Radiation Medicine Commons^™

Radiation Exposure Determination In A Secure, Cloud-Based Online Environment, Ben C. Shirley, Eliseos J. Mucaki, Peter Rogan

Biochemistry Publications

Rapid sample processing and interpretation of estimated exposures will be critical for triaging exposed individuals after a major radiation incident. The dicentric chromosome (DC) assay assesses absorbed radiation using metaphase cells from blood. The Automated Dicentric Chromosome Identifier and Dose Estimator System (ADCI) identifies DCs and determines radiation doses. This study aimed to broaden accessibility and speed of this system, while protecting data and software integrity. ADCI Online is a secure web-streaming platform accessible worldwide from local servers. Cloud-based systems containing data and software are separated until they are linked for radiation exposure estimation. Dose estimates are identical to ADCI …

Improved Radiation Expression Profiling In Blood By Sequential Application Of Sensitive And Specific Gene Signatures, Eliseos J. Mucaki, Ben C. Shirley, Peter K. Rogan

Biochemistry Publications

Purpose. Combinations of expressed genes can discriminate radiation-exposed from normal control blood samples by machine learning based signatures (with 8 to 20% misclassification rates). These signatures can quantify therapeutically-relevant as well as accidental radiation exposures. The prodromal symptoms of Acute Radiation Syndrome (ARS) overlap those present in Influenza and Dengue Fever infections. Surprisingly, these human radiation signatures misclassified gene expression profiles of virally infected samples as false positive exposures. The present study investigates these and other confounders, and then mitigates their impact on signature accuracy.

Methods. This study investigated recall by previous and novel radiation signatures independently derived …

Estimating Partial Body Ionizing Radiation Exposure By Automated Cytogenetic Biodosimetry, Peter Rogan

Biochemistry Publications

Purpose: Inhomogeneous exposures to ionizing radiation can be detected and quantified with the Dicentric Chromosome Assay (DCA) of metaphase cells. Complete automation of interpretation of the DCA for whole body irradiation has significantly improved throughput without compromising accuracy, however low levels of residual false positive dicentric chromosomes (DCs) have confounded its application for partial body exposure determination.

Materials and Methods: We describe a method of estimating and correcting for false positive DCs in digitally processed images of metaphase cells. Nearly all DCs detected in unirradiated calibration samples are introduced by digital image processing. DC frequencies of irradiated calibration …

Evidence Of Y Chromosome Long Non-Coding Rnas Involved In The Radiation Response Of Male Non-Small Cell Lung Cancer Cells, Tayvia Brownmiller

Graduate Theses, Dissertations, and Problem Reports

Non-small cell lung cancer (NSCLC) is the number one cause of cancer related mortality in the United States and worldwide. Advanced and therapeutically resistant lung tumors contribute to the high rate of mortality from NSCLC, therefore there is a need for new methods of diagnosing and treating this disease. Long non-coding RNAs (lncRNAs) have been shown to be a crucial component of human molecular biology, regulating nearly every cellular pathway from chromatin condensation to transcription and translation. Furthermore, many lncRNAs have been classified as oncogenes or tumor suppressors, highlighting the various molecular mechanisms they are involved in regarding the formation …

Radiation Dose Estimation By Completely Automated Interpretation Of The Dicentric Chromosome Assay, Peter Rogan, Yanxin Li, Ben Shirley, Ruth Wilkins, Farrah Norton, Joan Knoll

Biochemistry Publications

Accuracy of the automated dicentric chromosome (DC) assay relies on metaphase image selection. This study validates a software framework to find the best image selection models that mitigate inter-sample variability. Evaluation methods to determine model quality include the Poisson goodness-of-fit of DC distributions for each sample, residuals after calibration curve fitting and leave-one-out dose estimation errors. The process iteratively searches a pool of selection model candidates by modifying statistical and filter cut-offs to rank the best candidates according to their respective evaluation scores. Evaluation scores minimize the sum of squared errors relative to the actual radiation dose of the calibration …

Mechanisms Of T Helper Cell Modulation In A Simulated Space Radiation Environment, Asma Rizvi

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure to solar particle events (SPEs) poses the most serious threat to astronaut health. Due to this radiation environment, exploration of the solar system beyond Earth’s orbit entails many risks for the crew on these deep space missions. Depression or dysfunction of the immune system is a major concern due to its high radio-sensitivity; potential consequences include overwhelming infection, development of cancer, fibrosis, and poor wound healing. Astronauts are also exposed to low dose/low dose rate (LDR) radiation. A three month stay at the international space station exposes them to ~ 0.05 Gy of radiation.

C57BL/6 mice received LDR gamma-radiation …

Radiation-Induced Increases In Pkc Modulate Integrin Expression And Contribute To Fibrotic Changes, Pinal Rushikesh Pandya

Loma Linda University Electronic Theses, Dissertations & Projects

The sequences of events in fibrosis are similar to those in wound healing; however, the normal termination and resolution stages do not take place. The initial cellular response following ionizing radiation involves accumulation of the ECM (extracellular matrix) including collagen, fibronectin and the interaction of many growth factors (cytokines) with their receptors. There are a number of unanswered questions regarding many aspects of radiation-induced fibrosis, including the initial triggers and physical changes that initiate the process. We have confirmed that elevated pKC and other cellular changes following radiation are similar to those found at sites of inflammation. This information leads …

Effects Of Liposome-Encapsulated Tnf-Alpha And Radiation Against Colon Cancer, Dong Won Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies have shown that tumor necrosis factor-α (TNF-α) can augment the antitumor effects of radiation, inhibiting tumor progression to a greater extent than either modality alone. However, nonspecific toxicities associated with TNF-α have limited its use as an adjuvant. This limitation is potentially resolved with the encapsulation of TNF-α in sterically stabilized, PEGylated liposomes (STEALTH®). Thus, the overall hypothesis of the research was that the combination of radiation with STEALTH® liposome encapsulated TNF-α (SL-TNF-α) will have greater efficacy and fewer dose-limiting side effects in the LS174T human colorectal tumor xenograft model compared to the combination of free TNF-α and …

Connexin-32 Contributes To Radiation Resistance In Thyroid Follicles, Da-Thao Dinh Tran

Loma Linda University Electronic Theses, Dissertations & Projects

The objective of this study was to examine the role of gap junctions in the radiation resistance of thyroid follicles. The question of whether gap junctional intercellular communication plays an important role in the “contact effect”, wherein cells in direct apposition are more resistant to the damaging effects of radiation, has been debated for years. We used the Fischer rat thyroid cell line (FRTL-5) to carry out our experiments. This thesis is divided into two parts: 1) characterization of gap junctional properties in FRTL-5 cells and, 2) exposure of these cells to radiation.

We found that, unlike primary thyroid cells, …

A Preclinical Model Of Ionizing Radiation And Tnf-Alpha Gene Therapy For Cancer, Jun Li

Loma Linda University Electronic Theses, Dissertations & Projects

Long term control of high-grade brain tumors is rarely achieved with current therapeutic regimens. This study sought to determine if pretreatment with plasmid DNA expressing Tumor Necrosis Factor-α (TNF-α) could enhance the effect of ionizing radiation in an aggressive, rapidly growing glioma tumor (C6) model. Plasmid DNA is an attractive vector system for delivery of foreign genes into eukaryotic cells due to its advantages including low immunogenicity in vivo, lesser toxicity and relatively low cost. We have constructed a plasmid-based mammalian expression vector (pGL1-TNF) to secrete human TNF-α from cancer cells. Plasmid DNA was successfully transfected into C6 cells …

A Model Using Radiation And Pws4-Htnf-Α Gene Therapy For Treatment Of Glioblastomas, Angelo G. Baher

Loma Linda University Electronic Theses, Dissertations & Projects

The efficacy of radiotherapy for cancer is limited by the dose that can be safely delivered to the tumor without causing debilitating side effects. In addition, successful treatment of highly malignant tumors such as glioblastomas is likely to require adjunctive therapies to enhance tumor response to radiation. Previous studies have shown immunomodulation and a synergestic reduction in tumor volume of malignant tumors when tumor necrosis factor-α (TNF-α) protein is administered prior to radiation. The major goal of the present investigation was to evaluate the efficacy of pWS4-human TNF-α (pWS4-hTNF-α), a new plasmid construct that expresses human TNF-α protein, together with …