Effect of Radiation Dose Fractionation and Radiation Energy on Gold Nanoparticle Enhancement of Radiation Therapy

Objective: Gold nanoparticles (GNPs) have the potential to enhance the effects of radiation therapy, using Auger electrons to cause additional damage to tumors. In this work, we explore the effect of two clinically important variables: dose fractionation and radiation energy. In clinical radiation therapy, radiation is fractionated (split into multiple sessions) and high-energy radiation is used. However, in the field of GNP research, radiation has generally been given in one session and lower radiation energies have generally been used. Methods: Mice with JC breast tumors implanted in the flank were given radiation therapy over 1, 2, or 4 fractions, with radiation energies of either 250 kilovolts peak or 350 kilovolts peak. A survival analysis and a weighted generalized estimating equation analysis were used to. Results: The use of multiple radiation fractions (between 1 and 4) and the use of radiation doses between 250-350 kVp were only different by statistically insignificant amounts, after the contributions from time, sex, age at irradiation and original tumor volume were accounted for. A survival analysis found a higher likelihood of death for female mice, mice given 350 kilovolts peak radiation (versus 250 kilovolts peak), and mice with larger tumors, as well as a lower likelihood of death for mice irradiated at an older age; fractionated radiation did not have a statistically significant effect. Conclusion: These results suggest that GNPs have the potential to enhance radiation therapy when used with fractionated radiation

Gene Expression as a Dosimeter in Irradiated Drosophila melanogaster

Biological indicators would be of use in radiation dosimetry in situations where an exposed person is not wearing a dosimeter, or when physical dosimeters are insufficient to estimate the risk caused by the radiation exposure. In this work, we investigate the use of gene expression as a dosimeter. Gene expression analysis was done on 15,222 genes of Drosophila melanogaster (fruit flies) at days 2, 10, and 20 postirradiation, with X-ray exposures of 10, 1000, 5000, 10,000, and 20,000 roentgens. Several genes were identified, which could serve as a biodosimeter in an irradiated D. melanogaster model. Many of these genes have human homologues. Six genes showed a linear response (R2 \u3e 0.9) with dose at all time points. One of these genes, inverted repeat-binding protein, is a known DNA repair gene and has a human homologue (XRCC6). The lowest dose, 10 roentgen, is very low for fruit flies. If the lowest dose is excluded, 13 genes showed a linear response with dose at all time points. This includes 5 of 6 genes that were linear with all radiation doses included. Of these 13 genes, 4 have human homologues and 8 have known functions. The expression of this panel of genes, particularly those with human homologues, could potentially be used as the biological indicator of radiation exposure in dosimetry applications

Increasing Depression Screening and Treatment

Aims for Improvement Increase response to depression advisory in EHR from 39% (January 2021) to 60% or greater (March 2021) Increase referrals to behavioral health from baseline of 39/month (January 2021) by 25% (March 2021

Effects of Nanoparticle Size and Radiation Energy on Copper-Cysteamine Nanoparticles for X-ray Induced Photodynamic Therapy

The Copper-cysteamine (Cu-Cy) nanoparticle is a novel sensitizer with a potential to increase the effectiveness of radiation therapy for cancer treatment. In this work, the effect of nanoparticle size and the energy of X-rays on the effectiveness of radiation therapy are investigated. The effect of the particle size on their performance is very complicated. The nanoparticles with an average size of 300 nm have the most intense photoluminescence, the nanoparticles with the average size of 100 nm have the most reactive oxygen species production upon X-ray irradiation, while the nanoparticles with the average size of 40 nm have the best outcome in the tumor suppression in mice upon X-ray irradiation. For energy, 90 kVp radiation resulted in smaller tumor sizes than 250 kVp or 350 kVp radiation energies. Overall, knowledge of the effect of nanoparticle size and radiation energy on radiation therapy outcomes could be useful for future applications of Cu-Cy nanoparticles

Enhancement of Radiation Effect on Cancer Cells by Gold-pHLIP

Previous research has shown that gold nanoparticles can increase the effectiveness of radiation on cancer cells. Improved radiation effectiveness would allow lower radiation doses given to patients, reducing adverse effects; alternatively, it would provide more cancer killing at current radiation doses. Damage from radiation and gold nanoparticles depends in part on the Auger effect, which is very localized; thus, it is important to place the gold nanoparticles on or in the cancer cells. In this work, we use the pH-sensitive, tumor-targeting agent, pH Low-Insertion Peptide (pHLIP), to tether 1.4-nm gold nanoparticles to cancer cells. We find that the conjugation of pHLIP to gold nanoparticles increases gold uptake in cells compared with gold nanoparticles without pHLIP, with the nanoparticles distributed mostly on the cellular membranes. We further find that gold nanoparticles conjugated to pHLIP produce a statistically significant decrease in cell survival with radiation compared with cells without gold nanoparticles and cells with gold alone. In the context of our previous findings demonstrating efficient pHLIP-mediated delivery of gold nanoparticles to tumors, the obtained results serve as a foundation for further preclinical evaluation of dose enhancement

Show a Threshold Effect in Response to Radiation

We investigate the biological effects of radiation using adult Drosophila melanogaster as a model organism, focusing on gene expression and lifespan analysis to determine the effect of different radiation doses. Our results support a threshold effect in response to radiation: no effect on lifespan and no permanent effect on gene expression is seen at incident radiation levels below 100 J/kg. We also find that it is more appropriate to compare radiation effects in flies using the absorbed energy rather than incident radiation levels

Gold nanoparticles enhance radiation therapy at low concentrations, and remain in tumors for days

Gold nanoparticles are a potential method for enhancing radiation therapy, causing extra damage to tumors when irradiated through the Auger effect. One of the major obstacles to using gold nanoparticles in human trials is the relatively large amount of gold required. This paper details an experiment where a relatively small amount of gold (200 g) was used to significantly reduce tumor volume in mice, as well as the results of an inter-tissue biodistribution experiment. Using a longitudinal analysis, tumor size as a function of time was found to be significantly reduced when mice were given 200 g of gold nanoparticles and 20 Gray of radiation, compared to radiation alone. 200 g in a 20-gram mouse would be mass equivalent to 750 mg of gold in a 75 kg person. Biodistribution measurements demonstrated that gold nanoparticles stayed in the tumor for at least one week after injection when targeted to tumors using pH-Low Insertion Peptide and intratumoral injections. These results show gold nanoparticles to be effective at one of the smallest amounts of gold ever attempted in a mouse, and showed that tumor targeting has the potential to keep gold nanoparticles available in tumors long enough to be beneficial to fractionated radiation treatments (a key component of radiation therapy in the clinic)

Comparative transcriptional profiling identifies takeout as a gene that regulates life span

A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR,increased dSir2 and decreased Dmp53 activity. We find twenty‐one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah.We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway