tbuckley/cabot-search huggingface dataset:
A Novel MYCN-Specific Antigene Oligonucleotide Deregulates Mitochondria and Inhibits Tumor Growth in MYCN-Amplified Neuroblastoma
Authors: Luca Montemurro, Salvatore Raieli, Silvia Angelucci, Damiano Bartolucci, Camilla Amadesi, Silvia Lampis, Anna Lisa Scardovi, Leonardo Venturelli, Giammario Nieddu, Lucia Cerisoli, Matthias Fischer, Gabriella Teti, Mirella Falconi, Andrea Pession, Patrizia Hrelia, Roberto Tonelli
Journal: Cancer Research (2019)

Approximately half of high-risk neuroblastoma is characterized by MYCN amplification. N-Myc promotes tumor progression by inducing cell growth and inhibiting differentiation. MYCN has also been shown to play an active role in mitochondrial metabolism, but this relationship is not well understood. Although N-Myc is a known driver of the disease, it remains a target for which no therapeutic drug exists. Here, we evaluated a novel MYCN-specific antigene PNA oligonucleotide (BGA002) in MYCN-amplified (MNA) or MYCN-expressing neuroblastoma and investigated the mechanism of its antitumor activity. MYCN mRNA and cell viability were reduced in a broad set of neuroblastoma cell lines following BGA002 treatment. Furthermore, BGA002 decreased N-Myc protein levels and apoptosis in MNA neuroblastoma. Analysis of gene expression data from patients with neuroblastoma revealed that MYCN was associated with increased reactive oxygen species (ROS), downregulated mitophagy, and poor prognosis. Inhibition of MYCN caused profound mitochondrial damage in MNA neuroblastoma cells through downregulation of the mitochondrial molecular chaperone TRAP1, which subsequently increased ROS. Correspondingly, inhibition of MYCN reactivated mitophagy. Systemic administration of BGA002 downregulated N-Myc and TRAP1, with a concomitant decrease in MNA neuroblastoma xenograft tumor weight. In conclusion, this study highlights the role of N-Myc in blocking mitophagy in neuroblastoma and in conferring protection to ROS in mitochondria through upregulation of TRAP1. BGA002 is a potently improved MYCN-specific antigene oligonucleotide that reverts N-Myc-dysregulated mitochondrial pathways, leading to loss of the protective effect of N-Myc against mitochondrial ROS. SIGNIFICANCE: A second generation antigene peptide oligonucleotide targeting MYCN induces mitochondrial damage and inhibits growth of MYCN-amplified neuroblastoma cells.
Human MICL Is An Early Marker In Myeloid Differentiation and Identifies a Subgroup Of CML Patients With Expanded Granulocyte-Macrophage Progenitor Populations At Diagnosis
Authors: Peter Buur van Kooten Niekerk, Anne Stidsholt Roug, Charlotte Christie Petersen, Line Nederby, Charlotte Guldborg Nyvold, Ole Weis Bjerrum, Andreja Dimitrijevic, Marianne T. Severinsen, Jesper Stentoft, Peter Hokland
Journal: Blood (2013)
Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream
Authors: Brian S. Kim, Michael D. Howell, Kang Sun, Kim Papp, Adnan Nasir, Michael E. Kuligowski
Journal: Journal of Allergy and Clinical Immunology (2019)

Atopic dermatitis (AD) is a highly pruritic chronic inflammatory skin disorder. Ruxolitinib, a selective inhibitor of Janus kinase 1 and Janus kinase 2, potently suppresses cytokine signaling involved in AD pathogenesis.We sought to evaluate the efficacy and safety of ruxolitinib (RUX) cream in adults with AD.In this phase 2 study (NCT03011892), 307 adult patients with AD, an Investigator's Global Assessment score of 2 or 3 (mild or moderate), and 3% to 20% affected body surface area were equally randomized for 8 weeks of double-blind treatment to RUX (1.5% twice daily [BID], 1.5% once daily [QD], 0.5% QD, 0.15% QD), vehicle, or triamcinolone cream (0.1% BID for 4 weeks, then vehicle for 4 weeks). Subsequently, patients could apply 1.5% RUX BID for 4 additional weeks of open-label treatment. The primary end point was the comparison between 1.5% RUX cream BID and vehicle in mean percentage change from baseline in Eczema Area and Severity Index at week 4.All RUX regimens demonstrated therapeutic benefit at week 4; 1.5% BID provided the greatest improvement in Eczema Area and Severity Index (71.6% vs 15.5%; P < .0001) and Investigator's Global Assessment responses (38.0% vs 7.7%; P < .001) versus vehicle. Rapid reductions in the itch numerical rating scale score occurred within 36 hours (1.5% BID vs vehicle, ‒1.8 vs ‒0.2; P < .0001) and were sustained through 12 weeks. Patients who transitioned to 1.5% RUX BID improved in all measures. RUX was not associated with clinically significant application-site reactions.RUX cream provided rapid and sustained improvements in AD symptoms and was well tolerated.
A Look at Lymphoid Neoplasms in Patients over 65: Are We Less Aggressive - and Does It Affect Outcome?
Authors: Jessica Trevino Jones, Sushanth Kakarla, Annie Hung, Michelle Janania Martinez, Prathibha Surapaneni, Juan Garza, David Gregorio, Elva Nora Osuna Salazar, Joel E Michalek, Qianqian Liu, Adolfo E Diaz
Journal: Blood (2018)
Host CD4+CD25+FoxP3+ Regulatory T Cells Facilitate Donor Engraftment Without Impacting Graft Versus Host Disease Onset After Major-Mismatched Hematopoietic Stem Cell Transplantation
Authors: Antonio Pierini, Hidekazu Nishikii, Mareike Florek, Dennis B Leveson-Gower, Yuqiong Pan, Byung-Su Kim, Jeanette Baker, Robert Negrin
Journal: Blood (2013)
Cognitive functional therapy compared with a group-based exercise and education intervention for chronic low back pain: a multicentre randomised controlled trial (RCT)
Authors: Mary O'Keeffe, Peter O'Sullivan, Helen Purtill, Norma Bargary, Kieran O'Sullivan
Journal: British Journal of Sports Medicine (2019)

Background One-size-fits-all interventions reduce chronic low back pain (CLBP) a small amount. An individualised intervention called cognitive functional therapy (CFT) was superior for CLBP compared with manual therapy and exercise in one randomised controlled trial (RCT). However, systematic reviews show group interventions are as effective as one-to-one interventions for musculoskeletal pain. This RCT investigated whether a physiotherapist-delivered individualised intervention (CFT) was more effective than physiotherapist-delivered group-based exercise and education for individuals with CLBP. Methods 206 adults with CLBP were randomised to either CFT (n=106) or group-based exercise and education (n=100). The length of the CFT intervention varied according to the clinical progression of participants (mean=5 treatments). The group intervention consisted of up to 6 classes (mean=4 classes) over 6–8 weeks. Primary outcomes were disability and pain intensity in the past week at 6 months and 12months postrandomisation. Analysis was by intention-to-treat using linear mixed models. Results CFT reduced disability more than the group intervention at 6 months (mean difference, 8.65; 95% CI 3.66 to 13.64; p=0.001), and at 12 months (mean difference, 7.02; 95% CI 2.24 to 11.80; p=0.004). There were no between-group differences observed in pain intensity at 6 months (mean difference, 0.76; 95% CI -0.02 to 1.54; p=0.056) or 12 months (mean difference, 0.65; 95% CI -0.20 to 1.50; p=0.134). Conclusion CFT reduced disability, but not pain, at 6 and 12 months compared with the group-based exercise and education intervention. Future research should examine whether the greater reduction in disability achieved by CFT renders worthwhile differences for health systems and patients. Trial registration number ClinicalTrials.gov registry (NCT02145728 ).
Modeling Congenital Amegakaryocytic Thrombocytopenia Using Patient-Specific Induced Pluripotent Stem Cells
Authors: Naoya Takayama, Shinji Hirata, Ryoko Jono-Ohnishi, Sou Nakamura, Sho-ichi Hirose, Hiroshi Endo, Masanori Nishi, Yuhei Hamazaki, Shin Kaneko, Eiichi Ishii, Hiromitsu Nakauchi, Shinji Kunishima, Koji Eto
Journal: Blood (2011)
Haploidentical Stem Cell Transplantation With Posttransplant Cyclophosphamide Therapy vs Other Donor Transplantations in Adults With Hematologic Cancers
Authors: Nico Gagelmann, Andrea Bacigalupo, Alessandro Rambaldi, Dieter Hoelzer, Jörg Halter, Jaime Sanz, Francesca Bonifazi, Ellen Meijer, Maija Itälä-Remes, Markéta Marková, Carlos Solano, Nicolaus Kröger
Journal: JAMA Oncology (2019)

Use of haploidentical (HAPLO) stem cell transplantation with posttransplant cyclophosphamide is rapidly increasing in adults with hematologic cancers. However, its specific role compared with other transplant strategies has yet to be identified.To synthesize the existing evidence regarding outcomes of stem cell transplantations comparing HAPLO stem cell transplantation and posttransplant cyclophosphamide therapy with transplantations from matched related donors (MRDs), matched unrelated donors (MUDs), or mismatched unrelated donors (MMUDs).PubMed, Cochrane Library, ClinicalTrials.gov, and meeting abstracts were searched for the key words haploidentical and cyclophosphamide from inception through March 1, 2019.Studies comparing HAPLO stem cell transplantation and posttransplant cyclophosphamide therapy with transplantations from other donors in adults with hematologic cancers were eligible for meta-analysis.Pooled odds ratios (ORs) and 95% CIs were calculated using a random-effects model.Main outcomes were all-cause mortality, nonrelapse mortality, and relapse.A total of 30 studies including 22 974 participants were analyzed. HAPLO stem cell transplantation with posttransplant cyclophosphamide therapy was associated with increased all-cause mortality compared with MRDs (OR, 1.17; 95% CI, 1.05-1.30), similar all-cause mortality compared with MUDs (OR, 1.06; 95% CI, 0.96-1.18), and reduced all-cause mortality compared with MMUDs (OR, 0.75; 95% CI, 0.61-0.92). Regarding nonrelapse mortality, HAPLO stem cell transplantation with posttransplant cyclophosphamide was associated with worse outcomes compared with MRDs (OR, 1.20; 95% CI, 1.04-1.40) but better outcomes compared with MUDs (OR, 0.75; 95% CI, 0.61-0.92) and MMUDs (OR, 0.51; 95% CI, 0.25-1.02). In terms of relapse, HAPLO stem cell transplantation with posttransplant cyclophosphamide was associated with similar outcome compared with MRDs (OR, 1.01; 95% CI, 0.86-1.17) and MMUDs (OR, 1.06; 95% CI, 0.77-1.47) but showed increased relapse compared with MUDs (OR, 1.20; 95% CI, 1.03-1.40).Results of this meta-analysis suggest that MRDs, if available, remain the optimal donors regarding mortality and HAPLO stem cell transplantation with posttransplant cyclophosphamide may be preferred over MMUDs. Prospective comparisons with MUDs are needed.
A Multicenter Retrospective Noninterventional Follow-up Study in Patients with Sickle Cell Pain Crisis Who Previously Participated in the Sustain Trial in the United States Successor Study
Authors: Nirmish Shah, Ralph Boccia, Walter K. Kraft, Brandon M. Hardesty, Jincy Paulose, Dram Laine, Das Purkayastha, Savita Nandal, Abdullah Kutlar
Journal: Blood (2018)
Outcome of Lymphocyte Predominant Hodgkin Lymphoma: A Single Institutional Analysis
Authors: Daniel E Ezekwudo, Nwabundo Anusim, Anish S Konde, Bolanle Gbadamosi, John Khoury, David Macari, Dana Zakalik, Leann Blankenship, Susanna Gaikazian, Ishmael Jaiyesimi
Journal: Blood (2018)
Prognostication of Diffuse Large B-Cell Lymphoma By Lympho2Cx Assay and BCL2 and MYC Expression: Application in a Real Life Context of 154 Patients
Authors: Stefania Bettelli, Raffaella Marcheselli, Samantha Manfredini, Alessia Bari, Samantha Pozzi, M. Christina Christina Cox, Luigi Marcheselli, Arianna Di Napoli, Ilana Levy, Elisa Forti, Tamar Tadmor, Antonino Maiorana, Stefano Sacchi
Journal: Blood (2018)
Lenalidomide, Adriamycin and Dexamethasone (RAD) As An Induction Regimen In Newly Diagnosed Multiple Myeloma – Interim Results From a German Multicenter Phase II Trial
Authors: Stefan Knop, Christian Langer, Monika Engelhardt, Lars O Muegge, Wolf Roesler, Albrecht Reichle, Christoph Röllig, Bernd Hertenstein, Martin Gramatzki, Florian Bassermann, Helmut Ostermann, Isrid Sturm, Mark Ringhoffer, Kerstin Schaefer-Eckart, Sabrina Kraus, Hermann Einsele, Ralf C. Bargou
Journal: Blood (2013)
Patologic IL 17 Producing Helper T Cells In Acute Myeloid Leukemia Patients
Authors: Gerardo Musuraca, Serena De Matteis, Roberta Napolitano, Francesco Fabbri, Delia Cangini, Michela Ceccolini, Maria Benedetta Giannini, Alessandro Lucchesi, Sonia Ronconi, Cristina Papayannidis, Viviana Guadagnuolo, Giovanni Martinelli, Paolo Savini, Monica Tani, Patrizia Tosi, Dino Amadori, Pier Paolo Fattori, Wainer Zoli, Silvia Carloni
Journal: Blood (2013)
The role of DDR1 and DDR2 collagen receptors in tumor progression
Authors: Iker Badiola, Yves Declerck, Steven Wall, Fernando Vidal-Vanaclocha, Elvira Olaso
Journal: Cancer Research (2006)

1670  The discoidin domain receptors (DDRs) are two novel collagen receptors of the receptor tyrosine kinase (RTK) family distinguished by an extracellular domain homologous to discoidin-I in Dictyosteium discoideum, and by a catalytic tyrosine kinase domain in the cytoplasmic tail. A unique feature of DDRs is the fact that both receptors have collagens as their ligands. Whereas DDR1 activation is achieved by type I to VI, and type VIII collagens, DDR2 is only activated by fibrilar collagens. Another characteristic of DDRs is their low phosphorilation in comparison with other RTKs. Interestingly, DDR1 is present in tumor cells of highly aggressive carcinomas, while DDR2 is expressed by the tumor-associated estromal cells.. The aim of our study was to elucidate the role of DDRs in tumor cell behaviour by in vitro silencing of DDR1 and DDR2 mRNAs. Results: Using RT-PCR, western blot and flow citometry analyses, we observed DDR1 and DDR2 expression and phosphorylation by collagen in A375 melanoma, HT29 colon carcinoma and SK-Hep hepatocarcinoma.. In vitro silencing of DDR1 or DDR2 with 20 bp antisense probes to each DDR mRNA result in a significant inhibition of cell proliferation, migration, adhesion to collagen and metalloproteinase activity in all tested human tumor cell lines. In conclusion, silencing the expression of DDRs diminish three key functional characteristics of. tumor cells to progress and metastasize. On-going in vivo experiments are needed to demonstrate the direct role of DDRs in the tumour progression and their feasibility as future therapeutic targets.
HSP90 Inhibition Targets JAK2 and Is Highly Effective in CRLF2-Rearranged Acute Lymphoblastic Leukemia
Authors: Oliver Weigert, Liat Bird, Nadja Kopp, Andrew A. Lane, Bjoern Chapuy, Diederik van Bodegom, Sachie Marubayashi, Akinori Yoda, Vincent Romanet, Masato Murakami, Stephen E. Sallan, Ross L Levine, Andrew L. Kung, Thomas Radimerski, David M Weinstock
Journal: Blood (2011)
Small cell lung cancer: Sociodemographic factors in patients’ decisions for treatment.
Authors: Thanh P. Ho, Narjust Duma, Urshila Durani, Shealeigh Funni, Jonathan Inselman, Julian R. Molina, Aaron Scott Mansfield
Journal: Journal of Clinical Oncology (2019)

144 Background: Small cell lung cancer (SCLC) is highly responsive to cytotoxic therapy and can be cured in early stages of disease. In this setting, disparities in patient refusal despite provider recommendations are unknown. Methods: All incident limited stage (LS)-SCLC cases from the National Cancer Database were identified from 2004 to 2014. Logistic regression was used to determine factors associated with treatment refusal. Results: 65,664 patients (pts) were identified with LS-SCLC: 44% male, median age 68 years. 3.4% of pts refused radiation and 3.8% refused chemotherapy. The proportion of chemotherapy refusal increased over the study period: 3% in 2004-2006 compared to 5.4% in 2013-2014 [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.55-2.01]; this was not observed for radiation. In multivariate analysis, women were more likely to refuse radiation (OR 1.18, 95% CI 1.06-1.32) and chemotherapy (OR 1.30, 95% CI 1.19-1.43) than men. Women who accepted treatment had higher overall survival compared to those who refused radiation (19.8 vs 5.2 months) or chemotherapy (17.4 vs 3.9 months) (both p &lt; 0.001). Hispanic, Black, and Asian pts were not more likely to refuse treatment than White pts. Older pts were more likely to refuse radiation (OR 1.09 per year, 95% CI 1.08-1.09) and chemotherapy (OR 1.10 per year, 95% CI 1.09-1.11). Charlson comorbidity index (CCI) of 2 was associated with more frequent treatment refusal compared to CCI of 0 (radiation OR 1.96, 95% CI 1.68-2.30; chemotherapy OR 1.54, 95% CI 1.34-1.76). Medicaid as primary insurance predicted a higher risk of refusal compared to private insurance for radiation (OR 2.36, 95% CI 1.81-3.07) and chemotherapy (OR 2.23, 95% CI 1.78-2.80). Treatment at an academic facility predicted a lower risk of radiation refusal (OR 0.71, 95% CI 0.59-0.84) but not chemotherapy refusal. Conclusions: Female sex, comorbidities, and Medicaid insurance were predictors of treatment refusal in LS-SCLC, suggesting that socioeconomic and sex disparities may affect treatment decisions in this life-threatening disease. Further research to identify reasons for refusal via patient and provider interviews can improve care of vulnerable populations with potentially curable cancer.
A Single-Center Phase IIa Study Evaluating the Safety and Tolerability of Umbralisib and Ibrutinib in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Authors: Matthew A. Lunning, Philip Bierman, R. Gregory Bociek, James O. Armitage, Peggy Heires, Maribeth Hohenstein, Susan Blumel, Jonathan Tefft, Elizabeth R. Lyden, Michael R Green, Julie M. Vose
Journal: Blood (2018)
Myeloma-Specific Oncolytic Adenovirus Induces Significant Tumour Oncolysis In Vitro and In Vivo and Prevents Cell Line Regrowth
Authors: Georgia Rose Stewart, Simon Tazzyman, Darren Lath, Jenny Down, John A Snowden, Michelle Lawson, Munitta Muthana, Andrew D Chantry
Journal: Blood (2018)
Early Biomarkers for the Anti-Angiogenic and Anti-Tumor Activity of the Superoxide Dismutase 1 (SOD1) Inhibitor Tetrathiomolybdate.
Authors: M.J. Braunstein, E. Smith, C. Timucin, F. Doñate, J.C. Juarez, M. Burnett, M. Manuia, D.E. Shaw, A.P. Mazar, O. Batuman
Journal: Blood (2007)
The Novel KSP Inhibitor ARRY-520 Demonstrates Single-Agent Activity in Refractory Myeloma: Results From a Phase 2 Trial in Patients with Relapsed/Refractory Multiple Myeloma (MM)
Authors: Sagar Lonial, Adam Cohen, Jeffrey Zonder, William I Benzinger, Jonathan L. Kaufman, Robert Z. Orlowski, R. Donald Harvey, Raymond Alexanian, Sheeba K Thomas, Donna Weber, Duncan Walker, Brandi Hilder, Ann Ptaszynski, Jatin J Shah
Journal: Blood (2011)
Single-cell analysis of bone marrow–derived CD34+ cells from children with sickle cell disease and thalassemia
Authors: Peng Hua, Noemi Roy, Josu de la Fuente, Guanlin Wang, Supat Thongjuea, Kevin Clark, Anindita Roy, Bethan Psaila, Neil Ashley, Yvonne Harrington, Claus Nerlov, Suzanne M. Watt, Irene Roberts, James O. J. Davies
Journal: Blood (2019)
Reversal of P-Glycoprotein-Dependent Resistance to Adriamycin by 5-bromotetrandrine in K562/A02 Cell Line.
Authors: Bao-An Chen, Jue-Qiong Wang, Jia-Hua Ding, Feng Gao, Jian Chen, Chong Gao, Yun-Yu Sun, Gang Zhao, Ning-Na Chen, Xiao-Ping Pei, Yong-Yuan Dai, Qian Shun
Journal: Blood (2007)
Treatment of Epstein-Barr Virus Associated Central Nervous System Diseases after Allogeneic Hematopoietic Stem Cell Transplantation with Intrathecal Donor Lymphocyte Infusion
Authors: Juanjuan Zhao, Yingling Zu, Lu Han, Yanli Zhang, Ruirui Gui, Fengkuan Yu, Zhen Li, Huifang Zhao, Baijun Fang, Quande Lin, Yongping Song, Delong Liu, Jian Zhou
Journal: Blood (2018)
Abstract 842: Protein kinase G - Regulator of G protein Signaling 2 Axis of Cardiac Myocytes Critically Determines Cardiac Performance in Early Cardiac Remodeling
Authors: Genri Numata, Eiki Takimoto, Taro Kariya, Kazutaka Ueda, Robert M Blanton, Richard H Karas, Michael E Mendelsohn, Issei Komuro
Journal: Circulation Research (2019)

Introduction: Regulator of G protein signaling 2 (RGS2) is a negative regulator of G protein-coupled signaling, and is potentiated by cGMP-PKG. Our prior work using a global deletion model demonstrated the protective role for RGS2 against mal-adaptive cardiac remodeling, which is essential to the cGMP-PDE5 inhibitor efficacy; however, cell type-specific contribution remains to be determined, given the expression of RGS2 in myocytes, fibroblasts and vascular smooth muscle cells. We hypothesized that myocyte RGS2 might serve as a primary contributor to the cardio-protection and mediates cGMP-PKG benefits. Method: We generated cardiomyocyte-specific RGS2 knockout mice (cKO) on a C57BL/6 background. Pressure overload was produced by transverse aortic constriction (TAC) in male RGS2-cKO mice (RGS2cKO) and their littermate controls (WT). To investigate cGMP-PKG enhancing effects, a soluble guanylyl cyclase stimulator (riociguat) was orally administrated daily (3mg/kg/day). Invasive hemodynamics, anatomy, histology and molecular signaling were assessed at 1wk after TAC. Results: RGS2-cKO revealed exacerbated dilative cardiac remodeling (LVDD: cKO 3.57±0.36 vs WT 2.90±0.16) and severely impaired cardiac function (dPdt/IP: cKO 166±3.49 vs WT 195±7.40), while their basal phenotype was undistinguishable from WT. cKO-TAC hearts showed larger cardiomyocyte size and more fibrosis than WT-TAC hearts, associated with aberrant gene expression induction including Myh6, Myh7, Col1a2, and TGFβ . Intriguingly, concomitant riociguat treatment reduced LV chamber size and fibrosis but failed to improve cardiac performance in cKO-TAC hearts, while riociguat ameliorated all these in WT-TAC hearts. Conlusion: These results suggest that RGS2-PKG axis in cardiac myocytes critically contributes to cardiac functional performance and that cGMP-PKG exerts anti-fibrotic effects independently of myocyte conditions.
Abstract 760: Metabolic Syndrome Impairs Cardiac Remodeling During Pregnancy in Mice
Authors: Yijun Yang, Chunya Kang, Giulia Borghetti, Anna M Lucchese, Yunichel Joo, Shavonn Harper, Christopher Bryan, Sadia Mohsin, Steven R Houser
Journal: Circulation Research (2019)

Rationale: Due to the change of life style in the past decades, the incidence of metabolic syndrome (MetS) and obesity in women of childbearing age has been increased. Evidences have shown that complications during pregnancy, such as obesity and gestational diabetes, strongly link to future heart diseases. During normal pregnancy, the heart undergoes a physiological remodeling with mild ventricular dilation and hypertrophy. However, the effects of MetS on cardiac phenotype during pregnancy are not well understood. Moreover, animal models for MetS so far are not well established, which are usually species limited, gender limited and lack of translational significance. Thus, it’s important to develop an animal model which resembles the etiology of MetS in human beings. Objective: Establish a model of MetS in female C57BL/6J mice and determine the effects of MetS on cardiac remodeling during pregnancy. Methods and Results: To establish a mouse model of MetS, high fat (49% kcal)/high carbohydrates (HF-HC) diet were given to C57BL/6J female mice at the age of 8-week. Mice fed with normal diet (10% kcal fat) served as control. After 14 weeks feeding, mice fed with HF-HC diet showed significantly higher body weight and gonadal fat weight compared with control mice. Moreover, mice fed with HF-HC diet showed impaired glucose tolerance and higher serum total cholesterol level. The symptoms of obesity, impaired glucose tolerance and dyslipidemia suggest the development of MetS. Female mice after 14-week special diet feeding were subjected to breeding. Cardiac function was evaluated by echocardiography during pregnancy and 1-day post-partum, then the mice were terminated 1-day post-partum. Female mice that developed MetS showed impaired cardiac function and pathological remodeling during pregnancy. Moreover, mice fed with HF-HC diet showed more myocardium interstitial fibrosis accompanied with upregulation of fibrosis related genes in the heart compared with Ctrl diet. Conclusion: We’ve developed a mouse model of MetS in C57BL/6J mice strain with 14 weeks feeding of HF-HC diet, which resemble the western diet that affects human beings nowadays. Females that have MetS showed impaired cardiac function and pathological remodeling during pregnancy.