The specific molecular profiles of ovarian cancer interface zones (IZ), the region between tumors and normal tissues, were evaluated using a new method involving matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS). We analyzed three ovarian serous carcinomas using MALDI-IMS. Principal component analysis (PCA) was used to evaluate the quality of tissue spatial features based on MALDI-IMS, and for analysis of large data sets of MALDI-IMS. Two-dimensional gel electrophoresis and fluorescence microscopy were used to verify interface-specific proteins. Unique profiles were identified for the tumors, the normal zone, and the IZ. Through MALDI analysis, two interface-specific proteins, plastin 2 and peroxiredoxin 1 (PRDX 1), were identified as differentially regulated between zones. Fluorescence microscopy revealed high expression levels of plastin 2 and PRDX 1 along the IZ of ovarian tumors. This comparative proteomics study using tissue MALDI-IMS suggested that the IZ is different from the adjacent tumor and normal zones, and that plastin 2 and PRDX 1 may be interface markers specific to ovarian tumors.
The Automated Radiation Measurements for Aerospace Safety (ARMAS) program has successfully deployed a fleet of six instruments measuring the ambient radiation environment at commercial aircraft altitudes. ARMAS transmits real‐time data to the ground and provides quality, tissue‐relevant ambient dose equivalent rates with 5 min latency for dose rates on 213 flights up to 17.3 km (56,700 ft). We show five cases from different aircraft; the source particles are dominated by galactic cosmic rays but include particle fluxes for minor radiation periods and geomagnetically disturbed conditions. The measurements from 2013 to 2016 do not cover a period of time to quantify galactic cosmic rays' dependence on solar cycle variation and their effect on aviation radiation. However, we report on small radiation “clouds” in specific magnetic latitude regions and note that active geomagnetic, variable space weather conditions may sufficiently modify the magnetospheric magnetic field that can enhance the radiation environment, particularly at high altitudes and middle to high latitudes. When there is no significant space weather, high‐latitude flights produce a dose rate analogous to a chest X‐ray every 12.5 h, every 25 h for midlatitudes, and every 100 h for equatorial latitudes at typical commercial flight altitudes of 37,000 ft (~11 km). The dose rate doubles every 2 km altitude increase, suggesting a radiation event management strategy for pilots or air traffic control; i.e., where event‐driven radiation regions can be identified, they can be treated like volcanic ash clouds to achieve radiation safety goals with slightly lower flight altitudes or more equatorial flight paths.
The predominant mucins in human whole saliva, MG1 and MG2, serve to protect and to lubricate the oral cavity. In this study, both unstimulated and stimulated whole salivas were collected from two groups of subjects: young (18-35 years of age) and aged (65-83 years of age). The subjects were in apparent good health. Saliva samples from each subject were analyzed by SDS-PAGE. The gels were stained with Stains-all, and both MG1 and MG2 were quantitated by video-image densitometry. The protocol gave reproducible values for each mucin. The stimulated and unstimulated salivas from aged subjects showed significant reductions in concentrations of both MG1 and MG2, as quantitated in mucin dye-binding units. Possible associations of these reductions with the aging process are discussed.
The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDAC. The detection and inhibition of autophagy offers a potential therapeutic target for PDAC.
Background/Aim. Autophagy, a cellular degradation process, has paradoxical roles in tumorigenesis and the progression of human cancers. The aim of this study was to investigate the expression levels of autophagy-related proteins in colorectal cancer (CRC) and to evaluate their prognostic significance. Methods. This study is a retrospective review of immunohistochemical and clinicopathological data. All specimens evaluated were obtained from 263 patients with colorectal cancer who had undergone surgery between November 1996 and August 2007. The primary outcomes measured were the expression levels of three autophagy-related proteins (ATG5, BECN1/Beclin 1, and Microtubule-associated protein 1 light chain 3B (LC3B)) by immunohistochemistry and its association in clinicopathological parameters and patient survival. Results. The autophagy-related protein expression frequencies were 65.1% (151/232) for ATG5, 71.3% (174/244) for BECN1, and 74.7% (186/249) for LC3B for the 263 patients. Correlation between the expression of autophagy-related proteins was significant for all protein pairs. Multivariate analysis showed that negative LC3B expression and absence of autophagy-related proteins expression were independently associated with poor prognosis. Conclusion. Absence of autophagy-related proteins expression is associated with poor clinical outcome in CRC, suggesting that these proteins have potential uses as novel prognostic markers.
Air safety is tied to the phenomenon of ionizing radiation from space weather, primarily from galactic cosmic rays but also from solar energetic particles. A global framework for addressing radiation issues in this environment has been constructed, but more must be done at international and national levels. Health consequences from atmospheric radiation exposure are likely to exist. In addition, severe solar radiation events may cause economic consequences in the international aviation community due to exposure limits being reached by some crew members. Impacts from a radiation environment upon avionics from high-energy particles and low-energy, thermalized neutrons are now recognized as an area of active interest. A broad community recognizes that there are a number of mitigation paths that can be taken relative to the human tissue and avionics exposure risks. These include developing active monitoring and measurement programs as well as improving scientific modeling capabilities that can eventually be turned into operations. A number of roadblocks to risk mitigation still exist, such as effective pilot training programs as well as monitoring, measuring, and regulatory measures. An active international effort toward observing the weather of atmospheric radiation must occur to make progress in mitigating radiation exposure risks. Stakeholders in this process include standard-making bodies, scientific organizations, regulatory organizations, air traffic management systems, aircraft owners and operators, pilots and crew, and even the public. Aviation Radiation Is an Unavoidable Space Weather PhenomenonAir safety has improved significantly in many meteorological areas over the past decades with the exception of space weather, which includes ionizing radiation. While a framework for addressing radiation issues has been constructed, we believe that more can and must be done at international and national levels. In particular, measurement programs must be expanded and linked with models to provide current epoch and, eventually, forecast information for the aviation ionizing radiation environment. A diverse radiation measurement and modeling community exists with a strong interest in improving international air safety.There are two challenges in our ever more mobile, technologically dependent global society. First, pilots, crew, and passengers, which include fetuses between their first and second trimesters, might face additional radiation hazards in terms of dose equivalent rate (rate of absorbed dose multiplied by the quality factor), particularly when flying at commercial aviation altitudes above 26,000 ft. (7924.8 m) (8 km) (see Figure 1). Second, avionics can experience single event effects (SEEs) from both the ambient high-energy and thermal neutron environments. The source of this radiation in either case is twofold-from the continuous bombardment by primary background galactic cosmic rays (GCRs) and also from solar energetic particles (SEPs) emitted during occasional solar flare events lasting up to a ...
Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas.
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