Neutron radiation enhances cisplatin cytotoxicity independently of apoptosis in human head and neck carcinoma cells.

Recent advances in combined modality treatment of locally advanced head and neck cancer have improved local and regional disease control and survival with better functional outcome. However, the local and regional failure rate after radiation therapy is still high for tumors that respond poorly to cisplatin-based neoadjuvant chemotherapy. This clinical observation suggests a common biological mechanism for resistance to cisplatin and photon irradiation. In this report, we investigated the molecular basis underlying cisplatin resistance in head and neck squamous carcinoma (HNSCC) cells and asked if fast neutron radiation enhances cisplatin cytotoxicity in cisplatin-resistant cells. We found that cisplatin sensitivity correlates with caspase induction, a cysteine proteinase family known to initiate the apoptotic cell death pathway, suggesting that apoptosis may be a critical determinant for cisplatin cytotoxicity. Neutron radiation effectively enhanced cisplatin cytotoxicity in HNSCCs including cisplatin-resistant cells, whereas photon radiation had little effect on cisplatin cytotoxicity. Interestingly, neutron-enhanced cisplatin cytotoxicity was associated neither with apoptosis nor with cell cycle regulation, as determined by caspase activity assay, annexin V staining, and flow cytometric analysis. Taken together, the present study provides a molecular insight into cisplatin resistance and may also provide a basis for more effective multimodality protocols involving neutron radiation for patients with locally advanced head and neck cancer.

Comparing methods for maintaining the safety of a child with pica.

Pica, a potentially life-threatening behavior problem exhibited among persons with mental retardation is sometimes addressed by methods such as application of restraints to reduce or eliminate associated risks (Rojahn, Schroeder, & Mulick, 1980). However, restraints may be associated with decreases in social interaction and negative impact on quality of life. We evaluated two methods (restraint vs. no restraint) for maintaining the safety of a client with pica on three dimensions: (a) level of pica, (b) therapist effort, and (c) impact on quality of life. Both methods prevented pica, however, the no restraint condition required less therapist effort and had less negative impact on quality of life. All three dimensions were included in a clinical decision-making model to determine the least restrictive, safe level of restraint for a 4-year-old girl while assessment and treatment procedures were conducted. The clinical utility of this multifactor decision-making model is discussed.