Cell-cycle-dependent efficacy of photodynamic therapy with ATX-S10(Na).

Photodynamic therapy (PDT) is a useful strategy for treating various cancers. Details of the mechanisms of PDT have not been made clear yet. We intended to study the efficacy of PDT in relation to the cell cycle. HeLa S3 cells were synchronized by the thymidine block method. Cells in different cell cycle phases after release were treated with the water-soluble photosensitizer, ATX-S10(Na). The cellular viability after PDT was determined by the MTT assay. Intracellular levels of ATX-S10(Na) in different cell cycle phases were also determined. We found that cells in the S and G(2)/M phases were hypersensitive to PDT with ATX-S10(Na) in comparison with those in the G(1) phase, and that cellular levels of ATX-S10(Na) were increased in cells in the S and G(2)/M phases compared to those in the G(1) phase. We conclude that cellular ATX-S10(Na) levels differ among the different cell cycle phases, which is associated with the cell-cycle-dependent efficacy of PDT with ATX-S10(Na).

Apoptosis of gastric cancer cell line MKN45 by photodynamic treatment with photofrin.

The aim of this study was to investigate the mechanism of cell death by photodynamic therapy (PDT) in the gastric cancer cell line MKN45 with focus on the mechanism of apoptosis. Gastric cancer cells (MKN45) were incubated with Photofrin for up to 24 h before exposure to He-Cd laser (441 nm, 1 J/cm2). Cell viability was assessed by the methyl-tetra-zolium assay after exposure to light. A 95% cell death (LD95) was measured with 10 microg/ml of Photofrin. DNA ladder formation and chromatin condensation were seen within 60 min. Caspase-3-like and caspase-9-like activities increased from 15 min after exposure to light. Reduction of rhodamine 123 uptake started at 30 min. Caspase-inhibitor VAD-fmk (10 mM) inhibited apoptosis, but did not influence cell viability. In conclusion, Photofrin-mediated PDT in the gastric cancer cell line MKN45 induces apoptosis within 60 min, and mitochondrial damage is likely as the first event of apoptosis.

Severe strongyloidiasis complicated by meningitis and hydrocephalus in an HTLV-1 carrier with increased proviral load.

We report a 47-year-old Japanese man who was a human T-cell leukemia virus type 1 (HTLV-1) carrier with strongyloidiasis, and who was born in an area endemic for both Strongyloides stercoralis ( S. stercoralis) and HTLV-1. He presented with edema of both legs. Laboratory examination on admission revealed hypoalbuminemia, and S. stercoralis rhabditiform larvae were found by stool microscopy. Purulent meningitis, which was suspected to be due to disseminated strongyloidiasis, developed during the first and second treatment for S. stercoralis infection. After the meningitis was alleviated, hydrocephalus with gait disturbance developed, and these features were attenuated by a ventriculo-peritoneal shunt. Impaired immunity and increased HTLV-1 proviral load, with an increased titer of HTLV-1 antibody, were observed in this patient. These results suggest that HTLV-1 proviral load and/or antibody titer of HTLV-1 can be used for the identification of carriers who are at increased risk of developing severe strongyloidiasis among those patients who are infected with both S. stercoralis and HTLV-1.

A Japanese case of familial Mediterranean fever with family history demonstrating a mutation in MEFV.

We describe a 17-year-old woman with a family history of FMF who suffered from recurrent fever accompanied by pains in the left chest and abdomen. During a five-year period she experienced attacks about once every six months. The metaraminol provocative test was positive. Genomic DNA extracted from peripheral blood lymphocytes from both her and her parents were analyzed by polymerase chain reaction (PCR), followed by cycle sequencing. We detected a mutation (ATG to ATA) in codon 694 in exon 10 of the FMF gene, MEFV, that resulted in a substitution of isoleucine for methionine (M6941) in both her and her father. This is the first Japanese case of FMF with a mutation in MEFV identified in the family history.