WIP1 stimulates migration and invasion of salivary adenoid cystic carcinoma by inducing MMP-9 and VEGF-C.

The wild-type p53 induced phosphatase 1 (WIP1) is an oncogene overexpressed in a variety of human cancers. Here, we demonstrated that WIP1 silencing reduced MMP-9 and VEGF-C expression as well as migration and invasion of salivary adenoid cystic carcinoma (ACC) cells. Overexpression of MMP-9 or VEGF-C restored migration and invasion in WIP1 knockdown cells, indicating that MMP-9 and VEGF-C are downstream targets of WIP1 signaling. Levels of cyclin D1 and c-Myc, targets of Wnt/ß-catenin pathway, were significantly decreased by WIP1 silencing. In addition, WIP1 expression was positively associated with metastasis and prognosis of ACC patients as well as with MMP-9 or VEGF-C in ACC tissues.

Phase II trial of sorafenib in advanced salivary adenoid cystic carcinoma of the head and neck.

BACKGROUND: There is a need to improve the systemic treatment of advanced adenoid cystic carcinoma (ACC). Response rates to chemotherapy are poor and preliminary investigations of molecularly targeted agents have been disappointing. In this study, we evaluate sorafenib, an oral multikinase inhibitor, which has an attractive targeting profile for this disease. METHODS: In a single-arm phase II trial, patients with unresectable locally recurrent and/or metastatic ACC were treated with sorafenib 400 mg bid. RESULTS: Twenty-three patients, median age 51 years, were recruited from 2009 to 2011. Median progression-free survival (PFS) and overall survival (OS) were 11.3 and 19.6 months, respectively. PFS at 6 and 12 months were 69.3% and 46.2%, respectively. Sorafenib was only reasonably well tolerated, and 13 patients (57%) experienced grade 3 toxicity. CONCLUSION: Sorafenib showed modest activity in ACC with a 12-month PFS of 46.2%. Sorafenib 400 mg bid was associated with significant toxicity and, taken together with limited effectiveness, cannot be enthusiastically recommended for further evaluation.

Epirubicin, cisplatin and protracted venous infusion 5-Fluorouracil chemotherapy for advanced salivary adenoid cystic carcinoma.

AIMS: Adenoid cystic carcinoma (ACC) is a rare tumour that usually arises in the salivary glands. Initial management is surgery often combined with adjuvant radiotherapy. Chemotherapy is reserved for treatment of symptomatic recurrence. We evaluated the combination of epirubicin, cisplatin and protracted venous infusion 5-fluorouracil (ECF) in the management of ACC. MATERIALS AND METHODS: Patients referred for treatment of advanced, symptomatic ACC were considered. The drugs given were epirubicin 50 mg/m(2) 3-weekly, cisplatin 60 mg/m(2) 3-weekly and protracted venous infusion 5-fluorouracil 200 mg/m(2)/day. RESULTS: Eight patients (median age 46 years) received a median of five cycles of chemotherapy. All patients had had previous surgery, seven had had previous radiotherapy and one had had previous chemotherapy. One patient showed a partial response (duration 34 months) and five showed stable disease (median duration 13.6 months [6.8-15.9+ months]). Median survival was 27 months (3.5-62.3 months). CONCLUSIONS: The activity of ECF in ACC of the head and neck seems to be similar to the combination of cisplatin and 5-fluorouracil and single-agent epirubicin.

The role of skull base surgery for the treatment of adenoid cystic carcinoma of the sinonasal tract.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the sinonasal tract is an aggressive malignancy associated with a poor 5-year survival rate. The role of skull base surgery for the treatment of patients presenting with sinonasal ACC and its impact upon their survival has not previously been evaluated. METHODS: A retrospective review of 35 patients with ACC of the sinonasal tract who were treated with surgery and radiation therapy at the University of Pittsburgh Medical Center was performed to evaluate patient outcome. RESULTS: Local recurrence of tumor following surgery and radiation therapy was observed in 36% of the patients originally treated at the University of Pittsburgh Medical Center. Fourteen percent of these patients developed a regional tumor recurrence, and 21% developed distant metastases. We did not identify any tumor-related factors that predicted patient outcome. Local recurrences were treated with salvage surgical excision, and, despite aggressive management, only 1 of 17 patients with local recurrence was considered cured (NED) at 24 months (follow-up after salvage surgery). Overall, disease-free survival was 46.4%, at a median follow-up of 40 months. CONCLUSIONS: ACC of the sinonasal tract is an aggressive malignancy. Skull base surgery has facilitated the gross total excision of advanced lesions that were deemed inoperable in the past, but has not resulted in an overall improvement in disease-free survival. Local recurrence portends a very poor prognosis, despite aggressive salvage regimens. Alternative therapies for local recurrences warrant further investigation. Prospective, randomized studies are necessary to evaluate the outcome of patients treated with aggressive multimodal treatment regimens, including chemotherapeutic regimens.

[Results in combined hyperthermia/radiotherapy of adenoid cystic carcinomas compared with conventional treatment]. / Erfahrungen mit der kombinierten Hyperthermie/Strahlentherapie adenoidzystischer Karzinome im Vergleich mit herkömmlicher Behandlung.

158 patients with advanced malignancies of the head and neck area were treated by a combined hyperthermia/radiotherapy since 1972. 16 were adenoid cystic carcinoma (ACC). Their treatment results are compared with 28 ACC after radiotherapy alone. All 16 patients with hyperthermia achieved a complete remission. CR in 28 ACC-patients without hyperthermia was 61%. 113 patients with hyperthermia-treated squamous cell carcinomas had a comparatively low CR-rate of 49%. Five-year-survival on the other hand was 50% for ACC after hyperthermia, 57% after a planned postoperative radiation without hyperthermia and 37.5% after a radiotherapy alone in cases of inoperability. The combination of hyperthermia and radiotherapy is indicated in cases of advanced inoperable ACC and leads to a high percentage of local tumour control.