Guggulsterone-Mediated Enhancement of Radiosensitivity in Human Tumor Cell Lines

Purpose: To observe the effect of guggulsterone (GS) on the radiation response in human cancer cell lines. Materials and methods: The radiation response of cancer cells treated with GS was observed by cell survival studies, cell growth assay, NF-κB activity assay, western blotting of some key growth promoting receptors, the DNA repair protein γH2AX, and flow cytometry for DNA analyses. Results: GS inhibited radiation induced NF-κB activation and enhanced radiosensitivity in the pancreatic cell line, PC-Sw. It reduced both cell cycle movement and cell growth. GS reduced ERα protein in MCF7 cells and IGF1-Rβ protein in colon cancer cells and pancreatic cancer cells and inhibited DNA double strand break (DSB) repair following radiation. Conclusion: GS induced radiation sensitization may be due to several different mechanisms including the inhibition of NF-κB activation and reductions in IGF1-Rβ. In addition, GS induced γH2AX formation, primarily in the S-phase, indicates that DNA DSB's in the S-phase may be another reason for GS induced radiosensitivity. ERα down-regulation in response to GS suggests that it can be of potential use in the treatment of estrogen positive tumors that are resistant to tamoxifen

Ionizing Radiation-Induced Oxidative Stress Alters miRNA Expression

). treatment, and 45 after etoposide treatment. Substantial overlap between the miRNA expression changes between agents was observed suggesting a signature miRNA response to cell stress. Changes in the expression of selected miRNA species varied in response to radiation dose and time. Finally, production of reactive oxygen species (ROS) increased with increasing doses of radiation and pre-treatment with the thiol antioxidant cysteine decreased both ROS production and the miRNA response to radiation., and etoposide. Additionally, pre-treatment with cysteine prevented radiation-induced alterations in miRNA expression which suggests that miRNAs are responsive to oxidative stress. Taken together, these results imply that miRNAs play a role in cellular defense against exogenous stress and are involved in the generalized cellular response to genotoxic oxidative stress

Cardiac Complications in Patients with Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Observational Studies

Vicente Corrales-Medina and colleagues report estimates of the risk of cardiac complications among patients with community-acquired pneumonia from a systematic review and meta-analysis

The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design

<p>Abstract</p> <p>Background</p> <p>The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO_2peak), patient-reported outcomes, and the organ components that govern VO_2peakin post-operative non-small cell lung cancer (NSCLC) patients.</p> <p>Methods/Design</p> <p>Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO_2peakfor aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO_2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression.</p> <p>Discussion</p> <p>VO_2peakis becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum.</p> <p>Trial Registration</p> <p>NCT00018255</p

Dod Modeling And Simulation Standards Vetting Process/Tool - Common &Amp; Cross-Cutting

This paper updates the Modeling and Simulation (M&S) community on the status of the M&S Project Department of Defense (DoD) Modeling and Simulation Standards Vetting Tool sponsored by the DoD M&S Steering Committee. At the Spring Simulation Interoperability Workshop (SIW), paper 06S-SIW-069 titled, Joint Automated Modeling and Simulation Standards Vetting and Repository Tool introduced the project and provided some background information. Leveraging the efforts and lessons learned from the Army, Navy and AF M&S standard vetting programs, a common vetting process and tool was created. The objective of the standards vetting process is to establish and promote common and effective M&S standards for the M&S Community. A common process and tool increases collaboration among stakeholders, encourages broad community input, minimizes duplication of effort from multiple tools and provides shared access to approved M&S Standards. The DoD Standards Vetting Tool (DSVT) is a single, integrated capability for nominating, vetting and distributing M&S standards across the DoD, Joint and all Services. The tool and adoption process for M&S Standards consists of seven stages associated to three key concepts: 1) Nominate, 2) Evaluate, and 3) Promulgate M&S Standards. The evaluation stages include technical, business and community reviews, then an independent ballot and final approval by the appropriate approval authorities. The DSVT supporting functions include 1) a set of M&S Standard\u27s informational web pages; 2) a dynamic online decision support vetting application tool; and 3) a repository system for storing and searching nominated and approved M&S standards. The DSVT supports the processes and information needed for potential submission to the Defense Standardization Program (DSP) and the DoD Information Technology Standards Registry (DISR) programs. This paper will discuss the project\u27s progress, the capabilities, and benefits and proposed way-ahead

Enhancement of 5-Aminolevulinic acid-induced oxidative stress on two cancer cell lines by gold nanoparticles

5-Aminolevulinic acid (5-ALA) and its methyl ester (5-ALA-Me) at mM concentration levels induce oxidative stress via the production of reactive oxygen species (ROS). Human cancer cell lines (MCF-7 and HepG2) incubated in the dark in the simultaneous presence of 5.0 mM or more 5-ALA or 5-ALA-Me (for MCF-7) and 7 g/mL of 15 nm citrate capped gold nanoparticles (AuNPs) were damaged more seriously compared to those in the presence of the levulinic acid alone. Damage is visible in electron micrographs which reveal similar morphology both in the presence or absence of AuNPs. Cytotoxicity was observed irrespective of the presence of serum and medium. Production of ROS in cell free samples containing 5-ALA-Me was monitored by EPR as the DMPO-OH spin adduct and also showed a catalytic effect of AuNPs. Both SOD and CAT inhibited the production of ROS and also reduced cytotoxicity in the cell samples. These observations can be explained by initial attack on the cell membrane by ROS produced in the medium outside the cell and provide insight into possible uses of 5-ALA in cancer chemotherapy