A new modular approach to nanoassembly: stable and addressable DNA nanoconstructs via orthogonal click chemistries.

Thermodynamic instability is a problem when assembling and purifying complex DNA nanostructures formed by hybridization alone. To address this issue, we have used photochemical fixation and orthogonal copper-free, ring-strain-promoted, click chemistry for the synthesis of dimeric, trimeric, and oligomeric modular DNA scaffolds from cyclic, double-stranded, 80-mer DNA nanoconstructs. This particular combination of orthogonal click reactions was more effective for nanoassembly than others explored. The complex nanostructures are stable to heat and denaturation agents and can therefore be purified and characterized. They are addressable in a sequence-specific manner by triplex formation, and they can be reversibly and selectively deconstructed. Nanostructures utilizing this orthogonal, chemical fixation methodology can be used as building blocks for nanomachines and functional DNA nanoarchitectures.

I-125 seed planning: an alternative method of urethra definition.

BACKGROUND AND PURPOSE: To investigate the use of aerated aqueous gel rather than a catheter to define the urethra during permanent I-125 seed implant planning. MATERIALS AND METHODS: Twenty patients were treated between September 2007 and March 2008, each having two sequential volume studies: one visualizing the urethra with a catheter and the other using aerated gel. Two individually optimised plans were produced for each patient: one from the gel and the other from the catheter image set, and the plans were analysed dosimetrically. The plans were also interchanged (putting gel plan onto catheter image set and vice versa), and dose homogeneity within a slice was investigated. Three patients had MRI post-implant to check urethral position and dosimetry. RESULTS: The urethra appears larger when defined with gel rather than when defined with a catheter, with volumes of 0.9+/-0.3 [range: 0.6-1.6]cc and 0.7+/-0.2 [range: 0.4-1.0]cc, respectively. Catheter plans appear dosimetrically slightly preferable to gel plans with V(100) prostate being 99.7+/-0.2 [range: 99.3-100.0]% and 99.5+/-0.5 [range: 98.12-99.9]% for catheter and gel, respectively (p=0.048). The urethra appears to receive a higher dose when defined with gel with V(150) being 0.5+/-0.7 [range: 0-2.8]% and 0.2+/-0.2 [range: 0-2.6]% for gel- and catheter-defined urethras. Seed density, COIN and number of seeds were almost equivalent. Statistically, only V(100) prostate and D(90) prostate are significantly different. Putting the catheter plan on the gel image set shows a significant increase in urethral dose with V(150) urethra increasing significantly from 0.2+/-0.2 [range: 0-0.6]% from the catheter plan to 15.3+/-11.9 [range: 0.8-47.0]% for the catheter plan on gel image set (p<0.001). D(90) for the inner core of gel and catheter plans was 193.9+/-6.7 [range: 180.3-202.3]Gy and 198.7+/-4.7 [range: 190.7-211.5]Gy (p=0.023). Gel plans are cooler centrally and less homogeneous, which could be counteracted by increasing seed activity and/or prescription dose, though the clinical significance of this should be investigated before implementation. CONCLUSIONS: This investigation has shown that the urethral position is distorted by the presence of a urinary catheter. The dosimetry may be different from that planned if this is not taken into account.

Radiation dose, chemotherapy and risk of soft tissue sarcoma after solid tumours during childhood.

Soft tissue sarcoma (STS) is one of the most frequent second primary cancer that occurs during the first 20 years following treatment for a solid cancer in childhood. Our aim was to quantify the risk of STS as a second malignant neoplasm and to investigate its relationship with radiotherapy and chemotherapy. A cohort study of 4,400 3-year survivors of a first solid cancer diagnosed during childhood in France or the United Kingdom, between 1942 and 1985, was followed 15 years on average. In a partially nested case-control study, we matched 25 cases of STS and 121 controls for sex, type of first cancer, age at first cancer and duration of follow-up. Sixteen STS occurred in the cohort, as compared to 0.3 expected from the general population (Standardized Incidence Radio, SIR = 54 (95%CI: 34-89)). The SIR was 113 (95% CI: 62-185) after chemotherapy plus radiotherapy (13 STS), whereas it was 28 (95%CI: 2-125) after chemotherapy alone (1 STS) and 19 (95%CI: 3-60) after radiotherapy alone (2 STS). After adjustment for treatment, there was no evidence of variation in the annual excess of incidence or in the SIR with either age at first cancer or time since 1st cancer. In the case-control study, the risk of a STS was increased with the square of the dose of radiation to the site of STS development and with the administration of Procarbazine. The increased risk of soft tissue sarcoma that occurred after childhood cancer is independently related to exposure to radiotherapy and Procarbazine. A closer surveillance of children treated with this treatment combination is strongly recommended.

Brachytherapy of glioblastoma recurring in previously irradiated territory: predictive value of tumor volume.

PURPOSE: To evaluate the impact of tumor volume on survival of patients reirradiated with (192)Ir for recurrent glioblastoma. METHODS AND MATERIALS: Between 1993 and 1997, 42 patients with recurrent glioblastomas (29 males and 13 females, age 18-69 years, median age 49) were treated with (192)Ir implantation. Previous treatments included surgery, external beam radiotherapy, and chemotherapy. Maximum diameter of the recurrent tumor was 1.2-10.1 cm (median: 5.7 cm) and tumor volume was 1.6-122 cm(3) (median: 23 cm(3)). Karnofsky performance status score was 50-100 (median: 80). Brachytherapy dose was 40-60 Gy. RESULTS: Probability of overall survival was 80% at 6 months, 48% at 1 year, and 11% at 2 years. Median survival was 50 weeks. Univariate analysis showed that both tumor volume (T < or T > or = 30 cm(3)) and Karnofsky performance status score were significant predictors of survival. Multivariate analysis showed that smaller tumor volumes were associated with a higher probability of survival (p < 0.001). CONCLUSION: Tumor volume less than 30 cm(3) was associated with a higher probability of, and quality of, survival than larger lesions for patients reirradiated by brachytherapy for recurrent glioblastoma.