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Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-κB activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or γ-glutamyl transpeptidase activity. Radiation activated NF-κB was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-κB activity, without toxicity to bone marrow, liver, and kidney. [Copyright &y& Elsevier]

Purpose: Point A, used for dose specification for intracavitary brachytherapy for cervical cancer, is the point at which the uterine artery and ureter cross. This study assessed compatibility of commonly used traditional point A (TPA) and actual anatomic point A (APA). Methods and Materials: We visualized and placed radiopaque clips at the APA during pelvic and paraaortic lymphadenectomy in 11 patients with cervical carcinoma. Orthogonal and oblique radiographs were obtained after insertion of brachytherapy applicators. We measured the distance between the TPA and APA and estimated the brachytherapy dose to each of the two points. Results: A total of 64 brachytherapy treatments were performed. The mean distances between the TPA and APA were 5.2 +/- 1.0 cm on the right and 5.4 +/- 1.1 cm on the left. The estimated brachytherapy doses delivered to the APA as a percentage of the presumed 500-cGy fraction size to the TPA were 35.2% (176.6 +/- 59.0 cGy) on the right and 30.0% (150.2 +/- 42.9 cGy) on the left. The marked discrepancy in the position of the two points was not related to individual kinetic variations during brachytherapy treatment, tumor size, or bladder filling. Conclusions: The conventional TPA does not provide an accurate estimate of the APA determined during lymphadenectomy, indicating a need to reevaluate the current practice for determining the brachytherapy prescription for cervical cancer. (ClinicalTrials.gov Identifier, NCT00319462). [ABSTRACT FROM AUTHOR]