Dosimetric verification of dose optimisation algorithm during endovascular brachytherapy of the peripheral vessels

AbstractAimDosimetric verification of the dose optimisation model used in endovascular brachytherapy, evaluation of the optimised dose distributions using elaborated indices.BackgroundThe equipment used for standard radiotherapy is used in vascular brachytherapy for prevention of restenosis after angioplasty.Material and MethodA paraffin-wax phantom, thermoluminescent detectors and MD-55 Gafchromic® films were used for dose measurements. The edge dose index (EDI), central dose index (CDI) and treatment length index (TLI) were introduced to compare dose distributions calculated and measured.ResultsObtained values (p>0.05) show no statistically significant differences between calculated doses and measured doses. EDI values showed improvement in dose homogeneity on the edges of the application after optimisation. After optimisation CDI values from 0.9% to 1.6% for calculated and from −1.8% to 3.1% for measured showed improvement in dose homogeneity in the central part of the application. Observed values of TLI from 3% to 21% for calculated doses and from 7% to 24% for doses measured by Gafchromic® films showed increase of RIL for optimised treatment plans.Conclusions1/ The designed phantom allowed repeatable dosimetric verification of dose distributions in endovascular brachytherapy. 2/ Measurements with thermoluminescent detectors and Gafchromic films proved the accuracy of the calculation algorithm in endovascular brachytherapy conditions. 3/ Elaborated indices were found to be a useful tool in describing dose homogeneity. They allowed the process of optimisation to be controlled and thus an increase in dose homogeneity by 30% at the edges and by 7% in the middle of the treated volume to be achieved

Hyperthermia – description of a method and a review of clinical applications

SummaryThe aim of this paper is to give a concise description of hyperthermia and a brief review of its clinical applications. Hyperthermia (HT, thermal therapy) is thought to be one of the cancer therapies and is considered to be an artificial way of increasing the body tissue temperature by delivering heat obtained from external sources to destroy cancerous cells or prevent their further growth. The first principles of hyperthermic biology are presented. The phenomena of thermotolerance and radiosensitization are briefly described, as well as the concept of thermal dose delivered to the tissues.Three main clinical applications of HT are presented. They include local, regional or part-body HT and whole-body HT that deliver heat to localized, advanced or deep-seated and disseminated malignancies, respectively, depending on location, depth and staging of the tumour. Energies used to apply heat to the tumour include microwaves, radiofrequency energy, ultrasound, infrared radiators and different kinds of hot sources (hot water, ferromagnetic seeds, nanoparticles, resistive implants). General indications for each HT subtype and possible combinations of HT with other cancer treatment modalities are presented.Substantially, HT is used as an adjuvant therapy and in such a role it is being evaluated in many clinical randomized trials throughout the scientific medical centres. Their first preliminary results are already available, but still time is needed to produce firm conclusions and strict indications for hyperthermia treatment

A homology model of restriction endonuclease SfiI in complex with DNA

BACKGROUND: Restriction enzymes (REases) are commercial reagents commonly used in recombinant DNA technologies. They are attractive models for studying protein-DNA interactions and valuable targets for protein engineering. They are, however, extremely divergent: the amino acid sequence of a typical REase usually shows no detectable similarities to any other proteins, with rare exceptions of other REases that recognize identical or very similar sequences. From structural analyses and bioinformatics studies it has been learned that some REases belong to at least four unrelated and structurally distinct superfamilies of nucleases, PD-DxK, PLD, HNH, and GIY-YIG. Hence, they are extremely hard targets for structure prediction and homology-based inference of sequence-function relationships and the great majority of REases remain structurally and evolutionarily unclassified. RESULTS: SfiI is a REase which recognizes the interrupted palindromic sequence 5'GGCCNNNN^NGGCC3' and generates 3 nt long 3' overhangs upon cleavage. SfiI is an archetypal Type IIF enzyme, which functions as a tetramer and cleaves two copies of the recognition site in a concerted manner. Its sequence shows no similarity to other proteins and nothing is known about the localization of its active site or residues important for oligomerization. Using the threading approach for protein fold-recognition, we identified a remote relationship between SfiI and BglI, a dimeric Type IIP restriction enzyme from the PD-DxK superfamily of nucleases, which recognizes the 5'GCCNNNN^NGGC3' sequence and whose structure in complex with the substrate DNA is available. We constructed a homology model of SfiI in complex with its target sequence and used it to predict residues important for dimerization, tetramerization, DNA binding and catalysis. CONCLUSIONS: The bioinformatics analysis suggest that SfiI, a Type IIF enzyme, is more closely related to BglI, an "orthodox" Type IIP restriction enzyme, than to any other REase, including other Type IIF REases with known structures, such as NgoMIV. NgoMIV and BglI belong to two different, very remotely related branches of the PD-DxK superfamily: the α-class (EcoRI-like), and the β-class (EcoRV-like), respectively. Thus, our analysis provides evidence that the ability to tetramerize and cut the two DNA sequences in a concerted manner was developed independently at least two times in the evolution of the PD-DxK superfamily of REases. The model of SfiI will also serve as a convenient platform for further experimental analyses

Crystal structure and mechanism of action of the N6-methyladenine-dependent type IIM restriction endonuclease R.DpnI.

DNA methylation-dependent restriction enzymes have many applications in genetic engineering and in the analysis of the epigenetic state of eukaryotic genomes. Nevertheless, high-resolution structures have not yet been reported, and therefore mechanisms of DNA methylation-dependent cleavage are not understood. Here, we present a biochemical analysis and high-resolution DNA co-crystal structure of the N(6)-methyladenine (m6A)-dependent restriction enzyme R.DpnI. Our data show that R.DpnI consists of an N-terminal catalytic PD-(D/E)XK domain and a C-terminal winged helix (wH) domain. Surprisingly, both domains bind DNA in a sequence- and methylation-sensitive manner. The crystal contains R.DpnI with fully methylated target DNA bound to the wH domain, but distant from the catalytic domain. Independent readout of DNA sequence and methylation by the two domains might contribute to R.DpnI specificity or could help the monomeric enzyme to cut the second strand after introducing a nick

Dosimetric verification of dose optimisation algorithm during endovascular brachytherapy of the peripheral vessels

AimDosimetric verification of the dose optimisation model used in endovascular brachytherapy, evaluation of the optimised dose distributions using elaborated indices.BackgroundThe equipment used for standard radiotherapy is used in vascular brachytherapy for prevention of restenosis after angioplasty.Material and MethodA paraffin-wax phantom, thermoluminescent detectors and MD-55 Gafchromic® films were used for dose measurements. The edge dose index (EDI), central dose index (CDI) and treatment length index (TLI) were introduced to compare dose distributions calculated and measured.ResultsObtained values (p>0.05) show no statistically significant differences between calculated doses and measured doses. EDI values showed improvement in dose homogeneity on the edges of the application after optimisation. After optimisation CDI values from 0.9% to 1.6% for calculated and from −1.8% to 3.1% for measured showed improvement in dose homogeneity in the central part of the application. Observed values of TLI from 3% to 21% for calculated doses and from 7% to 24% for doses measured by Gafchromic® films showed increase of RIL for optimised treatment plans.Conclusions1/ The designed phantom allowed repeatable dosimetric verification of dose distributions in endovascular brachytherapy. 2/ Measurements with thermoluminescent detectors and Gafchromic films proved the accuracy of the calculation algorithm in endovascular brachytherapy conditions. 3/ Elaborated indices were found to be a useful tool in describing dose homogeneity. They allowed the process of optimisation to be controlled and thus an increase in dose homogeneity by 30% at the edges and by 7% in the middle of the treated volume to be achieved

Intraluminal pulsed dose rate (PDR) brachytherapy and trans-hepatic technique in treatment of locally advanced bile duct cancer – preliminary assessment

BackgroundTreatment options for bile duct cancer remain limited due to the large number of patients with advanced disease at the time of diagnosis. Radical surgery is possible in less than 10–15% of these cases. Unresectable bile duct cancers are very difficult to treat with external beam therapy alone due to the proximity of adjacent normal organs and the high doses required to effectively irradiate these neoplasms. Indications for brachytherapy include all malignant strictures of the bile duct which can be cannulated. Patients should be fit enough for the procedure and should have been reviewed to confirm that they are not suitable for resection. Combined treatment is possible in patients who are in good condition; it is usual to combine bile duct brachytherapy (BT) with external beam radiation therapy (EBRT).AimTo assess the feasibility of intraluminal palliative pulsed dose rate brachytherapy (PDR-BT) in the treatment of locally advanced bile duct cancer.Materials/MethodsSeventeen patients with advanced inoperable bile duct cancer were treated between May 2002 and December 2005 in Greatpoland Cancer Centre. Patients were disqualified from surgery or radical external beam radiation therapy (EBRT). Thirteen patients were treated exclusively with PDR brachytherapy, 4 patients were qualified for combined treatment: PDR brachytherapy and palliative EBRT. Percutaneous trans-hepatic technique was used to implant a catheter into the bile duct. All patients received 25 pulses of 0.8Gy hourly to the total dose of 20Gy. In 4 cases PDR was repeated after one week. Target Volume encompassed tumour visualized at cholangiography and a one or two cm margin taken proximally and distally. Dose was prescribed at 10mm from the source axis. For palliative EBRT 15MV photons were used.ResultsIn all 17 cases trans-hepatic technique allowed insertion of the BT catheter into the bile duct and safe application of PDR-BT. In 13/17 (76.5%) cases improvement in jaundice was noted at the first check-up after 4 weeks. Median overall survival time (OS) was 10 months, longest survival time was 36 months, shortest was 2 months. Acute and late complications were not observed.Conclusions1. It was established that the use of pulsed dose rate brachytherapy was feasible and had a low early complication rate. A new percutaneous trans-hepatic technique allowed whole treatment (insertion of catheter, PDR brachytherapy) to be performed in one day. 2. In most cases a satisfactory palliative effect was achieved

Benefit of Whole Pelvic Radiotherapy Combined with Neoadjuvant Androgen Deprivation for the High-Risk Prostate Cancer

Aim. To study whether use of neoadjuvant androgen deprivation therapy (N-ADT) combined with whole pelvic radiotherapy (WPRT) for high-risk prostate cancer patients was associated with survival benefit over prostate radiotherapy (PORT) only. Material and Methods. Between 1999 and 2004, 162 high-risk prostate cancer patients were treated with radiotherapy combined with long-term androgen deprivation therapy (L-ADT). Patients were prospectively assigned into two groups: A (N-ADT + WPRT + L-ADT) n = 70 pts, B (PORT + L-ADT) n = 92 pts. Results. The 5-year actuarial overall survival (OS) rates were 89% for A and 78% for B (P = .13). The 5-year actuarial cause specific survival (CSS) rates were A = 90% and B = 79% (P = .01). Biochemical progression-free survival (bPFS) rates were 52% versus 40% (P = .07), for groups A and B, respectively. Conclusions. The WPRT combined with N-ADT compared to PORT for high-risk patients resulted in improvement in CSS and bPFS; however no OS benefit was observed