Comparison of Doxycycline Delivery Methods for Tet-Inducible Gene Expression in a Subcutaneous Xenograft Model

Doxycycline (Dox) controlled Tet systems provide a powerful and commonly used method for functional studies on the consequences of gene overexpression/downregulation. However, whereas Dox delivery in tissue culture in vitro is relatively simple, the situation in vivo is more complex. Several methods of Dox delivery in vivo have been described—e.g., in drinking water containing alcohol, in drinking water containing various concentrations of sucrose, and in feed. Unfortunately there are no reports directly comparing the advantages and disadvantages of these diverse methods, and there is no generally accepted standard. We therefore compared four non-invasive methods of Dox delivery in vivo—in drinking water, by gavage, as a jelly, and in standard feed. To assess the delivery of Dox by these methods, we used a subcutaneous xenograft model based on colorectal carcinoma cells engineered for Dox-inducible expression of an activated mutant of c-Src and the luciferase reporter gene. Our results indicate that feed represents the most favorable method of Dox administration

Three weeks radiotherapy for T1 glottic cancer: The Christie and Royal Marsden Hospital Experience

Three weeks radiotherapy for T1 glottic cancer: the Christie and Royal Marsden Hospital Experience. Background and purpose: Radiotherapy for laryngeal carcinoma is conventionally given over a 6-7-week period. However, ill a number of UK centres early lesions are treated over 3 weeks. We review recent results of this policy and discuss file reasons wily short treatment times may be advantageous. Materials and methods: Two hundred patients (100 from each centre) with T1 glottic invasive squamous cell carcinoma treated with definitive radiotherapy between 1989 and 1997 were analysed. The median age was 68 years. All patients received once daily fractionation, 5 days a week to a total tumour dose of 50.0-52.5 Gy in 16 fractions over 21 days; the fraction size ranged from 3.12 to 3.28 Gy. The median follow-up period was 5 years and 10 months. Results: The 5-year local control rates with radiotherapy for the whole group was 93%: there were 14 recurrences of which seven were salvaged by laryngectomy giving an ultimate local control of 96%. The 5-year overall survival was 80% and cause specific survival at 5 years was 97%. Univariate analysis revealed that T1 substaging (P = 0.82) and anterior commissure involvement (P = 0.47) did not significantly influence local control. A severe late radiation complication was seen in only one patient who continued to smoke heavily after treatment. There were no severe acute complications. Conclusions: Once daily radiotherapy over 3 weeks gives excellent local control in patients with T1 glottic squamous-cell carcinoma and has a low rate of severe complications. The short overall treatment time and large fraction size may be advantageous in radiotherapy of these well-differentiated tumours. (C) 2003 Elsevier Ireland Ltd. All rights reserved