ABSTRACT
BACKGROUND/AIM: 5-Aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), is now used for photodynamic therapy (PDT) of pre-cancers of the skin and photodynamic diagnosis (PDD) of brain tumors. Sonodynamic therapy (SDT) of cancers with ultrasound has been studied using 5-ALA as a sonosensitizer. In this article, we evaluated the sonosensitizing activity and mode of action of 5-ALA/PpIX by using mouse mammary tumor EMT6 cells. RESULTS: 5-ALA-SDT showed significant antitumor effects toward EMT6 cells in vitro and in vivo. The fluorescence of MitoSOX Red, an indicator specific for mitochondrial superoxide, was significantly increased by 5-ALA-SDT. Moreover, the fluorescence derived from JC-1, an indicator of mitochondrial membrane potential, was also significantly increased by 5-ALA-SDT. These findings suggest that mitochondria are one of the target organelles of 5-ALA-SDT. PpIX enhanced reactive oxygen species (ROS) production from tert-butyl hydroperoxide (tBHP), suggesting that PpIX might stabilize or promote ROS generation from tBHP. CONCLUSION: 5-ALA-SDT showed an antitumor effect in mouse mammary tumor EMT6 cells through oxidation of the mitochondrial membrane via ROS production.
Subject(s)
Aminolevulinic Acid/administration & dosage , Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Mammary Neoplasms, Experimental/drug therapy , Animals , Apoptosis , Cell Line, Tumor , Drug Screening Assays, Antitumor , Female , Humans , Mice , Mice, Inbred BALB C , Mitochondria/drug effects , Mitochondria/metabolism , Neoplasm Transplantation , Oxidation-Reduction , Reactive Oxygen Species/metabolism , Ultrasonic WavesABSTRACT
BACKGROUND: We conducted a retrospective study to investigate the adequacy of the Efficacy Criteria for Primary Lesions in the Japanese Classification of Gastric Cancer (Japanese criteria) for evaluating the anti-tumor efficacy of chemotherapies and the relationship between tumor regression and the prognosis of gastric cancer.METHODS: The data for 90 patients with inoperable ad-vanced gastric cancer who received various chemotherapies, consisting of fluorinated pyrimidines and cisplatin, were retrospectively analyzed. Based on the Japanese criteria, we investigated the efficacy of the chemotherapies and the relationship between the response in primary lesions and survival. We also compared the efficacy of chemotherapies evaluated by the Japanese criteria to that evaluated by the WHO criteria.RESULTS: All 90 patients were evaluable by the Japanese criteria. The overall response rate was 53.3% (Partial response [PR] in 48 patients and no change + progressive disease [NC + PD] in 42 patients). The primary lesions were classified as measurable (a-lesions) in 27 patients, evaluable but not measurable (b-lesions) in 31 patients, and diffusely infiltrating (c-lesions) in 32 patients. Overall median survival time (MST) was 9.4 months. The MSTs of the responders and non-responders were 12.6 and 7.8 months, respectively. In contrast, by the WHO criteria, 49 patients (54.4%) were evaluable; the other 41 patients had gastric primary lesions alone but were not measurable by WHO criteria. The overall response rate was 67.3% (33/49), and overall MST was 9.4 months. The MSTs of the responders evaluated by both sets of criteria were both 12.6 months.CONCLUSIONS: We suggest that the Japanese criteria are useful for evaluating the anti-tumor effect of gastric cancer chemotherapies and that prospective studies to reconfirm their usefulness are warranted in Japan, and in Western countries.
