Novel low-kVp beamlet system for choroidal melanoma.

BACKGROUND: Treatment of choroidal melanoma with radiation often involves placement of customized brachytherapy eye-plaques. However, the dosimetric properties inherent in source-based radiotherapy preclude facile dose optimization to critical ocular structures. Consequently, we have constructed a novel system for utilizing small beam low-energy radiation delivery, the Beamlet Low-kVp X-ray, or "BLOKX" system. This technique relies on an isocentric rotational approach to deliver dose to target volumes within the eye, while potentially sparing normal structures. METHODS: Monte Carlo N-Particle (MCNP) transport code version 5.0(14) was used to simulate photon interaction with normal and tumor tissues within modeled right eye phantoms. Five modeled dome-shaped tumors with a diameter and apical height of 8 mm and 6 mm, respectively, were simulated distinct positions with respect to the macula iteratively. A single fixed 9 x 9 mm2 beamlet, and a comparison COMS protocol plaque containing eight I-125 seeds (apparent activity of 8 mCi) placed on the scleral surface of the eye adjacent to the tumor, were utilized to determine dosimetric parameters at tumor and adjacent tissues. After MCNP simulation, comparison of dose distribution at each of the 5 tumor positions for each modality (BLOKX vs. eye-plaque) was performed. RESULTS: Tumor-base doses ranged from 87.1-102.8 Gy for the BLOKX procedure, and from 335.3-338.6 Gy for the eye-plaque procedure. A reduction of dose of at least 69% to tumor base was noted when using the BLOKX. The BLOKX technique showed a significant reduction of dose, 89.8%, to the macula compared to the episcleral plaque. A minimum 71.0 % decrease in dose to the optic nerve occurred when the BLOKX was used. CONCLUSION: The BLOKX technique allows more favorable dose distribution in comparison to standard COMS brachytherapy, as simulated using a Monte Carlo iterative mathematical modeling. Future series to determine clinical utility of such an approach are warranted.

Questions and answers concerning applicability of proteomics and transcriptomics in EMF research.

The applicability of high-throughput screening techniques of transcriptomics, proteomics and metabolomics in the search for biological and health effects of electromagnetic fields is a hotly debated issue. On the one hand, use of these modern screening technologies speeds up the discovery process and gives broader insight into biochemical events that follow the exposure to electromagnetic fields. On the other hand these modern screening technologies have the problem of reproducibility and variability between experiments and are prone to produce false positive results. These and other issues concerning the applicability of modern screening technologies were the topic of a workshop held at STUK in 2005 (30 October to 1 November) in Helsinki, Finland, and this Report summarizes the discussions at this workshop.

FDTD analysis of a gigahertz TEM cell for ultra-wideband pulse exposure studies of biological specimens.

Gigahertz transverse electromagnetic (GTEM) transmission cells have been previously used to experimentally study exposure of biological cells to ultra-wideband (UWB), monopolar, electromagnetic pulses. Using finite-difference time-domain (FDTD) simulations we examine the time-dependent electric field waveforms and energy dose spatial distributions within a finite volume of biological cell culture medium during these experiments. The simulations show that when one or more flasks containing cell culture media are placed inside the GTEM cell, the uniform fields of the empty GTEM cell are significantly perturbed. The fields inside the cell culture medium, representing the fields to which the biological cells are exposed, are no longer monopolar and are spatially highly nonuniform. These effects result from a combination of refraction and distortion of the incident wave, combined with excitation of resonant eigenmodes within the cell culture medium volume. The simulations show that these distortions of the incident waveform may be mitigated by supporting the sample on a high permittivity pedestal and modifying the incident waveform to more closely approximate a Gaussian pulse. Under all simulated conditions, the estimated maximum temperature rises are completely negligible, ensuring that any experimentally observed unusual cell function or histopathology can be associated with nonthermal effects.

Radiofrequency exposure and mammalian cell toxicity, genotoxicity, and transformation.

The published in vitro literature relevant to the issue of the possible induction of toxicity, genotoxicity, and transformation of mammalian cells due to radiofrequency field (RF) exposure is examined. In some instances, information about related in vivo studies is presented. The review is from the perspective of technical merit and also biological consistency, especially with regard to those publications reporting a positive effect. The weight of evidence available indicates that, for a variety of frequencies and modulations with both short and long exposure times, at exposure levels that do not (or in some instances do) heat the biological sample such that there is a measurable increase in temperature, RF exposure does not induce (a). DNA strand breaks, (b). chromosome aberrations, (c). sister chromatid exchanges (SCEs), (d). DNA repair synthesis, (e). phenotypic mutation, or (f). transformation (cancer-like changes). While there is limited experimental evidence that RF exposure induces micronuclei formation, there is abundant evidence that it does not. There is some evidence that RF exposure does not induce DNA excision repair, suggesting the absence of base damage. There is also evidence that RF exposure does not inhibit excision repair after the induction of thymine dimers by UV exposure, as well as evidence that indicates that RF is not a co-carcinogen or a tumor promoter. The article is in part a tutorial, so that the reader can consider similarities and discrepancies between reports of RF-induced effects relative to one another.

Basis for the extraordinary genetic stability of anthrax.

Over 500 isolates of anthrax bacillus from around the world represent one of the most genetically homogeneous microbes. There are three possibilities for this genetic stability: (1) anthrax has an extraordinarily high fidelity repair system, (2) genetic damage to anthrax is usually lethal, and/or (3) a highly demanding and selective process exists in its environment that is necessary for the completion of its life cycle. Using probes made from genes selected by growth of an Escherichia coli expression vector Bacillus anthracis library on hypertrophic high nitrate concentration medium, genes unique to B. anthracis were isolated. High nitration conditions generated stable chromosomal mutants that displayed altered morphology and life-cycle progression. Therefore, life-cycle progression connected to nitration, associated with host inflammatory response, selects for mutants that show life-cycle progression tightly coupled to progression of the inflammatory response to anthrax. Significant variation from this coupled progression leads to failure of anthrax to complete its life-cycle at the death of its host.

NF-kappaB DNA-binding activity after high peak power pulsed microwave (8.2 GHz) exposure of normal human monocytes.

The hypothesis investigated is that exposure of a mammalian cell to high peak power pulsed RF, at the frequency of 8.2 GHz, can result in the activation of an important eukaryotic transcriptional regulator, nuclear factor kappa B (NF-kappaB). This DNA-binding protein controls genes involved in long term cellular regulation. The selection of 8.2 GHz was based on the availability of a high peak power pulsed RF transmitter. In these studies, triplicate cultures of human monocytes (Mono Mac-6) were exposed to the pulsed wave radiation. The peak to average power ratio was 455:1 (2.2 micros pulse width and pulse repetition rate of 1000 pulses/s). The average power density at the position of exposure was 50 W/m(2), and the mean SAR at the bottom of the culture flask was 10.8 +/- 7.1 W/kg. The FDTD analysis indicated that 10% of the cells had an SAR of 22-29 W/kg. The cells were exposed continuously for 90 min at 37 degrees C, reincubated at this temperature, and harvested 4 h postexposure. The nuclear extracts were analyzed by electrophoretic mobility shift assay. The results showed a profound increase (3.6-fold) in the DNA binding activity of NF-kappaB in monocytes at 4 h after the pulsed RF exposure compared to sham irradiated controls. Competition experiments with cold NF-kappaB- specific oligonucleotides confirmed the specificity of the DNA binding activity. These results provide evidence that high peak power pulsed radiofrequency radiation can perturb the cell and initiate cell signaling pathways. However, at this point, we are not prepared to advocate that the cause is a nonthermal mechanism. Because of the broad distribution of SAR's in the flask, experiments need to be performed to determine if the changes observed are associated with cells exposed to high or low SARs.

Influence of radiotherapy on 6-sulphatoxymelatonin levels in the urine of brain cancer patients.

OBJECTIVES: The synthesis of melatonin, an endogenous compound synthesized by the pineal gland in the brain, is reported to be depressed in patients with primary cancers of the breast, prostate, stomach and rectum. It is not known whether patients with brain cancer exhibit altered melatonin synthesis. Also unknown is whether radiotherapy given to the region of the brain where the pineal gland is located affects the synthesis of melatonin. This information could be relevant to the clinician for the successful treatment of brain cancer patients since melatonin has been reported to be a potent oncostatic agent. METHODS: Urinary levels of 6-sulphatoxymelatonin, the chief metabolite of melatonin, are routinely used as an index of pineal melatonin production and secretion. In this study, the concentrations of 6-sulphatoxymelatonin (aMT6S) excreted in the urine before and during radiotherapy of patients with primary or metastatic brain cancer were determined and compared with the values obtained in breast or lung cancer patients who also received radiotherapy (excluding exposure of the brain where the pineal gland is located). RESULTS: The results showed a wide variation in the mean concentration of aMT6S excreted in the urine. CONCLUSION: The data from this preliminary study suggested that radiotherapy given to the region of human brain, where the pineal gland is located, does not significantly affect the excretion of aMT6S, the chief metabolite of melatonin.