[en] We describe a unique method that allows the comparison of spatially registered ultrasound (SRUS) images and computed tomography-derived contours (CTDCs) that were acquired with a minimal time lapse. As such, we have a tool that will provide validation of the spatial accuracy of the US system and that will allow comparison of anatomical boundaries derived via the two different imaging modalities. We describe the method by which the commercial US system is mechanically registered to a CT simulator and a unique data processing procedure. This data processing procedure circumvents the standard data acquisition and manual contouring sequence, thus reducing the time lapse from CT to US image acquisition to 10 minutes on average. Verification using a phantom demonstrated the method to be spatially accurate to within ±1 mm in the anterior-posterior (AP) and lateral directions and ±3 mm in the inferior-superior (IS) direction. Early clinical results gathered on 8 patients demonstrated alignment between the US and the CTDCs to be 0 mm in the AP and lateral directions and 2 mm in the IS direction, on average. The technique was used to compare the appearance of the prostate using US and CT imaging. The lateral dimension of the prostate indicated by the CTDCs was larger than that indicated by US imaging in all cases and on average by 0.9 cm. The height of the prostate in the AP direction was larger on average by 0.3 cm using CTDCs than US, and was larger by 5 mm or more in 3 out of 7 cases. The role of uncertainties in the determination of the CTDCs is examined as a possible cause and implications for treatment planning are described

[en] Optical density (OD) of a radiographic film plays an important role in radiation dosimetry, which depends on various parameters, including beam energy, depth, field size, film batch, dose, dose rate, air film interface, postexposure processing time, and temperature of the processor. Most of these parameters have been studied for Kodak XV and extended dose range (EDR) films used in radiation oncology. There is very limited information on processor temperature, which is investigated in this study. Multiple XV and EDR films were exposed in the reference condition (d_max., 10 × 10 cm², 100 cm) to a given dose. An automatic film processor (X-Omat 5000) was used for processing films. The temperature of the processor was adjusted manually with increasing temperature. At each temperature, a set of films was processed to evaluate OD at a given dose. For both films, OD is a linear function of processor temperature in the range of 29.4–40.6°C (85–105°F) for various dose ranges. The changes in processor temperature are directly related to the dose by a quadratic function. A simple linear equation is provided for the changes in OD vs. processor temperature, which could be used for correcting dose in radiation dosimetry when film is used.

[en] In normal prostate epithelium the TMPRSS2 gene encoding a type II serine protease is directly regulated by male hormones through the androgen receptor. In prostate cancer ERG protooncogene frequently gains hormonal control by seizing gene regulatory elements of TMPRSS2 through genomic fusion events. Although, the androgenic activation of TMPRSS2 gene has been established, little is known about other elements that may interact with TMPRSS2 promoter sequences to modulate ERG expression in TMPRSS2-ERG gene fusion context. Comparative genomic analyses of the TMPRSS2 promoter upstream sequences and pathway analyses were performed by the Genomatix Software. NKX3.1 and ERG genes expressions were evaluated by immunoblot or by quantitative Real-Time PCR (qRT-PCR) assays in response to siRNA knockdown or heterologous expression. QRT-PCR assay was used for monitoring the gene expression levels of NKX3.1-regulated genes. Transcriptional regulatory function of NKX3.1 was assessed by luciferase assay. Recruitment of NKX3.1 to its cognate elements was monitored by Chromatin Immunoprecipitation assay. Comparative analysis of the TMPRSS2 promoter upstream sequences among different species revealed the conservation of binding sites for the androgen inducible NKX3.1 tumor suppressor. Defects of NKX3.1, such as, allelic loss, haploinsufficiency, attenuated expression or decreased protein stability represent established pathways in prostate tumorigenesis. We found that NKX3.1 directly binds to TMPRSS2 upstream sequences and negatively regulates the expression of the ERG protooncogene through the TMPRSS2-ERG gene fusion. These observations imply that the frequently noted loss-of-function of NKX3.1 cooperates with the activation of TMPRSS2-ERG fusions in prostate tumorigenesis

[en] Some treatment planning systems (TPSs), when used for large-field (>14 cm) intensity-modulated radiation therapy (IMRT), create split fields that produce excessive multiple-leaf collimator segments, match-line dose inhomogeneity, and higher treatment times than nonsplit fields. A new method using a fixed-jaw technique (FJT) forces the jaw to stay at a fixed position during optimization and is proposed to reduce problems associated with split fields. Dosimetric comparisons between split-field technique (SFT) and FJT used for IMRT treatment is presented. Five patients with head and neck malignancies and regional target volumes were studied and compared with both techniques. Treatment planning was performed on an Eclipse TPS using beam data generated for Varian 2100C linear accelerator. A standard beam arrangement consisting of nine coplanar fields, equally spaced, was used in both techniques. Institutional dose-volume constraints used in head and neck cancer were kept the same for both techniques. The dosimetric coverage for the target volumes between SFT and FJT for head and neck IMRT plan is identical within ±1% up to 90% dose. Similarly, the organs at risk (OARs) have dose-volume coverage nearly identical for all patients. When the total monitor unit (MU) and segments were analyzed, SFT produces statistically significant higher segments (17.3 ± 6.3%) and higher MU (13.7 ± 4.4%) than the FJT. There is no match line in FJT and hence dose uniformity in the target volume is superior to the SFT. Dosimetrically, SFT and FJT are similar for dose-volume coverage; however, the FJT method provides better logistics, lower MU, shorter treatment time, and better dose uniformity. The number of segments and MU also has been correlated with the whole body radiation dose with long-term complications. Thus, FJT should be the preferred option over SFT for large target volumes.

[en] Purpose: To investigate the moving gap region dosimetry in proton beam cranio-spinal irradiation (CSI) to provide optimal dose uniformity across the treatment volume. Material and methods: Proton beams of ranges 11.6 cm and 16 cm are used for the spine and the brain fields, respectively. Beam profiles for a 30 cm snout are first matched at the 50% level (hot match) on the computer. Feathering is simulated by shifting the dose profiles by a known distance two successive times to simulate a 2 x feathering scheme. The process is repeated for 2 mm and 4 mm gaps. Similar procedures are used to determine the dose profiles in the moving gap for a series of gap widths, 0-10 mm, and feathering step sizes, 4-10 mm, for a Varian iX 6MV beam. The proton and photon dose profiles in the moving gap region are compared. Results: The dose profiles in the moving gap exhibit valleys and peaks in both proton and photon beam CSI. The dose in the moving gap for protons is around 100% or higher for 0 mm gap, for both 5 and 10 mm feathering step sizes. When the field gap is comparable or larger than the penumbra, dose minima as low as 66% is obtained. The dosimetric characteristics for 6 MV photon beams can be made similar to those of the protons by appropriately combining gap width and feathering step size. Conclusion: The dose in the moving gap region is determined by the lateral penumbras, the width of the gap and the feathering step size. The dose decreases with increasing gap width or decreasing feathering step size. The dosimetric characteristics are similar for photon and proton beams. However, proton CSI has virtually no exit dose and is beneficial for pediatric patients, whereas with photon beams the whole lung and abdomen receive non-negligible exit dose

[en] Dosimetric comparison of manual beam angle selection (MBS) and beam angle optimization (BAO) for IMRT plans is investigated retrospectively for 15 head and neck and prostate patients. The head and neck and prostate had planning target volumes (PTVs) ranging between 96.0 and 319.9 cm³ and 153.6 and 321.3 cm³, whereas OAR ranged between 8.3 and 47.8 cm³ and 68.3 and 469.2 cm³, respectively. In MBS, a standard coplanar 7-9 fields equally spaced gantry angles were used. In BAO, the selection of gantry angle was optimized by the algorithm for the same number of beams. The optimization and dose-volume constraints were kept the same for both techniques. Treatment planning was performed on the Eclipse treatment planning system. Our results showed that the dose-volume histogram for PTV are nearly identical in both techniques but BAO provided superior sparing of the organs at risk compared with the MBS. Also, MBS produced statistically significant higher monitor units (MU) and segments than the BAO; 13.1 ± 6.6% (p = 0.012) and 10.4 ± 13.6% (p = 0.140), and 14.6 ± 5.6% (p = 1.003E-5) and 12.6 ± 7.4% (p = 0.76E-3) for head and neck and prostate cases, respectively. The reduction in MU translates into the reduction in total body and integral dose. It is concluded that BAO provides advantage over MBS for most intenisty-modulated radiation therapy cases.

[en] Understanding prostate stem cells may provide insight into the origin of prostate cancer. Primary cells have been cultured from human prostate tissue but they usually survive only 15-20 population doublings before undergoing senescence. We report here that RC-170N/h/clone 7 cells, a clonal cell line from hTERT-immortalized primary non-malignant tissue-derived human prostate epithelial cell line (RC170N/h), retain multipotent stem cell properties. The RC-170N/h/clone 7 cells expressed a human embryonic stem cell marker, Oct-4, and potential prostate epithelial stem cell markers, CD133, integrin α2β1^hi and CD44. The RC-170N/h/clone 7 cells proliferated in KGM and Dulbecco's Modified Eagle Medium with 10% fetal bovine serum and 5 μg/ml insulin (DMEM + 10% FBS + Ins.) medium, and differentiated into epithelial stem cells that expressed epithelial cell markers, including CK5/14, CD44, p63 and cytokeratin 18 (CK18); as well as the mesenchymal cell markers, vimentin, desmin; the neuron and neuroendocrine cell marker, chromogranin A. Furthermore the RC170 N/h/clone 7 cells differentiated into multi tissues when transplanted into the sub-renal capsule and subcutaneously of NOD-SCID mice. The results indicate that RC170N/h/clone 7 cells retain the properties of multipotent stem cells and will be useful as a novel cell model for studying the mechanisms of human prostate stem cell differentiation and transformation

[en] In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents