Resistance to cisplatin is a major obstacle to successful treatment of head and neck squamous cell carcinoma (HNSCC). To investigate the molecular mechanism of this resistance, we compared the gene expression profiles between the cisplatin‐sensitive SCC cell lines (Sa‐3, H‐1 and KB) and the cisplatin‐resistant cell lines established from them (Sa‐3R, H‐1R and KB‐R) using Affymetrix U133 Plus 2.0 microarray. We identified 199 genes differentially expressed in each group. To identify important functional networks and ontologies to cisplatin resistance, the 199 genes were analyzed using the Ingenuity Pathway Analysis Tool. Fifty‐one of these genes were mapped to genetic networks, and we validated the top‐10 upregulated genes by real‐time reverse transcriptase‐polymerase chain reaction. Five novel genes, LUM, PDE3B, PDGF‐C, NRG1 and PKD2, showed excellent concordance with the microarray data. In 48 patients with oral SCC (OSCC), positive immunohistochemical staining for the five genes correlated with chemoresistance to cisplatin‐based combination chemotherapy. In addition, the expression of the five genes predicted the patient outcomes with chemotherapy. Furthermore, siRNA‐directed suppressed expression of the five genes resulted in enhanced susceptibility to cisplatin‐mediated apoptosis. These results suggested that these five novel genes have great potential for predicting the efficacy of cisplatin‐based chemotherapy against OSCC. Global gene analysis of cisplatin‐resistant cell lines may provide new insights into the mechanisms underlying clinical cisplatin resistance and improve the efficacy of chemotherapy for human HNSCC.

Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor of the ErbB family, which is expressed or highly expressed in a variety of solid tumors, including oral cancers. High EGFR expression has been correlated with tumor size, metastasis and survival. In recent years, EGFR has been considered a promising target for monoclonal antibody therapy. A total of 52 patients with oral squamous cell carcinoma (OSCC) were selected for EGFR and phosphorylated EGFR (p-EGFR) detection. Immunohistochemical staining was performed to evaluate EGFR and p-EGFR expression. Positive EGFR and p-EGFR staining was present in 92.3% (48/52) and 98.0% (51/52) of all cases, respectively. High EGFR and p-EGFR expression was present in 63.4% (33/52) and 69.2% (36/52) of all cases, respectively. EGFR and p-EGFR expression did not correlate with the clinical factors tumor stage, regional lymph node metastasis, or distant metastasis. However, a statistically significant correlation was identified between high EGFR expression and the pathologic factor tumor invasion. As a conclusion, the majority of OSCCs highly express EGFR and p-EGFR, indicating the importance of studying the efficacy of anticancer therapy targeting these signal factors.

Epidermal growth factor receptor (EGFR) is involved in multiple aspects of cancer cell biology. EGFR has already been identified as an important target for cancer therapy, with various kinds of EGFR inhibitors currently used in treatment of several human cancers. Recently, EGFR and its downstream signaling pathways were identified as being associated with cisplatin sensitivity. In addition, EGFR inhibitors have shown significant promise for patients who failed cisplatin-based therapy. In this study, we investigated whether treatment with an EGFR inhibitor improves cisplatin sensitivity in oral squamous cell carcinoma (OSCC) cell lines. The effects of a combination of AG1478, a specific EGFR tyrosine kinase inhibitor, with cisplatin were evaluated in cultured OSCC cell lines and cisplatin-resistant sublines. Higher expression of EGFR and p-EGFR was found in the two cisplatin-resistant cell lines compared with the corresponding parental cell lines. In addition, augmented inhibition of OSCC cell growth by the combination of AG1478 with cisplatin was found in both cell lines. These results suggest that the combination of an EGFR inhibitor and cisplatin may be useful as a rational strategy for the treatment of patients with oral cancer with acquired cisplatin resistance.

Background No large-scale study of the timing of autism spectrum disorder (ASD) diagnosis has been performed in Japan to date. The aim of this study was to examine sex differences and annual trends in age at diagnosis of ASD using clinical data. Methods Clinical data for children aged less than 18 years diagnosed with ASD between January 1, 2009, and December 31, 2013, and in whom follow-up was possible 1 year after diagnosis, were extracted. Results The mean age at ASD diagnosis was 7.2 ± 4.2 years and the mode age was 3 years. No sex difference was observed for age at diagnosis (p = 0.157). An annual trend of earlier diagnosis was observed when fiscal years were compared (p < 0.001). Conclusion This study highlighted the need to develop and provide appropriate early intervention methods and services for ASD children in Japan.

Abstract.A 10-year-old, female, mongrel showed hemorrhage from vulva. By magnetic resonance image (MRI) and endoscopic examination, a multipapillary mass with a grape-like appearance was found around the urethral opening. Histologically, the mass consisted of variable-sized round-, spindleto-polygonal-shaped tumor cells including many multinuclear cells. Mitotic figures were also frequently observed. In some areas, that tumor cells were loosely arranged, with intercellular myxoid components. Immunohistochemically, these tumor cells were strongly positive for vimentin and focally positive for desmin but negative for myoglobin. Thus, the case was diagnosed as a relatively poorly differentiated botryoid rhabdomyosarcoma by the macroscopic, histopathologic, and immunohistochemical identification. This is the first report of botryoid rhabdomyosarcoma developing in the vagina of a dog.Key words: Dogs; histopathology; rhabdomyosarcoma; vagina.Rhabdomyosarcoma is a malignant tumor of striated muscles, and it rarely occurs in domestic animals. On the basis of histologic features, rhabdomyosarcomas are classified into four categories: embryonal, botryoid, alveolar, and pleomorphic.3 Of these subtypes, botryoid rhabdomyosarcoma has been regarded as a variant of embryonal rhabdomyosarcoma and is characterized by polypoid, grape-like growth pattern. It has been reported to occur most commonly in the urinary bladder of large-breed dogs aged less than 2 years and has also been reported to occur in the urinary bladder of a smallbreed dog (Maltese) and a horse. 7,9 There is only one report of its occurrence in an organ other than the urinary bladder, i.e., in the uterus of a horse. 8In this article, we describe the histopathology of botryoid rhabdomyosarcoma of the vagina in dogs. To our knowledge, this is the first report of a botryoid rhabdomyosarcoma observed in an organ other than the urinary bladder in dogs.We report the case of a 10-year-old, spayed female mongrel who had continuous hemorrhaging from the vulva. The dog was referred to a veterinary hospital; endometritis was diagnosed, and the dog was ovariectomized. However, the hemorrhage did not stop, and a mass was found at the vestibulum vaginae. This mass was removed and diagnosed as a malignant tumor of unknown origin. A few months later, recurrence was observed at the same site, and hemorrhage was observed again. The dog was brought to the Animal Medical Center, College of Bioresource Sciences, Nihon University. Endoscopy revealed a grape-like, multipapillary mass (approximately 1-3 cm in diameter) around the urethral opening (Fig. 1). This mass was fragile and hemorrhaged easily, and the urethral opening was difficult to find. Magnetic resonance imagining (MRI) revealed that the urethra had translocated, and the mass had developed invasively but had a relatively clear border between it and the neighboring tissues. This mass was surgically removed, and recurrence and metastasis were not observed after this operation.The tissue samples were fixed in 10% neutral buffe...