Antihormone treatment differentially regulates PSA secretion, PSMA expression and 68Ga-PSMA uptake in LNCaP cells.

BACKGROUND: In recent years, a variety of innovative therapeutics for castration-resistant prostate cancer have been developed, including novel anti-androgenic drugs, such as abiraterone or VPC-13566. Therapeutic monitoring of these pharmaceuticals is performed either by measuring PSA levels in serum or by imaging. PET using PSMA ligands labeled with Fluor-18 or Gallium-68 is the most sensitive and specific imaging modality for detection of metastases in advanced prostate cancer. To date, it remains unclear how PSMA expression is modulated by anti-hormonal treatment and how it correlates with PSA secretion. METHODS: We analyzed modulation of PSMA-mRNA and protein expression, 68Ga-PSMA uptake and regulation of PSA secretion by abiraterone or VPC-13566 in LNCaP cells in vitro. RESULTS: We found that abiraterone and VPC-13566 upregulate PSMA protein and mRNA expression but block PSA secretion in LNCaP cells. Both anti-androgens also enhanced 68Ga-PSMA uptake normalized by the number of cells, whereas abiraterone and VPC-13566 reduced 68Ga-PSMA uptake in total LNCaP monolayers treated due to cell death. CONCLUSION: Our data indicate that PSA secretion and PSMA expression are differentially regulated upon anti-androgen treatment. This finding might be important for the interpretation of 68Ga-PSMA PET images in monitoring therapies with abiraterone and VPC-13566 in prostate cancer patients, but needs to be validated in vivo.

[Treatment of congenital lacrimal duct obstruction: A prospective clinical cohort study]. / Behandlung kindlicher Tränenwegsstenosen : Eine prospektive klinische Kohortenstudie.

BACKGROUND: Pressurized probing and irrigation is the method of choice for congenital lacrimal duct obstruction after conservative therapeutic strategies have failed. The aim of this study was to evaluate age dependence and success rates of different therapeutic options. MATERIAL AND METHODS: A prospective cohort study of children with congenital lacrimal duct obstruction was performed. All children treated during the period between May 2009 and June 2010 were included. Surgical success was defined as the absence of epiphora and mucous discharge for a postoperative follow-up of 3 months. Odds ratios (OR) and 95 % confidence intervals (CI) of different variables were estimated using logistic regression. RESULTS: A total of 111 children (137 eyes) underwent treatment for congenital lacrimal duct obstruction. The mean age of the children was 7.7 months (range 1-30 months). The success rate of probing under local anesthesia was 85.5 % (n = 100). Probing under general anesthesia without intubation of the lacrimal pathway was successful in 28.6 % (n = 2). Treatment under general anesthesia with intubation of the lacrimal pathway had a success rate of 94.2 %. If the primary treatment was complicated the OR was 1.9 (95 % CI: 0.7-5.1), for males the OR was 1.7 (95 % CI: 0.8-3.5) and in cases of a positive family history the OR was 1.5 (95 % CI: 0.7-3.3). With every increasing month of age the risk not to be treated successfully increased (OR: 1.3, 95 % CI: 1.2-1.5). CONCLUSION: Syringing under local anesthesia is an effective therapy. The highest success rates were found at the ages of 1-6 months. Therapy with additional silicone tube intubation was highly successful.