Replacing LNT: The Integrated LNT-Hormesis Model.

Many scientists and regulators utilize the linear no-threshold (LNT) relationship to estimate the likelihood of carcinogenesis. The LNT model is incorrect and was adopted based upon false pretenses. The use of the model has been corrupted by many to claim that even the smallest ionizing radiation dose may initiate carcinogenesis.

Management of Metastatic Spinal Cord Compression.

Cancer metastasis is a key event in tumor progression associated not only with mortality but also significant morbidity. Metastatic disease can promote end-organ dysfunction and even failure through mass effect compression of various vital organs including the spinal cord. In such cases, prompt medical attention is needed to restore neurological function, relieve pain, and prevent permanent damage.

Treatment-Related Death during Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Studies.

Treatment related death (TRD) is the worst adverse event in chemotherapy and radiotherapy for patients with cancer, the reports for TRDs were sporadically. We aimed to study TRDs in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT), and determine whether high radiation dose and newer chemotherapy regimens were associated with the risk of TRD. Data from randomized clinical trials for locally advanced/unresectable NSCLC patients were analyzed.

Review of evolving etiologies, implications and treatment strategies for the superior vena cava syndrome.

Superior vena cava syndrome (SVCS) is a relatively common sequela of mediastinal malignancies and may cause significant patient distress. SVCS is a medical emergency if associated with laryngeal or cerebral edema. The etiologies and management of SVCS have evolved over time.

Radiation dose-fractionation effects in spinal cord: comparison of animal and human data.

Purpose: Recognizing spinal cord dose limits in various fractionations is essential to ensure adequate dose for tumor control while minimizing the chance of radiation-induced myelopathy (RIM). This study aimed to determine the α/β ratio of the spinal cord and the cord dose limit in terms of BED50, the biological equivalent dose (BED) that induces 50 % chance of RIM, by fitting data collected from published animal and patient studies.

Methods: RIM data from five rat studies; three large animal studies on monkeys, dogs, and pigs; and 18 patient studies were included for the investigation.

A MLC-based inversely optimized 3D spatially fractionated grid radiotherapy technique.

This study presents a MLC-based, 3D grid-therapy technique with characteristics of both 3D-conformal-radiotherapy and grid-therapy. It generates a brachytherapy-like dose distribution, with D50% of 20, 9.8, 5.

Can radiation risks to patients be reduced without reducing radiation exposure? The status of chemical radioprotectants.

Objective: Medical radiation exposure has increased sixfold since 1980 and is the largest controllable source of exposure. Many efforts have been devoted to reducing dose or eliminating unnecessary examinations but with limited success. The concern regarding nuclear terrorism has focused a large amount of attention on radioprotective drugs.

NIAID/NIH radiation/nuclear medical countermeasures product research and development program.

One of the greatest national security threats to the United States is the detonation of an improvised nuclear device or a radiological dispersal device in a heavily populated area. The U.S.

Helper-independent piggyBac plasmids for gene delivery approaches: strategies for avoiding potential genotoxic effects.

Efficient integration of functional genes is an essential prerequisite for successful gene delivery such as cell transfection, animal transgenesis, and gene therapy. Gene delivery strategies based on viral vectors are currently the most efficient. However, limited cargo capacity, host immune response, and the risk of insertional mutagenesis are limiting factors and of concern.

DNA demethylation in retinal neurocytes contributes to the upregulation of DNA repair protein, Ku80.

Ku80 plays a critical role in DNA double strand breaks repair. However, Ku80 is silenced in mature neurocytes. In this study, the mechanism of Ku80 silencing and its role in DNA double strand break repair in retinal neurocytes was investigated.

Rapid radiation dose assessment for radiological public health emergencies: roles of NIAID and BARDA.

A large-scale radiological incident would result in an immediate critical need to assess the radiation doses received by thousands of individuals to allow for prompt triage and appropriate medical treatment. Measuring absorbed doses of ionizing radiation will require a system architecture or a system of platforms that contains diverse, integrated diagnostic and dosimetric tools that are accurate and precise. For large-scale incidents, rapidity and ease of screening are essential.

piggyBac transposon/transposase system to generate CD19-specific T cells for the treatment of B-lineage malignancies.

Nonviral integrating vectors can be used for expression of therapeutic genes. piggyBac (PB), a transposon/transposase system, has been used to efficiently generate induced pluripotent stems cells from somatic cells, without genetic alteration. In this paper, we apply PB transposition to express a chimeric antigen receptor (CAR) in primary human T cells.

Lithium chloride protects retinal neurocytes from nutrient deprivation by promoting DNA non-homologous end-joining.

Lithium chloride is a therapeutic agent for treatment of bipolar affective disorders. Increasing numbers of studies have indicated that lithium has neuroprotective effects. However, the molecular mechanisms underlying the actions of lithium have not been fully elucidated.

Medical countermeasures against nuclear threats: radionuclide decorporation agents.

Exposure to radionuclides disseminated by a radiological dispersion device or deposited as fallout after a nuclear power plant accident or detonation of an improvised nuclear device could result in internal contamination of a significant number of individuals. Internalized radionuclides may cause both acute and chronic radiation injury and increase an individual's risk of developing cancer. This damage and risk can be mitigated by the use of decorporation agents that reduce internal contamination.

Use of intracytoplasmic sperm injection (ICSI) to generate transgenic animals.

Even though intracytoplasmic sperm injection (ICSI) has been widely used for the production of offspring in human infertility clinics and in reproductive research laboratories using mice, many researchers engaged in animal transgenesis still consider it somewhat cumbersome. The greatest advantage of ICSI-mediated transgenesis is that it allows introduction of very large DNA transgenes (e.g.

TSP-1 secreted by bone marrow stromal cells contributes to retinal ganglion cell neurite outgrowth and survival.

Background: Bone marrow stromal cells (BMSCs) are pluripotent and thereby a potential candidate for cell replacement therapy for central nervous system degenerative disorders and traumatic injury. However, the mechanism of their differentiation and effect on neural tissues has not been fully elucidated. This study evaluates the effect of BMSCs on neural cell growth and survival in a retinal ganglion cell (RGCs) model by assessing the effect of changes in the expression of a BMSC-secreted protein, thrombospondin-1 (TSP-1), as a putative mechanistic agent acting on RGCs.

Medical countermeasures for radiation combined injury: radiation with burn, blast, trauma and/or sepsis. report of an NIAID Workshop, March 26-27, 2007.

Non-clinical human radiation exposure events such as the Hiroshima and Nagasaki bombings or the Chernobyl accident are often coupled with other forms of injury, such as wounds, burns, blunt trauma, and infection. Radiation combined injury would also be expected after a radiological or nuclear attack. Few animal models of radiation combined injury exist, and mechanisms underlying the high mortality associated with complex radiation injuries are poorly understood.

Steps toward targeted insertional mutagenesis with class II transposable elements.

Insertional mutagenesis can be achieved by a variety of approaches, including both random and targeted methods. In contrast to chemical mutagenesis, insertional mutagens provide a molecular tag, thereby allowing rapid identification of the mutated genomic region. Integration into defined genomic locations has great utility for both gene insertion and mutagenesis.

The role of mTOR inhibition in augmenting radiation induced autophagy.

Radiation affects both tumor and normal tissues, limiting the total delivered radiation dose. Therefore, novel ways to exploit molecular targets and improve the therapeutic ratio are continually being investigated. Autophagy plays an important role in cancer cell death decisions, particularly in solid tumors.