Effect Of Different Radiation Doses Research Articles

MLNAN: Multi-level noise-aware network for low-dose CT imaging implemented with constrained cycle Wasserstein generative adversarial networks

Low-dose CT techniques attempt to minimize the radiation exposure of patients by estimating the high-resolution normal-dose CT images to reduce the risk of radiation-induced cancer. In recent years, many deep learning methods have been proposed to solve this problem by building a mapping function between low-dose CT images and their high-dose counterparts. However, most of these methods ignore the effect of different radiation doses on the final CT images, which results in large differences in the intensity of the noise observable in CT images. What’more, the noise intensity of low-dose CT images exists significantly differences under different medical devices manufacturers. In this paper, we propose a multi-level noise-aware network (MLNAN) implemented with constrained cycle Wasserstein generative adversarial networks to recovery the low-dose CT images under uncertain noise levels. Particularly, the noise-level classification is predicted and reused as a prior pattern in generator networks. Moreover, the discriminator network introduces noise-level determination. Under two dose-reduction strategies, experiments to evaluate the performance of proposed method are conducted on two datasets, including the simulated clinical AAPM challenge datasets and commercial CT datasets from United Imaging Healthcare (UIH). The experimental results illustrate the effectiveness of our proposed method in terms of noise suppression and structural detail preservation compared with several other deep-learning based methods. Ablation studies validate the effectiveness of the individual components regarding the afforded performance improvement. Further research for practical clinical applications and other medical modalities is required in future works.

Histological and Physiological Effects of Treatment of Rudbeckia hirta with Gamma Radiation.

The breeding of resistant, high-yield, decorative ornamental plant varieties may be impacted by climate change in the future. The use of radiation induces mutations in plants, thereby increasing the genetic variability of plant species. Rudbeckia hirta has long been a very popular species in urban green space management. The goal is to examine whether gamma mutation breeding can be applied to the breeding stock. Specifically, differences were measured between the M1 and M2 generations, as well as the effect of different radiation doses belonging to the same generation. Morphological measurements showed that gamma radiation has an effect on the measured parameters in several cases (larger crop size, faster development, larger number of trichomes). Physiological measurements (examination of chlorophyll and carotenoid content, POD activity, and APTI) also showed a beneficial effect of radiation, especially at higher doses (30 Gy), for both tested generations. The treatment was also effective in the case of 45 Gy, but this radiation dose resulted in lower physiological data. The measurements show that gamma radiation has an effect on the Rudbeckia hirta strain and may play a role in breeding in the future.

Low-dose localised electron radiotherapy in a case of refractory mycosis fungoides

We present a case of refractory mycosis fungoides (MF) that responded to low-dose localised electron radiotherapy. A 59-year-old man presented with a 5-year history of a generalised, pruritic, scaly, red skin rash that had recently become more nodular. Skin biopsy confirmed MF. After a variable initial response to topical steroids and oral methotrexate, progressive tumours were treated with low-dose electron radiotherapy. We describe the clinical effect of different radiation doses and fractionation schedules applied over a 2-year period. Our experience in this case of MF suggests that low-dose localised electron radiotherapy offers excellent palliation by effectively resolving tumorous lesions, improving quality of life and allowing for retreatment of refractory lesions.

The Effects of Additional Filtration on Image Quality and Radiation Dose in Cone Beam CT: An In Vivo Preliminary Investigation.

Purpose The aim of this study was to investigate the effect of reduced radiation doses on the image quality of cone-beam computed tomography scans and the suitability of such imaging for orthodontics, oral surgery, dental implantology, periodontology, and endodontology. Materials and Methods Cone-beam computed tomography scans of a live patient were performed using seven attenuation filters with increased thickness to decrease the effective radiation dose from 22.4 to 1.8 μSv, and the effects of different radiation doses on image quality were further analysed. Quantitative image quality was calculated using dedicated measures, such as signal and contrast-to-noise ratio and sharpness. A panel of five certified raters assessed the cone-beam computed tomography scans qualitatively. Nine anatomical structures relevant to dentistry were identified, and the overall acceptance was assessed. Results Linear reduction of the effective radiation dose had a nonlinear effect on image quality. A 5-fold reduction in the effective dose led to acceptable quantitative and qualitative image quality measures, and the identification rate of dental anatomical structures was 80% or greater. The use of less than 40% of the reference dose was unacceptable for all dental specialties. Conclusions The ideal radiation dose for specific diagnostic requirements remains a patient-related and specialty-related decision that must be made on an individual basis. Based on the results of this study, it is possible to reduce exposure in selected patients, and at the same time obtain sufficient quality of images for clinical purposes.

Application Of Cell Culture System In Radiation Dose Optimization Of Breast Cancer Radiotherapy

Introduction: Metastatic breast cancer causes high mortality in women. Therefore, the search for effective treatment continues. A suitable radiation dose should be determined to cause only a minimum damage to the surrounding tissue. We aimed to determine if cell culture systems can be used to demonstrate the effects of different radiation doses on breast cancer cells. Methods: Here, MDA-MB-231 breast cancer cells were used. The antiproliferative effect of different doses of X-rays was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide test. A wound healing test was performed to assess the metastatic potential, and flow cytometry analysis was used to evaluate the cell cycle. Results: It is found that 2 Gy, 4 Gy, and 8 Gy radiation doses were applied to the cells. Cell proliferation was significantly decreased at all doses (p<0.05). However, there was no significant decrease between the different dose groups (p>0.05). The lateral mobilization potential of MDA-MB-231 cells was decreased significantly in radiation applied cells as compared with the control. Cell cycle analyses showed that different doses of radiation delayed the cells in G1 as compared with control cells in the S phase. Discussion and Conclusion: In the cell culture system, a decrease in proliferation and metastatic potential of breast cancer cells by the application of different doses of radiation is found. Therefore, for effective planning of radiation therapy, additional parameters of radiation should also be assessed via cell culture systems. It has been shown that cell culture systems may be used for dosimetry studies of radiation therapy for breast cancer.

Effects of Fe-Ions Irradiation on the Microstructure and Mechanical Properties of FeCrAl-1.5wt.% ZrC Alloys.

Fe-13Cr-3.5Al-2.0Mo-1.5wt.% ZrC alloy was irradiated by 400 keV Fe+ at 400 °C at different doses ranging from 6.35 × 1014 to 1.27 × 1016 ions/cm2 with a corresponding damage of 1.0–20.0 dpa, respectively, to investigate the effects of different radiation doses on the hardness and microstructure of the reinforced FeCrAl alloys in detail by nanoindentation, transmission electron microscopy (TEM), and atom probe tomography (APT). The results show that the hardness at 1.0 dpa increases from 5.68 to 6.81 GPa, which is 19.9% higher than a non-irradiated specimen. With an increase in dose from 1.0 to 20.0 dpa, the hardness increases from 6.81 to 8.01 GPa, which is an increase of only 17.6%, indicating that the hardness has reached saturation. TEM and APT results show that high-density nano-precipitates and low-density dislocation loops forme in the 1.0 dpa region, compared to the non-irradiated region. Compared with 1.0 dpa region, the density and size of nano-precipitates in the 20.0 dpa region have no significant change, while the density of dislocation loops increases. Irradiation results in a decrease of molybdenum and carbon in the strengthening precipitates (Zr, Mo) (C, N), and the proportionate decrease of molybdenum and carbon is more obvious with the increase in damage.

Synthesis and characterization of polyvinyl alcohol/water-hyacinth (Eichhornia crassipes) based hydrogel by applying gamma radiation

A simple Gamma radiation (Cobalt-60 γ-ray source) technique was employed for the preparation of hydrogel based on Polyvinyl Alcohol (PVA)/water-hyacinth (Eichhornia crassipes) (PW hydrogel) without using any external cross-linker. The structure of the synthesized hydrogels was characterized using Fourier Transform Infrared-Attenuated Total Reflection Spectroscopy (FTIR-ATR) and Scanning Electron Microscopy (SEM). The effects of different radiation doses, the concentration of water-hyacinth on the properties of the prepared hydrogel, such as gel fraction, swelling ratio, water uptake, and mechanical properties including the tensile strength (TS), percentage elongation at break (EB) and biodegradability were investigated. The hydrogels showed a porous and interconnected network and flexible structure. The presence of water-hyacinth significantly escalated the swelling capacity of PVA hydrogels from 97.9% to 136.24% along with acceptable tensile strength. And the degradation percentage of PW hydrogel was remarkably higher than the pure PVA hydrogel. Furthermore, the weight loss of PW hydrogel was 12.86%, whereas 3.19% was for pure PVA hydrogel. Hence, this novel hydrogel showed some favorable potentials to be applied in various fields, especially, adsorption to remove the dye and heavy metals.

Investigation the Effect of Low, Medium and High Dose of X-Radiation on the Expression of E-cadherin in Colorectal Cancer Cell Line.

Background: Radiotherapy has become a part of therapeutic process of more than 50 percent of patients suffering from cancer. However, recent studies have shown that radiation therapy might affect the expression of adhesive molecule related genes such as E-cadherin and cause cancer cells to move and migrate. Besides, various studies have reported that the expression of E-cadherin changes differently after radiation treatment. There are several studies which showed the loss of E-cadherin function after radiation; however, this reduction has not been observed in others.Objective: This study aims to investigate the effect of different radiation doses of X-ray on changes that might occur in the expression of E-cadherin gene in colorectal cancer cell line HT-29.Material and Methods: In this experimental study, the cells cultured in flasks were irradiated with X- rays in different doses, including 0.1, 2.5, 5, and 10 Gy; then, the expression of E-cadherin gene was measured using real-time PCR.Results: The expression of E-cadherin did not change significantly in post-irradiated HT-29 cell line after different radiation doses of X-ray. Conclusion: The results showed that low, medium and high doses of X- radiation did not change the expression of E-cadherin gene in HT-29 cancer cells. However, it has been reported that radiation mostly downregulated the expression of E-cadherin and mediated metastasis formation and invasiveness in different cancer cell lines. Therefore, further studies need to be conducted to investigate the effects of radiation dose on the molecular pathways contributing to regulation of E-cadherin in HT-29 cell line.

Quantitative analysis of collagen and capillaries of 3.8-μm laser-induced cutaneous thermal injury and wound healing.

The biological effects of cutaneous thermal injury and wound healing after 3.8-μm laser radiation were investigated by observing the effects of different radiation doses on in vivo cutaneous tissue. A 3.8-μm laser with a radiation dose that changes from small (5.07) to large (15.74J/cm2) was used to irradiate mouse skin with the 2 × 4 grid array method. The healing progress of laser-injured spots, pathological morphology (H&E staining), and collagen structure changes (Sirius Red staining) were dynamically observed from one hour to 21days after laser radiation, and the capillary count and collagen content were quantitatively and comparatively analyzed. When the radiation doses were 5.07, 6.77, 8.21, and 9.42J/cm2, a white coagulation spot predominantly occurred, and when the radiation doses were 11.09 12.23, 14.13, 15.74J/cm2, a small injured spot predominantly occurred. One hour after radiation, the collagen structure was obviously damaged. Three to fourteen days after radiation, the hyperplasia and morphology of the collagen in the 5.07J/cm2 group were significantly better than those in the other dose groups. The number of capillaries in the 5.07J/cm2 and 6.77J/cm2 groups was significantly higher than that in the normal group (P < 0.01 or P < 0.05). Twenty-one days after radiation, only the collagen in the 5.07J/cm2 group was densely arranged, and it was basically close to the normal group level. The collagen content in the 5.07J/cm2 group was approximately 10.7%, but it was still lower than that in the normal group (with a collagen content of approximately 14.1%). The collagen in the other dose groups was diminished and had not returned to the normal group level. As the dose of the 3.8-μm laser increased, skin thermal injury gradually increased, the full-thickness skin increased, and the collagen content decreased, showing better dose-dependent and time-dependent effect relationships. The increase in capillaries in the early stage of laser radiation and the significant increase in collagen content in the middle and late stages of laser radiation were two important factors that promoted wound healing.

The effect of different dose and sites of irradiation on lymphocyte subsets in peripheral blood of patients with lung cancer.

e21032 Background: To explore the effect of different radiation doses and sites on systemic immunity in patients with lung cancer by detecting the changes in the percentage of lymphocyte subsets in peripheral blood before and after radiotherapy. Methods: Peripheral blood in 48 patients with lung cancer receiving radiotherapy were collected (before, during and after radiation), and the lymphocyte subsets as follow were examined: total T cell (CD3+), CD4+T cell, CD8+T cell, CD3+CD4+/CD3+CD8+, NK cell, memory T-helper cell subpopulation (CD4+ CD45RO+), CD4+ naïve T-cell subset (CD4+CD45RA+), cytotoxic T cell (CD8+CD28+), IL-2 receptor α(CD25+), B cells (CD3-CD19+), regulatory T cells (CD4+CD25+). The results were statistically analyzed with unpaired Student's t-test using GraphPrism6 software. Results: Among non-small cell lung cancer (NSCLC) patients treated with thoracic radiation (n = 21), B cells in patients receiving 20Gy/10F (P = 0.0072), 40Gy/ 20F (P = 0.0001), 60Gy/30F (P = 0.0002) irradiation were significantly lower than that before radiotherapy. However, CD4+ naïve T-cells decreased significantly at each dose point compared with that before radiotherapy, P values were 0.0394, 0.0081 and 0.0007, respectively. NK cells after completion of 60Gy/30F irradiation were distinctly lower than those after receiving 20Gy/10F of radiotherapy (P = 0.0278), and no significant difference was found in other immune cell subsets. Patients with small cell lung cancer (n = 6) who underwent thoracic radiation showed a similar trend of changes in B cells. However, the CD4+CD45RA+ subset decreased evidently after completing radiation compared with that after 10 fractions of irradiation (P = 0.0390). The NSCLC patients (n = 4) who received radiation for bone metastases (regimen: 36Gy/12F) had evidently lower B cells (CD3-CD19+) at the end of radiotherapy than that at the start of radiotherapy (P = 0.0286). Patients with NSCLC (n = 10) who received brain radiation (regimen: 40Gy/20F for whole brain, 54-56Gy/20F for multiple brain metastases) had a significantly reduced CD4+CD45RA+ subsets after finishing radiation (20F) compared with those after 10 fraction of radiation (P = 0.0497). The changes of other subsets were not statistically significant. Conclusions: The effect of radiation in different sites and doses on peripheral blood lymphocyte subsets is not identical.It is urgent to expand the sample size to explore the law for the optimization of radiation combined with immunotherapy.Funding: 81972853, 81572279, 2016J004, LC2019ZD009, 2018CR033

Blood RNA Integrity is a Direct and Simple Reporter of Radiation Exposure and Prognosis: A Pilot Study.

In the event of a mass casualty radiation scenario, rapid assessment of patients' health and triage is required for optimal resource utilization. Identifying the level and extent of exposure as well as prioritization of care is extremely challenging under such disaster conditions. Blood-based biomarkers, such as RNA integrity numbers (RIN), could help healthcare personnel quickly and efficiently determine the extent and effect of multiple injuries on patients' health. Evaluation of the effect of different radiation doses, alone or in combination with burn injury, on total RNA integrity over multiple time points was performed. Total RNA integrity was tallied in blood samples for potential application as a marker of radiation exposure and survival. Groups of aged mice (3-6 mice/group, 13-18 months old) received 0.5, 1, 5, 10 or 20 Gy ionizing radiation. Two additional mouse groups received low-dose irradiation (0.5 or 1 Gy) with a 15% total body surface area (TBSA) burn injury. Animals were euthanized at 2 or 12 h and at day 1, 2, 3, 7 or 14 postirradiation, or when injury-mediated mortality occurred. Total RNA was isolated from blood. The quality of RNA was evaluated and RNA RIN were obtained. Analysis of RIN indicated that blood showed the clearest radiation effect. There was a time- and radiation-dose-dependent reduction in RIN that was first detectable at 12 h postirradiation for all doses in animals receiving irradiation alone. This effect was reversible in lower-dose groups (i.e., 0.5, 1 and 5 Gy) that survived to the end of the study (14 days). In contrast, the effect persisted for 10 and 20 Gy groups, which showed suppression of RIN values <4.5 with high mortalities. Radiation doses of 20 Gy were lethal and required euthanasia by day 6. A low RIN (<2.5) at any time point was associated with 100% mortality. Combined radiation-burn injury produced significantly increased mortality such that no dually-injured animals survived beyond day 3, and no radiation dose >1 Gy resulted in survival past day 1. More modest suppression of RIN was observed in the surviving dually challenged mice, and no statistically significant changes were identified in RIN values of burn-only mice at any time point. In this study of an animal model, a proof of concept is presented for a simple and accurate method of assessing radiation dose exposure in blood which potentially predicts lethality. RIN assessment of blood-derived RNA could form the basis for a clinical decision-support tool to guide healthcare providers under the strenuous conditions of a radiation-based mass casualty event.

Abstract P6-10-18: Development and validation of novel biomarkers of response to radiotherapy in breast cancer

Abstract Background: Radiotherapy (RT) plays an important role in the multimodal treatment of breast cancer (BC). Despite improvements in the accuracy of delivering radiation to specific biological target volumes, the clinical response of BC to RT is still affected by intrinsic/acquired radioresistance. These resistant cancer cells can contribute to the development of recurrent disease and poor patient outcomes. Clinical signs of RT response are often not apparent for several weeks post-treatment; patients who fail to respond will therefore initially go undetected. There are currently no clinically validated biomarkers that can predict which patients will respond to RT or assess response during treatment. Our study aims to address this major clinical need through the identification and validation of biomarkers of radiation responsiveness. Methods: The effects of different radiation doses (2 - 10Gy) at a range of time points (1 - 24h) were investigated by analysing the protein secretion profiles from 3 BC cell lines: MCF-7 (ER+), ZR-751 (ER+) and MDA-MB-231 (ER-). Conditioned media was collected from each dose/time point and proteins isolated for mass spec analysis. For comparison, radioresistant models were derived from each of the 3 cell lines and were characterized by proliferation and colony formation assays, invasion and migration assays, whole-genome transcriptomic sequencing (WGTS) analysis and western blotting. To assess intrinsic response to RT a panel of 16 BC cell lines were evaluated by colony formation assays following a 2Gy dose of radiation. WGTS of a patient cohort of 230 (138 ER+ve, 92 ER-ve) post-menopausal women with BC, treated with breast conserving surgery and adjuvant RT but no systemic adjuvant therapy, with a median follow-up of 14 years, is currently underway. Results: 9 biomarkers emerged whose secretion was significantly increased with radiation. These were evaluated by western blotting of conditioned media 24h after a 2Gy dose of RT in matched radio-sensitive and resistant cell lines; this confirmed significantly higher levels of radiation induced secretion from sensitive cells compared to resistant. Radioresistant cell lines were characterised by epithelial-to-mesenchymal-transition, enhanced invasion/migration, loss of ER and PgR and increased EGFR and PI3K signaling activity. Initial mechanistic investigations suggest that biomarker release in response to radiation occurs via microvesicles. A blood-based assay to test the level of these secreted biomarkers is currently under development. Pre-treatment levels of the 9 biomarkers were also found to be associated with prediction of intrinsic response to RT at both gene and protein level. A gene expression signature comprising the 9 candidates is strongly associated with the intrinsic response to RT across the 16 BC cell lines studied, with higher expression found in those more sensitive to RT compared with those less sensitive or resistant. Validation of the predictive power of these biomarkers in terms of recurrence-free and overall BC specific survival is currently being assessed at gene and protein level in the patient cohort. Conclusions: We have identified 9 biomarkers which are released from BC cells sensitive to radiation 24h after a 2Gy dose (in line with current clinical standards) but not from radio-resistant derivatives.A blood based assay is currently under development which has the potential to monitor response to RT in the neoadjuvant and palliative settings.Intracellular levels of the 9 biomarkers are strongly associated with intrinsic response to RT and may hold predictive potential.These biomarkers may have the potential to improve patient care by identifying patients less likely to benefit from RT, paving the way for personalization of treatment, including altered dosing schedules and the future use of emerging radio-sensitizers. Citation Format: James Meehan, Mark Gray, Carlos Martinez-Perez, Charlene Kay, J Michael Dixon, Jimi Wills, Carol Ward, Alex von Kriegsheim, Niall Quinn, Olga Oikonomidou, David Cameron, Simon P Langdon, David Argyle, Ian H Kunkler, Arran K Turnbull. Development and validation of novel biomarkers of response to radiotherapy in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-18.

The Evaluation of Survivin and Bcl-2 Expression on the Medical Radiation Doses for Neural Tube Defect Development.

To investigate the effects of different radiation doses on the development of the neural tube defect in chick embryos using computed tomography (CT), and assess its correlation with survivin and Bcl-2 expressions. A total of 150 chicken eggs were used and grouped into five categories. In Group 1 (n=30), the embryos were not exposed to radiation. In Group 2 (n=30), the embryos were irradiated using lung cancer screening chest CT protocol. In Groups 3 and 4 (n=30 each), the abdominopelvic and adult routine head CT protocols, respectively, were used to irradiate the embryos. In Group 5 (n=30), the embryos were irradiated using adult brain perfusion CT protocol. Subsequently, the embryos were examined under a stereomicroscope to assess the presence of neural tube developmental abnormalities. Moreover, immunohistochemical staining was performed to determine the survivin and Bcl-2 expression levels. The risk of developing neural tube defect increased with the amount of exposed radiation. Moreover, no significant correlation was observed between the survivin and Bcl-2 expression levels and the radiation dose. Overall, the results of this study indicate that the radiation from CT may cause neural tube defect in chicken embryos.

Abstract 3927: Radium-223 α-particle radiation: Characterization of the in vitro effects on cancer cells in monotherapy and in combination with DNA repair inhibitors

Abstract Purpose: Targeted alpha therapy (TAT) represents an emerging treatment approach attempting to deliver systemic radiation selectively to cancer cells and bypassing mechanisms of acquired resistance while minimizing systemic toxic effects. Radium-223 dichloride (Ra-223) is a first-in-class TAT shown to prolong survival in patients with metastatic castration-resistant prostate cancer and bone metastases. Yet, the understanding of the biological effects of α-particle irradiation is still limited. Here, we used a novel in vitro assay designed to assess alpha irradiation specific effects to investigate the biological effects of Ra-223 in various cancer cell lines. Furthermore, the combination of α-particle irradiation with DNA repair inhibitors was tested. Methods: The following cancer cell lines were used: lung (H460), ovarian (OVCAR-3, COV362, COV644, ES2) and prostate (22Rv1, LNCaP). The effects of different radiation doses and exposure times of Ra-223 on various biological parameters were analyzed using a Transwell® system where cells grow on a 10 µm membrane located on top of an underlying Ra-223 coating. Results: After 4 hours of exposure to α-particle irradiation (5, 10 and 20 kBq/3.8 cm2), a dose-dependent induction of DNA double strand breaks (DSB) as assessed by 53BP1 positivity was observed. Exposure to α-particle irradiation (10 and 20 kBq/3.8 cm2) for 1 hour dose-dependently induced DNA damage in a comet assay. Exposure to α-particle irradiation (5 kBq/3.8 cm2) for 1, 4 and 8 hours time-dependently reduced the surviving fraction in the subsequent colony formation assay. The frequency of micronuclei formation was increased in an activity- and time-dependent manner after α-particle exposure at 5, 10, 20, 40 kBq/3.8 cm2 for 1, 4 and 8 hours. In the same assay, the number of dead cells was significantly increased after an 8-hour exposure in all dose groups tested. Pre-incubation with the ATR inhibitor BAY 1895344 (5 nM for 2 hours prior to radiation) synergistically enhanced micronuclei formation (&amp;lt; 5% vs 12% vs 42% in ATR inhibitor only vs α-particle irradiation only vs ATR inhibitor + α-particle irradiation, respectively). Conclusion: Using several cancer cell lines, we demonstrated that short term exposure to α-particle irradiation in the range of 1 to 8 hours is sufficient to induce DNA damage including DNA DSB which leads to cellular damage and cell death. Synergistic effects were observed when Ra-223 was combined with the ATR inhibitor BAY 1895344 . Citation Format: Kristina Bannik, Sabine Zitzmann-Kolbe, Arne Scholz, Sabrina Jarke, Marco Jarzombek, Andreas Sutter, Gerhard Siemeister, Dominik Mumberg. Radium-223 α-particle radiation: Characterization of the in vitro effects on cancer cells in monotherapy and in combination with DNA repair inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3927.

Abstract P3-12-24: Tumor-secreted predictive biomarkers of response to radiotherapy in breast cancer

Abstract Background:In breast cancer (BC), radiotherapy (RT) is used adjuvantly to prevent recurrence and also in the palliative setting. Clinical signs of RT response are often not apparent for several weeks post-treatment and we currently lack tools to predict or monitor tumor response to RT early during treatment. The aim was to identify tumor-secreted biomarkers whose release reflects response to RT, which could be monitored during treatment in the blood or intratumorally by an implantable biosensor, currently under development within the Implantable Microsystems for Personalised Anti-Cancer Therapy (IMPACT) program. Methods: A series of experiments assessed the effect of different radiation doses (2-10Gy) on 3 human BC cell lines – MDA-MB-231 (ER-), MCF-7 (ER+) and HBL-100 (ER-) –, 1 canine breast cancer and 2 sheep lung cancer lines. Culture media was collected from each dose experiment at a range of post-radiation time-points (1-24 hours). Proteins were isolated from collected media for secretome mass spectrometry (MS) analysis. A subset of treatment/time conditions were repeated in the same BC cell lines and radioresistant (RR) derivatives from which RNA was extracted and analysed using Lexogen QuantSeq for whole-genome transcriptomics.In-lab candidate biomarker validation was carried out using immuhistochemistry (IHC), immunofluorescence (IF) and western blotting (WB) using validated antibodies. Levels of candidate biomarkers were also assessed in normal and untreated BC tissues using IHC. ELISA-based methods are currently under investigation for detection of the lead candidate biomarkers in the blood of large animal cancer models treated with RT. Results: Biomarker discovery using the MS data revealed 4 promising candidates: EIF3G, SEC24C, YBX3 and TK1. These are released from BC and animal cancer cells sensitive to radiation in a dose-dependent manner 24 hours after treatment. Analysis of the transcriptomic data showed an 8-fold higher expression of the genes encoding the 4 candidates in the radio-sensitive parental cell lines compared to the RR cell lines. IF and WB confirmed lower intracellular expression of the 4 proteins in RR cells compared to the parental lines. WB of collected culture media confirmed release of each of the 4 candidates 24 hours after a 2Gy dose of radiation in only the parental lines. GAPDH was not found in these media samples, demonstrating that protein release was not due to cell lysis. Conclusions: · We have identified 4 promising biomarkers which are released from cancer cells sensitive to RT and not released from RR derivatives. · All 4 candidates are released 24 hours after a 2Gy radiation dose, which fits with the current clinical dosing schedule where radiation is administered at 24 hour intervals. Ongoing work will elucidate if these biomarkers can be reliably detected in blood or intratumorally using implantable biosensors. · There are currently no validated predictive tools to monitor RT response during treatment. If successfully validated, these biomarkers could have a clinical role in personalising RT dosing schedules and durations for solid tumors in the neoadjuvant and palliative setting, thus optimising treatment and preventing the administration of ineffective RT and its associated side effects. Citation Format: Meehan J, Gray M, Turnbull AK, Martinez-Perez C, Bonello M, Ward C, Langdon SP, McLaughlin S, MacLennan M, Dixon JM, Wills J, Quinn N, Finich AJ, von Kriegsheim A, Cameron D, Kunkler IH, Murray A, Argyle D. Tumor-secreted predictive biomarkers of response to radiotherapy in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-24.

Radiation-induced mutants with increased cane number in sugarcane variety CoJ 85

ABSTRACTCoJ 85 is an early-maturing, commercial sugarcane (Saccharum spp. complex) variety grown in Punjab, India. Farmers have adopted it because of its high sucrose content. However, it is shy in tillering and produces a low number of millable canes. It is also prone to lodging at maturity. Conventional breeding approaches are not feasible to further improve this variety, as it does not flower even under optimum tropical conditions. In this paper, we report on the use of gamma radiation-mediated in vivo mutagenesis to generate variation for cane number in CoJ 85.Contrary to general practice of irradiating tissue culture-derived calli (in vitro approach), single-bud cane setts (in vivo approach) of CoJ 85 were exposed to gamma rays to induce mutations for cane number. Our in vivo, standardized approach avoided tedious tissue culture cycles that cause undesirable somaclonal variation. Based on the germination data of buds, 25 Gy was found to be the 50% lethal dose (LD50). Thus, a mutant population of CoJ 85 was generated using 25 Gy gamma radiation and advanced to M1V2. The effects of different radiation doses were evaluated for number of tillers, number of millable canes, cane height (cm), cane weight (kg), and Brix (%) [Brix refers to total soluble solids content in juice; expressed in percentage) in the field-grown M1V2 population. A total of 38 elite mutant lines, which exhibited a significant increase in number of millable canes and Brix, were advanced for field evaluation and possible commercial use. We have demonstrated gamma rays-induced in vivo mutagenesis to be an effective method to generate stable mutants for increased cane number in CoJ 85.

Synthesis and characterization of polyethylene oxide (PEO)—N,N-dimethylacrylamide (DMA) hydrogel by gamma radiation

Novel polyethylene oxide (PEO)/N,N-dimethylacrylamide (DMA) blend hydrogel (PD hydrogel) has been prepared by applying gamma radiation on aqueous mixture of PEO and DMA. Different concentrations of DMA have been blended with aqueous solution of PEO and then gamma radiation of different doses was applied to form the hydrogels. The synthesized hydrogels were characterized using Fourier transform infrared-attenuated total reflection spectroscopy (FTIR-ATR) and scanning electron microscopy (SEM). The effect of different radiation doses, concentration of monomers on the properties of prepared hydrogel (PD hydrogel), such as gel content, swelling behavior, and mechanical properties (Tensile strength) was investigated thoroughly. Results showed that hydrogels were formed at the experimental conditions without the use of any external cross-linker. All the prepared hydrogels showed a significantly larger swelling ratio and improved mechanical strength.

Study the Characterization of Spectral Absorbance on Irradiated Milk Protein

The milk has been adopted as a structural nature food for a long era since it is containing most of the growth factors, protective agents, and enzymes needed for the body. a few attempts have been conducted to treat the dairy products especially raw milk by the means of ionizing radiation. as its production has been an expanding industry for many years due to the high demands from the consumers worldwide, there is still some doubt about preserving these products by irradiation. In this work, a preliminary effort to describe the influences of ionizing radiation on raw milk’s protein will be devoted to measuring the spectral absorbance of the total protein (after subjected to varied radiation doses) by UV-VIS-NIR spectroscopy analysis. The absorbance spectrum then analyzed based on absorbance spectra of organic compounds. A comparison is made between the effects of different radiation doses to estimate the influence in milk’s structure.

Effects of different radiation doses on the microhardness, superficial morphology, and mineral components of human enamel

ObjectiveTo evaluate the effects of three different radiotherapy doses (20, 40, and 70Gy) on the microhardness, superficial morphology, and mineral content (based on Ca and P values) of three different depths of human enamel (cervical, middle, and occlusal). DesignThirty-four third molars were cut, separated, and prepared. Microhardness samples (n=30) were embedded in acrylic resin and then polished, and depths were delimited. Microhardness tests were performed on cervical, middle, and occlusal enamel pre- and post-radiotherapy with a load of 50g for 30s. For the scanning electron microscopy (SEM) analysis (n=4) and energy dispersive X-ray spectroscopy (EDS) (n=12), samples were fixed in a 3% glutaraldehyde solution, washed in 0.1M cacodylate solution, and dehydrated in crescent concentrations of ethanol. Microhardness data were tested for significant differences using a two-way analysis of variance (ANOVA) and Tukey’s test (p<0.05), while SEM and EDS were evaluated qualitatively. ResultsThe results showed a decrease in microhardness values only in the cervical enamel, regardless of the radiation dose used; no morphological or mineral change was observed. ConclusionRadiotherapy can affect the microhardness values of only cervical enamel without compromising the morphological or mineral (Ca and P) content at any depth.

Drosophila melanogaster 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.