tbuckley/cabot-search huggingface dataset:
Biodistribution of gadolinium- and near infrared-labeled human umbilical cord mesenchymal stromal cell-derived exosomes in tumor bearing mice
Authors: Javier Abello, Tuyen Duong Thanh Nguyen, Ramesh Marasini, Santosh Aryal, Mark Louis Weiss
Journal: Theranostics (2019)

We speculate that exosomes derived from human umbilical cord mesenchymal stromal cells (HUC-MSCs) will accumulate within tumors and have the potential for both tumor location or drug delivery.Methods: To determine proof of concept, HUC-MSC exosomes were labeled with an MRI contrast agent, gadolinium, or a near infrared dye.Exosome accumulation within ectopic osteosarcoma tumor-bearing mice was determined by 14.1 T MRI or bioimaging over 24-48 h after injection.In vitro studies examine the accumulation and physiological effect of exosomes on human and mouse osteosarcoma cell lines by MTT assay, confocal microscopy, and flow cytometry.Results: Systemic HUC-MSC exosomes accumulated continuously in tumor over a 24-48 h post-injection period.In contrast, synthetic lipid nanoparticles accumulate in tumor only for the first 3 h post-injection.Conclusion: These results suggest that HUC-MSCs exosomes accumulate within human or mouse osteosarcoma cells in vitro and in vivo over a 24 to 48 h after infusion.
Analysis of cell-free circulating tumor DNA in patients with glioblastoma and other primary brain tumors.
Authors: David Eric Piccioni, Richard Burnham Lanman, Rebecca J Nagy, AmirAli Talasaz, Sandeep C. Pingle, Santosh Kesari
Journal: Journal of Clinical Oncology (2015)

11072 Background: Glioblastoma is the most aggressive type of primary brain tumor with a median survival of 15 months and limited therapy options. Trials of genomically targeted matched therapies for brain tumors requiring recent tissue samples for next generation sequencing (NGS) has limited progress. Recently, a cell-free circulating tumor DNA (ctDNA) NGS panel of 54 genes has become available. We sought to evaluate whether this biopsy-free approach would allow us to interrogate genomic alterations in glioblastoma and other primary brain tumor patients. Methods: Fifty-nine consecutive patients with primary brain tumors were tested prospectively with the Guardant360 ctDNA panel at a CLIA-certified, CAP-accredited clinical laboratory. Single nucleotide variants (SNVs) in 54 genes and copy number variants (CNVs) in 3 genes (EGFR, ERBB2 and MET) are reported quantitatively as the fractional mutant allele concentrations in cell-free DNA and the absolute copy numbers of the genes measured, respectively. The test is sensitive to a single DNA fragment of mutated ctDNA in a 10 ml blood sample and analytic specificity is 99.999%. Results: Average patient age was 53 (range 24-87) and 61% were male. Histopathological subtypes tested were glioblastoma (34), astrocytoma (9), meningioma (6), oligodendroglioma (5), glioma NOS (4) and ependymoma (1). 22 (37.3%) of patients had at least one genomic alteration detected and 4(6.8%) had two genomic alterations detected. SNVs detected included TP53 (7), NOTCH (4), JAK2 (2), and KIT, ERBB2, ALK, APC, ATM, EGFR, AR and HNF1A (1 each). A single copy number amplification in MET was reported. Cell-free DNA was sufficient to complete the sequencing assay in 100% of cases. Conclusions: Contrary to other ctDNA studies where it was postulated that ctDNA would not cross the blood-brain barrier and reach the systemic circulation, we found that over one-third of primary brain tumor patients, including glioblastoma patients, had detectable ctDNA with the Guardant360 assay.
Febrile neutropenia risk factors: A subanalysis of the NEXT study.
Authors: Nicolas Jovenin, Frederic Maloisel, Stephane Leprêtre, Didier Kamioner, Christian Berthou, Helene Albrand
Journal: Journal of Clinical Oncology (2015)

9603 Background: Biosimilar filgrastim is a Granulocyte-Colony Stimulating Factor (G-CSF) licensed for the treatment of neutropenia and febrile neutropenia (FN) induced by myelosuppressive chemotherapy (CT). This subanalysis of the NEXT study attempts to assess the impact of each of the FN risk factors defined in the EORTC guidelines for the use of G-CSF. Methods: NEXT was a prospective, post-marketing, non-interventional, longitudinal, national multicenter study aimed to assess the safety of biosimilar filgrastim in patients (pts) undergoing CT for malignancies (excluding chronic myeloproliferative and myelodysplastic syndrome). FN risk factors defined in the EORTC guidelines were tested by univariate analyzes and were also included in a logistic regression model. A search of the age at which pts in the NEXT study were significantly more likely to have a FN was also conducted. Results: Overall, the NEXT study analyzed 2102 pts but only 1838 pts who received primary prophylaxis (PP) with biosimilar filgrastim were included in this subanalysis. Apart from CT-related FN risk, other factors that may increase the FN risk are in order of importance: age > 65 years, advanced disease, history of prior FN, no antibiotic prophylaxis, no G-CSF use, poor performance and/or nutritional status, female gender, Hemoglobin < 12 g/dL, liver, renal or cardiovascular disease. The analysis of age distribution of pts with FN, who received PP in NEXT study, shows a threshold at 62 years. The only factor statistically significantly associated with FN occurrence among those included in the logistic regression is age > 62 years, confirming the age-related high risk of FN. Indeed, patients older than 62 years are more likely to have a FN than younger patients (OR [95% CI]: 2.1 [1.1 - 4.0]). The limit to 65 years stated in the EORTC guidelines is not significant in our analysis. Conclusions: According with the EORTC guidelines, this analysis confirms the age-related high risk of FN. Caution is required even before the 65 years stated in these guidelines. Indeed, we might wonder about the need for G-CSF prophylactic use in > 62-years patients with a CT-related FN risk 10-20%. Clinical trial information: NCT01574235.
Abstract 13938: Anthropometric Measures vs. CT-Measures of Adiposity and Risk of Incident Heart Failure With Preserved Ejection Fraction: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Vishal N Rao, Di Zhao, Matthew A Allison, Eliseo Guallar, Kavita Sharma, Michael H Criqui, Mary Cushman, Roger S Blumenthal, Erin D Michos
Journal: Circulation (2017)

Background: Obesity is a risk factor for heart failure (HF), particularly HF with preserved ejection fraction (HFpEF), but it is unknown which measures of adiposity are most predictive of HF. Methods: We studied 1,747 MESA participants without baseline cardiovascular disease (CVD) who underwent anthropometric measurements [body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC)], serum insulin and adipokines (leptin, adiponectin) measurements, and an abdominal CT. Subcutaneous and visceral fat area (cm3) were measured from a single CT slice at L2-L3. We used Cox proportional-hazard models to estimate risk of incident overall HF and HFpEF outcomes for each adiposity measure (per 1 SD). Results: Over 9 (SD 2.2) years of follow-up, there were 61 HF and 26 HFpEF events. Participant mean age was 64.6 (SD 9.6) years and 49% were men. All adiposity measures were more strongly associated with HFpEF than overall HF. In models adjusted for demographics and lifestyle factors, anthropometric-mea...
SAT-048-Changes in the intestinal microbiome during probiotic intervention in cirrhosis
Authors: Angela Horvath, Marija Durdevic, Bettina Leber, Katharina di Vora, Florian Rainer, Philipp Douschan, Elisabeth Krones, Walter Spindelboeck, Franziska Durchschein, Gernot Zollner, Rudolf Stauber, Peter Fickert, Philipp Stiegler, Vanessa Stadlbauer
Journal: Journal of Hepatology (2019)
Quest for Tangible Biomarkers for Triple-Negative Breast Cancer
Authors: Dipali Sharma
Journal: Cancer Research (2019)

Abstract Identification of key molecular networks involved in triple-negative breast cancer (TNBC) growth and metastasis will increase our mechanistic understanding of this disease and pave the way for the development of novel therapeutic interventions. The study by Khawaled and colleagues points to a direct antimetastatic function of WW domain–containing oxidoreductase (WWOX) in TNBC and identifies the Myc/miR-146a/fibronectin axis as a molecular mediator of the tumor-suppressive function of WWOX. This information can potentially be used to identify actionable nodes for targeting TNBC, a breast cancer subtype otherwise characterized by the absence of markers. See related article by Khawaled et al., p. 1784
Abstract 10254: Silent Cerebral Lesions After Atrial Fibrillation Ablation Using Different Ablation Technologies
Authors: Thomas Deneke, Karin Nentwich, Joachim Krug, Rainer Schmitt, Georgios Christopoulos, Andreas Muegge, Johannes W Dietrich, Patrick Müller, Sebastian Kerber, Anja Schade
Journal: Circulation (2013)

Silent cerebral lesions (SCL) have been identified on magnetic resonance imaging (MRI) in patients after atrial fibrillation (AF) ablation. SCL represent irreversible cerebral damage, comparative a...
FRI-190-Incidence and predictors of flares after discontinuing nucleos (t) ide analogue therapy in HBeAg negative patients with chronic hepatitis B: Results from the randomized controlled STOP study
Authors: Seng Liem, Scott Fung, David Wong, Colina Yim, Jenny Chen, Seham Noureldin, Jordan Feld, Bettina Hansen, Harry Janssen
Journal: Journal of Hepatology (2019)
THU-482-A human anti-MICA/B antibody boost NK cell responses in hepatocellular carcinoma
Authors: STEFANIA MANTOVANI, Matteo Donadon, Cristiana Soldani, Barbara Franceschini, Roberto Santambrogio, Claudia Cigala, Marcello Maestri, Camillo Porta, Stefania Varchetta, Dalila Mele, Mario Umberto Mondelli, Barbara Oliviero
Journal: Journal of Hepatology (2019)
Genetic variability and clinical presentation of patients with non-small cell lung cancer (NSCLC) harboring <i>MET</i>-amplifications.
Authors: Anna Eisert, Matthias Scheffler, Sebastian Yves Friedrich Michels, Anne Maria Schultheis, Rieke Frank, Katharina Koenig, Sabine Merkelbach-Bruse, Rieke Fischer, Monika Heidi Serke, Yon-Dschun Ko, Ulrich Gerigk, Thomas Geist, Lukas Carl Heukamp, Reinhard Büttner, Juergen Wolf
Journal: Journal of Clinical Oncology (2015)

8088 Background: Amplification of cMET has been described as mechanism underlying resistance to EGFR-targeted therapy in EGFR-mutated NSCLC. Nevertheless, few is known about cMET amplification beside the EGFR-resistance setting. This study was performed in order to characterize patients with low-level, intermediate-level and high-level cMET amplification focusing on frequency, co-occuring driver mutations and clinical outcome. Methods: Within a regional molecular screening network cMET amplification status was analyzed by fluorescence in-situ hybridization (FISH) in 588 patients with NSCLC regardless of histology. Next-generation parallel sequencing (NGS) using 102 amplicons and 14 genes was performed in all analyzed samples. Clinical parameters (age, sex, UICC tumor stage, smoking status and medical and therapeutical history) of all patients were assessed. Results: 171 patients (29.1%) with cMET amplification were identified, whereof 17 (9.9%) had high-level amplification. cMET amplifications co-occured in 98 patients (57.3%) with a large spectrum of other driver mutations (EGFR, KRAS, HER2, STK11, NRAS, BRAF) or amplifications (FGFR1) in both adenocarcinoma (60.2%) and squamous cell carcinoma (21.1%). 9 patients of the high-level-amplified patients did not have an additional driver mutation, while the remaining 8 patients had mutations within EGFR, KRAS, PIK3CA, BRAF and STK11. cMET amplification was associated with a history of smoking and detected in all UICC tumor stages. Conclusions: Our data suggest a high prevalence of cMET amplification in NSCLC patients with many oncogenic driver mutations. Most patients with an additional mutations had KRAS mutations. These data show that screening for MET-amplified patients in order to identify patients for MET-targeted treatment should not be performed on the basis of sequencing results.
Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration
Authors: Pengfei Chen, Lin Zheng, Yiyun Wang, Min Tao, Ziang Xie, Chen Xia, Chenhui Gu, Jiaxin Chen, Pengcheng Qiu, Sheng Mei, Lei Ning, Yiling Shi, Chen Fang, Shunwu Fan, Xianfeng Lin
Journal: Theranostics (2019)

Mitochondrial dysfunction and oxidative stress damage are hallmarks of osteoarthritis (OA). Mesenchymal stem cell (MSC)-derived exosomes are important in intercellular mitochondria communication. However, the use of MSC exosomes for regulating mitochondrial function in OA has not been reported. This study aimed to explore the therapeutic effect of MSC exosomes in a three dimensional (3D) printed scaffold for early OA therapeutics. Methods: We first examined the mitochondria-related proteins in normal and OA human cartilage samples and investigated whether MSC exosomes could enhance mitochondrial biogenesis in vitro. We subsequently designed a bio-scaffold for MSC exosomes delivery and fabricated a 3D printed cartilage extracellular matrix (ECM)/gelatin methacrylate (GelMA)/exosome scaffold with radially oriented channels using desktop-stereolithography technology. Finally, the osteochondral defect repair capacity of the 3D printed scaffold was assessed using a rabbit model. Results: The ECM/GelMA/exosome scaffold effectively restored chondrocyte mitochondrial dysfunction, enhanced chondrocyte migration, and polarized the synovial macrophage response toward an M2 phenotype. The 3D printed scaffold significantly facilitated the cartilage regeneration in the animal model. Conclusion: This study demonstrated that the 3D printed, radially oriented ECM/GelMA/exosome scaffold could be a promising strategy for early OA treatment.
Expert consensus on multidisciplinary therapy of colorectal cancer with lung metastases (2019 edition)
Authors: Jian Li, Ying Yuan, Fan Yang, Yi Wang, Xu Zhu, Zhenghang Wang, Shu Zheng, Desen Wan, Jie He, Jianping Wang, Yi Ba, Chunmei Bai, Li Bai, Wei Bai, Feng Bi, Kaican Cai, Muyan Cai, Sanjun Cai, Gong Chen, Keneng Chen, Lin Chen, Pengju Chen, Pan Chi, Guanghai Dai, Yanhong Deng, Kefeng Ding, Qingxia Fan, Weijia Fang, Xuedong Fang, Fengyi Feng, Chuangang Fu, Qihan Fu, Yanhong Gu, Yulong He, Baoqing Jia, Kewei Jiang, Maode Lai, Ping Lan, Enxiao Li, Dechuan Li, Jin Li, Leping Li, Ming Li, Shaolei Li, Yexiong Li, Yongheng Li, Zhongwu Li, Xiaobo Liang, Zhiyong Liang, Feng Lin, Guole Lin, Hongjun Liu, Jianzhong Liu, Tianshu Liu, Yunpeng Liu, Hongming Pan, Zhizhong Pan, Haiping Pei, Meng Qiu, Xiujuan Qu, Li Ren, Zhanlong Shen, Weiqi Sheng, Chun Song, Lijie Song, Jianguo Sun, Lingyu Sun, Yingshi Sun, Yuan Tang, Min Tao, Chang Wang, Haijiang Wang, Jun Wang, Shubin Wang, Xicheng Wang, Xishan Wang, Ziqiang Wang, Aiwen Wu, Nan Wu, Lijian Xia, Yi Xiao, Baocai Xing, Bin Xiong, Jianmin Xu, Jianming Xu, Nong Xu, Ruihua Xu, Zhongfa Xu, Yue Yang, Hongwei Yao, Yingjiang Ye, Yonghua Yu, Yueming Yu, Jinbo Yue, Jingdong Zhang, Jun Zhang, Suzhan Zhang, Wei Zhang, Yanqiao Zhang, Zhen Zhang, Zhongtao Zhang, Lin Zhao, Ren Zhao, Fuxiang Zhou, Jian Zhou, Jing Jin, Jin Gu, Lin Shen
Journal: Journal of Hematology & Oncology (2019)

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts' clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.
Cost-Effectiveness of the US Food and Drug Administration Added Sugar Labeling Policy for Improving Diet and Health
Authors: Yue Huang, Chris Kypridemos, Junxiu Liu, Yujin Lee, Jonathan Pearson-Stuttard, Brendan Collins, Piotr Bandosz, Simon Capewell, Laurie Whitsel, Parke Wilde, Dariush Mozaffarian, Martin O’Flaherty, Renata Micha
Journal: Circulation (2019)

Excess added sugars, particularly from sugar-sweetened beverages, are a major risk factor for cardiometabolic diseases including cardiovascular disease and type 2 diabetes mellitus. In 2016, the US Food and Drug Administration mandated the labeling of added sugar content on all packaged foods and beverages. Yet, the potential health impacts and cost-effectiveness of this policy remain unclear.A validated microsimulation model (US IMPACT Food Policy model) was used to estimate cardiovascular disease and type 2 diabetes mellitus cases averted, quality-adjusted life-years, policy costs, health care, informal care, and lost productivity (health-related) savings and cost-effectiveness of 2 policy scenarios: (1) implementation of the US Food and Drug Administration added sugar labeling policy (sugar label), and (2) further accounting for corresponding industry reformulation (sugar label+reformulation). The model used nationally representative demographic and dietary intake data from the National Health and Nutrition Examination Survey, disease data from the Centers for Disease Control and Prevention Wonder Database, policy effects and diet-disease effects from meta-analyses, and policy and health-related costs from established sources. Probabilistic sensitivity analysis accounted for model parameter uncertainties and population heterogeneity.Between 2018 and 2037, the sugar label would prevent 354 400 cardiovascular disease (95% uncertainty interval, 167 000-673 500) and 599 300 (302 400-957 400) diabetes mellitus cases, gain 727 000 (401 300-1 138 000) quality-adjusted life-years, and save $31 billion (15.7-54.5) in net healthcare costs or $61.9 billion (33.1-103.3) societal costs (incorporating reduced lost productivity and informal care costs). For the sugar label+reformulation scenario, corresponding gains were 708 800 (369 200-1 252 000) cardiovascular disease cases, 1.2 million (0.7-1.7) diabetes mellitus cases, 1.3 million (0.8-1.9) quality-adjusted life-years, and $57.6 billion (31.9-92.4) and $113.2 billion (67.3-175.2), respectively. Both scenarios were estimated with >80% probability to be cost saving by 2023.Implementing the US Food and Drug Administration added sugar labeling policy could generate substantial health gains and cost savings for the US population.
PS-007-Differential therapeutic effects of pan- and single PPAR agonists on steatosis, inflammation, macrophage composition and fibrosis in a murine model of non-alcoholic steatohepatitis
Authors: Sander Lefere, Tobias Puengel, Oliver Krenkel, Jana Hundertmark, Vanessa Adarbes, Céline Estavilet, Anja Geerts, Lindsey Devisscher, Guillaume Wettstein, Frank Tacke
Journal: Journal of Hepatology (2019)
Renal toxicity from platinum/pemetrexed and pembrolizumab in the era of combination therapy
Authors: D. Dumoulin, S. Visser, R. Cornelissen, J.G. Aerts
Journal: Annals of Oncology (2019)

Background: Recently, the phase 3 keynote-189 trial showed that in previously untreated patients with advanced non-squamous NSCLC without targetable mutations, the progression-free and overall survival were significantly longer with addition of pembrolizumab to chemotherapy than with chemotherapy alone. Both chemotherapy and pembrolizumab can give renal toxicity, which can be a major challenge in the clinical setting. Methods: In a prospective multicenter observational real-life cohort study [Visser Eur Respir J 2018], we evaluated the incidence of acute/chronic kidney disease (AKD/CKD), its related treatment discontinuation frequency and associated clinical variables with AKD in patients with stage IIIB/IV NSCLC treated with platinum/pemetrexed. In addition, the Keynote 189 toxicity data was used for the combination treatment. We thereafter reviewed literature to generate an algorithm for diagnosis and treatment in increased creatinine levels. Results: 149 patients received pemetrexed platinum, of whom 44 patients (30%) continued maintenance. During induction therapy 48 patients (50%) treated with cisplatinum/pemetrexed developed AKD and 15 patients (29%) treated with carboplatin/pemetrexed. During maintenance 13 patients (30%) developed AKD, leading to CKD and treatment discontinuation in eight patients (62%). In the Keynote 189 trial combining pembrolizumab with chemotherapy, nephritis has been reported in 1,7% of patients in any grade (1,5% grade 3-4). However, when looking at an increased blood creatinine in the group that was treated with carboplatin, a total of 12,2% of patients showed any increase (0,7% grade 3-4). Conclusions: Increased blood creatinine levels from pemetrexed and pembrolizumab is a common entity, probably more common in a real-life setting. This elevation is clinically challenging in a population that receives three agents that can cause a creatinine increase. Currently, there are no markers to distinguish between renal failure due to chemotherapy of immunotherapy. We will present an algorithm based on current knowledge for clinicians as guidance for renal dysfunction in patients treated with chemotherapy and pd-(l)1 checkpoint inhibitors. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: D. Dumoulin: Speakers fee: BMS, Roche, Pfizer, Novartis. R. Cornelissen: Consultancy: Roche, Boehringer Ingelheim, BMS, MSD; Speakers fee: Roche, Pfizer, Boehringer Ingelheim, Novartis, BMS. J.G. Aerts: Advisory boards: BMS, Boehringer Ingelheim, MSD, AstraZeneca, Eli Lilly, Takeda, Amphera; Stock owner: Amphera B.V. All other authors have declared no conflicts of interest.
THU-022-CM-101-a Novel anti CCL24 monoclonal antibody reduces cholangiocytes proliferation in experimental cholestasis models
Authors: Michal Segal, Neta Barashi, Avi Katav, Victoria Edelshtein, Arnon Aharon, Sharon Hashmueli, Massimo Pinzani, Douglas Thorburn, Jacob George, Adi Mor
Journal: Journal of Hepatology (2019)
Abstract 17028: Neighborhood Income is Associated With Prevalence of Myocardial Infarction and Heart Failure Independent of Individual Demographic Factors in Densely Populated Urban Seniors
Authors: Sanjum S Sethi, Richard Bordowitz, Kimberly B Morland, Evelyn C Granieri, Michael E Farkouh
Journal: Circulation (2013)

Background: Individual socioeconomic status (SES) is associated with cardiovascular disease (CVD), but few studies have investigated neighborhood SES and CVD. We hypothesized that CVD prevalence may differ by urban neighborhoods even after adjusting for individual SES. Methods: Adults 59-99 years old from New York City were enrolled in the NHLBI-funded Cardiovascular Health of Seniors and the Built Environment Study from 2009 to 2011 (n=1,453). Geocoded maps using participants addresses were correlated to 2010 US census tract data. Neighborhood median incomes were stratified into the following categories: (highest (H) [$51,712_$160,833], med-high (MH) [$37,084_$51,711], med-low (ML) [$25,615_$37,083], lowest (L) [<$25,615]). Log-linear models generated crude and adjusted (age, race and income) effect estimates. Results: There were 153 cases of myocardial infarction (MI) and 92 cases of heart failure (HF) detected. Over 90% of participants had health insurance. There was a geographic association between ca...