The purpose of this study was to estimate the CTV-PTV margin required for prostate and head and neck cancer treatments at the radiotherapy departments of Karolinska University Hospital.    Portal image data from patients treated at the radiotherapy departments during the period of 2009-2011 was used to estimate the set-up displacements for each treatment area. By using the acquired images the magnitude of the systematic, i.e. preparatory, and random, i.e. execution, error was determined in the anterior-posterior (AP), superior-inferior (SI) and right-left (RL) direction. The calculated PTV margin is based on the systematic and random errors of the entire patient populations. A total of 40 patients were used for the analysis of prostate treatments and 47 patients for head and neck treatments. The evaluation of the PTV margin was done for three different matching protocols; no matching (skin marker alignment), five day matching and daily matching.      With no image verification in prostate treatments the calculated PTV margin taking both inter- and intrafractional errors into account was 13.6, 9.2 and 7.9 mm in AP, SI, and RL direction respectively. The corresponding PTV margin in head and neck treatments was found to be 6.7, 5.3 and 4.9 mm. Using a five day matching protocol of the bony anatomy showed no considerable reductions in margins for neither prostate nor head and neck treatments. With daily matching of the bony anatomy in prostate treatments the calculated margins was reduced to 8.1, 7.9 and 2.4 mm in the AP, SI and RL direction respectively.  Measurements of the residual deviations of individual cervical vertebrae after daily image verification and correction in head and neck cancer treatments showed that all matching protocols will require larger margins in the lower vertebrae in order to account for the set-up error in the AP direction. The corresponding margins needed using daily matching of the bony anatomy would be 3.9, 5.4 and 6.0 mm for C1, C4 and C5 respectively in the AP direction.    In the absence of daily imaging the currently used PTV margins might be inadequate for covering to movement of the targets. The deviations in the AP direction of the cervical vertebrae in head and neck cancer treatments should be investigated further in order to ensure that the motion of the target is covered and that no risk organs are subjected to harmful dose levels.

A beta-emitting glass seed was proposed for the brachytherapy treatment of prostate cancer. Criteria for seed design were derived and several beta-emitting nuclides were examined for suitability. 142Pr was selected as the isotope of choice. Seeds 0.08 cm in diameter and 0.9 cm long were manufactured for testing. The seeds were activated in the Texas A&M University research reactor. The activity produced was as expected when considering the meta-stable state and epi-thermal neutron flux. The MCNP5 Monte Carlo code was used to calculate the quantitative dosimetric parameters suggested in the American Association of Physicists in Medicine (AAPM) TG-43/60. The Monte Carlo calculation results were compared with those from a dose point kernel code. The dose profiles agree well with each other. The gamma dose of 142Pr was evaluated. The gamma dose is 0.3 Gy at 1.0 cm with initial activity of 5.95 mCi and is insignificant to other organs. Measurements were performed to assess the 2-dimensional axial dose distributions using Gafchromic radiochromic film. The radiochromic film was calibrated using an X-ray machine calibrated against a National Institute of Standards and Technology (NIST) traceable ion chamber. A calibration curve was derived using a least squares fit of a second order polynomial. The measured dose distribution agrees well with results from the Monte Carlo simulation. The dose was 130.8 Gy at 6 mm from the seed center with initial activity of 5.95 mCi. AAPM TG-43/60 parameters were determined. The reference dose rate for 2 mm and 6 mm were 0.67 and 0.02 cGy/s/mCi, respectively. The geometry function, radial dose function and anisotropy function were generated.

Thèse de doctorat : Sciences du vivant : Strasbourg 1 : 2007. / Titre provenant de l'écran-titre. Bibliogr. f. 144-155.

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 71-100). Also available in print.

Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Pharmaceutical Science." Includes bibliographical references (p. 178-196).

Thesis (M.S.)--University of Delaware, 2009. / Principal faculty advisor: Kenneth L. Van Golen, Dept. of Biological Sciences. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 1989.

No description available.

The link between obesity and the risk of prostate cancer (PCa) is inconclusive. However, studies demonstrate a correlation between obesity, advanced PCa and mortality. Investigating the underlying biological mechanisms by which obesity promotes advanced PCa is necessary to develop potential therapeutic targets that may aid in the efficacy of treating obese men. Obesity-associated changes in tumor biology may modulate key aspects of the hallmarks of cancer; acquisition of characteristics essential for the development and progression of cancer. We hypothesized obesity-induced inflammation promotes PCa progression. Our studies incorporated cell culture and murine models to investigate the role of obesity-related systemic factors on AR signaling, inflammation-stimulated invasive PCa, and the paracrine interaction of the tumor-microenvironment (TME). We sought to recapitulate the systemic effects of obesity to investigate characteristics of the metastatic cascade. Briefly, sera from mice fed 60% or 10% kcal from fat diet for 12 weeks were used for in vitro studies. PCa cells exposed to sera from obese mice increased AR transcriptional activity, proliferation, invasion, migration, MMP-9 activity and EMT: e-cadherin, vimentin and β-catenin. PCa cells exposed to sera from 1 hour maintained the invasive phenotypes similar to PCa cells directly exposed to sera from obese mice. IL-6 is associated with advanced PCa cancer. Depleting sera of IL-6 or IL-6 shRNA suppressed obesity-induced proliferation, invasion, migration and MMP-9 activity in LNCaP cells. Furthermore, in a PTEN spontaneous model of PCa, IL-6 protein and mRNA levels corresponded with progression of PCa in mice fed a high-fat diet. These results suggest IL-6 mediates obesity-induced PCa progression. Stromal cells that comprise the TME vary in their contribution to the growth of tumors. Our studies show macrophage-like and myofibroblasts increased NF-kB activity in PCa cells exposed to sera from obese mice. An increase in NF-kB activity corresponded with proliferation, prostaglandin E2, and invasion and recruitment of stromal cells by PCa cells. In summary, obesity-related systemic factors promote an invasive PCa phenotype, which may be mediated by Akt, AR, IL-6 and the TME. Obesity-induced changes in tumor biology and the microenvironment provide a niche suitable for invasive prostate cancer. / text

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences