Ikuko Takeda

Salivary gland carcinoma treated with concomitant chemoradiation with intraarterial cisplatin and docetaxel

Malignant neoplasms of the salivary gland are uncommon entities in which surgical resection of the primary lesion has been accepted as a standard therapeutic option. The efficacy of radiation and systemic chemotherapy has been limited for patients with recurrent, metastatic, or unresectable disease because of unfavorable response rates and the short duration of the response. We treated one patient with recurrent adenoid cystic carcinoma arising from the sublingual gland and one patient with primary adenocarcinoma arising from the parotid gland with transfemoral intraarterial chemotherapy, based on full-dose cisplatin and docetaxel and concurrent external-beam radiotherapy. The doses of cisplatin and docetaxel in the two patients were 80–100 mg/m2 and 10–15 mg/m2, respectively. Docetaxel was infused first, followed by cisplatin. Both patients obtained complete responses. Although complications such as mucositis, anorexia, neutropenia, and ischemic colitis were observed, they were well tolerated and manageable. The concomitant chemoradiotherapy of cisplatin and docetaxel seemed to be a practicable option for patients with recurrent and unresectable salivary gland carcinomas.

Simvastatin inactivates β1‐integrin and extracellular signal‐related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells

The 3‐hydroxy‐3‐methylglutaryl (HMG)‐CoA reductase inhibitors, also called statins, are commonly used as lipid‐lowering drugs that inhibit cholesterol biosynthesis. An anticancer effect, as a pleiotropic function of certain statins, has been hypothesized. In the present study, we investigated the effect of simvastatin, one of the natural statins, on cell proliferation, cell cycle, invasive activity, and molecular expressions associated with cell–extracellular matrix adhesion, signal transduction, and DNA synthesis in Tu167 and JMAR cells from head and neck squamous cell carcinoma. The addition of simvastatin resulted in a dose‐dependent inhibition of cell growth and migration into the extracellular matrix. Considerable morphological changes occurred after treatment with simvastatin, demonstrating loss of cell adhesion and disruption of actin filaments in cytoplasm. The inhibitory effect of simvastatin on cell proliferation seemed to be associated with cell cycle arrest and increased expression of p21, p27, and activated caspase‐3. The expression of β1‐integrin, a counter adhesion for the extracellular matrix, phosphorylated FAK, and phosphorylated ERK was decreased by treatment with simvastatin. The proapoptotic effect of simvastatin was inhibited by treatment with mevalonate. cDNA microarray assay demonstrated that molecular changes resulting from treatment with simvastatin included the up‐regulation of cell cycle regulators and apoptosis‐inducing factors and the down‐regulation of integrin‐associated molecules and cell proliferation markers. Of down‐regulated genes induced by simvastatin treatment, a significant depletion of thymidylate synthase was confirmed using western blot analysis. These results imply that simvastatin has the potential to be effective for the prevention of the growth and metastasis of cancer cells. (Cancer Sci 2007; 98: 890–899)

The role of periostin in eosinophilic otitis media

Abstract Conclusion: We investigated the localization of periostin in middle ear specimens from patients with eosinophilic otitis media (EOM) and from a newly constructed animal model for EOM. Periostin-positive immunostaining was observed in the middle ear sections obtained from the EOM patients. Immunoreactivity for periostin was also seen in the animal model. These results suggest that periostin plays an important role in subepithelial fibrosis in the middle ear in EOM. Objective: The purpose of the present study was to investigate the role of periostin in the middle ear of EOM patients and an animal model. Methods: Histological and immunohistochemical analyses for periostin were carried out in the middle ear specimens of six EOM patients with/without asthma. An animal model of EOM was constructed by intraperitoneal and topical sensitization with ovalbumin (OVA). Histological and immunocytochemical analyses for periostin were also performed in this model. Results: Immunoreactivities for periostin were observed in the basement membrane and extracellular matrix of the middle ear sections obtained from all EOM patients with/without asthma. In the animal model, eosinophil infiltration and middle ear mucosa thickness were observed. Moreover, periostin-positive immunostaining was shown in the extracellular matrix of the middle ear mucosa on the side topically boosted by OVA.