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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 1,207 records · Page 67
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Skeletal muscle mass as a predictor of the response to neo-adjuvant chemotherapy in locally advanced esophageal cancer

Undernutrition and sarcopenia are associated with a higher incidence of chemotherapy-related toxicity and a poor prognosis in several kinds of cancer, but the impact of sarcopenia on the outcomes of chemotherapy for esophageal cancer remains unclear. Thus, the purpose of this retrospective study was to investigate whether sarcopenia affects the efficacy and toxicities of chemotherapy for advanced esophageal cancer patients. Data were collected from 31 esophageal cancer patients who underwent neo-adjuvant chemotherapy followed by surgery. Body composition was assessed at the start of chemotherapy by bioelectrical impedance analysis, and outcomes of chemotherapy were compared between sarcopenic and non-sarcopenic groups. Of the 31 patients, sarcopenia was observed in 16 (51.6%). The incidence of toxicities was not different between the two groups. However, as for pathologic response, a good therapeutic effect (Grade 2 or higher) was more common in the non-sarcopenic group than in the sarcopenic group (53.3% vs. 25.0%). Multivariate analysis showed that sarcopenia was an independent predictor of poor pathological response (odds ratio 8.02; P = 0.037). The results of this study suggest the potential utility of sarcopenia assessment in neoadjuvant patient selection strategies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

MPC-1 expression in myeloma cells is associated with the efficacy of bortezomib therapy

The use of bortezomib in the clinic has significantly improved outcomes for patients with multiple myeloma (MM), even those harboring high-risk cytogenetic abnormalities or those classified in the high-risk category according to the International Staging System (ISS). In this study, we analyzed the association between immunophenotyping on myeloma cells and the clinical outcomes of patients who received bortezomib-based regimens as first-line therapy. Immunophenotypic analysis before bortezomib therapy was performed by flow cytometry, and whether the immunophenotyping results influenced the clinical outcomes of the patients was investigated. Seventy-four newly diagnosed patients with MM were included in this study. We found that the expression of MPC-1 significantly predicted the time to next therapy (TNT), with a longer TNT in the MPC-1 positive group (p = 0.005), whereas it did not affect overall survival (OS; p = 0.773). In addition, we found that CD45-positivity was associated with shorter TNT (p = 0.0432). Following ISS assessment at treatment initiation, patients who were classified as stage I showed a slightly longer OS compared to those at stage II or III; however, these results were not significant (p = 0.0987). Furthermore, multivariate analysis revealed the prognostic significance of MPC-1 expression, as MPC-1-negativity was associated with a worse TNT. The combination of MPC-1 and CD45 status more sensibly predicted the TNT for bortezomib therapy. Our results demonstrate the clinical importance of immunophenotyping on myeloma cells to determine patient prognoses in this era of novel therapeutic agents.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Programmed death-1 receptor (PD-1) and PD-ligand-1 (PD-L1) expression in non-small cell lung cancer and the immune-suppressive effect of anaerobic glycolysis

The microenvironment of a tumor may regulate the anti-tumor immune response. Intratumoral acidosis and hypoxia may suppress lymphocyte proliferation and migration, and this may have important implications in modern immunotherapy. The expression of PD-L1 by cancer cells and of PD-1 by tumor infiltrating lymphocytes (TILs) was assessed in tissue specimens from 98 operable NSCLC patients. Their prognostic role and their association with makers of glycolysis and anaerobic metabolism were assessed. Strong cytoplasmic/membrane PD-L1 expression was noted in 45/98 cases. Intense presence of TILs was noted in 42/98 cases (high TIL-score), and intense presence of PD-1 expressing TILs (high PIL-score) in 17/98 cases. PD-L1 expression was directly correlated with high PIL-score (p = 0.005). A significant inverse relationship was found between lactate dehydrogenase LDH5 expression and PIL-score (p = 0.008). Similarly, low PIL-score was significantly linked with high-hexokinase HXKII and monocarboxylate transporter MCT2 expression (p < 0.04). Cases with both intense TIL-score and PIL-score had significantly better survival (p < 0.05). For patients with high TIL-score or high PIL-score, PD-L1 overexpression defined significantly poorer survival (p = 0.01 and p = 0.03, respectively). In multivariate analysis, stage (p = 0.002, HR 3.33, 95%CI 1.4–4.5) and TIL-score (p = 0.02, HR 2.12, 95%CI 1.1–4.0) were independent predictive variables of death events. Given the low specificity of PD-L1 as a biomarker for anti-PD-1/PD-L1 immunotherapy, a combined assessment of TIL, PD-L1, PD-1, and LDH5 provides a tool for an immunological/metabolic classification of NSCLC tumors, with a different prognosis and different expected response to anti-PD-1/PD-L1 immunotherapy, which should be considered in relevant clinical trials.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Impact of cardiac reverse remodeling after cardiac resynchronization therapy assessed by myocardial perfusion imaging on ventricular arrhythmia

Background: Although cardiac resynchronization therapy (CRT) has been a useful treatment of heart failure, patients with CRT are still in risk of sudden cardiac death due to ventricular arrhythmia. The aim of this study was to investigate the impact of cardiac reverse remodeling after CRT on the prevalence of ventricular tachycardia or fibrillation (VT/VF). Methods and Results: Forty-one heart failure patients (26 men, age 66 ± 10 years), who were implanted with CRT for at least 12 months, were enrolled. All patients received myocardial perfusion imaging (MPI) under CRT pacing to evaluate left ventricle (LV) function, dyssynchrony, and scar. VT/VF episodes during the follow-up period after MPI were recorded by the CRT devices. Sixteen patients (N = 16/41, 39%) were found to have VT/VF. Multivariate Cox regression analysis and receiver operating characteristic curve analysis showed that five risk factors were significant predictors of VT/VF, including increased left ventricle ejection fraction (LVEF) by ≤7% after CRT, low LVEF after CRT (≤30%), change of intrinsic QRS duration (iQRSd) by ≤7 ms, wide iQRSd after CRT (≥121 ms), and high systolic dyssynchrony after CRT (phase standard deviation ≥45.6°). For those patients with all of the 5 risk factors, 85.7% or more developed VT/VF. Conclusions: The characteristics of cardiac reverse remodeling after CRT as assessed by MPI are associated with the prevalence of ventricular arrhythmia.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Assessment of left ventricular contraction patterns using gated SPECT MPI to predict cardiac resynchronization therapy response

Background: The U-shaped left ventricular (LV) contraction pattern, identified by MRI or echocardiography, is associated with improved CRT response. Gated SPECT MPI can measure both myocardial viability and mechanical dyssynchrony in a single scan. The aim of this study is to examine the relationship of the LV contraction pattern and the response of CRT in patients with left bundle branch block (LBBB). Methods: Fifty-eight patients who met CRT guidelines and who had pre-CRT MPI were enrolled. Myocardial segments with tracer uptake < 50% of maximum were considered as scar. The LV contraction pattern was considered as U-shaped or non-U-shaped (U-shaped has a block line in the direction of contraction propagation). CRT response was defined as an increase in left ventricular ejection fraction ≥ 5% after 6-month follow-up. Results: Twenty-eight patients (48%) had a U-shaped contraction pattern and thirty patients (52%) had a non-U-shaped contraction pattern. The U-shaped group showed a significantly higher response rate than the non-U-shaped group (90% vs. 57%; P = 0.005). By univariate and multivariate logistic regression analysis, the U-shaped pattern was an independent predictor of CRT response. Conclusion: Non-invasive gated SPECT MPI can characterize LV mechanical contraction patterns. A U-shaped contraction pattern identified is associated with improved CRT response. This may prove useful for improved patient selection for CRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Complete revascularization determined by myocardial perfusion imaging could improve the outcomes of patients with stable coronary artery disease, compared with incomplete revascularization and no revascularization

Objectives: To compare the outcomes among patients treated by complete coronary revascularization (CCR) or incomplete coronary revascularization (ICR) and no coronary revascularization (NCR) by myocardial perfusion imaging (MPI), as well as to evaluate the impact of severity of ischemia on patients with coronary artery disease (CAD) by different therapy strategies. Background: Using myocardial ischemia severity determined by MPI guiding treatment strategies for CAD patients still lacks strong clinical evidences. Methods: Consecutive patients (N = 286) underwent clinical stress-rest SPECT MPI and were retrospectively followed-up. For assessment of outcome of treatment, all patients were classified into three groups (CCR, ICR, and NCR), and further divided into two subgroups as mild ischemia (< 10% ischemic myocardium) and moderate-severe ischemia (≥ 10% ischemic myocardium). All-cause death was defined as the primary endpoint, and the composite of deaths, nonfatal myocardial infarction, and repeat revascularization (MACE) as the secondary endpoint. Results: Two-hundred eighty-six patients were followed-up for 46 ± 21 months. Thirty deaths and 65 MACEs were recorded. Patients treated by revascularization had significantly lower MACE (P < .001) but not mortality (P = .158) than patients treated by NCR. Outcomes of CCR related to mortality rate were greater than ICR and NCR (death: P = .019, MACE: P < .001). In patients with moderate-severe ischemia, CCR showed improved outcomes than ICR and NCR (death: P = .034; and MACE: P < .001). In patients with mild ischemia, the outcomes of CCR, ICR, and NCR had no significant difference (P > .05). Multivariate regression Cox analysis revealed that summed difference score [death: HR 1.09 (1.03, 1.15), P = .004] was an independent risk factor and CCR was an independent negative predictor [death: HR 0.31 (0.12, 0.81), P = .017; MACE: HR 0.30 (0.16, 0.57), P < .001]. Conclusions: Outcomes of patients treated by CCR were most likely more promising in comparison with treatment of ICR and NCR, especially when patients had over 10% ischemic myocardium.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Left ventricular mechanical dyssynchrony assessment in long-standing type II diabetes mellitus patients with normal gated SPECT-MPI

Background: Assessment of left ventricular mechanical dyssynchrony (LVMD) using phase analysis of gated SPECT-MPI is well established. However, there is little information about the influence of diabetes mellitus on phase analysis. The present work was to evaluate the LVMD in longstanding type II diabetes mellitus (DM) patients with normal gated SPECT-MPI. Methods: Retrospective analysis of 146 (86 type II diabetics for > 5 years’ duration and 60 nondiabetics) consecutive patients with normal gated SPECT-MPI and adequate LVEF was done. Sixty age- and sex-matched nondiabetic served as control. LVMD was determined from the cutoff values (> mean + 2 SD) observed for phase standard deviation (PSD) and phase bandwidth (PBW) from the control subjects. Multivariate logistic regression analysis was applied to assess the correlation between various confounding factors. Results: LVMD was detected in 24 (28%) diabetic patients with the pre-defined cut-off values for PSD (> 10.8) and PBW (> 35.6) derived from the controls. Hyperlipidemia, overweight/obesity, duration of DM and its long-term complications were independently associated with LVMD, with long-term complications being the highest risk factor (OR 28.00; P < .001). Conclusion: The evolution time of the patients with type II diabetes mellitus affects the left ventricular mechanical synchrony.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

MALDI Orbitrap Mass Spectrometry Profiling of Dysregulated Sulfoglycosphingolipids in Renal Cell Carcinoma Tissues

Matrix-assisted laser desorption/ionization coupled with Orbitrap mass spectrometry (MALDI-Orbitrap-MS) is used for the clinical study of patients with renal cell carcinoma (RCC), as the most common type of kidney cancer. Significant changes in sulfoglycosphingolipid abundances between tumor and autologous normal kidney tissues are observed. First, sulfoglycosphingolipid species in studied RCC samples are identified using high mass accuracy full scan and tandem mass spectra. Subsequently, optimization, method validation, and statistical evaluation of MALDI-MS data for 158 tissues of 80 patients are discussed. More than 120 sulfoglycosphingolipids containing one to five hexosyl units are identified in human RCC samples based on the systematic study of their fragmentation behavior. Many of them are recorded here for the first time. Multivariate data analysis (MDA) methods, i.e., unsupervised principal component analysis (PCA) and supervised orthogonal partial least square discriminant analysis (OPLS-DA), are used for the visualization of differences between normal and tumor samples to reveal the most up- and downregulated lipids in tumor tissues. Obtained results are closely correlated with MALDI mass spectrometry imaging (MSI) and histologic staining. Important steps of the present MALDI-Orbitrap-MS approach are also discussed, such as the selection of best matrix, correct normalization, validation for semiquantitative study, and problems with possible isobaric interferences on closed masses in full scan mass spectra. .

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2019

Surrogate Model Selection for Design Space Approximation And Surrogatebased Optimization

Surrogate models are used to map input data to output data when the actual relationship between the two is unknown or computationally expensive to evaluate for sensitivity analysis, uncertainty propagation and surrogate based optimization. This work evaluates the performance of eight surrogate modeling techniques for design space approximation and surrogate based optimization applications over a set of generated datasets with known characteristics. With this work, we aim to provide general rules for selecting an appropriate surrogate model form solely based on the characteristics of the data being modeled. Furthermore, the computational experiments revealed that, in general, multivariate adaptive regression spline models (MARS) and single hidden layer feed forward neural networks (ANN) yielded the most accurate predictions over the design space while Random Forest (RF) models most reliably identified the locations of the optimums when used for surrogate-based optimization.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2025

Uncertainty quantification of a physics-informed model based on sparse identification of a Thermal Energy Distribution System

Integrated energy systems (IES)s are crucial for enhancing the economy and efficiency of power generation sources (e.g., nuclear energy) necessary to unleash American energy dominance. These systems can be integrated with thermal energy storage (TES) and intermittent renewable energies to optimize overall energy use, peak-load regulation, and demand-side responses. However, the stabilization of energy generation, transport, and utilization introduces operational complexities that exceed the challenges of managing each sub-component individually. Currently, though IESs rely on human operators for efficiency and stability, reducing human error risk and enhancing performance through automation is highly desirable. Recent advances at Idaho National Laboratory have demonstrated successful control of the Thermal Energy Distributed System (TEDS). However, the automatic control system depends on a deterministic Sparse Identification of Nonlinear Dynamics with Control (SINDyC) model, which are trained based on simulation data from physics-based simulations. Because of uncertainties in physics-based simulation, SINDyC model results in large discrepancies against experimental data and cannot be reliably used in automatic control. In this paper, we present an innovative approach to address these discrepancies by quantifying uncertainties and developing a more robust model. We first generated trajectories by using first-principles physics codes to encapsulate the experiment. Next, we trained thousands of models by randomly sampling these trajectories. We then collapsed all those models into one probabilistic SINDyC by fitting a multivariate Gaussian distribution onto the resulting coefficient’s distribution. Despite its simplicity, our approach successfully produced 95% confidence intervals that captured the experimental trajectories. It even did so with a higher probability and better U-pooling score across six of the seven relevant quantities of interest (QoIs), as compared to other classical approaches. In conclusion, ongoing research is focusing on generating new experimental trajectories to validate this approach, and on employing Bayesian calibration to refine parametric uncertainties and guide future model development efforts.

22 - GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2018

Disordered crystals from first principles I: Quantifying the configuration space

This work represents the first chapter of a project on the foundations of first-principle calculations of the electron transport in crystals at finite temperatures. We are interested in the range of temperatures, where most electronic components operate, that is, room temperature and above. The aim is a predictive first-principle formalism that combines ab-initio molecular dynamics and a finite-temperature Kubo-formula for homogeneous thermodynamic phases. The input for this formula is the ergodic dynamical system (Ω,G,dP) defining the thermodynamic crystalline phase, where Ω is the configuration space for the atomic degrees of freedom, G is the space group acting on Ω and dP is the ergodic Gibbs measure relative to the G-action. The present work develops an algorithmic method for quantifying (Ω,G,dP) from first principles. Using the silicon crystal as a working example, we find the Gibbs measure to be extremely well characterized by a multivariate normal distribution, which can be quantified using a small number of parameters. The latter are computed at various temperatures and communicated in the form of a table. Using this table, one can generate large and accurate thermally-disordered atomic configurations to serve, for example, as input for subsequent simulations of the electronic degrees of freedom.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2013

{sup 1}H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis

Highlights: •Twenty ulcerative colitis patients and nineteen healthy controls were enrolled. •Increased 3-hydroxybutyrate, glucose, phenylalanine, and decreased lipid were found. •We report early stage diagnosis of ulcerative colitis using NMR-based metabolomics. -- Abstract: Ulcerative colitis (UC) has seriously impaired the health of citizens. Accurate diagnosis of UC at an early stage is crucial to improve the efficiency of treatment and prognosis. In this study, proton nuclear magnetic resonance ({sup 1}H NMR)-based metabolomic analysis was performed on serum samples collected from active UC patients (n = 20) and healthy controls (n = 19), respectively. The obtained spectral profiles were subjected to multivariate data analysis. Our results showed that consistent metabolic alterations were present between the two groups. Compared to healthy controls, UC patients displayed increased 3-hydroxybutyrate, β-glucose, α-glucose, and phenylalanine, but decreased lipid in serum. These findings highlight the possibilities of NMR-based metabolomics as a non-invasive diagnostic tool for UC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma

Highlights: • FGFR4 is significantly related with N stage in IHCC, with T stage and TNM stage in PHCC. • FGFR4 is an independent prognostic factor in IHCC and PHCC. • FGFR4 promotes proliferation, invasion and EMT in cholangiocarinoma cell lines. • Inhibitor AP24354 can decrease proliferation, invasion and induce apoptosis of CCA. - Abstract: Fibroblast growth factor receptor 4 (FGFR4) is related to poor prognosis of several cancers, but the correlation between FGFR4 expression and cholangiocarcinoma (CCA) has not been well elucidated. We investigated the expression of FGFR4 in 83 intrahepatic cholangiocarcinomas (IHCCs), 75 perihilar cholangiocarcinomas (PHCCs) and 41 distal cholangiocarcinomas (DCCs) by immunohistochemistry (IHC), and subsequently evaluated association of FGFR4 with clinicopathologic parameters and survival rate. The rate of FGFR4 higher expression was 61.4% (51/83) in IHCCs, 53.3% (40/75) in PHCCs and 56.1% (23/41) in DCCs. FGFR4 expression was significantly related to poor prognosis of IHCC (P = 0.002) and PHCC (P = 0.019) with univariate analysis, and also identified as an independent prognostic factor in IHCC (P = 0.045) and PHCC (P = 0.049) with multivariate analysis. Additionally, with functional assays in vitro, we found FGFR4 can induce proliferation, invasion and epithelial–mesenchymal transition (EMT) of CCA cell lines with FGF19 stimulation. Moreover, FGFR4 inhibitor AP24354 can suppress proliferation, invasion and induce apoptosis of CCA cells. In conclusion, FGFR4 expression can be identified as a significant independent prognostic biomarker of IHCC and PHCC. FGFR4 played a pivotal role in proliferation, invasion and EMT of CCA. FGFR4 inhibitor can suppress proliferation, invasion and induce apoptosis of CCA, indicating that FGFR4 may act as a potential therapeutic target.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in colorectal cancer

The THO complex 1 (Thoc1) is a nuclear matrix protein playing vital roles in transcription elongation and mRNA export. Recently, aberrant expression of Thoc1 has been reported in an increasing array of tumor types. However, the clinical significance of Thoc1 expression in colorectal cancer (CRC) is still unknown. The present study aimed to characterize the expression of Thoc1 in human CRC and evaluate its clinical significance. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses showed that the mRNA and protein expression of Thoc1 in CRC specimens was significantly higher than that in adjacent normal colon mucosae. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of Thoc1 in 185 archived paraffin-embedded CRC specimens. Statistical analyses revealed that high levels of Thoc1 expression were associated with the clinical stages and tumor differentiation. CRC patients with high levels of Thoc1 expression had poorer overall-survival and disease-free survival, whereas those with lower levels of Thoc1 expression survived longer. Furthermore, multivariate Cox regression analyses demonstrated that Thoc1 expression remained an independent prognostic factor for increased disease recurrence and decreased survival. Our results suggest for the first time that Thoc1 is involved in the development and progression of CRC, and elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in CRC. These findings may prove to be clinically useful for developing a new therapeutic target of CRC treatment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

TROP2 overexpression promotes proliferation and invasion of lung adenocarcinoma cells

Recent studies suggest that the human trophoblast cell-surface antigen TROP2 is highly expressed in a number of tumours and is correlated with poor prognosis. However, its role in non-small cell lung carcinoma (NSCLC) remains largely unknown. Here we examined TROP2 expression by immunohistochemistry in a series of 68 patients with adenocarcinoma (ADC). We found significantly elevated TROP2 expression in ADC tissues compared with normal lung tissues (P < 0.05), and TROP2 overexpression was significantly associated with TNM (tumour, node, metastasis) stage (P = 0.012), lymph node metastasis (P = 0.038), and histologic grade (P = 0.013). Kaplan–Meier survival analysis revealed that high TROP2 expression correlated with poor prognosis (P = 0.046). Multivariate analysis revealed that TROP2 expression was an independent prognostic marker for overall survival of ADC patients. Moreover, TROP2 overexpression enhanced cell proliferation, migration, and invasion in the NSCLC cell line A549, whereas knockdown of TROP2 induced apoptosis and impaired proliferation, migration, and invasion in the PC-9 cells. Altogether, our data suggest that TROP2 plays an important role in promoting ADC and may represent a novel prognostic biomarker and therapeutic target for the disease.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

miR-625 suppresses cell proliferation and migration by targeting HMGA1 in breast cancer

Dysregulation of microRNA contributes to the high incidence and mortality of breast cancer. Here, we show that miR-625 was frequently down-regulated in breast cancer. Decrease of miR-625 was closely associated with estrogen receptor (P = 0.004), human epidermal growth factor receptor 2 (P = 0.003) and clinical stage (P = 0.001). Kaplan–Meier and multivariate analyses indicated miR-625 as an independent factor for unfavorable prognosis (hazard ratio = 2.654, 95% confident interval: 1.300–5.382, P = 0.007). Re-expression of miR-625 impeded, whereas knockdown of miR-625 enhanced cell viabilities and migration abilities in breast cancer cells. HMGA1 was confirmed as a direct target of miR-625. The expressions of HMGA1 mRNA and protein were induced by miR-625 mimics, but reduced by miR-625 inhibitor. Re-introduction of HMGA1 in cells expressing miR-625 distinctly abrogated miR-625-mediated inhibition of cell growth. Taken together, our data demonstrate that miR-625 suppresses cell proliferation and migration by targeting HMGA1 and suggest miR-625 as a promising prognostic biomarker and a potential therapeutic target for breast cancer. - Highlights: • miR-625 expression was significantly decreased in breast cancer. • Decrease of miR-625 was associated with poor clinical outcomes and unfavorable overall survival. • miR-625 overexpression inhibits cell proliferation and migration in vitro. • miR-625 directly targets and suppresses the expression of HMGA1.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Synchrotron FTIR microspectroscopy reveals early adipogenic differentiation of human mesenchymal stem cells at single-cell level

Human mesenchymal stem cells (hMSCs) have been used as an ideal in vitro model to study human adipogenesis. However, little knowledge of the early stage differentiation greatly hinders our understanding on the mechanism of the adipogenesis processes. In this study, synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy was applied to track the global structural and compositional changes of lipids, proteins and nucleic acids inside individual hMSCs along the time course. The multivariate analysis of the SR-FTIR spectra distinguished the dynamic and significant changes of the lipids and nucleic acid at early differentiation stage. Importantly, changes of lipid structure during early days (Day 1–3) of differentiation might serve as a potential biomarker in identifying the state in early differentiation at single cell level. These results proved that SR-FTIR is a powerful tool to study the stem cell fate determination and early lipogenesis events. - Highlights: • Molecular events occur in the early adipogenic differentiation stage of hMSCs are studied by SR-FTIR. • SR-FTIR data suggest that lipids may play an important role in hMSCs determination. • As potential biomarkers, lipids peaks can identify the state of cell in early differentiation stage at single-cell level.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

The up-regulation of long non-coding RNA CCAT2 indicates a poor prognosis for prostate cancer and promotes metastasis by affecting epithelial-mesenchymal transition

Recently, long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in human cancer biology. LncRNA CCAT2 is a novel identified lncRNA that was previously reported to be up-regulated in different cancers, however, its role in prostate cancer remains unclear. The aim of this study was to investigate the expression and role of lncRNA CCAT2 in prostate cancer. The expression levels of lncRNA CCAT2 in PCa tissues and cell lines (DU145 and 22RV1) were evaluated by quantitative real-time PCR (qRT-PCR), and its association with prognosis of patients was analyzed by statistical analysis. Furthermore, the effect of CCAT2 on proliferation, migration, and invasion was studied in PCa cells. We found that the expression level of CCAT2 was higher in PCa tissues and cells compared to adjacent non-tumor tissues and normal prostate stromal immortalized cells WPMY-1. Kaplan-Meier survival analysis revealed that patients with high CCAT2 expression level had poorer overall survival and progression-free survival than those with low CCAT2 expression. Furthermore, multivariate analysis showed that the status of CCAT2 expression was an independent prognostic indicator for this disease. We also found that knockdown of CCAT2 could inhibit cell growth, migration, and invasion in vitro. In addition, knockdown of CCAT2 stimulated epithelial-mesenchymal transition (EMT) through abrogating N-cadherin, vimentin expression and intensifing the expression levels of E-cadherin. In conclusion, our data suggested that lncRNA CCAT2 was a novel molecule involved in PCa progression, which provided a potential prognostic biomarker and therapeutic target for new therapies in patients with prostate cancer. - Highlights: • LncRNA CCAT2 is identified with overexpression in prostate cancer tissues and cell lines. • High expression of lncRNA CCAT2 can be an independent prognostic factor for overall survival and progression-free survival. • Knockdown of lncRNA CCAT2 can inhibit cell growth, migration, and invasion in vitro study. • Knockdown of lncRNA CCAT2 stimulates metastasis of prostate cancer cell through regulating EMT-associated gene expression including N-cadherin, Vimentin and E-cadherin.

60 APPLIED LIFE SCIENCES↗