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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 1,315 records · Page 73
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Integrating Cloud Processes in the Community Atmosphere Model, Version 5.

This paper provides a description on the parameterizations of global cloud system in CAM5. Compared to the previous versions, CAM5 cloud parameterization has the following unique characteristics: (1) a transparent cloud macrophysical structure that has horizontally non-overlapped deep cumulus, shallow cumulus and stratus in each grid layer, each of which has own cloud fraction, mass and number concentrations of cloud liquid droplets and ice crystals, (2) stratus-radiation-turbulence interaction that allows CAM5 to simulate marine stratocumulus solely from grid-mean RH without relying on the stability-based empirical empty stratus, (3) prognostic treatment of the number concentrations of stratus liquid droplets and ice crystals with activated aerosols and detrained in-cumulus condensates as the main sources and evaporation-sedimentation-precipitation of stratus condensate as the main sinks, and (4) radiatively active cumulus. By imposing consistency between diagnosed stratus fraction and prognosed stratus condensate, CAM5 is free from empty or highly-dense stratus at the end of stratus macrophysics. CAM5 also prognoses mass and number concentrations of various aerosol species. Thanks to the aerosol activation and the parameterizations of the radiation and stratiform precipitation production as a function of the droplet size, CAM5 simulates various aerosol indirect effects associated with stratus as well as direct effects, i.e., aerosol controls both the radiative and hydrological budgets. Detailed analysis of various simulations revealed that CAM5 is much better than CAM3/4 in the global performance as well as the physical formulation. However, several problems were also identifed, which can be attributed to inappropriate regional tuning, inconsistency between various physics parameterizations, and incomplete model physics. Continuous efforts are going on to further improve CAM5.

CAM5↗
DOE OSTI2017

The MERRA-2 Aerosol Reanalysis, 1980 Onward. Part I: System Description and Data Assimilation Evaluation

The Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2), updates NASA’s previous satellite-era (1980 onward) reanalysis system to include additional observations and improvements to the Goddard Earth Observing System, version 5 (GEOS-5), Earth system model. As a major step toward a full Integrated Earth Systems Analysis (IESA), in addition to meteorological observations, MERRA-2 now includes assimilation of aerosol optical depth (AOD) from various ground- and space-based remote sensing platforms. Here, in the first of a pair of studies, the MERRA-2 aerosol assimilation is documented, including a description of the prognostic model (GEOS-5 coupled to the GOCART aerosol module), aerosol emissions, and the quality control of ingested observations. Initial validation and evaluation of the analyzed AOD fields are provided using independent observations from ground, aircraft, and shipborne instruments. The positive impact of the AOD assimilation on simulated aerosols is demonstrated by comparing MERRA-2 aerosol fields to an identical control simulation that does not include AOD assimilation. Fianlly, after showing the AOD evaluation, this paper takes a first look at aerosol–climate interactions by examining the shortwave, clear-sky aerosol direct radiative effect. The companion paper (Part II) evaluates and validates available MERRA-2 aerosol properties not directly impacted by the AOD assimilation (e.g., aerosol vertical distribution and absorption). Importantly, while highlighting the skill of the MERRA-2 aerosol assimilation products, both studies point out caveats that must be considered when using this new reanalysis product for future studies of aerosols and their interactions with weather and climate.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Impact of Vegetation Assimilation on Flash Drought Characteristics across the Continental United States

Predicting and managing the impacts of flash droughts is difficult owing to their rapid onset and intensification. Flash drought monitoring often relies on assessing changes in root-zone soil moisture. However, the lack of widespread soil moisture measurements means that flash drought assessments often use process-based model data like that from the North American Land Data Assimilation System (NLDAS). Such reliance opens flash drought assessment to model biases, particularly from vegetation processes. Here, we examine the influence of vegetation on NLDAS-simulated flash drought characteristics by comparing two experiments covering 1981–2017: open loop (OL), which uses NLDAS surface meteorological forcing to drive a land surface model using prognostic vegetation, and data assimilation (DA), which instead assimilates near-real-time satellite-derived leaf area index (LAI) into the land surface model. The OL simulation consistently underestimates LAI across the United States, causing relatively high soil moisture values. Both experiments produce similar geographic patterns of flash droughts, but OL produces shorter duration events and regional trends in flash drought occurrence that are sometimes opposite to those in DA. Across the Midwest and Southern United States, flash droughts are 4 weeks (about 70%) longer on average in DA than OL. Moreover, across much of the Great Plains, flash drought occurrence has trended upward according to the DA experiment, opposite to the trend in OL. This sensitivity of flash drought to the representation of vegetation suggests that representing plants with greater fidelity could aid in monitoring flash droughts and improve the prediction of flash drought transitions to more persistent and damaging long-term droughts.

Drought↗
DOE OSTI2015

A Hybrid Global Ocean Data Assimilation System at NCEP

Seasonal forecasting with a coupled model requires accurate initial conditions for the ocean. A hybrid data assimilation has been implemented within the National Centers for Environmental Prediction (NCEP) Global Ocean Data Assimilation System (GODAS) as a future replacement of the operational three-dimensional variational data assimilation (3DVar) method. This Hybrid-GODAS provides improved representation of model uncertainties by using a combination of dynamic and static background error covariances, and by using an ensemble forced by different realizations of atmospheric surface conditions. An observing system simulation experiment (OSSE) is presented spanning January 1991 to January 1999, with a bias imposed on the surface forcing conditions to emulate an imperfect model. The OSSE compares the 3DVar used by the NCEP Climate Forecast System (CFSv2) with the new hybrid, using simulated in situ ocean observations corresponding to those used for the NCEP Climate Forecast System Reanalysis (CFSR). The Hybrid-GODAS reduces errors for all prognostic model variables over the majority of the experiment duration, both globally and regionally. Compared to an ensemble Kalman filter (EnKF) used alone, the hybrid further reduces errors in the tropical Pacific. The hybrid eliminates growth in biases of temperature and salinity present in the EnKF and 3DVar, respectively. A preliminary reanalysis using real data shows that reductions in errors and biases are qualitatively similar to the results from the OSSE. Finally, the Hybrid-GODAS is currently being implemented as the ocean component in a prototype next-generation CFSv3, and will be used in studies by the Climate Prediction Center to evaluate impacts on ENSO prediction.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Physics-Dynamics Coupling in Weather, Climate, and Earth System Models: Challenges and Recent Progress

Geophysical models of the atmosphere and ocean invariably involve parameterizations. These represent two distinct areas: a) Subgrid processes which the model cannot (yet) resolve, due to its discrete resolution, and b) sources in the equation, due to radiation for example. Hence coupling between these physics parameterizations and the resolved fluid dynamics and also between the dynamics of the different fluids in the system (air and water) is necessary. This coupling is an important aspect of geophysical models. However, often model development is strictly segregated into either physics or dynamics. Hence, this area has many more unanswered questions than in-depth understanding. Furthermore, recent developments in the design of dynamical cores (significant increase of resolution, move to non-hydrostatic equation sets etc), extended process physics (prognostic micro physics, 3D turbulence, non-vertical radiation etc) and predicted future changes of the computational infrastructure (Exascale with its need for task parallelism, data locality and asynchronous time stepping for example) is adding even more complexity and new questions.

Gross, Markus↗
DOE OSTI2021

A Bimodal Diagnostic Cloud Fraction Parameterization. Part II: Evaluation and Resolution Sensitivity

A wide range of approaches exists to account for subgrid cloud variability in regional simulations of the atmosphere. This paper addresses the following questions: 1) Is there still benefit in representing subgrid variability of cloud in convection-permitting simulations? 2) What is the sensitivity to the cloud fraction parameterization complexity? 3) Are current cloud fraction parameterizations scale-aware across convection-permitting resolutions? These questions are addressed for regional simulations of a 6-week observation campaign in the U.S. southern Great Plains. Particular attention is given to a new diagnostic cloud fraction scheme with a bimodal subgrid saturation-departure PDF, described in Part I. The model evaluation is performed using ground-based remote sensing synergies, satellite-based retrievals, and surface observations. It is shown that not using a cloud fraction parameterization results in underestimated cloud frequency and water content, even for stratocumulus. The use of a cloud fraction parameterization does not guarantee improved cloud property simulations, however. Diagnostic and prognostic cloud schemes with a symmetric subgrid saturation-departure PDF underestimate cloud fraction and cloud optical thickness, and hence overestimate surface shortwave radiation. These schemes require empirical bias-correction techniques to improve the cloud cover. The new cloud fraction parameterization, introduced in Part I, improves cloud cover, liquid water content, cloud-base height, optical thickness, and surface radiation compared to schemes reliant on a symmetric PDF. Furthermore, cloud parameterizations using turbulence-based, rather than prescribed constant subgrid variances, are shown to be more scale-aware across convection-permitting resolutions.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2012

Deficiency of the p53/p63 target Perp alters mammary gland homeostasis and promotes cancer

Perp is a transcriptional target of both p53 during DNA damage-induced apoptosis and p63 during stratified epithelial development. Perp-/- mice exhibit postnatal lethality associated with dramatic blistering of the epidermis and oral mucosa, reflecting a critical role in desmosome-mediated intercellular adhesion in keratinocytes. However, the role of Perp in tissue homeostasis in other p63-dependent stratified epithelial tissues is poorly understood. Given that p63 is essential for proper mammary gland development and that cell adhesion is fundamental for ensuring the proper architecture and function of the mammary epithelium, here we investigate Perp function in the mammary gland. Immunofluorescence and Western blot analysis were performed to characterize Perp expression and localization in the mouse mammary epithelium throughout development. The consequences of Perp deficiency for mammary epithelial development and homeostasis were examined by using in vivo mammary transplant assays. Perp protein levels in a variety of human breast cancer cell lines were compared with those in untransformed cells with Western blot analysis. The role of Perp in mouse mammary tumorigenesis was investigated by aging cohorts of K14-Cre/+;p53 fl/fl mice that were wild-type or deficient for Perp. Mammary tumor latency was analyzed, and tumor-free survival was assessed using Kaplan-Meier analysis. We show that Perp protein is expressed in the mammary epithelium, where it colocalizes with desmosomes. Interestingly, although altering desmosomes through genetic inactivation of Perp does not dramatically impair mammary gland ductal development, Perp loss affects mammary epithelial homeostasis by causing the accumulation of inflammatory cells around mature mammary epithelium. Moreover, we show reduced Perp expression in many human breast cancer cell lines compared with untransformed cells. Importantly, Perp deficiency also promotes the development of mouse mammary cancer. Together, these observations demonstrate an important role for Perp in normal mammary tissue function and in mammary cancer suppression. In addition, our findings highlight the importance of desmosomes in cancer suppression and suggest the merit of evaluating Perp as a potential prognostic indicator or molecular target in breast cancer therapy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Systematic review of type 1 diabetes biomarkers reveals regulation in circulating proteins related to complement, lipid metabolism, and immune response

Type 1 diabetes (T1D) results from an autoimmune attack of the pancreatic β cells that progresses to dysglycemia and symptomatic hyperglycemia. Current biomarkers to track this evolution are limited, with development of islet autoantibodies marking the onset of autoimmunity and metabolic tests used to detect dysglycemia. Therefore, additional biomarkers are needed to better track disease initiation and progression. Multiple clinical studies have used proteomics to identify biomarker candidates. However, most of the studies were limited to the initial candidate identification, which needs to be further validated and have assays developed for clinical use. Here we curate these studies to help prioritize biomarker candidates for validation studies and to obtain a broader view of processes regulated during disease development. This systematic review was registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/N8TSA). Using PRISMA guidelines, we conducted a systematic search of proteomics studies of T1D in the PubMed to identify putative protein biomarkers of the disease. Studies that performed mass spectrometry-based untargeted/targeted proteomic analysis of human serum/plasma of control, pre-seroconversion, post-seroconversion, and/or T1D-diagnosed subjects were included. For unbiased screening, 3 reviewers screened all the articles independently using the pre-determined criteria. A total of 13 studies met our inclusion criteria, resulting in the identification of 266 unique proteins, with 31 (11.6%) being identified across 3 or more studies. The circulating protein biomarkers were found to be enriched in complement, lipid metabolism, and immune response pathways, all of which are found to be dysregulated in different phases of T1D development. We found 2 subsets: 17 proteins (C3, C1R, C8G, C4B, IBP2, IBP3, ITIH1, ITIH2, BTD, APOE, TETN, C1S, C6A3, SAA4, ALS, SEPP1 and PI16) and 3 proteins (C3, CLUS and C4A) have consistent regulation in at least 2 independent studies at post-seroconversion and post-diagnosis compared to controls, respectively, making them strong candidates for clinical assay development. Biomarkers analyzed in this systematic review highlight alterations in specific biological processes in T1D, including complement, lipid metabolism, and immune response pathways, and may have potential for further use in the clinic as prognostic or diagnostic assays.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Analytical platform evaluation for quantification of ERG in prostate cancer using protein and mRNA detection methods

Background: The established methods for detecting prostate cancer (CaP) are based on tests using PSA (blood), PCA3 (urine), and AMACR (tissue) as biomarkers in patient samples. The demonstration of ERG oncoprotein overexpression due to gene fusion in CaP has thus provided ERG as an additional biomarker. Based on this, we hypothesized that ERG protein quantification methods can be of use in the diagnosis of prostate cancer. Methods: Therefore, an antibody-free assay for ERG3 protein detection was developed based on PRISM (high-pressure high-resolution separations with intelligent selection and multiplexing)-SRM (selected reaction monitoring) mass spectrometry. We utilized TMPRSS2-ERG positive VCaP and TMPRSS2-ERG negative LNCaP cells to simulate three different sample types (cells, tissue, and post-DRE urine sediment). Results: Recombinant ERG3 protein spiked into LNCaP cell lysates could be detected at levels as low as 20 pg by PRISM-SRM analysis. The sensitivity of the PRISM-SRM assay was around approximately 10,000 VCaP cells in a mixed cell population model of VCaP and LNCaP cells. Interestingly, ERG protein could be detected in as few as 600 VCaP cells spiked into female urine. The sensitivity of the in-house enzyme-linked immunosorbent assay (ELISA) was similar to the PRISM-SRM assay, with detection of 30 pg of purified recombinant ERG3 protein and 10,000 VCaP cells. On the other hand, qRT-PCR exhibited a higher sensitivity, as TMPRSS2-ERG transcripts were detected in as few as 100 VCaP cells, in comparison to NanoString methodologies which detected ERG from 10,000 cells. Conclusions: Based on this data, we propose that the detection of both ERG transcriptional products with RNA-based assays, as well as protein products of ERG using PRISM-SRM assays, may be of clinical value in developing diagnostics and prognostics assays for prostate cancer given their sensitivity, specificity, and reproducibility.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Diagnosis and management of inhalation injury: an updated review

In this article we review recent advances made in the pathophysiology, diagnosis, and treatment of inhalation injury. Historically, the diagnosis of inhalation injury has relied on nonspecific clinical exam findings and bronchoscopic evidence. The development of a grading system and the use of modalities such as chest computed tomography may allow for a more nuanced evaluation of inhalation injury and enhanced ability to prognosticate. Supportive respiratory care remains essential in managing inhalation injury. Adjuncts still lacking definitive evidence of efficacy include bronchodilators, mucolytic agents, inhaled anticoagulants, nonconventional ventilator modes, prone positioning, and extracorporeal membrane oxygenation. Recent research focusing on molecular mechanisms involved in inhalation injury has increased the number of potential therapies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

β1 and β4 integrins: from breast development to clinical practice

Following a highly dynamic and complex dialogue between the epithelium and the surrounding microenvironment, the mammary gland develops into a branching structure during puberty, buds during pregnancy, forms intricate polar acini during lactation and, once the babies are weaned, remodels and involutes. At every stage of menstrual and pregnancy cycles, interactions between the cells and the extracellular matrix (ECM) and homotypic and heterotypic cell–cell interactions give rise to the architecture and function of the gland at that junction. These orchestrated programs would not be possible without the important role of the ECM receptors, integrins being the prime examples. The ECM–integrin axis regulates many crucial cellular functions including survival, migration and quiescence; the imbalance in any of these processes could contribute to oncogenesis. In this review we spotlight the involvement of two prominent integrin subunits, β1 and β4 integrins, in cross-talk with tyrosine kinase receptors, and we discuss the roles of these integrin subunits in the biology of normal breast differentiation and as potential prognostic and therapeutic targets in breast cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

The FBXW7-binding sites on FAM83D are potential targets for cancer therapy

Increasing evidence shows the oncogenic function of FAM83D in human cancer, but how FAM83D exerts its oncogenic function remains largely unclear. Here, we investigated the importance of FAM83D/FBXW7 interaction in breast cancer (BC). We systematically mapped the FBXW7-binding sites on FAM83D through a comprehensive mutational analysis together with co-immunoprecipitation assay. Mutations at the FBXW7-binding sites on FAM83D led to that FAM83D lost its capability to promote the ubiquitination and proteasomal degradation of FBXW7; cell proliferation, migration, and invasion in vitro; and tumor growth and metastasis in vivo, indicating that the FBXW7-binding sites on FAM83D are essential for its oncogenic functions. A meta-evaluation of FAM83D revealed that the prognostic impact of FAM83D was independent on molecular subtypes. The higher expression of FAM83D has poorer prognosis. Moreover, high expression of FAM83D confers resistance to chemotherapy in BCs, which is experimentally validated in vitro. We conclude that identification of FBXW7-binding sites on FAM83D not only reveals the importance for FAM83D oncogenic function, but also provides valuable insights for drug target.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Fluorescent Tissue Assessment of Colorectal Cancer Liver Metastases Ablation Zone: A Potential Real-Time Biomarker of Complete Tumor Ablation

Background: This study aimed to evaluate whether rapid fluorescent tissue examination immediately after colorectal cancer liver metastasis (CLM) ablation correlates with standard pathologic and immunohistochemical (IHC) assessments. Methods: This prospective, National Institutes of Health-supported study enrolled 34 consecutive patients with 53 CLMs ablated between January 2011 and December 2014. Immediately after ablation, core needle sampling of the ablation zone was performed. Tissue samples were evaluated with fluorescent viability (MitoTracker Red) and nuclear (Hoechst) stains. Confocal microscope imaging was performed within 30 min after ablation. The same samples were subsequently fixed and stained with hematoxylin and eosin (H&E). Identified tumor cells underwent IHC staining for proliferation (Ki67) and viability (OxPhos). The study pathologist, blinded to the H&E and IHC assessment, evaluated the fluorescent images separately to detect viable tumor cells. Sensitivity, specificity, and overall concordance of the fluorescent versus H&E and IHC assessments were calculated. Results: A total of 63 tissue samples were collected and processed. The overall concordance rate between the immediate fluorescent and the subsequent H&E and IHC assessments was 94% (59/63). The fluorescent assessment sensitivity and specificity for the identification of tumor cells were respectively 100% (18/18) and 91% (41/45). Conclusions: The study showed a high concordance rate between the immediate fluorescent assessment and the standard H&E and IHC assessment of the ablation zone. Given the documented prognostic value of ablation zone tissue characteristics for outcomes after ablation of CLM, the fluorescent assessment offers a potential intra-procedural biomarker of complete tumor ablation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Increased Expression of DNAJC12 is Associated with Aggressive Phenotype of Gastric Cancer

Background: Identification of gastric cancer-related molecules is necessary to elucidate the pathological mechanisms of this heterogeneous disease. The purpose of this study was to identify novel genes associated with aggressive phenotypes of gastric cancer. Methods: Global expression profiling was conducted using tissues from four patients with metastatic gastric cancer to identify genes overexpressed in gastric cancer. Fifteen gastric cell lines and 262 pairs of surgically resected gastric tissues were subjected to mRNA expression analysis. The contribution of the candidate gene on gastric cancer cell proliferation, invasion, adhesion, and migration were evaluated using small interfering RNA. Results: DnaJ heat shock protein family (Hsp40) member C12 (DNAJC12) was identified as a candidate gene by transcriptome analysis. In clinical samples, DNAJC12 mRNA levels were higher in gastric cancer tissues compared with normal adjacent tissues. Patients with high DNAJC12 expression showed significantly shorter overall survival in our cohort and in the extra-validation cohort analyzed by a published microarray dataset. High DNAJC12 expression in gastric cancer tissues was significantly associated with lymphatic involvement, infiltrative growth type, lymph node metastasis, and advanced stage and was identified as an independent prognostic factor for overall survival in multivariable analysis. Increased expression of DNAJC12 was found in 12 of 14 examined gastric cancer cell lines. Knockdown of DNAJC12 expression significantly decreased the proliferation and invasion abilities of gastric cancer cells. Conclusions: Our findings support DNAJC12 as a candidate gene associated with aggressive phenotypes of gastric cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Adjuvant Therapy is Associated with Improved Survival in pT1N1 Gastric Cancer in a Heterogeneous Western Patient Population

Background: Two recent South Korean studies showed adjuvant therapy (AT) was not associated with improved survival in pT1N1 gastric adenocarcinoma (GAC). We established the prognostic utility of lymph node status, determined the pattern of use of AT, and compared survival stratified by type of AT in pT1N1 GAC in a Western patient population. Methods: We identified patients with pT1N0 and pT1N1 GAC using the National Cancer Database from 2004 to 2012. Clinicopathologic variables, treatment regimens, and overall survival (OS) were compared. Results: We compared 4516 (86.6%) pT1N0 to 696 (13.4%) pT1N1 patients. pT1N1 tumors were larger (median size 2.5 vs. 1.8 cm, p < 0.001), more often poorly differentiated (56.2% vs. 39.6%, p < 0.001), and had higher median retrieved lymph nodes (RLN) (14 vs. 12, p < 0.001) compared with pT1N0. pT1N1 was associated with worse median overall survival (OS) (6.9 vs. 9.9 years for pT1N0, p < 0.001). pN1 was independently associated with worse OS (hazard ratio [HR] 2.17, 95% confidence interval [CI] 1.84–2.56). Increased RLN was associated with improved OS (HR 0.73, 95% CI 0.65–0.83). Among pT1N1 patients, 330 (47.4%) had observation (OBS), 77 (11.1%) received adjuvant chemotherapy (ACT), 68 (9.8%) received adjuvant radiation therapy (ART), and 221 (31.8%) received adjuvant chemoradiation therapy (ACRT). ACT and ACRT were independently associated with improved OS (HR 0.37, 95% CI 0.22–0.65 and HR 0.40, 95% CI 0.28–0.57). Conclusions: pN1 was associated with worse survival and RLN ≥ 15 was associated with improved survival in pT1 GAC. ACT and ACRT were independently associated with improved survival in pT1N1 gastric cancer suggesting a valuable role in Western patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Homeobox C10 Influences on the Malignant Phenotype of Gastric Cancer Cell Lines and its Elevated Expression Positively Correlates with Recurrence and Poor Survival

Background: The detection of molecules and mechanisms affecting the malignant phenotype of gastric cancer cells may contribute to the identification of biomarkers for metastasis and recurrence, and such molecules may serve as targets of therapy. For this purpose, in this study transcriptome analysis was performed using surgically resected specimens from patients with gastric cancer with synchronous metastasis. We identified homeobox C10 (HOXC10) as the most highly expressed gene in gastric cancer tissues compared with the adjacent noncancerous gastric mucosa. Methods: Polymerase chain reaction (PCR) array analysis was performed to identify genes coordinately expressed with HOXC10. The effects of inhibiting HOXC10 on malignant phenotype was evaluated using HOXC10 knockout gastric cancer cell lines, and antibody array analysis was performed to assess the effect of HOXC10 knockout on intracellular signaling. We used a mouse subcutaneous xenograft model to evaluate the tumorigenicity. HOXC10 expression was determined in gastric cancer tissues acquired from 300 patients with gastric cancer. Results: PCR array analysis revealed that the levels of HOXC10 messenger RNA positively correlated with those of FGFBP1 and SOX10. The phosphorylation of ERK1/2 was decreased in HOXC10 knockout cells. HOXC10 knockout significantly suppressed proliferation by increasing apoptosis and reducing the migration and invasiveness of gastric cancer cells. Mouse xenograft models revealed that the tumorigenicity of HOXC10 knockout cells was attenuated compared with the parental cells. The relatively high expression levels of HOXC10 in gastric cancer tissues were significantly associated with hepatic and peritoneal recurrence, as well as worse prognosis. Conclusions: Our results indicated that HOXC10 enhances the malignant phenotype of gastric cancer cells. The expression levels of HOXC10 may therefore serve as a prognostic biomarker and the products of HOXC10 may provide targets of therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Femoral Fracture in Primary Soft-Tissue Sarcoma of the Thigh and Groin Treated with Intensity-Modulated Radiation Therapy: Observed versus Expected Risk

Purpose: This study was designed to compare the observed risk of femoral fracture in primary soft-tissue sarcoma (STS) of the thigh/groin treated with intensity-modulated radiation therapy (IMRT) to expected risk calculated using the Princess Margaret Hospital (PMH) nomogram. Methods: Expected femoral fracture risk was calculated by using the PMH nomogram. Cumulative risk of fracture was estimated by using Kaplan–Meier statistics. Prognostic factors were assessed with univariate and multivariate analysis using Cox’s stepwise regression. Results: Between February 2002 and December 2010, 92 consecutive eligible patients were assessed. Median follow-up was 73 months (106 months in surviving patients). IMRT was delivered preoperatively (50 Gy) in 13 (14%) patients and postoperatively in 79 (86%) patients (median dose, 63 Gy; range, 59.4–66.6 Gy). The observed crude risk of fractures was 6.5% compared with 25.6% expected risk from the nomogram; the cumulative risk of fracture using IMRT at 5 years was 6.7% (95% CI 2.8–16.0%). The median time to fracture was 23 months (range, 6.9–88.6). Significant predictors of fracture on univariate analysis were age ≥ 60 years (p = 0.03), tumor location in the anterior thigh (p = 0.008), and periosteal stripping to > 20 cm (p < 0.0001). On multivariate analysis, age ≥ 60 years and periosteal stripping > 20 cm retained significance (p = 0.04 and p = 0.009, respectively). Conclusions: In this study, the cumulative risk of femur fracture in patients treated with IMRT (6.7%) is less than the expected risk using the PMH nomogram (25.6%). Established predictors of femur fracture, such as gender, tumor size, and dose of RT, seem to have less impact on fracture risk when using IMRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Predicting Outcome in Mammary Phyllodes Tumors: Relevance of Clinicopathological Features

Background: Phyllodes tumors (PTs) of the breast are uncommon fibroepithelial neoplasms. Most behave in a benign fashion but they also have the potential to recur locally or to metastasize. Methods: In the current study involving 290 PTs (181 benign, 76 borderline, and 33 malignant) from three hospitals over an 11-year period, we assessed the relationship between histologic parameters (including histologic features affecting grade and surgical margin status), postoperative adjuvant treatment, and local recurrences and distant metastases. Results: An involved surgical margin was the only factor associated with increased risk of local recurrences (hazard ratio [HR] 4.673, p = 0.003), but not for distant metastases. For local recurrences, a wider margin did not confer additional benefits. None of the histologic factors were predictive for local recurrences. In contrast, distant metastases were correlated with histologic parameters, particularly an infiltrative border (HR 10.935, p = 0.012) and the presence of necrosis (HR 15.311, p = 0.007). In this series, all local recurrences were found in patients without radiotherapy, regardless of surgical margin status. Conclusion: A negative surgical margin is mandatory for the effective local control of PT recurrence, and a minimal margin clearance may be sufficient. For distant metastases, the inherent characteristics of PTs are important, thus it may be prudent to evaluate additional histologic features, including necrosis, for patients’ prognostication.

62 RADIOLOGY AND NUCLEAR MEDICINE↗