Analyses of cancer incidence and other morbidities in gamma irradiated B6CF1 mice

ABSTRACTWith increasing medical radiation exposures, it is important to understand how different modes of delivery of ionizing radiation as well as total doses of exposure impact health outcomes. Our lab studied the risks associated with ionizing radiation by analyzing the Northwestern University Radiation Archive for animals (NURA). NURA contains detailed data from a series of 10 individual neutron and gamma irradiation experiments conducted on over 50,000 mice. Rigorous statistical testing on control mice from all Janus experiments enabled us to select studies that could be compared to one another and uncover unexpected differences among the controls as well as experimental animals. For controls, mice sham irradiated with 300 fractions died significantly earlier than those with fewer sham fractions. Using the integrated dataset of gamma irradiated and control mice, we found that fractionation significantly decreased the death hazard for animals dying of lymphomas, tumors, non-tumors, and unknown causes. Gender differences in frequencies of causes of death were identified irrespective of irradiation and dose fractionation, with female mice being at a greater risk for all causes of death, except for lung tumors. Irradiated and control male mice were at a significantly greater risk for lung tumors, the opposite from observations noted in humans. Additionally, we discovered that lymphoma deaths can occur quickly after exposures to high doses of gamma rays. This study systematically cross-compared outcomes of different modes of fractionation across a wide span of total doses to demonstrate that protraction modulated survival and disease status differently based on the total dose, cause of death, and sex of an animal. This novel method for analyzing the Janus datasets will lead to insightful new mechanistic hypotheses and research in the fields of radiation biology and protection.

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Imaging Studies Expose MI Patients To High Doses of Ionizing Radiation

Hospitalist News ◽

10.1016/s1875-9122(09)70261-5 ◽

2009 ◽

Vol 2 (12) ◽

pp. 2

Author(s):

Bruce Jancin

Keyword(s):

Ionizing Radiation ◽

Imaging Studies ◽

High Doses

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Exceeding Radiation Dose to Volume Parameters for the Proximal Airways with Stereotactic Body Radiation Therapy Is More Likely for Ultracentral Lung Tumors and Associated with Worse Outcome

Cancers ◽

10.3390/cancers13143463 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3463

Author(s):

Mark Farrugia ◽

Sung Jun Ma ◽

Mark Hennon ◽

Chukwumere Nwogu ◽

Elisabeth Dexter ◽

...

Keyword(s):

Radiation Therapy ◽

Propensity Score ◽

Stereotactic Body Radiation Therapy ◽

Performance Status ◽

Bronchial Tree ◽

Lung Tumors ◽

Gender Performance ◽

Dose Fractionation ◽

Stereotactic Body Radiation ◽

History Of

The preferred radiotherapeutic approach for central (CLT) and ultracentral (UCLT) lung tumors is unclear. We assessed the toxicity and outcomes of patients with CLT and UCLT who underwent definitive five-fraction stereotactic body radiation therapy (SBRT). We reviewed the charts of patients with either CLT or UCLT managed with SBRT from June 2010–April 2019. CLT were defined as gross tumor volume (GTV) within 2 cm of either the proximal bronchial tree, trachea, mediastinum, aorta, or spinal cord. UCLT were defined as GTV abutting any of these structures. Propensity score matching was performed for gender, performance status, and history of prior lung cancer. Within this cohort of 83 patients, 43 (51.8%) patients had UCLT. The median patient age was 73.1 years with a median follow up of 29.9 months. The two most common dose fractionation schemes were 5000 cGy (44.6%) and 5500 cGy (42.2%) in five fractions. Multivariate analysis revealed UCLT to be associated with worse overall survival (OS) (HR = 1.9, p = 0.02) but not time to progression (TTP). Using propensity score match pairing, UCLT correlated with reduced non-cancer associated survival (p = 0.049) and OS (p = 0.03), but not TTP. Within the matched cohort, dosimetric study found exceeding a D4cc of 18 Gy to either the proximal bronchus (HR = 3.9, p = 0.007) or trachea (HR = 4.0, p = 0.02) was correlated with worse non-cancer associated survival. In patients undergoing five fraction SBRT, UCLT location was associated with worse non-cancer associated survival and OS, which could be secondary to excessive D4cc dose to the proximal airways.

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Effect of Ionizing Radiation on the Bacterial and Fungal Endophytes of the Halophytic Plant Kalidium schrenkianum

Microorganisms ◽

10.3390/microorganisms9051050 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1050

Author(s):

Jing Zhu ◽

Xiang Sun ◽

Zhi-Dong Zhang ◽

Qi-Yong Tang ◽

Mei-Ying Gu ◽

...

Keyword(s):

Genetic Diversity ◽

Ionizing Radiation ◽

Endophytic Bacteria ◽

Fungal Endophytes ◽

Root Endophytes ◽

Fungal Community Structure ◽

Geochemical Factors ◽

Bacteria And Fungi ◽

High Level ◽

And Control

Endophytic bacteria and fungi colonize plants that grow in various types of terrestrial and aquatic ecosystems. Our study investigates the communities of endophytic bacteria and fungi of halophyte Kalidium schrenkianum growing in stressed habitats with ionizing radiation. The geochemical factors and radiation (at low, medium, high level and control) both affected the structure of endophytic communities. The bacterial class Actinobacteria and the fungal class Dothideomycetes predominated the endophytic communities of K. schrenkianum. Aerial tissues of K. schrenkianum had higher fungal diversity, while roots had higher bacterial diversity. Radiation had no significant effect on the abundance of bacterial classes. Soil pH, total nitrogen, and organic matter showed significant effects on the diversity of root endophytes. Radiation affected bacterial and fungal community structure in roots but not in aerial tissues, and had a strong effect on fungal co-occurrence networks. Overall, the genetic diversity of both endophytic bacteria and fungi was higher in radioactive environments, however negative correlations were found between endophytic bacteria and fungi in the plant. The genetic diversity of both endophytic bacteria and fungi was higher in radioactive environments. Our findings suggest that radiation affects root endophytes, and that the endophytes associated with aerial tissues and roots of K. schrenkianum follow different mechanisms for community assembly and different paradigms in stress response.

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Behavior of new ZnSe(Te,O) semiconductor scintillators under high doses of ionizing radiation

IEEE Transactions on Nuclear Science ◽

10.1109/23.958396 ◽

2001 ◽

Vol 48 (4) ◽

pp. 1561-1564 ◽

Cited By ~ 8

Author(s):

V.D. Ryzhikov ◽

N.G. Starzhinskiy ◽

L.P. Gal'chinetskii ◽

M. Guttormsen ◽

A.A. Kist ◽

...

Keyword(s):

Ionizing Radiation ◽

High Doses

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High-dose enoxaparin in the treatment of abdominal angiostrongyliasis in Swiss mice

Journal of Helminthology ◽

10.1017/s0022149x17000852 ◽

2017 ◽

Vol 92 (6) ◽

pp. 662-667 ◽

Cited By ~ 2

Author(s):

A.S.S. Sandri ◽

R. Rodriguez ◽

M.M. Costa ◽

S.M. Porto ◽

D. Schwingel ◽

...

Keyword(s):

Survival Rates ◽

Mesenteric Arteries ◽

High Dose ◽

Control Groups ◽

Intestinal Infarction ◽

Intestinal Lesions ◽

Group 2 ◽

High Doses ◽

And Control ◽

Group 1

AbstractAbdominal angiostrongyliasis (AA) is caused by Angiostrongylus costaricensis, which inhabits mesenteric arteries. There is no drug treatment for AA, and since intestinal infarction due to thrombi is one of the main complications of the disease, the use of anticoagulants may be a treatment option. Thus, we aimed to assess the effect of high doses of enoxaparin on the prevention of ischaemic intestinal lesions and on the survival of mice infected with A. costaricensis. Twenty-four mice were infected with L3 of A. costaricensis and divided equally into two groups: Group 1, control treated with placebo, and Group 2, treated daily with enoxaparin (2.5 mg/kg) for 50 days. All mice were subjected to necropsy and histological analysis. The results from gross and microscopic assessments showed no variation in the prevalence of lesions between the groups. An analysis was also performed among survivors and non-survivors, showing that animals that died often presented lesions, such as granulation tissue in the serosa, and intestinal infarction and adhesion. The mortality rate did not vary between the enoxaparin-treated and control groups. Thus, we showed that high doses of enoxaparin have no protective effect against AA, as the survival rates and lesions of mice did not vary between the treated and control groups. Considering that the use of prophylactic doses was also shown to be ineffective in a previous study, we do not recommend the use of enoxaparin for AA treatment.

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Long-Term Damages among Survivors of High Doses of Ionizing Radiation

Radiation Injury Prevention and Mitigation in Humans ◽

10.1201/b11719-7 ◽

2012 ◽

pp. 98-129

Keyword(s):

Ionizing Radiation ◽

High Doses

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VectorMOD: Method for Bottom-Up Proteomic Characterization of rAAV Capsid Post-Translational Modifications and Vector Impurities

Frontiers in Immunology ◽

10.3389/fimmu.2021.657795 ◽

2021 ◽

Vol 12 ◽

Author(s):

Neil G. Rumachik ◽

Stacy A. Malaker ◽

Nicole K. Paulk

Keyword(s):

Mass Spectrometry ◽

Process Development ◽

Cell Protein ◽

Macromolecular Complex ◽

Bottom Up ◽

Post Translational Modifications ◽

Simple Step ◽

Product And Process ◽

High Doses ◽

And Control

Progress in recombinant AAV gene therapy product and process development has advanced our understanding of the basic biology of this critical delivery vector. The discovery of rAAV capsid post-translational modifications (PTMs) has spurred interest in the field for detailed rAAV-specific methods for vector lot characterization by mass spectrometry given the unique challenges presented by this viral macromolecular complex. Recent concerns regarding immunogenic responses to systemically administered rAAV at high doses has highlighted the need for investigators to catalog and track potentially immunogenic vector lot components including capsid PTMs and PTMs on host cell protein impurities. Here we present a simple step-by-step guide for academic rAAV laboratories and Chemistry, Manufacturing and Control (CMC) groups in industry to perform an in-house or outsourced bottom-up mass spectrometry workflow to characterize capsid PTMs and process impurities.

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Effect of ionizing radiation on the bacterial and fungal endophytes of the halophytic plant Kalidium schrenkianum

10.22541/au.160587754.47033775/v1 ◽

2020 ◽

Author(s):

Jing Zhu ◽

翔(Xiang) 孙(Sun) ◽

Zhidong Zhang ◽

Qiyong Tang ◽

Meiying Gu ◽

...

Keyword(s):

Ionizing Radiation ◽

Aquatic Ecosystems ◽

Endophytic Bacteria ◽

Fungal Endophytes ◽

High Radiation ◽

Halophytic Plant ◽

Geochemical Factors ◽

Bacteria And Fungi ◽

High Level ◽

And Control

Endophytes are microbes found within tissues of plants in various types of terrestrial and aquatic ecosystems, including those habitats with ionizing radiation. Our study investigates the differences in composition of bacterial and fungal endophytes associated with the halophytic plant Kalidium schrenkianum and the effects of geochemical factors and radiation (at low, medium, high level and control) on the community structure of endophytic bacteria and fungi. The bacterial class Actinobacteria and the fungal class Dothideomycetes predominated the endophytic communities of K. schrenkianum. Aboveground parts had higher fungal diversity while belowground parts had higher bacterial diversity. Soil pH, total nitrogen, and organic matter showed significant effects on the diversity of root endophytes. Radiation had no significant effect on the abundance of different bacterial classes. Sordariomycetes predominated the root fungal microbiota under high radiation intensity. Differences in the endophytic communities between aboveground and belowground parts were more than that between the radiation levels. No significant differences were found in the aboveground bacterial communities among the radiation levels. Radiation showed a significant effect on the fungal co-occurrence networks. Negative correlations were found between endophytic bacteria and fungi in the plant. The genetic diversity of both endophytic bacteria and fungi was higher in radioactive environments. Our findings suggest that the endophytes associated with aboveground and belowground parts of K. schrenkianum follow different mechanisms for community assembly and different paradigms in stress response.

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Radiation Produces Irreversible Chronic Dysfunction in the Submandibular Glands of the Rat

The Open Dentistry Journal ◽

10.2174/1874210601206010008 ◽

2012 ◽

Vol 6 (1) ◽

pp. 8-13 ◽

Cited By ~ 8

Author(s):

C De la Cal ◽

J Fernández-Solari ◽

CE Mohn ◽

JP Prestifilippo ◽

A Pugnaloni ◽

...

Keyword(s):

Single Dose ◽

Salivary Gland ◽

Ionizing Radiation ◽

Salivary Secretion ◽

Maximal Response ◽

Chronic Effect ◽

Post Irradiation ◽

Gland Function ◽

High Doses ◽

Rat Salivary Gland

The exposure to high doses of ionizing radiation during radiotherapy results in severe morphological and functional alterations of the salivary glands, such as xerostomia. In the present study we investigated the chronic effect of a single radiation dose of 15 Gray (Gy) limited to head and neck on rat salivary gland function (salivary secretion and gland mass) and histology. Results indicate that norepinephrine (NE)-induced salivary secretion was reduced significantly at 30, 90, 180 and 365 days after the administration of a single dose of 15 Gy of ionizing radiation compared to non-irradiated animals. The maximal secretory response was reduced by 33% at 30 and 90 days post irradiation. Interestingly, a new fall in the salivary response to NE was observed at 180 days and was maintained at 365 days post irradiation, showing a 75% reduction in the maximal response. The functional fall of the salivary secretion observed at 180 days post irradiation was not only associated with a reduction of gland mass but also to an alteration of the epithelial architecture exhibiting a changed proportion of ducts and acini, loss of eosinophilic secretor granular material, and glandular vacuolization and fibrosis. On the basis of the presented results, we conclude that ionizing radiation produces irreversible and progressive alterations of submandibular gland (SMG) function and morphology that leads to a severe salivary hypo-function.

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