Satoshi Fukuda

Tripartite Motif Protein 32 Facilitates Cell Growth and Migration via Degradation of Abl-Interactor 2

Tripartite motif protein 32 (TRIM32) mRNA has been reported to be highly expressed in human head and neck squamous cell carcinoma, but the involvement of TRIM32 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that TRIM32 binds to Abl-interactor 2 (Abi2), which is known as a tumor suppressor and a cell migration inhibitor, and we showed that TRIM32 mediates the ubiquitination of Abi2. Overexpression of TRIM32 promoted degradation of Abi2, resulting in enhancement of cell growth, transforming activity, and cell motility, whereas a dominant-negative mutant of TRIM32 lacking the RING domain inhibited the degradation of Abi2. In addition, we found that TRIM32 suppresses apoptosis induced by cis-diamminedichloroplatinum (II) in HEp2 cell lines. These findings suggest that TRIM32 is a novel oncogene that promotes tumor growth, metastasis, and resistance to anticancer drugs.

Superselective high-dose cisplatin infusion with concomitant radiotherapy in patients with advanced cancer of the nasal cavity and paranasal sinuses: a single institution experience.

The current study aimed to evaluate the efficacy of superselective high‐dose cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with advanced cancer of the nasal cavity and paranasal sinuses.

Voice-Related Quality of Life After Treatment of Laryngeal Cancer

OBJECTIVE To determine patient-perceived voice-related quality of life in patients treated with various methods based on the results of Voice-Related Quality of Life (VRQOL) and Voice Handicap Index-10 (VHI-10) questionnaires. DESIGN The VRQOL and VHI-10 questionnaires. SETTING University hospital. PATIENTS One hundred thirty-seven patients who had received definitive treatment of laryngeal cancer were followed-up at Hokkaido University Hospital, Sapporo, Japan, and were alive with no evidence of malignancy at the time of the survey. MAIN OUTCOME MEASURE Patient-perceived voice-related quality of life based on the results of the VRQOL and VHI-10 questionnaires. RESULTS The mean VRQOL scores for patients who had undergone radiotherapy (n = 63), chemoradiotherapy (n = 29), laser surgery (n = 14), or total laryngectomy (n = 27) as final treatment of laryngeal cancer were 92.6, 92.9, 85.5, and 68.4, respectively; the mean VHI-10 scores were 2.87, 2.34, 5.43, and 11.26, respectively. CONCLUSION The VRQOL and VHI-10 questionnaires are important in judging the overall effectiveness of treatment options for laryngeal cancer.

Increased mitochondrial DNA induces acquired docetaxel resistance in head and neck cancer cells.

Docetaxel is one of the most effective chemotherapeutic agents against cancer; nevertheless, some patients develop resistance. Unfortunately, their causes and mechanisms remain unknown. We created docetaxel-resistant DRHEp2 from human laryngeal cancer HEp2 and investigated the roles of mitochondrial DNA (mtDNA) and reactive oxygen species (ROS) on docetaxel resistance. DRHEp2 had greatly increased mtDNA content. Reduction of mtDNA content in DRHEp2 by ethidium bromide treatment reduced the resistance. These results indicate the possible roles of mtDNA-coded enzymes in mitochondrial respiratory chain (MRC) in resistant mechanisms. Oligomycin A, an Fo-ATPase inhibitor, eliminated docetaxel resistance in DRHEp2; in contrast, inhibitors of other MRC did not. RNA interference targeted to Fo-ATPase d-subunit restored docetaxel-induced cytotoxicity to DRHEp2. These results indicate the roles of Fo-ATPase for resistant mechanisms. Docetaxel induced ROS generation in HEp2 but not in DRHEp2 and antioxidant pyrrolidine dithiocarbamate eliminated docetaxel-induced cytotoxicity, suggesting roles of ROS in docetaxel-induced cell death. Furthermore, inhibition of Fo-ATPase by Oligomycin A induced docetaxel-mediated ROS generation in DRHEp2. Taken together, DRHEp2 acquired docetaxel resistance through increasing Fo-ATPase, which led to diminish docetaxel-induced ROS generation and subsequently inhibited cell death. In conclusion, mtDNA plays an important role in developing docetaxel resistance through the reduction of ROS generation by regulating Fo-ATPase.

Concomitant Weekly Cisplatin and Radiotherapy for Head and Neck Cancer

OBJECTIVE The most common chemoradiotherapy regimen is high-dose (100 mg/m(2)) three-weekly cisplatin with concomitant radiotherapy; however, this protocol is associated with acute and late toxicities. Here, we reviewed the dose intensity and toxicity for concomitant weekly cisplatin and radiotherapy in patients with head and neck cancer. METHODS Fifty-three patients with untreated head and neck cancer were enrolled and evaluated at our institution from April 2006 to April 2010. Weekly cisplatin (40 mg/m(2)) was given on weeks 1, 2, 3, 5, 6 and 7 with radiotherapy, which comprised a standard dose of 70 Gy delivered in 35 daily fractions over 7 weeks. RESULTS Fifty-one patients (96.2%) received the full dose of radiotherapy, while the course was disrupted by adverse events in two. Over the course of the chemotherapy, 31 patients (58.5%) received more than 200 mg/m(2) cisplatin. The toxicity was manageable in all except one patient, who died of sepsis after completing treatment. The 2-year overall survival rate and local progression-free rate for all patients were 93.7% and 88.0%, respectively. The primary site showed a complete response in 52 patients (98.1%) and a partial response in 1 patient (1.9%). The primary disease was well controlled by chemoradiotherapy in 47 patients (88.7%). CONCLUSIONS Weekly cisplatin could be easier to manage than three-weekly cisplatin, because patients can be monitored more regularly for toxicity allowing the schedule to be altered if required. This regimen appears to be a suitable alternative to three-weekly high-dose cisplatin with concomitant radiotherapy.

Salvage surgery for local recurrence after chemoradiotherapy or radiotherapy in hypopharyngeal cancer patients.

This retrospective study aimed to assess the role of salvage surgery for local recurrence in hypopharyngeal cancer (HPC) patients who had received radiotherapy (RT) or concomitant chemoradiotherapy (CRT) as an initial treatment. The local recurrence rate, salvage rate after local recurrence and overall survival rate were investigated in 104 HPC patients who received treatment between 1991 and 2005. Local recurrence in the primary site was observed in 41 patients (rate, 39.4%) of whom only 12 could undergo further salvage surgery. Disease control was achieved in seven of these patients (successful salvage rate, 17.1%). The 5-year overall survival rate was 40.6% in the RT/CRT patient group and successful salvage rates for T1, T2, T3 and T4 primary disease were 33.3% (1/3), 20.0% (4/20), 16.7% (2/12) and 0% (0/6), respectively. Severe postoperative complications such as pharyngo-cutaneous fistula were seen in six patients (50.0%). Prognosis of patients with locally recurring HPC after RT/CRT is poor at any primary T-stage and the incidence of postoperative complication is relatively high. This should be taken into consideration when the initial treatment plan is decided and the choice of salvage surgery for such recurrent cases should be carefully determined.

Importance of comorbidity in hypopharyngeal cancer

Comorbidity has an impact on survival in laryngeal cancer in several reports. However, the importance of comorbidity in hypopharyngeal cancer (HPC) has not been reported.

Nasal manifestations of immunoglobulin G4‐related disease

Immunoglobulin (Ig)G4‐related disease is a systemic syndrome, characterized by sclerosing lesions that mainly affect the exocrine tissue. Although some patients with IgG4‐related disease complain of nasal symptoms, there are few reports concerning the nasal manifestations of this disease. We investigated the clinical and pathological features of the nasal manifestations of IgG4‐related disease.

Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer

Background:The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS).Methods:Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100–120 mg m−2 per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65–70 Gy).Results:One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n=5), brain necrosis (n=1), and ocular/visual problems (n=14) were observed as late adverse reactions.Conclusion:We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.

Malignant melanoma of the head and neck: A multi‐institutional retrospective analysis of cases in Northern Japan

Mucosal melanoma of the head and neck is rare and is associated with a poor prognoses because of locoregional failure and distant metastasis. The aim of our study was to review the characteristics of these patients in northern Japan and to analyze their outcomes.