Publications by authors named "Michael C Joiner"

67 Publications

Final Report from IBPRO: Impact of Multidisciplinary Collaboration on Research in Radiation Oncology.

Radiat Res 2020 08;194(2):188-190

Wayne State University School of Medicine, Detroit, Michigan.

An important hallmark of the field of radiation oncology has traditionally been multidisciplinary collaboration among its clinicians and scientists. Increased specialization, resulting from increased complexity, threatens to diminish this important characteristic. This article evaluates the success of a short-term educational environment developed specifically to enhance multidisciplinary collaboration. This NIH-funded educational course, named "Integration of Biology and Physics into Radiation Oncology (IBPRO)," was developed at Wayne State University, and designed to facilitate engagement among radiation oncologists, medical physicists and radiobiologists in activities that foster collaborative investigation. The question we address here is, "Did it work?" The 240 clinicians and researchers participating in IBPRO over the five years of the course were surveyed to quantify its effectiveness. In total, 95 respondents identified 45 institutional protocols, 52 research grant applications (19 of which have been funded thus far), 94 research manuscripts and 106 research presentations as being attributable to participation in IBPRO. The majority (66%) of respondents reported generating at least one of these research metrics attributable to participation in IBPRO, and these participants reported an average of nearly five such quantitative research metrics per respondent. This represents a remarkable contribution to radiation oncology research within a relatively short period through an intervention involving a relatively small number of radiation oncology professionals. Nearly two thirds of respondents reported ongoing collaborative working relationships generated by IBPRO. In addition, approximately 50% of respondents stated that specific information presented at IBPRO changed the way they practice, and 95% of respondents practicing in a clinical setting stated that, since participation in IBPRO, they have approached clinical dilemmas more collaboratively. Many collaborative working relationships generated by this course continue to actively drive research productivity. Additionally, one of the many enduring legacies of this course is the creation of a new debate series in a professional journal. IBPRO serves as a model for our ability to leverage collaborative learning in an educational intervention to foster multidisciplinary clinical and research collaboration. It has already had a profound impact on the profession of radiation oncology, and this impact can be anticipated to increase in the future.
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http://dx.doi.org/10.1667/RADE-20-00117.1DOI Listing
August 2020

Dosimetric evaluation of incorporating the revised V4.0 calibration protocol for breast intraoperative radiotherapy with the INTRABEAM system.

J Appl Clin Med Phys 2020 Feb 10;21(2):50-59. Epub 2020 Feb 10.

Department of Oncology, Gershenson Radiation Oncology Center, Wayne State University, Detroit, USA.

In breast-targeted intraoperative radiotherapy (TARGIT) clinical trials (TARGIT-B, TARGIT-E, TARGIT-US), a single fraction of radiation is delivered to the tumor bed during surgery with 1.5- to 5.0-cm diameter spherical applicators and an INTRABEAM x-ray source (XRS). This factory-calibrated XRS is characterized by two depth-dose curves (DDCs) named "TARGIT" and "V4.0." Presently, the TARGIT DDC is used to treat patients enrolled in clinical trials; however, the V4.0 DDC is shown to better represent the delivered dose. Therefore, we reevaluate the delivered prescriptions under the TARGIT protocols using the V4.0 DDC. A 20-Gy dose was prescribed to the surface of the spherical applicator, and the TARGIT DDC was used to calculate the treatment time. For a constant treatment time, the V4.0 DDC was used to recalculate the dosimetry to evaluate differences in dose rate, dose, and equivalent dose in 2-Gy fractions (EQD2) for an α/β = 3.5 Gy (endpoint of locoregional relapse). At the surface of the tumor bed (i.e., spherical applicator surface), the calculations using the V4.0 DDC predicted increased values for dose rate (43-16%), dose (28.6-23.2 Gy), and EQD2 (95-31%) for the 1.5- to 5.0-cm diameter spherical applicator sizes, respectively. In general, dosimetric differences are greatest for the 1.5-cm diameter spherical applicator. The results from this study can be interpreted as a reevaluation of dosimetry or the dangers of underdosage, which can occur if the V4.0 DDC is inadvertently used for TARGIT clinical trial patients. Because the INTRABEAM system is used in TARGIT clinical trials, accurate knowledge about absorbed dose is essential for making meaningful comparisons between radiation treatment modalities, and reproducible treatment delivery is imperative. The results of this study shed light on these concerns.
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http://dx.doi.org/10.1002/acm2.12807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020998PMC
February 2020

Evaluation of the dosimetric impact of manufacturing variations for the INTRABEAM x-ray source.

J Appl Clin Med Phys 2020 Mar 24;21(3):20-31. Epub 2020 Jan 24.

Wayne State University School of Medicine, Gershenson Radiation Oncology Center, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.

Introduction: INTRABEAM x-ray sources (XRSs) have distinct output characteristics due to subtle variations between the ideal and manufactured products. The objective of this study is to intercompare 15 XRSs and to dosimetrically quantify the impact of manufacturing variations on the delivered dose.

Methods And Materials: The normality of the XRS datasets was evaluated with the Shapiro-Wilk test, the accuracy of the calibrated depth-dose curves (DDCs) was validated with ionization chamber measurements, and the shape of each DDC was evaluated using depth-dose ratios (DDRs). For 20 Gy prescribed to the spherical applicator surface, the dose was computed at 5-mm and 10-mm depths from the spherical applicator surface for all XRSs.

Results: At 5-, 10-, 20-, and 30-mm depths from the source, the coefficient of variation (CV) of the XRS output for 40 kVp was 4.4%, 2.8%, 2.0%, and 3.1% and for 50 kVp was 4.2%, 3.8%, 3.8%, and 3.4%, respectively. At a 20-mm depth from the source, the 40-kVp energy had a mean output in Gy/Minute = 0.36, standard deviation (SD) = 0.0072, minimum output = 0.34, and maximum output = 0.37 and a 50-kVp energy had a mean output = 0.56, SD = 0.021, minimum output = 0.52, and maximum output = 0.60. We noted the maximum DRR values of 2.8% and 2.5% for 40 kVp and 50 kVp, respectively. For all XRSs, the maximum dosimetric effect of these variations within a 10-mm depth of the applicator surface is ≤ 2.5%. The CV increased as depth increased and as applicator size decreased.

Conclusion: The American Association of Physicist in Medicine Task Group-167 requires that the impurities in radionuclides used for brachytherapy produce ≤ 5.0% dosimetric variations. Because of differences in an XRS output and DDC, we have demonstrated the dosimetric variations within a 10-mm depth of the applicator surface to be ≤ 2.5%.
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http://dx.doi.org/10.1002/acm2.12809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075384PMC
March 2020

Dosimetric evaluation of the INTRABEAM system for breast intraoperative radiotherapy: A single-institution experience.

Med Dosim 2020 Summer;45(2):e1-e6. Epub 2019 Oct 9.

Department of Oncology, Wayne State University School of Medicine, Gershenson Radiation Oncology Center, Barbara Ann Karmanos Cancer Institute, Detroit, MI.

Breast intraoperative radiotherapy (IORT) with the INTRABEAM system uses a 50 kV x-ray source to deliver a single fraction of radiation therapy to the lumpectomy cavity during breast-conserving surgery. We seek to perform a dosimetric analysis of the lumpectomy cavity for rigid spherical applicators. Water phantom measurements were acquired to validate the vendor-provided x-ray calibration. The planning target volume (PTV) was defined as a 10 mm expansion beyond the spherical applicator, a dose-volume histogram (DVH) was generated and dose-volume parameters [D, D, V, V, V, HI] were reported. Additionally, the therapeutic treatment depth using the 90 and 80% isodose level was computed [R, R]. When the percent depth dose (PDD) is normalized to the surface of the applicator, smaller applicators have a steeper PDD. For a prescription dose of 20 Gy to the surface of the applicator, the range of dose-volume parameters for the PTV was: 3.15 to 6.84 Gy for D, 16.2 to 17.6 Gy for D, 2.6 to 6.9% for V, 5.5 to 15.1% for V, and 21.1 to 55.6% for V. For applicators 15 to 50 mm in diameter, the reported values were: 6.35 to 2.9 for HI, 0.53 to 0.85 mm for R, and 1.18 to 1.85 mm for R. Smaller applicators have reduced PTV coverage but elevated HI because the attenuation of the beam proximal to the source is more pronounced. Additionally, the presence of the aluminum filter for small applicators (≤30 mm) increases PTV coverage but reduces the dose rate on the applicator surface. The delivery of IORT is performed in the OR without the use of image-based planning. To overcome this limitation, we have generated sample DVH's and report dosimetric parameters to offer clinicians a unique dosimetric perspective.
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http://dx.doi.org/10.1016/j.meddos.2019.09.002DOI Listing
February 2021

In Reply to Malicki.

Int J Radiat Oncol Biol Phys 2018 12;102(5):1592-1593

Karmanos Cancer Center, Wayne State University School of Medicine, Detroit, Michigan.

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http://dx.doi.org/10.1016/j.ijrobp.2018.07.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482837PMC
December 2018

…of Radiation Oncology, Biology, and Physics.

Int J Radiat Oncol Biol Phys 2018 04 31;100(5):1289-1290. Epub 2018 Jan 31.

Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.

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http://dx.doi.org/10.1016/j.ijrobp.2018.01.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937706PMC
April 2018

Improving Research in Radiation Oncology through Interdisciplinary Collaboration.

Radiat Res 2018 07 25;190(1):1-4. Epub 2018 Apr 25.

a   Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan.

The contribution of radiation oncology to the future of cancer treatment depends significantly on our continued clinical progress and future research advancements. Such progress relies on multidisciplinary collaboration among radiation oncologists, medical physicists and radiobiologists. Cultivating collaborative educational and research opportunities among these three disciplines and further investing in the infrastructure used to train both clinicians and researchers will therefore help us improve the future of cancer care. This article evaluates the success of a short-term educational environment to foster multidisciplinary collaboration. The NIH-funded educational course developed at Wayne State University, called "Integration of Biology and Physics into Radiation Oncology" (IBPRO), was designed to facilitate the engagement of radiation oncologists, medical physicists and radiobiologists in activities that enhance collaborative investigation. Having now been delivered to nearly 200 participants over the past four years, the relative success of IBPRO in fostering productive interdisciplinary collaboration and producing tangible research outcomes can be evaluated. The 140 IBPRO participants from the first three years were surveyed to quantify the effectiveness of the course. In total, 62 respondents reported developing 23 institutional protocols, submitting more than 25 research grants (nine of which have been funded thus far), and publishing more than 30 research manuscripts attributable to participation in IBPRO. Nearly one-half (45%) of respondents reported generating at least one of these research metrics attributable to participation in IBPRO and these participants reported an average of over four such quantitative research metrics per respondent. This represents a very substantial contribution to radiation oncology research by a relatively small number of researchers within a relatively short time. Nearly one-half of respondents reported ongoing collaborative working relationships generated by IBPRO. In addition, approximately one-half of respondents stated that specific information presented at IBPRO changed the way they practice, and over 80% of respondents practicing in a clinical setting stated that, since participation in IBPRO, they have approached clinical dilemmas more collaboratively. We believe that educational opportunities such as IBPRO can have a significant impact on interdisciplinary collaborative research. In addition, such interventions have the ability to effect significant clinical change. Both of these should have a positive impact on future advancements in radiation oncology and affect the future contribution of radiation oncology to the treatment of cancer.
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http://dx.doi.org/10.1667/RR15023.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052437PMC
July 2018

Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells.

Cell Rep 2017 Sep;20(13):3199-3211

CEA/DRF/IBFJ/iRCM/LRTS, 92265 Fontenay-aux-Roses Cedex, France; Inserm U967, 92265 Fontenay-aux-Roses Cedex, France; Université Paris-Diderot, Paris 7, France; Université Paris-Sud, Paris 11, France. Electronic address:

Despite numerous observations linking protracted exposure to low-dose (LD) radiation and leukemia occurrence, the effects of LD irradiation on hematopoietic stem cells (HSCs) remain poorly documented. Here, we show that adult HSCs are hypersensitive to LD irradiation. This hyper-radiosensitivity is dependent on an immediate increase in the levels of reactive oxygen species (ROS) that also promotes autophagy and activation of the Keap1/Nrf2 antioxidant pathway. Nrf2 activation initially protects HSCs from the detrimental effects of ROS, but protection is transient, and increased ROS levels return, promoting a long-term decrease in HSC self-renewal. In vivo, LD total body irradiation (TBI) does not decrease HSC numbers unless the HSC microenvironment is altered by an inflammatory insult. Paradoxically, such an insult, in the form of granulocyte colony-stimulating factor (G-CSF) preconditioning, followed by LD-TBI facilitates efficient bone marrow transplantation without myeloablation. Thus, LD irradiation has long-term detrimental effects on HSCs that may result in hematological malignancies, but LD-TBI may open avenues to facilitate autologous bone marrow transplantation.
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http://dx.doi.org/10.1016/j.celrep.2017.09.013DOI Listing
September 2017

Radiation injury to cardiac arteries and myocardium is reduced by soy isoflavones.

J Radiat Oncol 2017 Sep 22;6(3):307-315. Epub 2017 Mar 22.

Department of Oncology, Division of Radiation Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Research Center, room 515, 4100 John R, Detroit, MI 48201, USA.

Objective: The negative effects of incidental radiation on the heart and its vessels, particularly in the treatment of locally advanced non-small cell lung cancer, esophageal cancer, left-sided breast cancer, and lymphoma, are known. Late cardiac events induced by radiotherapy including coronary artery disease, ischemia, congestive heart failure, and myocardial infarction can manifest months to years after radiotherapy. We have previously demonstrated that soy isoflavones mitigate inflammatory responses induced in lungs by thoracic irradiation resulting in decreased vascular damage, inflammation, and fibrosis. In the current study, we investigate the use of soy isoflavones to protect cardiac vessels and myocardium from radiation injury.

Methods: Mice received a single dose of 10-Gy thoracic irradiation and daily oral treatment with soy isoflavones. At different time points, hearts were processed for histopathology studies to evaluate the effect of soy isoflavones on radiation-induced damage to cardiac vessels and myocardium.

Results: Radiation damage to arteries and myocardium was detected by 16 weeks after radiation. Soy isoflavones given in conjunction with thoracic irradiation were found to reduce damage to the artery walls and radiation-induced fibrosis in the myocardium.

Conclusion: Our histopathological findings suggest a radioprotective role of soy isoflavones to prevent cardiac injury. This approach could translate to the use of soy isoflavones as a safe complement to thoracic radiotherapy with the goal of improving the overall survival in patients whose cancer has been successfully controlled by the radiotherapy but who otherwise succumb to heart toxicity.
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http://dx.doi.org/10.1007/s13566-017-0301-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903690PMC
September 2017

IBPRO - A Novel Short-Duration Teaching Course in Advanced Physics and Biology Underlying Cancer Radiotherapy.

Radiat Res 2017 06 22;187(6):637-640. Epub 2017 Mar 22.

a   School of Medicine, Wayne State University, Detroit, Michigan 48201.

This article provides a summary and status report of the ongoing advanced education program IBPRO - Integrated course in Biology and Physics of Radiation Oncology. IBPRO is a five-year program funded by NCI. It addresses the recognized deficiency in the number of mentors available who have the required knowledge and skill to provide the teaching and training that is required for future radiation oncologists and researchers in radiation sciences. Each year, IBPRO brings together 50 attendees typically at assistant professor level and upwards, who are already qualified/certified radiation oncologists, medical physicists or biologists. These attendees receive keynote lectures and activities based on active learning strategies, merging together the clinical, biological and physics underpinnings of radiation oncology, at the forefront of the field. This experience is aimed at increasing collaborations, raising the level and amount of basic and applied research undertaken in radiation oncology, and enabling attendees to confidently become involved in the future teaching and training of researchers and radiation oncologists.
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http://dx.doi.org/10.1667/RR14723.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572066PMC
June 2017

Innate Immune Pathways Associated with Lung Radioprotection by Soy Isoflavones.

Front Oncol 2017 23;7. Epub 2017 Jan 23.

Department of Oncology, Division of Radiation Oncology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI, USA.

Introduction: Radiation therapy for lung cancer causes pneumonitis and fibrosis. Soy isoflavones protect against radiation-induced lung injury, but the mediators of radioprotection remain unclear. We investigated the effect of radiation on myeloid-derived suppressor cells (MDSCs) in the lung and their modulation by soy isoflavones for a potential role in protection from radiation-induced lung injury.

Methods: BALB/c mice (5-6 weeks old) received a single 10 Gy dose of thoracic irradiation and soy isoflavones were orally administrated daily before and after radiation at 1 mg/day. Arginase-1 (Arg-1) and nuclear factor κB (NF-κB) p65 were detected in lung tissue by western blot analysis and immunohistochemistry. Lung MDSC subsets and their Arg-1 expression were analyzed by flow cytometry. Cytokine levels in the lungs were measured by ELISA.

Results: At 1 week after radiation, CD11b cells expressing Arg-1 were decreased by radiation in lung tissue yet maintained in the lungs treated with radiation and soy isoflavones. Arg-1 was predominantly expressed by CD11bLy6CLy6G granulocytic MDSCs (gr-MDSCs). Arg-1 expression in gr-MDSCs was reduced by radiation and preserved by supplementation with soy isoflavones. A persistent increase in Arg-1 cells was observed in lung tissue treated with combined radiation and soy isoflavones at early and late time points, compared to radiation alone. The increase in Arg-1 expression mediated by soy isoflavones could be associated with the inhibition of radiation-induced activation of NF-κB and the control of pro-inflammatory cytokine production demonstrated in this study.

Conclusion: A radioprotective mechanism of soy isoflavones may involve the promotion of Arg-1-expressing gr-MDSCs that could play a role in downregulation of inflammation and lung radioprotection.
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http://dx.doi.org/10.3389/fonc.2017.00007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253714PMC
January 2017

Acrokeratosis Paraneoplastica Associated with Cervical Squamous Cell Carcinoma.

Case Rep Dermatol Med 2016 22;2016:7137691. Epub 2016 Dec 22.

Karmanos Cancer Institute, Wayne State University, 4100 John R St., Detroit, MI 48201, USA.

. Acrokeratosis paraneoplastica, or Bazex syndrome, is a paraneoplastic syndrome characterized by cutaneous psoriasiform lesions with associated acral erythema and scale, as well as nail changes, including onycholysis and ungual dystrophy. Its most advanced, severe form involves the trunk, elbows, and knees. It is typically associated with upper aerodigestive tract malignancies in males. Rare cases associated with gynecological cancers have been reported, including uterine adenocarcinoma, as well as ovarian and vulvar squamous cell carcinomas. Cutaneous manifestations often precede cancer diagnosis. In most reported cases, skin changes resolve when the underlying malignancy is adequately treated. . We present the case of a 56-year-old female diagnosed with acrokeratosis paraneoplastica following the discovery of FIGO stage IIB cervical squamous cell carcinoma (SCC). Scaling, hyperpigmentation, xerosis, and fissuring were noted on the patient's hands, feet, legs, arms, and lower back. Pitting was noted on her fingernails. Her cervical cancer was successfully treated with chemoradiotherapy, after which her cutaneous lesions persisted for two months before resolving. . The presentation of acrokeratosis paraneoplastica in this context is atypical. Reports of associations with gynecological cancers, as in our patient's case, are exceedingly rare.
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http://dx.doi.org/10.1155/2016/7137691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215458PMC
December 2016

Extrapolation Ionization Chamber Dosimetry of Fluorescent X-Ray Energies from 4.5 to 19.6 keV.

Radiat Res 2016 09 22;186(3):283-91. Epub 2016 Aug 22.

a   Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, Michigan;

Characteristic X rays of energies less than approximately 20 keV are of interest in radiobiology and radiation oncology. There is evidence that these low-energy photons produce higher relative biological effectiveness (RBE) and lower oxygen enhancement ratio (OER) relative to higher energies. Lower energy X rays also offer the advantage of healthy tissue sparing beyond the target treatment depth. Electronic brachytherapy systems that can deliver characteristic and bremsstrahlung X rays of varying energy are in clinical use as well as under development. We performed low-energy extrapolation ionization chamber dosimetry using two methods: 1. the exposure-to-dose method; and 2. the Burlin theory method combined with the extrapolation chamber method of Klevenhagen. We investigated fluorescent X rays emitted from seven metals: titanium (Ti, Z = 22); chromium (Cr, Z = 24); iron (Fe, Z = 26); cobalt (Co, Z = 27); copper (Cu, Z = 29); zinc (Zn, Z = 30); and molybdenum (Mo, Z = 42). X rays were produced by irradiation of the metals with a 55 kVp, 45 mA silver anode spectrum. The data obtained were air kerma rate (cGy/min), and radiation dose rate (cGy/min) in phosphate-buffered saline (PBS) solution and water. Air kerma rates ranged from 3.55 ± 0.10 to 14.36 ± 0.39 cGy/min. Dose rates ranged from 3.85 ± 0.10 to 16.96 ± 0.46 cGy/min in PBS and 3.59 ± 0.10 to 16.06 ± 0.43 cGy/min in water. Dose-rate energy dependence of both models was examined by taking a ratio of measured to Monte Carlo calculated dose rates. Dosimetry method 1 exhibited a linear relationship across all energies with a slope of 0.0127 keV(-1) and R(2) of 0.9276. Method 2 exhibited a linear relationship across all energies with a slope of 0.0467 keV(-1) and R(2) of 0.9933. Method 1 or 2 may be used as a relative dosimetry system to derive dose rates to water by using a second reference ion chamber with a NIST-traceable calibration for the molybdenum spectrum.
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http://dx.doi.org/10.1667/RR14384.1DOI Listing
September 2016

Soy Isoflavones Promote Radioprotection of Normal Lung Tissue by Inhibition of Radiation-Induced Activation of Macrophages and Neutrophils.

J Thorac Oncol 2015 Dec;10(12):1703-12

*Department of Immunology and Microbiology, †Division of Radiation Oncology, Department of Oncology, and ‡Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.

Introduction: Radiation therapy for lung cancer is limited by toxicity to normal lung tissue that results from an inflammatory process, leading to pneumonitis and fibrosis. Soy isoflavones mitigate inflammatory infiltrates and radiation-induced lung injury, but the cellular immune mediators involved in the radioprotective effect are unknown.

Methods: Mice received a single dose of 10 Gy radiation delivered to the lungs and daily oral treatment of soy isoflavones. At different time points, mice were either processed to harvest bronchoalveolar lavage fluid for differential cell counting and lungs for flow cytometry or immunohistochemistry studies.

Results: Combined soy and radiation led to a reduction in infiltration and activation of alveolar macrophages and neutrophils in both the bronchoalveolar and lung parenchyma compartments. Soy treatment protected F4/80CD11c interstitial macrophages, which are known to play an immunoregulatory role and are decreased by radiation. Furthermore, soy isoflavones reduced the levels of nitric oxide synthase 2 expression while increasing arginase-1 expression after radiation, suggesting a switch from proinflammatory M1 macrophage to an anti-inflammatory M2 macrophage phenotype. Soy also prevented the influx of activated neutrophils in lung caused by radiation.

Conclusions: Soy isoflavones inhibit the infiltration and activation of macrophages and neutrophils induced by radiation in lungs. Soy isoflavones-mediated modulation of macrophage and neutrophil responses to radiation may contribute to a mechanism of resolution of radiation-induced chronic inflammation leading to radioprotection of lung tissue.
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http://dx.doi.org/10.1097/JTO.0000000000000677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876621PMC
December 2015

Radiation-Induced Esophagitis is Mitigated by Soy Isoflavones.

Front Oncol 2015 21;5:238. Epub 2015 Oct 21.

Department of Immunology and Microbiology, Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, MI , USA ; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, MI , USA.

Introduction: Lung cancer patients receiving radiotherapy present with acute esophagitis and chronic fibrosis, as a result of radiation injury to esophageal tissues. We have shown that soy isoflavones alleviate pneumonitis and fibrosis caused by radiation toxicity to normal lung. The effect of soy isoflavones on esophagitis histopathological changes induced by radiation was investigated.

Methods: C57BL/6 mice were treated with 10 Gy or 25 Gy single thoracic irradiation and soy isoflavones for up to 16 weeks. Damage to esophageal tissues was assessed by hematoxylin-eosin, Masson's Trichrome and Ki-67 staining at 1, 4, 10, and 16 weeks after radiation. The effects on smooth muscle cells and leukocyte infiltration were determined by immunohistochemistry using anti-αSMA and anti-CD45, respectively.

Results: Radiation caused thickening of esophageal tissue layers that was significantly reduced by soy isoflavones. Major radiation alterations included hypertrophy of basal cells in mucosal epithelium and damage to smooth muscle cells in muscularis mucosae as well as disruption of collagen fibers in lamina propria connective tissue with leukocyte infiltration. These effects were observed as early as 1 week after radiation and were more pronounced with a higher dose of 25 Gy. Soy isoflavones limited the extent of tissue damage induced by radiation both at 10 and 25 Gy.

Conclusion: Soy isoflavones have a radioprotective effect on the esophagus, mitigating the early and late effects of radiation injury in several esophagus tissue layers. Soy could be administered with radiotherapy to decrease the incidence and severity of esophagitis in lung cancer patients receiving thoracic radiation therapy.
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http://dx.doi.org/10.3389/fonc.2015.00238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617099PMC
November 2015

Education and Training Needs in the Radiation Sciences: Problems and Potential Solutions.

Radiat Res 2015 Nov 19;184(5):449-55. Epub 2015 Oct 19.

f  Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan 48201-2013.

This article provides a summary of presentations focused on critical education and training issues in radiation oncology, radiobiology and medical physics from a workshop conducted as part of the 60th Annual Meeting of the Radiation Research Society held in Las Vegas, NV (September 21-24, 2014). Also included in this synopsis are pertinent comments and concerns raised by audience members, as well as recommendations for addressing ongoing and future challenges.
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http://dx.doi.org/10.1667/RR14199.1DOI Listing
November 2015

Effects of low oxygen levels on G2-specific cytogenetic low-dose hyper-radiosensitivity in irradiated human cells.

Environ Mol Mutagen 2015 Jul 25;56(6):545-55. Epub 2015 Mar 25.

Department of Biological Sciences, Wayne State University, Detroit, Michigan.

Low-dose hyper-radiosensitivity (HRS) has been reported in normal human lymphoblastoid cell lines for exposures at ≤ 20 cGy, but the cytogenetic effects of oxygen (O2 ) levels in tissue culture medium on HRS have not been evaluated. We asked whether HRS was lost in G2-irradiated cells grown in atmospheres of 2.5% or 5% O2 , compared to responses by cells cultured in ambient O2 (21%). The results indicate a loss of HRS when cells are cultured and irradiated either in 2.5% or 5% O2 . We then evaluated whether low O2 levels either before or after exposure were responsible for the loss of HRS. For cells irradiated in 5% O2 , subsequent immediate re-oxygenation to ambient O2 levels restored the HRS effect, while cells cultured and irradiated at ambient O2 levels and then transferred to 5% O2 exhibited little or no HRS, indicating that ambient O2 levels after, but not before, radiation substantially affect the amounts of cytogenetic damage. HRS was not observed when cells were irradiated in G1. At doses of 40-400 cGy there was significantly less cytogenetic damage when cells were recovering from radiation at low O2 levels than at ambient O2 levels. Here we provide the first cytogenetic evidence for the loss of HRS at low O2 levels in G2-irradiated cells; these results suggest that at low O2 levels for all doses evaluated there is either less damage to DNA, perhaps because of lower amounts of reactive oxygen species, or that DNA damage repair pathways are activated more efficiently.
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http://dx.doi.org/10.1002/em.21948DOI Listing
July 2015

Cytogenetic characterization of low-dose hyper-radiosensitivity in Cobalt-60 irradiated human lymphoblastoid cells.

Mutat Res 2014 Dec 27;770:69-78. Epub 2014 Sep 27.

Department of Biological Sciences, Wayne State University, Detroit, MI 48202, United States. Electronic address:

The dose-effect relationships of cells exposed to ionizing radiation are frequently described by linear quadratic (LQ) models over an extended dose range. However, many mammalian cell lines, when acutely irradiated in G2 at doses ≤0.3Gy, show hyper-radiosensitivity (HRS) as measured by reduced clonogenic cell survival, thereby indicating greater cell lethality than is predicted by extrapolation from high-dose responses. We therefore hypothesized that the cytogenetic response in G2 cells to low doses would also be steeper than predicted by LQ extrapolation from high doses. We tested our hypothesis by exposing four normal human lymphoblastoid cell lines to 0-400cGy of Cobalt-60 gamma radiation. The cytokinesis block micronucleus assay was used to determine the frequencies of micronuclei and nucleoplasmic bridges. To characterize the dependence of the cytogenetic damage on dose, univariate and multivariate regression analyses were used to compare the responses in the low- (HRS) and high-dose response regions. Our data indicate that the slope of the response for all four cell lines at ≤20cGy during G2 is greater than predicted by an LQ extrapolation from the high-dose responses for both micronuclei and bridges. These results suggest that the biological consequences of low-dose exposures could be underestimated and may not provide accurate risk assessments following such exposures.
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http://dx.doi.org/10.1016/j.mrfmmm.2014.09.006DOI Listing
December 2014

Cytogenetic low-dose hyperradiosensitivity is observed in human peripheral blood lymphocytes.

Int J Radiat Oncol Biol Phys 2015 Jan 25;91(1):82-90. Epub 2014 Oct 25.

Department of Biological Sciences, Wayne State University, Detroit, Michigan. Electronic address:

Purpose: The shape of the ionizing radiation response curve at very low doses has been the subject of considerable debate. Linear-no-threshold (LNT) models are widely used to estimate risks associated with low-dose exposures. However, the low-dose hyperradiosensitivity (HRS) phenomenon, in which cells are especially sensitive at low doses but then show increased radioresistance at higher doses, provides evidence of nonlinearity in the low-dose region. HRS is more prominent in the G2 phase of the cell cycle than in the G0/G1 or S phases. Here we provide the first cytogenetic mechanistic evidence of low-dose HRS in human peripheral blood lymphocytes using structural chromosomal aberrations.

Methods And Materials: Human peripheral blood lymphocytes from 2 normal healthy female donors were acutely exposed to cobalt 60 γ rays in either G0 or G2 using closely spaced doses ranging from 0 to 1.5 Gy. Structural chromosomal aberrations were enumerated, and the slopes of the regression lines at low doses (0-0.4 Gy) were compared with doses of 0.5 Gy and above.

Results: HRS was clearly evident in both donors for cells irradiated in G2. No HRS was observed in cells irradiated in G0. The radiation effect per unit dose was 2.5- to 3.5-fold higher for doses ≤0.4 Gy than for doses >0.5 Gy.

Conclusions: These data provide the first cytogenetic evidence for the existence of HRS in human cells irradiated in G2 and suggest that LNT models may not always be optimal for making radiation risk assessments at low doses.
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http://dx.doi.org/10.1016/j.ijrobp.2014.09.020DOI Listing
January 2015

Neutron exposures in human cells: bystander effect and relative biological effectiveness.

PLoS One 2014 4;9(6):e98947. Epub 2014 Jun 4.

Department of Biological Sciences, Wayne State University, Detroit, Michigan, United States of America.

Bystander effects have been observed repeatedly in mammalian cells following photon and alpha particle irradiation. However, few studies have been performed to investigate bystander effects arising from neutron irradiation. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy), and irradiated-cell conditioned media (ICCM) was transferred to unirradiated cells. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control), 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. However, the neutron beam has a photon dose-contamination of 5%, which may modulate a neutron-induced bystander effect. To determine whether these low doses of contaminating photons can induce a bystander effect, cells were irradiated with cobalt-60 at doses equivalent to the percent contamination for each neutron dose. No significant increase in the frequencies of micronuclei or bridges was observed at these doses of photons for either cell line when cultured in ICCM. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (p<0.0001). These data indicate that neutrons do not induce a bystander effect in these cells. Finally, neutrons had a relative biological effectiveness of 2.0 ± 0.13 for micronuclei and 5.8 ± 2.9 for bridges compared to cobalt-60. These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098947PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045982PMC
August 2015