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For the purpose of analyzing mechanisms related to the cis-diamminedichloroplatinum resistance in head and neck squamous cell carcinoma, we analyzed RPMI2650 and its derived previously established cis-diamminedichloroplatinum resistant cell line RPMI2650CR. To identify resistant phenotype-related microRNAs, we compared microRNA expressions between RPMI2650CR and RPMI2650 by microarray. One of the microRNAs as downregulated, miR-34a, was further investigated. Decreased expression of miR-34a in RPMI2650CR was confirmed by quantitative reverse transcription-polymerase chain reaction, but introduction of the miR-34a precursor into RPMI2650CR or the inhibitor of miR-34a into RPMI2650 did not change cis-diamminedichloroplatinum sensitivities. However, 24 patients with sinonasal squamous cell carcinomas treated with intra-arterial infusion of cis-diamminedichloroplatinum showed a significant association between decreased expression of miR-34a and poor disease specific survival (P = 0.0015), poor disease free survival (P = 0.0019), and poor local control rates (P = 0.017) (median follow-up period: 53 months). Furthermore, multivariate analyses demonstrated significant associations between miR-34a expression and the hazard ratios of disease free survival at 0.005 (95% confidence interval [CI] 0.00-0.29, P = 0.011) and local control rate at 0.008 (95% CI 0.00-0.44, P = 0.019), although other parameters such as age, gender, treatment method, T and N stages did not show any similar association. These results strongly suggest that miR-34a expression can be an independent prognostic biomarker in patients with sinonasal squamous cell carcinoma who are undergoing treatment with cis-diamminedichloroplatinum. (Cancer Sci 2012; 103: 1737-1743 H ead and neck squamous cell carcinoma (HNSCC) is a frequently occurring tumor with an estimated 550 000 new cases worldwide in 2008.(1) Because this region harbors indispensable sensory organs such as the eyes, nose, and tongue, it is very important to take into consideration the patients' quality of life (QOL) in addition to the goal of better disease prognosis. Therefore, chemotherapy has an important role, along with surgery and radiotherapy, in the treatment of these lesions.We previously reported on per se (2) and de novo (acquired) resistance (3) of platinum-containing compound cisplatin (cisdiamminedichloroplatinum; CDDP), a key drug for patients with HNSCC, (4)(5)(6) and we highlighted genes related to CDDP resistance per se and de novo in HNSCC using mRNA microarray platforms in HNSCC cell lines and identified IGF2 as one of the chemoresistant-associate genes of CDDP.(3) Antitumor effects of CDDP were recognized by disruption of DNA synthesis.(7) However, some tumor cells acquire resistance to this drug, and HNSCC is one of the tumors with frequent acquisition of this unfavorable resistance although only few reports were published to date.(3) Although such tumor cells with acquired CDDP resistance may also acquire increased sensitivity to other chemotherapeutic reagents such as tax...

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Esophageal cancer is one of the common malignancies worldwide, particularly in eastern African and Asian countries including Japan. Taxane (paclitaxel or docetaxel) is one of the effective chemotherapeutic reagents for patients with esophageal cancer, but acquisition of chemoresistance frequently occurs; this is one of the most frequent causes for therapeutic failure. In this study, we established three taxane resistant esophageal squamous cell carcinoma cell lines and explored possible mechanisms for the acquisition of chemoresistance. Microarray analyses indicated that the ABCB1 (ATP binding cassette subfamily B member 1) gene was significantly upregulated in taxane resistant esophageal cancer cell lines. Moreover, we found that siRNA mediated ABCB1 knockdown successfully restored drug sensitivity in both paclitaxel and docetaxel resistant esophageal cancer cell lines. In conclusion, we propose that ABCB1 might play a pivotal role in acquisition of taxane resistance and could be a promising target for treatment of patients with esophageal cancer after acquisition of taxane resistance.