Reactive oxygen species (ROS) have been extensively studied in the induction of inflammation and tissue damage, especially as it relates to aging. In more recent years, ROS have been implicated in the pathogenesis of autoimmune diseases. Here, ROS accumulation leads to apoptosis and autoantigen structural changes that result in novel specificities. ROS have been implicated not only in the initiation of the autoimmune response but also in its amplification and spreading to novel epitopes, through the unmasking of cryptic determinants. This review will examine the contribution of ROS to the pathogenesis of four organ specific autoimmune diseases (Hashimoto thyroiditis, inflammatory bowel disease, multiple sclerosis, and vitiligo), and compare it to that of a better characterized systemic autoimmune disease (rheumatoid arthritis). It will also discuss tobacco smoking as an environmental factor endowed with both pro-oxidant and anti-oxidant properties, thus capable of differentially modulating the autoimmune response.

The adenoviruses are essential tools for basic research and therapeutic development. Robust methods for the generation of mutant and recombinant viruses are crucial for these diverse applications. Here we describe a simple plasmid-based method that permits highly efficient modification of the adenoviral genome and rapid production of high-titer virus stocks. The 36-kilobase genome of adenovirus serotype 5 was divided into seven tractable blocks that could be individually modified in a single step and reassembled in vitro. Because the system is composed of compact modules, modifications at different loci can be readily recombined. Viral assemblies were delivered to packaging cells by electroporation, a strategy that consistently resulted in the de novo production of 108 infectious units in 3–5 days. In principle, a similar strategy could be applied to any other adenovirus serotype or to other double-strand DNA viruses.

Background: Patients with a high pretreatment IPSS may have higher rates of late urinary morbidity after radiation therapy for prostate cancer (1). Stereotactic body radiation therapy (SBRT) delivers fewer high-dose fractions of radiation, which may be radiobiologically favorable to the conventional low-dose external beam fractions. The urinary toxicity associated with SBRT, however, remains unclear in patients with a high IPSS (1). We report our experience using SBRT for localized prostate cancer in patients with pretreatment IPSS ≥ 15. Methods: Localized prostate cancer patients with a pre-treatment IPSS ≥ 15 treated with SBRT at Georgetown University Hospital from 2009 to 2016 were included in this retrospective review of prospectively collected data. These patients were treated to 35-36.25 Gy in five fractions delivered via CyberKnife (Accuray Inc., Sunnyvale, CA). Urinary toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4). Urinary quality of life was assessed using validated questionnaires (IPSS and EPIC-26). Results: 53 patients at a median age of 71 years (range 57-89 years) received SBRT with a minimum follow up of 3 years. The median prostate size was 37 cm 3 (range 12-100 cm 3) and 30.2% patients received ADT. The 3-years incidence rate of Grade 3 urinary toxicity was 7.5% with median time to toxicity of 2.9 years. There were no Grade 4 or 5 toxicities. A mean baseline IPSS score of 19.8 significantly decreased to 12.9 at 3 months post-SBRT (p = 0.002) and remained stable at 36 months (13.7). A mean baseline EPIC-26 obstructive/irritative score of 64.1 significantly improved to 80.2 at 3 months (p = 0.002). This improvement was maintained to 36 months. There was no significant change from the mean baseline EPIC-26 urinary incontinence score at any point during follow up. Aghdam et al. High IPSS Score and SBRT Conclusions: SBRT for clinically localized prostate cancer was well-tolerated in men with baseline IPSS ≥ 15 (1). Grade 3 toxicities occurred but resolved with time. Our data suggest that poor baseline urinary function does not worsen following SBRT and may even improve. High baseline IPSS score should not be considered a contraindication to SBRT.

PURPOSE: To evaluate the use of palliative radiotherapy (pRT) for osseous metastases among patients with gastrointestinal malignancies by sociodemographic factors, tumor type, and survival. METHODS: The NCDB was used to identify 9297 patients with GI cancers who received pRT to bony metastases from 2004 to 2013. Cancers assessed included esophageal, stomach, pancreatic, hepatocellular (HCC), bile duct & other, gallbladder, colon/sigmoid, and rectal. After excluding incomplete data, 5774 remained for analysis. Strata included age, race, sex, household income, Charlson-Deyo score (CDS), site of bony metastasis, Insurance status, treatment facility type, and distance from treatment site (crow-fly). Outcomes of interest included survival after diagnosis, survival after pRT, completion of pRT, and percent of remaining life spent receiving radiotherapy (PRLSRT). Chi-squared, Kaplan Meier curve with log rank analyses, and Cox Regression evaluated outcomes as a factor of sociodemographics. RESULTS: Patients were 69% male, 81% Caucasian (CA) and 13% African American (AA). Pancreas, HCC, and Colon/Sigmoid cancers made up 63% of primary tumors. The most commonly used pRT regimen was 30Gy in 10 fractions, and single-fraction 8Gy was increasingly utilized towards 2013. As survival decreased, use of single-fraction pRT increased indicating appropriate pairing of treatment duration to prognosis. This trend was consistent among both AA and CA patients. AA patients were younger and more likely to live <20mi from their treatment facility compared to CA’s. AA’s were more likely to have no insurance or Medicaid (9.7% vs 5.3%, or 18.1% vs 8% p<0.05), and have an annual household income below $30k (37.3 vs 11.4%) compared to CA’s. AA’s were less likely to have pancreatic cancer. Slightly more AA’s completed pRT than CA’s (69.2% vs 65.2%, p<0.05), and had longer survival after diagnosis compared to CA (10.2 vs 9.7 months) but shorter survival after pRT suggesting a delay in palliation. Additionally, those who lived 40-60 miles from treatment facility had higher mean survival. Patients with private insurance and those treated at integrated network programs survival advantages. PRLSRT did not differ by race, but decreased from 2004 to 2013. PRLSRT>50% (p50) did not differ by crow-fly or facility type, but men and those with Medicare were more likely to have p50. A PRLSRT of 10% or less (p10) was more frequent in those who were treated at an academic facility, lived >60mi away, had private insurance, a lower CDS, or earned $48-63k/yr in 2012. Sites with more p50 were the spine, skull, and spinal cord. Sites with higher p10 were extremity, shoulder, and ribs. CONCLUSION: This study evaluated trends of pRT use among patients and stratified analyses by sociodemographic factors. Further research may uncover mechanisms of these trends and highlight potential strategies to optimize the use of pRT. Citation Format: Jason Hirshberg, Charles Hsu, Jared Robbins. Palliative radiation to bony metastases from GI tumors: Disparities, outcomes, and practice patterns [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C001.