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ObjectiveTo determine the optimal drug and light dose for prostate ablation using WST11 (TOOKADâ Soluble) for vasculartargeted photodynamic (VTP) therapy in men with low-risk prostate cancer. Patients and MethodsIn all, 42 men with low-risk prostate cancer were enrolled in the study but two who underwent anaesthesia for the procedure did not receive the drug or light dose. Thus, 40 men received a single dose of 2, 4 or 6 mg/kg WST11 activated by 200 J/cm light at 753 nm. WST11 was given as a 10-min intravenous infusion. The light dose was delivered using cylindrical diffusing fibres within hollow plastic needles positioned in the prostate using transrectal ultrasonography (TRUS) guidance and a brachytherapy template. Magnetic resonance imaging (MRI) was used to assess treatment effect at 7 days, with assessment of urinary function (International Prostate Symptom Score [IPSS]), sexual function (International Index of Erectile Function [IIEF]) and adverse events at 7 days, 1, 3 and 6 months after VTP. TRUS-guided biopsies were taken at 6 months. ResultsIn all, 39 of the 40 treated men completed the follow-up. The Day-7 MRI showed maximal treatment effect (95% of the planned treatment volume) in men who had a WST11 dose of 4 mg/kg, light dose of 200 J/cm and light density index (LDI) of >1. In the 12 men treated with these parameters, the negative biopsy rate was 10/12 (83%) at 6 months, compared with 10/26 (45%) for the men who had either a different drug dose (10 men) or an LDI of <1 (16). Transient urinary symptoms were seen in most of the men, with no significant difference in IPSS score between baseline and 6 months after VTP. IIEF scores were not significantly different between baseline and 6 months after VTP. ConclusionTreatment with 4 mg/kg TOOKAD Soluble activated by 753 nm light at a dose of 200 J/cm and an LDI of >1 resulted in treatment effect in 95% of the planned treatment volume and a negative biopsy rate at 6 months of 10/12 men (83%).

S100A6 (Calcyclin) is a calcium-binding protein that has been implicated in a variety of biological functions as well as tumorigenesis. The aim of our study was to investigate the involvement of S100A6 during prostate cancer development and progression. Using immunohistochemistry, the expression of S100A6 was examined in benign (n=66), premalignant (n=10), malignant (n=66) and metastatic prostate (n=5) tissues arranged in a tissue-microarray or whole sections as well as in prostate cancer cell lines. The S100A6 immunostaining pattern in tissues was compared with that of cytokeratin 5 (a basal cell marker) and 18 (a benign luminal cell marker). In all cases of benign epithelium, intense S100A6 expression was seen in the basal cell layer with absent staining in luminal cells. In all cases of prostatic adenocarcinoma (matched), metastatic lesions and 3/10 high-grade prostatic intraepithelial neoplasia lesions, an absence of S100A6 was seen. Western blotting and RT–PCR analysis of cell lines showed S100A6 expression to be absent in LNCaP, LNCaP-LN3 and LNCaP-Pro5 but present in Du145, PC3, PC-3M and PC-3M-LN4. LNCaP cells treated with 5-Azacytidine, caused re-expression of S100A6 mRNA. Sequencing of bisulphite modified DNA showed CpG methylation within the S100A6 promoter region and exon 1 of LNCaP, LNCaP-LN3 and LNCaP-Pro5 cell lines but not in Du145 cells. Our data suggest that loss of S100A6 protein expression is common in prostate cancer development and may occur at an early stage. The mechanism of loss of expression may involve hypermethylation of CpG sites. The finding of intense S100A6 expression in the basal cells of benign glands but loss of expression in cancer could be useful as a novel diagnostic marker for prostate cancer.