BackgroundRisk of normal tissue toxicity limits the amount of thoracic radiation therapy (RT) that can be routinely prescribed to treat non-small cell lung cancer (NSCLC). An early biomarker of response to thoracic RT may provide a way to predict eventual toxicities—such as radiation pneumonitis—during treatment, thereby enabling dose adjustment before the symptomatic onset of late effects. MicroRNAs (miRNAs) were studied as potential serological biomarkers for thoracic RT. As a first step, we sought to identify miRNAs that correlate with delivered dose and standard dosimetric factors.MethodsWe performed miRNA profiling of plasma samples obtained from five patients with Stage IIIA NSCLC at five dose-points each during radical thoracic RT. Candidate miRNAs were then assessed in samples from a separate cohort of 21 NSCLC patients receiving radical thoracic RT. To identify a cellular source of circulating miRNAs, we quantified in vitro miRNA expression intracellularly and within secreted exosomes in five NSCLC and stromal cell lines.ResultsmiRNA profiling of the discovery cohort identified ten circulating miRNAs that correlated with delivered RT dose as well as other dosimetric parameters such as lung V20. In the validation cohort, miR-29a-3p and miR-150-5p were reproducibly shown to decrease with increasing radiation dose. Expression of miR-29a-3p and miR-150-5p in secreted exosomes decreased with radiation. This was concomitant with an increase in intracellular levels, suggesting that exosomal export of these miRNAs may be downregulated in both NSCLC and stromal cells in response to radiation.ConclusionsmiR-29a-3p and miR-150-5p were identified as circulating biomarkers that correlated with delivered RT dose. miR-150 has been reported to decrease in the circulation of mammals exposed to radiation while miR-29a has been associated with fibrosis in the human heart, lungs, and kidneys. One may therefore hypothesize that outlier levels of circulating miR-29a-3p and miR-150-5p may eventually help predict unexpected responses to radiation therapy, such as toxicity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-016-0636-4) contains supplementary material, which is available to authorized users.
a cluster of cases of severe respiratory syndrome was reported in patients with connections to a seafood market in Wuhan, Hubei Province, China. 1 Within 1 week, Chinese health authorities were able to link these cases to a novel, enveloped RNA coronavirus, SARS-CoV-2, now commonly known to cause COVID-19. 2 By February 14, 2020, over 66,000 cases of COVID-19 were reported in China. 3 On January 19, a 35-year-old man returning from Wuhan to his home in Snohomish County, Washington, presented to urgent care with several days of cough and fever and ultimately tested positive for COVID-19, becoming the first case in the United States. The first COVID-related death occurred 4 weeks later, associated with a separate site, a long-term care facility in Kirkland, Washington, which rapidly became a cluster of 30 fatal cases as of March 16th. At the writing of this article, March 17th, there are 1012 confirmed cases in the state of Washington, with 52 deaths, primarily in King County. Evergreen Health, the major medical center in Kirkland, has recently declared that they have no remaining critical care capacity.COVID-19 is now a global pandemic that is advancing at a pace thatdwithout immediate attenuationdwill rapidly overtake medical infrastructures. This has been Sources of support: This work had no specific funding. Disclosures: none. Research data are stored in an institutional repository and will be shared upon request to the corresponding author.
Background In pandemics such as COVID-19, shortages of personal protective equipment are common. One solution may be to decontaminate equipment such as facemasks for reuse. Aim To collect and synthesize existing information on decontamination of N95 filtering facepiece respirators (FFRs) using microwave and heat-based treatments, with special attention to impact on mask function (aerosol penetration, airflow resistance), fit, and physical traits. Methods A systematic review (PROSPERO CRD42020177036) of literature available from Medline, Embase, Global Health, and other sources was conducted. Records were screened independently by two reviewers, and data was extracted from studies that reported on effects of microwave- or heat-based decontamination on N95 FFR performance, fit, physical traits, and/or reductions in microbial load. Findings Thirteen studies were included that used dry/moist microwave irradiation, heat, or autoclaving. All treatment types reduced pathogen load by a log10 reduction factor of at least three when applied for sufficient duration (>30s microwave, >60 min dry heat), with most studies assessing viral pathogens. Mask function (aerosol penetration <5% and airflow resistance <25mmH 2 O) was preserved after all treatments except autoclaving. Fit was maintained for most N95 models, though all treatment types caused observable physical damage to at least one model. Conclusions Microwave irradiation and heat may be safe and effective viral decontamination options for N95 FFR reuse during critical shortages. The evidence does not support autoclaving or high-heat (>90 o C) approaches. Physical degradation may be an issue for certain mask models, and more real-world evidence on fit is needed.
Despite optimal chemotherapy, radiotherapy (RT), and/or surgery, non-small-cell lung carcinoma (NSCLC) remains the leading cause of cancer-related death in the US and worldwide. Thoracic RT, a mainstay in the treatment of locally advanced NSCLC, is often restricted in efficacy by a therapeutic index limited by sensitivity of tissues surrounding the malignancy. Therefore, radiosensitizers that can improve the therapeutic index are a vital unmet need. Inhibition of the NF-κB pathway is a proposed mechanism of radiosensitization. Here we demonstrate that inhibition of the canonical NF-κB pathway by dimethylaminoparthenolide (DMAPT) radiosensitizes NSCLC by blocking DNA double-strand break (DSB) repair. NF-κB inhibition results in significant impairment of both homologous recombination (HR) and non-homologous end joining (NHEJ), as well as reductions in ionizing radiation (IR)-induced DNA repair biomarkers. NF-κB inhibition by DMAPT shows preclinical potential for further investigation as a NSCLC radiosensitizer.
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