Galanin receptor 2 utilizes distinct signaling pathways to suppress cell proliferation and induce apoptosis in HNSCC.

Galanin and its receptors, GALR1 and GALR2, are tumor suppressors and represent therapeutic targets in head and neck squamous cell carcinoma (HNSCC). In the present study, it was demonstrated that the re­expression of GALR1 in GALR1 and GALR2­negative HNSCC cells suppresses tumor cell proliferation. This is mediated via extracellular­regulated protein kinase­1/2 (ERK1/2)­dependent effects on the cyclin­dependent kinase inhibitors (CKI) and cyclin D1. In combination with galanin, GALR2 also suppressed proliferation by increasing CKI and decreasing cyclin D1 levels. In contrast to GALR1, overexpression of GALR2 also induced caspase­3­dependent apoptosis. It was identified that in GALR2­transfected cells, galanin induced activation of ERK1/2 and suppressed cell proliferation. Galanin stimulation also decreased the expression of cyclin D1 and induced apoptotic DNA ladder formation in GALR2­transfected cells. Pretreatment with the ERK1/2­specific inhibitor U0126 and pertussis toxin prevented the suppression of cyclin D1 expression, however did not affect DNA ladder formation. In conclusion, GALR2 expression in the presence of galanin exerts antitumor effects via cell cycle arrest and apoptotic pathways, and reactivation of these pathways may have therapeutic benefits in HNSCC.

Rare case of malignant transformation of recurrent respiratory papillomatosis associated with human papillomavirus type 6 infection and p53 overexpression.

Recurrent respiratory papillomatosis (RRP), a chronic upper respiratory condition characterized by diffuse multiple recurring papillomas, is thought to result from human papillomavirus (HPV) type 6 or 11 infection. Although RRP is an intractable disease, malignant transformation of RRP is rare. The underlying mechanism, however, has not been elucidated. We describe the clinical course of a patient who underwent more than 130 operations for RRP associated with HPV type 6 infection and subsequently suffered spontaneous malignant transformation to squamous cell carcinoma. Immunohistochemical analysis revealed that malignant transformation might result from a genomic defect, such as p53 inactivation, leading to stimulation of uncontrolled cell proliferation by HPV type 6 for an extended period, but not directly because of HPV itself. Our results could help in the development of novel therapeutic strategies for severe RRP, although further studies are required before clinical application of molecular targeted therapies.

Multidisciplinary therapy consisting of minimally invasive resection, irradiation, and intra-arterial infusion of 5-fluorouracil for maxillary sinus carcinomas.

BACKGROUND: Current goals for the treatment of maxillary sinus carcinoma include the preservation of vision, eating, communication, and appearance, as well as the achievement of a cure. METHODS: Japanese patients (n = 121) with maxillary sinus carcinoma were analyzed retrospectively. All patients underwent multidisciplinary therapy including minimally invasive resection, 20 Gy irradiation, and intra-arterial infusion of 5-fluorouracil. RESULTS: The 5- and 10-year overall survival rates were 73% and 68%, respectively. In 97 patients with squamous cell carcinoma (SCC), the 5- and 10-year overall survival rates were 76% and 70%, respectively. All 29 patients with orbital invasion retained the orbital contents, and 21 of these patients demonstrated adequate visual acuity. There were 16 complications, including trismus (5 patients), double vision (5 patients), fistula formation (3 patients), and cataract (3 patients). CONCLUSION: A multidisciplinary therapy, consisting of minimally invasive resection, irradiation, and regional chemotherapy, can yield good patient prognosis and quality of life after treatment.

Case of high-risk epithelioid hemangioendothelioma of the neck.

BACKGROUND: Epithelioid hemangioendotheliomas (EHEs) of the head and neck region are uncommon malignant neoplasms that exhibit various biologic behaviors characteristic of both low- and high-grade malignancy. A subgroup of EHEs identified as "high-risk" EHEs because of their size and mitotic activity is associated with an unfavorable clinical course and poor prognosis. MATERIALS AND RESULTS: We describe the treatment of the first and, in terms of size, largest case of high-risk EHE arising from the neck. Despite wide excision, recurrence occurred 9 months after surgery, as had been expected. However, the tumor was found to express both vascular endothelial growth factor (VEGF) and VEGF receptor 2, indicating the potential of anti-VEGF therapy in the treatment of such cases. CONCLUSION: The finding that a high-risk EHE arising from the head and neck region is characterized by expression of VEGF and its receptor provides further support for the development of targeted molecular therapies.