Comparison of the epidermal growth factor receptor protein expression between primary non-small cell lung cancer and paired lymph node metastases: implications for targeted nuclide radiotherapy

<p>Abstract</p> <p>Background</p> <p>The knowledge of Epidermal growth factor receptor (EGFR) expression in metastases of NSCLC was limited. In receptor-mediated targeted nuclide radiotherapy, tumor cells are killed with delivered radiation and therapeutic efficiency is mainly dependent on the receptor expression. Thus, the level and stability of receptor expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target. The goal of this study was to evaluate whether EGFR is suitable as target for clinical therapy.</p> <p>Methods</p> <p>Expression of EGFR was investigated immunohistochemically in paired samples of lymph node metastases and corresponding NSCLC primary lesions (n = 51). EGFR expression was scored as 0, 1+, 2+ or 3+.</p> <p>Results</p> <p>Positive (1+, 2+ or 3+) EGFR immunostaining was evident in 36 of 47 (76.6%) analysed NSCLC primary tumors, and in 78.7% of the corresponding lymph node metastases. When EGFR expression is classified as positive or negative, discordance between the primary tumors and the corresponding metastases was observed in 5 cases (10.6%). EGFR overexpression (2+ or 3+) was found in 53.2% (25/47) of the NSCLC primary tumors and 59.6% of the corresponding metastases. Nine out of the 47 paired samples (19.2%) were discordant: Only three patients who had EGFR overexpression in the primary tumors showed EGFR downregulation (0 or 1+) in lymph node metastases, while six patients changed the other way around.</p> <p>Conclusions</p> <p>The EGFR expression in the primary tumor and the corresponding metastasis is discordant in about 10% of the patients. When overexpression is considered, the discordance is observed in about 20% of the cases. However, concerning EGFR overexpression in the primary tumors, similar expression in the metastases could be predicted with a reasonably high probability, which is encouraging for testing of EGFR targeted nuclide radiotherapy.</p

Comparison of initial learning algorithms for long short-term memory method on real-time respiratory signal prediction

AimThis study aimed to examine the effect of the weight initializers on the respiratory signal prediction performance using the long short-term memory (LSTM) model.MethodsRespiratory signals collected with the CyberKnife Synchrony device during 304 breathing motion traces were used in this study. The effectiveness of four weight initializers (Glorot, He, Orthogonal, and Narrow-normal) on the prediction performance of the LSTM model was investigated. The prediction performance was evaluated by the normalized root mean square error (NRMSE) between the ground truth and predicted respiratory signal.ResultsAmong the four initializers, the He initializer showed the best performance. The mean NRMSE with 385-ms ahead time using the He initializer was superior by 7.5%, 8.3%, and 11.3% as compared to that using the Glorot, Orthogonal, and Narrow-normal initializer, respectively. The confidence interval of NRMSE using Glorot, He, Orthogonal, and Narrow-normal initializer were [0.099, 0.175], [0.097, 0.147], [0.101, 0.176], and [0.107, 0.178], respectively.ConclusionsThe experiment results in this study indicated that He could be a valuable initializer in the LSTM model for the respiratory signal prediction

Urban Link Travel Time Estimation Based on Low Frequency Probe Vehicle Data

To improve the accuracy and robustness of urban link travel time estimation with limited resources, this research developed a methodology to estimate the urban link travel time using low frequency GPS probe vehicle data. First, focusing on the case without reporting points for the GPS probe vehicle on the target link in the current estimation time window, a virtual report point creation model based on the K-Nearest Neighbour Rule was proposed. Then an improved back propagation neural network model was used to estimate the link travel time. The proposed method was applied to a case study based on an arterial road in Changchun, China: comparisons with the traditional artificial neural network method and the spatiotemporal moving average method revealed that the proposed method offered a higher estimation accuracy and better robustness

Climate Extremes Dominating Seasonal and Interannual Variations in Carbon Export from the Mississippi River Basinariations in Carbon Export from the Mississippi River Basin

Knowledge about the annual and seasonal patterns of organic and inorganic carbon (C) exports from the major rivers of the world to the coastal ocean is essential for our understanding and potential management of the global C budget so as to limit anthropogenic modification of global climate. Unfortunately our predictive understanding of what controls the timing, magnitude, and quality of C export is still rudimentary. Here we use a process-based coupled hydrologic/ecosystem biogeochemistry model (the Dynamic Land Ecosystem Model) to examine how climate variability and extreme events, changing land use, and atmospheric chemistry have affected the annual and seasonal patterns of C exports from the Mississippi River basin to the Gulf of Mexico. Our process-based simulations estimate that the average annual exports of dissolved organic C (DOC), particulate organic C (POC), and dissolved inorganic C (DIC) in the 2000s were 2.6 ± 0.4 Tg C yr−1, 3.4 ± 0.3 Tg C yr−1, and 18.8 ± 3.4 Tg C yr−1, respectively. Although land use change was the most important agent of change in C export over the past century, climate variability and extreme events (such as flooding and drought) were primarily responsible for seasonal and interannual variations in C export from the basin. The maximum seasonal export of DIC occurred in summer while for DOC and POC the maximum occurred in winter. Relative to the 10 year average (2001–2010), our modeling analysis indicates that the years of maximal and minimal C export cooccurred with wet and dry years (2008: 32% above average and 2006: 32% below average). Given Intergovernmental Panel on Climate Change-predicted changes in climate variability and the severity of rain events and droughts of wet and dry years for the remainder of the 21st century, our modeling results suggest major changes in the riverine link between the terrestrial and oceanic realms, which are likely to have a major impact on C delivery to the coastal ocean

A Promising Future of Ferroptosis in Tumor Therapy

Currently, mechanisms and therapeutic approaches have been thoroughly studied in various prevalent malignant tumors, such as breast and lung cancer. However, there is inevitable tumor progression and drug resistance. Uncovering novel treatment strategies to inhibit tumor development is important. Ferroptosis, a form of cell death associated with iron and lipid peroxidation, has drawn extensive attention. In this paper, we reviewed the underlying mechanisms of ferroptosis (i.e., iron, glutathione, and lipid metabolism) and its role in various tumors (i.e., lung cancer, liver carcinoma, breast cancer, and pancreatic cancer). Moreover, we summarized ferroptosis-related anti-tumor drugs and emphasized the potential of combined treatment of anti-tumor drugs and radiotherapy in an effort to provide novel anti-tumor treatments

Soil Microbial Communities and Mineralization Responses to Penicillin and Tetracycline Loads

ABSTRACT Residual effects of pharmaceutical antibiotics on soil microorganisms and turnover processes have merely been investigated. Therefore, this study explored the possible toxic effects of penicillin and tetracycline on indigenous bacterial communities and nitrogen mineralization in soil. Concentrations of 10 and 100 mg.kg -1 of penicillin and tetracycline antibiotics in soil affected the microbial community. The effect became apparent by a small tolerance increase and change in the phospholipids fatty acid (PLFA) pattern. The PLFA content revealed that most of the microbial groups decreased, while some specific microbial groups, e.g., 18:1ω9c, did not change in the soils even when soils were exposed to high concentrations of penicillin and tetracycline. Both antibiotics reduced the concentration of ammonium significantly, but that of nitrate was affected slightly. It was concluded that even at higher concentration, pharmaceutical antibiotics exert only a temporary pressure on soil microorganisms and selective processes in nitrogen turnover were negatively influenced

Impact of grazing on shaping abundance and composition of active methanotrophs and methane oxidation activity in a grassland soil

The effect of grazing on the abundance, composition, and methane (CH4) uptake of methanotrophs in grasslands has been well documented in the past few decades, but the dominant communities of active methanotrophs responsible for CH4 oxidation activity in grazed soils are still poorly understood. In this study, we characterized the metabolically active, aerobic methanotrophs in grasslands with three different levels of grazing (light, medium, and heavy) by combining DNA-stable isotope probing (SIP) and quantitative PCR (qPCR) for methane monooxygenase (pmoA) gene– and 16S rRNA gene–based amplicon sequencing. The CH4 oxidation potential was as low as 0.51 μmol g dry weight−1 day−1 in the ungrazed control, while it decreased as grazing intensity increased in grazed fields, ranging from 2.25 μmol g dry weight−1 day−1 in light grazed fields to 1.59 in heavily grazed fields. Increased CH4 oxidation activity was paralleled by twofold increases in abundance of pmoA genes and relative abundance of methanotroph-affiliated 16S rRNA genes in the total microbial community in grazed soils. SIP and sequencing revealed that the genera Methylobacter and Methylosarcina (type I; Gammaproteobacteria) and Methylocystis (type II; Alphaproteobacteria) were active methanotrophs responsible for CH4 oxidation in grazed soils. Light and intermediate grazing stimulated the growth and activity of methanotrophs, while heavy grazing decreased the abundance and diversity of the active methanotrophs in the typical steppe. Redundancy and correlation analysis further indicated that the variation of bulk density and soil C and N induced by grazing determined the abundance, diversity of active methanotrophs, and methane oxidation activity in the long-term grazed grassland soil

Application and comparison of Kalman filters for coastal ocean problems : an experiment with FVCOM

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 114 (2009): C05011, doi:10.1029/2007JC004548.Twin experiments were made to compare the reduced rank Kalman filter (RRKF), ensemble Kalman filter (EnKF), and ensemble square-root Kalman filter (EnSKF) for coastal ocean problems in three idealized regimes: a flat bottom circular shelf driven by tidal forcing at the open boundary; an linear slope continental shelf with river discharge; and a rectangular estuary with tidal flushing intertidal zones and freshwater discharge. The hydrodynamics model used in this study is the unstructured grid Finite-Volume Coastal Ocean Model (FVCOM). Comparison results show that the success of the data assimilation method depends on sampling location, assimilation methods (univariate or multivariate covariance approaches), and the nature of the dynamical system. In general, for these applications, EnKF and EnSKF work better than RRKF, especially for time-dependent cases with large perturbations. In EnKF and EnSKF, multivariate covariance approaches should be used in assimilation to avoid the appearance of unrealistic numerical oscillations. Because the coastal ocean features multiscale dynamics in time and space, a case-by-case approach should be used to determine the most effective and most reliable data assimilation method for different dynamical systems.P. Malanotte-Rizzoli and J. Wei were supported by the Office of Naval Research (ONR grant N00014-06-1- 0290); C. Chen and Q. Xu were supported by the U.S. GLOBEC/Georges Bank program (through NSF grants OCE-0234545, OCE-0227679, OCE- 0606928, OCE-0712903, OCE-0726851, and OCE-0814505 and NOAA grant NA-16OP2323), the NSF Arctic research grants ARC0712903, ARC0732084, and ARC0804029, and URI Sea Grant R/P-061; P. Xue was supported through the MIT Sea Grant 2006-RC-103; Z. Lai, J. Qi, and G. Cowles were supported through the Massachusetts Marine Fisheries Institute (NOAA grants NA04NMF4720332 and NA05NMF4721131); and R. Beardsley was supported through U.S. GLOBEC/Georges Bank NSF grant OCE-02227679, MIT Sea Grant NA06OAR1700019, and the WHOI Smith Chair in Coastal Oceanography

EGFR and HER2 expression in primary cervical cancers and corresponding lymph node metastases: Implications for targeted radiotherapy

<p>Abstract</p> <p>Background</p> <p>Proteins overexpressed on the surface of tumor cells can be selectively targeted. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are among the most often targeted proteins. The level and stability of expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target for imaging in nuclear medicine and for various forms of therapy. So far, the expression of EGFR and HER2 has only been determined in primary cervical cancers, and we have not found published data regarding the receptor status in corresponding metastatic lesions. The goal of this study was to evaluate whether any of these receptors are suitable as target for clinical diagnosis and therapy.</p> <p>Methods</p> <p>Expression of EGFR and HER2 was investigated immunohistochemically in both lymph node metastases and corresponding primary cervical cancers (n = 53). HER2 and EGFR expression was scored using HercepTest criteria (0, 1+, 2+ or 3+).</p> <p>Results</p> <p>EGFR overexpression (2+ or 3+) was found in 64% (35/53) of the primary cervical tumors and 60% (32/53) of the corresponding lymph node metastases. There was a good concordance between the primary tumors and the paired metastases regarding EGFR expression. Only four patients who had 2+ or 3+ in the primary tumors changed to 0 or 1+ in lymph node metastases, and another two cases changed the other way around. None of the primary tumors or the lymph node metastases expressed HER2 protein.</p> <p>Conclusion</p> <p>The EGFR expression seems to be common and stable during cervical cancer metastasis, which is encouraging for testing of EGFR targeted radiotherapy. HER2 appears to be of poor interest as a potential target in the treatment of cervical cancer.</p