melanoma, as determined by immunohistochemical examination. The tumor cells were positive for S-100, Melan-A, HMB-45, and vimentin. The patient declined surgical treatment, so she received irradiation therapy. At a total dose of 10. Gy, the patient exhibited lassitude, so we terminated radiotherapy. Bleeding from the tumor persisted, and the patient developed anemia and hypouresis. She also contracted pneumonia. The patient's general condition worsened, and she died., Oral Science International, 8(2), pp.60-63; 2011

CT10 regulator of kinase (CRK) was originally identified as an oncogene product of v-CRK in a CT10 chicken retrovirus system. Overexpression of CRKII has been reported in several human cancers. CRKII regulates cell migration, morphogenesis, invasion, phagocytosis, and survival; however, the underlying mechanisms are not well understood. In the present study, we evaluated the possibility of CRKII as an appropriate molecular target for cancer gene therapy. The expression of CRKII in 71 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens was determined immunohistochemically, and the correlation of CRKII overexpression with clinicopathological factors was evaluated. Overexpression of CRKII was detected in 41 of 70 oral squamous cell carcinomas, the frequency being more significant than in normal oral mucosa. In addition, CRKII overexpression was more frequent in higher-grade cancers according to the T classification, N classification, and invasive pattern. Moreover, RNAi-mediated suppression of CRKII expression reduced the migration and invasion potential of an oral squamous cell carcinoma cell line, OSC20. Downregulation of CRKII expression also reduced the expression of Dock180, p130Cas, and Rac1, and the actin-associated scaffolding protein cortactin. These results indicate that the overexpression of CRKII is tightly associated with an aggressive phenotype of oral squamous cell carcinoma. Therefore, we propose that CRKII could be a potential molecular target of gene therapy by RNAi-targeting in oral squamous cell carcinoma., Cancer Letters, 303(2), pp.84-91; 2011

The p53R2 gene encodes the ribonucleotide reductase (RR) small subunit 2 homologue, and is induced by several stress signals activating p53, such as DNA-damaging agents. The p53R2 gene product causes an increase in the deoxynucleotide triphosphate (dNTP) pool in the nucleus, which facilitates DNA repair and synthesis. We hypothesized that p53R2 would be a good molecular target for cancer gene therapy. In this study, three human oral cancer cell lines (SAS, HSC-4 and Ca9-22), a human breast cancer cell line MCF-7, and a normal human fibroblast cell line NHDF were tested. We silenced the expression of p53R2 with the highly specific post-transcriptional suppression of RNA interference (RNAi). We investigated p53R2 expression with the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The sensitivity to anticancer agents was evaluated by a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The expression of p53R2 showed no association with the mutational status of p53. The cancer cell lines with higher p53R2 expression were more resistant to 5-FU. RNAi-mediated p53R2 reduction selectivity inhibited growth and enhanced chemosensitivity in cancer cell lines but not in normal fibroblasts. These results suggest that basal transcription of p53R2 could be associated with the sensitivity to anticancer agents. Moreover, we assessed the possibility that p53R2 would be a good molecular target, and report that RNAi targeting of p53R2 could be useful for oral cancer gene therapy.