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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 865 records · Page 48
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

CART peptide activates the Nrf2/HO-1 antioxidant pathway and protects hippocampal neurons in a rat model of Alzheimer's disease

Highlights: • CART peptide reduced the accumulation of Aβ in the hippocampus of AD rats. • CART peptide improved the cognitive function of AD rats. • CART peptide attenuated the oxidative stress damage in the hippocampus of AD rats. • CART activated the Nrf2/HO-1 pathway to exert antioxidation. • CART inhibit the apoptosis of hippocampal neurons. The accumulation of amyloid-beta (Aβ) and oxidative stress damage in the brain are recognized as early features of Alzheimer's disease (AD). The cocaine- and amphetamine-regulated transcript (CART) peptide may possibly play an antioxidative role in neurons. The aim of this study was to investigate the potential antioxidant mechanism of CART peptide in a rat model of AD. We microinjected of Aβ{sub 1-42} (2μl/4μg/hemisphere) into rat hippocampus to set a rat model of AD. A pre-microinjection of CART peptide (1μl/0.02μg/hemisphere) into rat hippocampus was administered for five consecutive days before Aβ{sub 1-42} treatment. We found that Aβ{sub 1-42} microinjection led to reduction of endogenous CART level in rat hippocampus. CART pretreatment improved the spatial memory and locomotor ability of AD rats. CART peptide decreased the Aβ{sub 1-42} and Aβ production-associated enzyme BACE1 levels. Moreover, CART peptide attenuated the oxidative stress damage with a concrete manifestation of increased MDA as well as decreased T-SOD, GSH and ATP levels in the hippocampus of Aβ{sub 1-42}-treated rat, which may be causatively implicated the activating of Nrf2/HO-1 signaling pathway. Furthermore, CART peptide attenuated neuronal apoptosis with decreased Bax, caspase-9 and caspase-3 levels and increased Bcl-2 level in rat hippocampus. Our results therefore indicate that CART peptide could serve as an antioxidant in early therapy for AD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Beta catenin is regulated by its subcellular distribution and mutant huntingtin status in Huntington's disease cell STHdhQ111/HdhQ111

Highlights: • Mutant Htt gain-of-function in Q111 cell increases miR-214 & decreases beta catenin. • Mutant Htt function in Q111 cell is aggregate independent. • Aggregate forming mutant Htt construct 83Q-DsRed increases beta catenin in Q7 cell. • Cytosolic localization of beta catenin in Q111 cell aids to its phosphorylation. Dysregulation of gene expression at RNA and protein level is a hallmark of Huntington's disease (HD). Altered levels of microRNAs and beta catenin in HD were studied earlier; however, any direct involvement of full length, basally-expressing mutant huntingtin (Htt) remained to be elusive. Here we reported that the gain-of-function mutation of full-length basally-expressing Htt in HD cell Q111 (STHdhQ111/HdhQ111) upregulated microRNA-214 and decreased beta catenin & its transcriptional activity in an aggregate-independent manner. The result was quite opposite of the function of aggregate-forming mutant Htt fragment 83Q-DsRed. Here, we also reported an elevated level of beta catenin phosphorylation in Q111 cell compared to Q7 cell (SThdhQ7/HdhQ7). We showed that in Q111 cell (compared to Q7), beta catenin was more localized in the cytosol than that of the plasma membrane. This is significant as Gsk3beta phosphorylates beta catenin in the cytosol. Hence, for the first time, our study identified beta catenin localization and mutant Htt status as two key factors of beta catenin regulation in HD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Faecal microRNA as a biomarker of the activity and prognosis of inflammatory bowel diseases

Highlights: • There is a significant difference in faecal miRNA between healthy subjects and IBD. • Faecal miRNAs might indicate the severity of IBD activity and prognosis. • Faecal miRNAs affect the proliferative activities of the gut microbiota. Reasons underlying the individual differences in the clinical manifestations of inflammatory bowel diseases (IBD) and the mechanism by which the host screens the intestinal microbiota remain unclear. The presence of miRNA in faeces might be a potential clue into differences in gut microbiota among these patients. In this study, we analysed the differences in miRNA levels in faecal samples from 117 patients diagnosed with IBD. There was a significant difference in faecal miRNAs between healthy subjects and those with inactive IBD. Further analysis showed that some miRNAs might indicate the severity of IBD activity and prognosis. Sequencing analysis of the 16S RNA V4 region in faecal microbiota in these IBD patients revealed significant differences in the phylogenetic architecture between subjects with active or inactive IBD and between IBD patients and healthy subjects. Finally, in vitro studies showed that these differentially expressed miRNAs have different effects on the proliferative activity of the intestinal microorganisms Fusobacterium nucleatum (Fn), Escherichia coli (E. coli) and segmental filamentous bacteria (SFB). We observed the dynamic uptake of miRNA by these bacteria using flow cytometry. This study reveals a potential link between faecal miRNA, intestinal microbiota, IBD activity and prognosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Lung tissue destruction by proteinase 3 and cathepsin G mediated elastin degradation is elevated in chronic obstructive pulmonary disease

Highlights: • Identification of elastin fragments specifically generated by cathepsin G (CG) and proteinase 3 (PR3) respectively. • Development of the two assays EL-CG and ELP-3 which are specific for the CG or PR3 degraded elastin neo-epitopes. • Significant higher concentrations of EL-CG and ELP-3 in patients diagnosed with COPD compared to healthy subjects. Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansion and recoil of the alveoli during breathing. The lung extracellular matrix is vulnerable to pathological structural changes upon upregulation of serine proteases, including cathepsin G (CG) and proteinase 3 (PR3). In this study, we explored the diagnostic features of elastin neo-epitopes generated by CG and PR3. Two novel competitive enzyme-linked immunosorbent assays (ELISA) measuring CG and PR3 generated elastin fragments (EL-CG and ELP-3 respectively) were developed for assessment in serum. Both assays were technically robust and biologically validated in serum from patients with COPD. Serological levels of both elastin fragments were significantly elevated in patients with COPD compared to healthy controls. These data suggest that EL-CG and ELP-3 may serve as plausible biologic markers of destructive changes in COPD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Salusin-β mediate neuroprotective effects for Parkinson's disease

Neuropeptides, small peptides found in many mammalian brain, play key roles in communicating with each other to modulate neuronal activity. Here, we reported that endogenous neuropeptide salusin-β has neuroprotective effects on the midbrain dopamine neurons and can be used as an effective therapeutic treatment for Parkinson's disease (PD). We found that the MrgprA1 receptor mediates the neuroprotective effects of salusin-β on the midbrain dopamine neurons. Importantly, intranasal administration of salusin-β in a PD mouse model show the neuroprotection of dopaminergic neurons and increased the survival of midbrain dopamine neurons. Furthermore, inhibition of the salusin-β receptor, MrgprA1, abolished the neuroprotective effects induced by salusin-β. Taken together, these results demonstrate the novel role of salusin-β in the central nervous system and salusin-β can be used as a novel therapeutic to effectively treat PD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Interleukin-22 receptor 1 upregulation and activation in hypoxic endothelial cells improves perfusion recovery in experimental peripheral arterial disease

Highlights: • Interleukin-22 and its receptor (IL22R1) are upregulated after hindlimb ischemia. • Loss of IL-22 by mAb reduced angiogenesis. • IL-22 overexpression improved angiogenesis after hindlimb ischemia. Inflammation induced by muscle ischemia is involved in tissue repair and perfusion recovery in peripheral arterial disease (PAD) patients. Interleukin (IL)-22 is an inflammatory cytokine discovered in recent years and shows versatile functions; however, its role in PAD remains unknown. Here, we test whether IL-22 and its receptors are involved in angiogenesis in experimental PAD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Structural basis for specific calcium binding by the polycystic-kidney-disease domain of Vibrio anguillarum protease Epp

Highlights: • Crystal structure of the first PKD domain of Vibrio anguillarum Epp is determined. • Epp-PKD1 contains a pentagonal-bipyramidal Ca{sup 2+}-binding site. • Specific binding to Ca{sup 2+} increases conformational stability of Epp-PKD1. • Epp-PKD1 differs in the oligomeric state and Ca{sup 2+} coordination from the homologous PrtV-PKD1. Extracellular proteases are often produced as pre-pro-enzyme and then undergo multiple processing steps to mature into the active form. The protease Epp, a virulent factor of Vibrio anguillarum, belongs to this family. Its maturation might be regulated by Ca{sup 2+} via its polycystic kidney disease (PKD) domain, but the molecular mechanism is unknown. Herein, we report the crystal structure of the first PKD domain from V. anguillarum Epp (Epp-PKD1) and its specific Ca{sup 2+}-binding capacity. Epp-PKD1 exists as a monomer, consisting of seven β-strands which form two β-sheets stacking with each other. One Ca{sup 2+} is bound by the residues Asn3, Gln4, Asp27, Asp29, Asp68 and a water molecule with a pentagonal bipyramidal geometry. Incubating the apo Epp-PKD1 with Ca{sup 2+} but not Mg{sup 2+}, Mn{sup 2+}, or Zn{sup 2+}, enhances the thermal and chemical stability of Epp-PKD1, indicating its specific binding to Ca{sup 2+}. Epp-PKD1 shares high similarity in both sequence and overall structure with that of Vibrio cholerae PrtV, a homologous protease of Epp, however, they differ in the oligomeric state and local structure at the Ca{sup 2+}-binding site, suggesting maturation of PrtV and Epp might be differently regulated by Ca{sup 2+}. Likely, proteases may take advantage of the structural diversity in PKD domains to tune their Ca{sup 2+}-regulated maturation process.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Liraglutide protects non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in a mouse model induced by high-fat diet

Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue that has recently become the first-line treatment for type 2 diabetes mellitus (T2DM), has also been reported to decrease fatty degeneration of the liver. The purpose of this study is to explore whether liraglutide improves high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) in mice through inhibiting the NLRP3 inflammasome in the liver. After daily intraperitoneal injection of liraglutide (0.6 mg/kg body weight) for four weeks, the liver, liver/body weight, serum levels of ALT, AST, total cholesterol, triglycerides and LDL were significantly decreased in a high-fat diet-induced NAFLD mouse model. The hepatic steatosis among sections of H&E and Oil Red O staining was also markedly reduced after treatment with liraglutide. The expressions of NLRP3 inflammasome components (including NLRP3, ASC, and caspase-1) in the liver of mice after treatment with liraglutide were decreased substantially. In vitro studies found that the mitochondrial dysfunction in Kupffer cells induced by palmitic acid was attenuated, and the protein levels of NLRP3, ASC and caspase-1 were also decrease markedly. These results demonstrate that liraglutide was able to alleviate high-fat diet-induced hepatic steatosis via inhibiting NLRP3 inflammasome activation, suggesting that liraglutide is a potent drug that can reverse the pathological hallmarks of NAFLD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The role of retinol-binding protein 4 and its relationship with sex hormones in coronary artery disease

Highlights: • The relationship between RBP4 and sex hormones in CAD. • RBP4 expression is down-regulated in male patients with CAD. • A positive relationship between RBP4 and T in male patients with CAD. • RBP4 is likely a protective factor for CAD among men. The role of retinol-binding protein 4 (RBP4) in patients with coronary artery disease (CAD) with different sexes has not been clearly established. Sex hormones, especially testosterone (T) and estradiol (E2), have been considered to play an important role in CAD. This study aimed to investigate the role of RBP4 and the possible association between RBP4 and T and E2 in CAD. The study included 658 individuals who underwent coronary angiography (CAG); they were assigned to CAD group (n = 440) and controls (n = 218). CAD group was subdivided into three subgroups. Serum RBP4 and T were assayed by enzyme-linked immunosorbent assay. Serum E2 was measured using electrochemiluminescence immunoassay. For men, RBP4 levels were lower in CAD group, especially those with acute myocardial infarction, than in controls (P P r = 0.124, P P = 0.007). In conclusion, RBP4 levels were significantly decreased and positively related with T in men with CAD. Higher RBP4 levels were associated with lower risk of CAD. RBP4 may play a potential protective role for CAD among men.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

IL-10 gene-modified dendritic cells-induced type 1 T regulatory cells inhibit graft-versus-host disease while preserving graft-versus-leukemia effect

To explore the role of type 1 regulatory T (Tr1) cells in allogeneic bone marrow transplantation (allo-BMT), we generated Tr1 cells from naïve CD4{sup +} T cells in donor mice that were subjected to stimulation of recipient interleukin (IL)-10 gene-modified dendritic cells (DCs). In animal models, the severity of graft-versus-host disease (GVHD) in the group co-infused with DC-induced Tr1 cells was markedly milder than that in the groups without infusion of Tr1 cells. Moreover, the co-infusion Tr1 cells significantly prolonged the leukemia-free survival in tumor-bearing mice. Besides, Tr1-induced cells mediated the shift from T helper (Th)1 to Th2 cytokines in allo-BMT recipients. In Conclusions, our findings suggest that IL-10 gene-modified DC-induced Tr1 cells could inhibit GVHD while maintaining Graft-versus-leukemia (GVL) through mediating the shift of Th1/Th2 cytokines in an allo-BMT mice model.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

IFN-γ, IL-17A, or zonulin rapidly increase the permeability of the blood-brain and small intestinal epithelial barriers: Relevance for neuro-inflammatory diseases

Highlights: • Zonulin rapidly (within 60 min) increases the permeability of the IEB and BBB in vitro. • Both IL-17A and IFN-γ enhance the permeability of the BBB and IEB within 1 h. • All three pro-inflammatory mediators rapidly modify IEB TJs, by causing mislocalization of ZO-1, claudin-5, and occludin. • Rapid TJ disassembly by all mediators was accompanied by dramatic depolymerization of the peri-junctional actin cytoskeleton. Breakdown of the blood-brain barrier (BBB) precedes lesion formation in the brains of multiple sclerosis (MS) patients. Since recent data implicate disruption of the small intestinal epithelial barrier (IEB) in the pathogenesis of MS, we hypothesized that the increased permeability of the BBB and IEB are mechanistically linked. Zonulin, a protein produced by small intestine epithelium, can rapidly increase small intestinal permeability. Zonulin blood levels are elevated in MS, but it is unknown whether zonulin can also disrupt the BBB. Increased production of IL-17A and IFN-γ has been implicated in the pathogenesis of MS, epilepsy, and stroke, and these cytokines impact BBB integrity after 24 h. We here report that primary human brain microvascular endothelial cells expressed the EGFR and PAR2 receptors necessary to respond to zonulin, and that zonulin increased BBB permeability to a 40 kDa dextran tracer within 1 h. Moreover, both IL-17A and IFN-γ also rapidly increased BBB and IEB permeability. By using confocal microscopy, we found that exposure of the IEB to zonulin, IFN-γ, or IL-17A in vitro rapidly modified the localization of the TJ proteins, ZO-1, claudin-5, and occludin. TJ disassembly was accompanied by marked depolymerization of the peri-junctional F-actin cytoskeleton. Our data indicate that IFN-γ, IL-17A, or zonulin can increase the permeability of the IEB and BBB rapidly in vitro, by modifying TJs and the underlying actin cytoskeleton. These observations may help clarify how the gut-brain axis mediates the pathogenesis of neuro-inflammatory diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Assessing the use of portable air cleaners for reducing exposure to airborne diseases in a conference room with thermal stratification

The COVID-19 pandemic has highlighted the need for strategies that mitigate the risk of aerosol disease transmission in indoor environments with different ventilation strategies. It is necessary for building operators to be able to estimate and compare the relative impacts of different mitigation strategies to determine suitable strategies for a particular situation. Using a validated CFD model, this study simulates the dispersion of exhaled contaminants in a thermally stratified conference room with overhead heating. The impacts of portable air-cleaners (PACs) on the room airflow and contaminant distribution were evaluated for different PAC locations and flow rates, as well as for different room setups (socially distanced or fully occupied). To obtain a holistic view of a strategy's impacts under different release scenarios, we simultaneously model the steady-state distribution of aerosolized virus contaminants from eight distinct sources in 18 cases for a total of 144 release scenarios. The simulations show that the location of the source, the PAC settings, and the room set-up can impact the average exposure and PAC effectiveness. For this studied case, the PACs reduced the room average exposure by 31%-66% relative to the baseline case. Some occupant locations were shown to have a higher-than-average exposure, particularly those seated near the airflow outlet, and occupants closest to sources tended to see the highest exposure from said source. We found that these PACs were effective at reducing the stratification caused by overhead heating, and also identified at least one sub-optimal location for placing a PAC in this space.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2017

Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis

The pathogenesis of human Ebola virus disease (EVD) is complex. EVD is characterized by high levels of virus replication and dissemination, dysregulated immune responses, extensive virus- and host-mediated tissue damage, and disordered coagulation. To clarify how host responses contribute to EVD pathophysiology, we performed multi-platform ’omics analysis of peripheral blood mononuclear cells and plasma from EVD patients. Our results indicate that EVD molecular signatures overlap with those of sepsis, imply that pancreatic enzymes contribute to tissue damage in fatal EVD, and suggest that Ebola virus infection may induce aberrant neutrophils whose activity could explain hallmarks of fatal EVD. Moreover, integrated biomarker prediction identified putative biomarkers from different data platforms that differentiated survivors and fatalities early after infection. We report this work reveals insight into EVD pathogenesis, suggests an effective approach for biomarker identification, and provides an important community resource for further analysis of human EVD severity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Resource distribution under spatiotemporal uncertainty of disease spread: Stochastic versus robust approaches

We consider the problem of optimizing locations of distribution centers (DCs) and plans for distributing resources such as test kits and vaccines, under spatiotemporal uncertainties of disease spread and demand for the resources. We aim to balance the operational cost (including costs of deploying facilities, shipping, and storage) and quality of service (reflected by demand coverage), while ensuring equity and fairness of resource distribution across multiple populations. We compare a sample-based stochastic programming (SP) approach with a distributionally robust optimization (DRO) approach using a moment-based ambiguity set. Numerical studies are conducted on instances of distributing COVID-19 vaccines in the United States and test kits, to compare SP and DRO models with a deterministic formulation using estimated demand and with the current resource distribution plans implemented in the US. We demonstrate the results over distinct phases of the pandemic to estimate the cost and speed of resource distribution depending on scale and coverage, and show the “demand-driven” properties of the SP and DRO solutions. Furthermore, our results further indicate that if the worst-case unmet demand is prioritized, then the DRO approach is preferred despite of its higher overall cost. Nevertheless, the SP approach can provide an intermediate plan under budgetary restrictions without significant compromises in demand coverage.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2018

DNA damage protection by bulk and nano forms of quercetin in lymphocytes of patients with chronic obstructive pulmonary disease exposed to the food mutagen 2-amino-3-methylimidazo [4,5-f]quinolone (IQ)

Highlights: • In COPD patients and healthy individuals IQ increased DNA damage and frequency of micronuclei. • Induction of catalase indicates a stimulation of the antioxidant enzyme system. • Quercetin significantly reduced oxidative stress in COPD patients and healthy individuals. • The bulk version of quercetin was compared directly to its nano form which caused greater reduction. Chronic obstructive pulmonary disease (COPD) in humans, describes a group of lung conditions characterised by airflow limitation that is poorly reversible. The airflow limitation usually progresses slowly and is related to an abnormal inflammatory response of the lung to toxic particles. COPD is characterised by oxidative stress and an increased risk of lung carcinoma. The 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) is one of a number of mutagenic/carcinogenic heterocyclic amines found mainly in well-cooked meats which are thus part of the regular diet. Antioxidants are very important in order to protect the cells against oxidative damage. The aim of the present study was to assess the effects of IQ on the level of DNA damage and susceptibility to a potent mutagen in peripheral blood cells of COPD patients. DNA damage and the frequency of micronuclei (MNi) were evaluated using the Comet and micronucleus assays, respectively. Differential expressions of both mRNA and protein of the endogenous antioxidant enzyme catalase were evaluated with quantitative polymerase chain reaction (qPCR) and Western blot analysis, respectively. Furthermore, the effect of bulk and nano forms of quercetin and their combination with IQ were examined. Results of the present study clearly demonstrated that MNi frequency in the peripheral blood lymphocytes exhibited a positive correlation with the DNA damage as evident from the different Comet assay parameters. Increase of the endogenous antioxidant catalase also showed there was a stimulation of this enzyme system by IQ. Whereas, the endogenous antioxidant quercetin significantly reduced oxidative stress in COPD patients and healthy individuals.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Metal hypersensitivity in the context of connective tissue disease – An opportunity for practice prevention

Highlights: • Metal implants are association with metal hypersensitivity reactions of the skin. • American Contact Dermatitis Society endorses nickel allergy testing. • Metal dental appliances may trigger cutaneous reactions. • Alternative include stainless steel, fiber composite, plastic, and resin-coated. • Alternatives may improve symptoms of fibromyalgia and connective tissue disease. Metal hypersensitivity reactions (MHR) are not associated with metal containing orthodontic implants unless there is a positive history of dermatitis from a high nickel-release item (piercing post, earring, watch). We wish to present this letter to highlight evidence surrounding orthodontic-related nickel hypersensitivity and to bring to the readers attention current American Contact Dermatitis Society (ACDS) guidelines that endorse the importance of addressing metal hypersensitivity reactions in the setting of implantable dental devices.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2013

Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases

Purpose: We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients. Methods and Materials: We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other). Results: With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004). Conclusions: In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Volume-Based Parameters of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Improve Disease Recurrence Prediction in Postmastectomy Breast Cancer Patients With 1 to 3 Positive Axillary Lymph Nodes

Purpose: To determine whether volume-based parameters on pretreatment {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography in breast cancer patients treated with mastectomy without adjuvant radiation therapy are predictive of recurrence. Methods and Materials: We retrospectively analyzed 93 patients with 1 to 3 positive axillary nodes after surgery, who were studied with {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography for initial staging. We evaluated the relationship between positron emission tomography parameters, including the maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), and clinical outcomes. Results: The median follow-up duration was 45 months. Recurrence was observed in 11 patients. Metabolic tumor volume and TLG were significantly related to tumor size, number of involved nodes, nodal ratio, nuclear grade, estrogen receptor (ER) status, and triple negativity (TN) (all P values were <.05). In receiver operating characteristic curve analysis, MTV and TLG showed better predictive performance than tumor size, ER status, or TN (area under the curve: 0.85, 0.86, 0.79, 0.74, and 0.74, respectively). On multivariate analysis, MTV was an independent prognostic factor of locoregional recurrence-free survival (hazard ratio 34.42, 95% confidence interval 3.94-882.71, P=.0008) and disease-free survival (DFS) (hazard ratio 13.92, 95% confidence interval 2.65-103.78, P=.0018). The 3-year DFS rate was 93.8% for the lower MTV group (<53.1; n=85) and 25.0% for the higher MTV group (≥53.1; n=8; P<.0001, log–rank test). The 3-year DFS rate for patients with both ER-positive status and MTV <53.1 was 98.2%; and for those with ER-negative status and MTV ≥53.1 it was 25.0% (P<.0001). Conclusions: Volume-based parameters improve recurrence prediction in postmastectomy breast cancer patients with 1 to 3 positive nodes. The addition of MTV to ER status or TN has potential benefits to identify a subgroup at higher risk for recurrence.

62 RADIOLOGY AND NUCLEAR MEDICINE↗