Acridine orange exhibits photodamage in human bladder cancer cells under blue light exposure.

Human bladder cancer (BC) cells exhibit a high basal level of autophagic activity with accumulation of acridine-orange(AO)-stained acidic vesicular organelles. The rapid AO relocalization was observed in treated BC cells under blue-light emission. To investigate the cytotoxic effects of AO on human BC cell lines under blue-light exposure, human immortalized uroepithelial (SV-Huc-1) and BC cell lines (5637 and T24) were treated with indicated concentrations of AO or blue-light exposure alone and in combination. The cell viability was then determined using WST-1, time-lapse imaging with a Cytosmart System and continuous quantification with a multi-mode image-based reader. Treatment of AO or blue-light exposure alone did not cause a significant loss of viability in BC cells. However, AO exhibited a dose-dependent increment of cytotoxicity toward BC cells under blue-light exposure. Furthermore, the tumor formation of BC cells with treatment was significantly reduced when evaluated in a mouse xenograft model. The photodamage caused by AO was nearly neglected in SV-Huc-1 cells, suggesting a differential effect of this treatment between cancer and normal cells. In summary, AO, as a photosensitizer, disrupts acidic organelles and induces cancer cell death in BC cells under blue-light irradiation. Our findings may serve as a novel therapeutic strategy against human BC.

[Prognostic value of microvolt level T-wave alternans in patients at high risk of sudden cardiac death].

OBJECTIVE: To explore the predict value of microvolt level T-wave alternans (MTWA) for malignant ventricular arrhythmia (MVA) and sudden cardiac death (SCD) in high risk patients. METHODS: A total of 105 healthy subjects (control group) and 138 patients with history of VT or VF or patients with LVEF < or = 45% (SCD high risk group) were included in this study (mean age 52 years old). MTWA, LVEF, HRV, NSVT, QRS, QTc values and MACE data (death, causes of death, MVA, re-hospitalization, syncope) during follow up (12.0 +/- 1.3) months were obtained. RESULTS: The normal reference value of MTWA was defined as < 37 microV. Positive rate in SCD high risk group was significantly higher than that in control group (45.7% vs. 4.8%, P < 0.01). There was no cardiovascular event report in control group. In SCD high risk group, there were 11 deaths (MTWA positive rate 81.8%) including 7 SCD (MTWA positive rate 85.7%), 17 MVA (MTWA positive rate 88.2%), 9 cases of syncope (MTWA positive rate 77.8%), 21 cases of re-hospitalization during the follow up (MTWA positive rate 85.7%). Logistic regression analysis revealed that positive MTWA, a history of myocardial infarction and LVDd > or = 60 mm were risk factors for all cause of death and positive MTWA was the only factor to predict SCD. The factors related to MVA in turn were positive MTWA, LVEF < or = 35%, a history of cardiopulmonary resuscitation and a history of syncope. Positive MTWA and LVEF < or = 35% are the independent risk factors for predicting MVA (P < 0.01). The sensitivity was 91% and specifity was 66% by combined use of positive MTWA and LVEF < or = 35% to predict MVA. MTWA positive rates were 68.3% and 87.5% respectively in 41 ICD patients and ICD patients with automatic shock during follow up. CONCLUSION: Non-invasive MTWA measurement could be used as a screening tool to predict SCD or MVA in high risk patients.