tbuckley/cabot-search huggingface dataset:
Abstract 113: Recombinant Tafazzin Enzyme Replacement Therapy Rescues Metabolic and Functional Defects in a Mouse Model of Barth Syndrome
Authors: Corinne J Thomas, Junya Awata, Ana A Dinca, Wei-Ming Chien, Robert Blanton, Mark Aronovitz, Gregory L Martin, Lauren Richey, Kelly Tam, Douglas Strathdee, Michael T Chin
Journal: Circulation Research (2019)

Barth syndrome (BTHS) is an X-linked recessive disease where patients most commonly die from cardiomyopathy-induced heart failure before middle age. BTHS is caused by mutations in the tafazzin (TAZ) gene, resulting in defective TAZ protein. TAZ is an enzyme that generates mature cardiolipin (CL) from monolysocardiolipin (MLCL) in the mitochondrial membrane, a reaction essential for normal mitochondrial function. Current therapies can only treat the symptoms of BTHS. In this study, we propose an enzyme replacement therapy for BTHS which utilizes recombinant human TAZ fused to a cell penetrating peptide (hTAZ-CTP) to facilitate tissue uptake. The efficacy of this protein was tested in vitro on C2C12 TAZ-knockout (TAZ-KO) skeletal myoblasts and in vivo on a myocardial-specific TAZ conditional knockout mouse, modelling the cardiomyopathy associated with BTHS. In vitro tests of TAZ-KO cells, using oxygen consumption rate as a measure of mitochondrial activity, showed treatment of the cells with hTAZ-CTP effected a partial rescue of the fatty acid oxidation capabilities of the TAZ-KO cells. In vivo tests showed that BTHS mice display increasing septal wall thickness over time, an effect halted upon treatment with hTAZ-CTP. Pressure-volume (PV) loop analysis indicated that heart function, impaired in the vehicle-treated BTHS mouse, was similar between treated mice and normal mice. The ratio of MLCL/CL, a direct measure of TAZ enzymatic activity, was measured in heart mitochondria isolated from BTHS and control mice after treatment. The vehicle treated BTHS mouse showed the high MLCL/CL ratio typical of BTHS patients, whereas the MLCL/CL ratios in protein-treated mice matched the much lower ratio of the control mice. Similarly, oxygen consumption rate measurements of these isolated heart mitochondria demonstrated partial rescue by hTAZ-CTP treatment. Coupled with the lack of toxicity observed in the liver, spleen, kidney, and heart due to hTAZ-CTP injection, these results indicate that TAZ enzyme replacement therapy has great potential as a future treatment for BTHS.
Allogeneic Stem Cell Transplantation - A Long-Term Curative Approach In Patients ≥ 60 Years With Advanced Disease AML/MDS, - The Freiburg Experience Of 250 Consecutive Patients
Authors: Hartmut Bertz, Michael Lübbert, Kristin Ohneberg, Ralph Wäsch, Robert Zeiser, Reinhard Marks, Jürgen Finke
Journal: Blood (2013)
Cost-effectiveness of pembrolizumab as first-line treatment of locally advanced or metastatic urothelial carcinoma ineligible for cisplatin-based therapy in the United States.
Authors: Yizhen Lai, Yichen Zhong, Haojie Li, Karl Patterson, Oliver Hale, Yang Meng, Tara L. Frenkl, James Luke Godwin, Ronac Mamtani
Journal: Journal of Clinical Oncology (2019)

93 Background: Pembrolizumab is indicated as first-line therapy for cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma (mUC) whose tumors express PD-L1 with a combined positive score (CPS) ≥ 10. This study aims to evaluate the cost‐effectiveness of pembrolizumab versus carboplatin plus gemcitabine in this setting from the US payer perspective. Methods: A partitioned-survival model was developed to measure the costs and effectiveness over a 20-year time horizon with an annual discount of 3%. Clinical outcomes of overall survival (OS) and progression-free survival, safety outcomes and time on treatment were modeled using data from the KEYNOTE-052 clinical trial for pembrolizumab and four clinical trials for carboplatin plus gemcitabine. Because clinical trials directly comparing these treatment strategies are not available, a simulation treatment comparison and a network meta-analysis were conducted to estimate comparative efficacy. Quality of life data extracted from EQ-5D questionnaires administered in KEYNOTE-052 were used to estimate utility, while cost data were estimated using US pricing lists and real-world data. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the results. Pembrolizumab was also compared with gemcitabine monotherapy in the scenario analyses. Results: Pembrolizumab was associated with a survival gain of 2.47 years and 1.90 quality adjusted life years (QALY), an incremental cost of $155,238, and an incremental cost per QALY gained of $81,493 versus carboplatin plus gemcitabine. Results were most sensitive to the time horizon, discount rate, pembrolizumab dosing intensity and OS hazard ratio. Pembrolizumab had 87% or 100% probability of being cost-effective vs. chemotherapy at a $100,000 or $150,000 willingness-to-pay threshold, respectively. Conclusions: Pembrolizumab appears cost-effective versus carboplatin plus gemcitabine as first-line treatment of cisplatin-ineligible and PD-L1 positive mUC patients in the US. The comparison of pembrolizumab with gemcitabine monotherapy yields similar conclusions.
Abstract 601: Radiation Therapy Induces Changes in the Endothelial Methylome Affecting Pro-angiogenic Lncrna Expression
Authors: Cristina Espinosa-Diez, RaeAnna Wilson, Rishima Mukherjee, Marlee Feltham, Clayton Hudson, Rebecca Ruhl, Sudarshan Anand
Journal: Circulation Research (2019)

Radiation therapy is a big part of standard of care in oncology. However, in the long- term patients treated with radiation are at higher risk of suffering cardiovascular events. It is well described that the genotoxic stress induced by Ionizing radiation in normal cardiovascular tissue triggers genetic and epigenetic changes. In addition to coding mRNAs, non-coding RNAs are also highly regulated by changes in methylation and transcription, leading to a tight regulatory response to damage. Genotoxic stress induces global hypomethylation due to decreased expression of DNA methyltransferases (DNMT). We observed that DNMT1, DNMT3A, and DNMT3b are downregulated in response to radiation treatment, in a dose-response manner in human endothelial cells. We have also observed that methylation changes produced by radiation affect a specific ncRNA cluster, DLK1-DIO3. Previous results from our lab indicate that ncRNAs from this cluster are highly responsive to different genotoxic agents, including radiation. Given the essential role of microRNAs and Long non- coding RNAs (lncRNAs) from the DLK1-DIO3 cluster in cardiovascular development and aging, we are interested in understanding how the epigenetic changes induced by radiotherapy affect to lncRNAs expression, and how they influence cardiovascular health in the long term after treatment. We have identified that a specific lncRNA from the DLK1-DIO3 cluster, MEG9, increases in ECs after exposure to ionizing radiation. Interestingly, knockdown of the individual DNMTs enzymes indicates a significant upregulation of MEG9 when DNMT3b is inhibited, more so after radiation treatment. To explore the role of this lncRNA, we performed loss-of-function studies. MEG9 inhibition not only diminished proliferation but also increased apoptosis through caspase 3/7 activation. Consistent with this phenotype, knockdown of MEG9 decreases growth factor-dependent angiogenesis in a 3D fibrin gel angiogenesis assay. Taken together, our findings illustrate how DNA methylation at particular lncRNA loci can regulate their expression and drive endothelial cell fate decisions. Our work illustrates how epigenetic changes may affect the long- term cardiovascular function of cancer patients submitted to radiation therapy.
Abstract 874: Role of Ginsenoside Rb1 in Resistin-Induced Vascular Smooth Muscle Cell Dysfunction
Authors: Weifeng Lu, Nezam Haider, Pricila Moly, Wei Zhou
Journal: Circulation Research (2019)

Background: Acetyl-LDL and resistin have been proved to play a critical role in inducing VSMC malfunction in the process of atherosclerosis. Ginsenoside Rb1, a major consitituent of Ginseng that has been used for thousands of years, was reported to have powerful vascular-protective effect. Here we aim to explore its protective effect on Acetyl-LDL and resistin induced dysfunction in VSMCs. Methods: Human coronary artery smooth muscle cells (HCASMC) were used at passage 5 to 8 for experiments. Cells were treated for various time points with or without resistin at 40 ng/mL and Acetyl-LDL in the presence or absence of Rb1. TBHP was also used as a positive control. Cell migration was analyzed using scratch wound assay, and cytosolic ROS (H2DCFDA as a dye probe) was measured by microplate reader and compared among groups. Results: Resistin time-dependently increased HCASMC migration, which could be significantly attenuated by Rb1 at 20μM. Resistin and Act-LDL increased ROS production in HCASMCs to a similar level, while pretreatment with Rb1 reversed the effects by resistin and acetyl-LDL. In addition, we demonstrated that both resistin and Rb1 had dose-dependent effect on ROS production in HCSMCs and that Rb1 at 40μM pre-treatment significantly reduced resistin (40ng/ml) induced cytosolic ROS in VSMCs. Conclusion: We demonstrated the protective effect of Rb1 on HCASMC and showed, for the first time, that Rb1 pre-treatment being more effective than co-treatment, suggesting that ginsenoside Rb1 has the potential of protecting against atherosclerosis. More in-dept study is needed.
Sequential Infusion of Anti-CD22 and Anti-CD19 Chimeric Antigen Receptor T Cells Following Autologous HSCT in Patients with B-NHL
Authors: Yang Cao, Na Wang, Gaoxiang Wang, Yi Xiao, Liang Huang, Chunrui Li, Min Xiao, Tongcun Zhang, Yicheng Zhang, Jianfeng Zhou
Journal: Blood (2018)
Immune Reconstitution and Preliminary Safety Analysis Of 9 Patients Treated With Somatic Gene Therapy For X-Linked Severe Combined Immunodeficiency (SCID-X1) With a Self-Inactivating Gammaretroviral Vector
Authors: Salima Hacein-Bey-Abina, Frederic Bushman, Myriam Armant, Stephane Blanche, Johanna Blondeau, Laure Caccavelli, Heather Daley, Colleen Dansereau, Satiro deOliveira, Dongjing Guo, Gregory Hopkins, Annick Lim, M.Sci, Wendy B. London, Nirav Malani, Frances Male, Punam Malik, Maria Angelica Marinovic, Sean McDonough, Matias Oleastro, Capucine Picard, Jerome Ritz, Axel Schambach, Leslie E Silberstein, Alla Tsytsykova, Johannes C.M. Van der Loo, Christopher Baum, H. Bobby Gaspar, Donald B. Kohn, Alexandra H. Filipovich, Luigi Daniele Notarangelo, Alain Fischer, Marina Cavazzana-Calvo, David A. Williams, Adrian J Thrasher
Journal: Blood (2013)
Abstract 15743: Highly Potent Visnagin Derivatives Inhibit CYP1 Induction and Prevent Doxorubicin-Mediated Cardiotoxicity in vivo
Authors: Aarti Asnani, Baohui Zheng, Yan Liu, You Wang, Howard Chen, An Chi, Ivan Taracido, Huijun Wang, Doug Johns, David Sosnovik, Randall Peterson
Journal: Circulation (2017)

Introduction: Doxorubicin is an effective chemotherapy, but its use is limited by cardiotoxicity. We previously identified the plant derivative visnagin as selectively protecting against doxorubici...
Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: A Single-Center Real Life Experience
Authors: Chiara Cantò, Elena Ranucci, Stefano Pulini, Fiorenzo Santoleri, Anna Maria Morelli, Francesca Fioritoni, Simona Falorio, Lorenza Torti, Antonio Spadano, Marianna D'Aloisio, Mauro Di Ianni, Stella Santarone, Paolo Di Bartolomeo
Journal: Blood (2018)
Preventing complications: Hepatitis B screening in cancer patients undergoing systemic therapy.
Authors: Rebecca M. Prince, Monika K. Krzyzanowska, Victoria Glinsky, David K Wong, Alyssa Macedo
Journal: Journal of Clinical Oncology (2019)

237 Background: Chemotherapy is a risk factor for HBV reactivation in pts with cancer and chronic HBV. Anti-viral prophylaxis can prevent reactivation but requires identification of infected pts. Many guidelines recommend universal HBV screening prior to cytotoxic/immunosuppressive-therapy, but lack of screening is common globally. A serious safety event and high prevalence of pts from HBV endemic regions receiving treatment at our institution led to a quality improvement project to increase HBV screening prior to chemotherapy. We aimed to increase HBV screening in pts starting systemic therapy at Princess Margaret by 100% by February 28, 2019. Methods: Starting April 2017, an interrupted time series study was undertaken. Baseline HBV screening rate was 43%. Diagnostics including interviews, process mapping and root cause analysis were performed. Interventions to address identified root causes were implemented including specifying required HBV tests, tips for ordering HBV tests, provision of electronic Hepatology referral form, a safety alert email, grand rounds presentation of serious safety event, including HBV screening rate in departmental monthly quality emails and Divisional meetings and adding positive HBV results to the laboratory alerting system. The main outcome measure was the proportion of pts starting systemic therapy screened for HBV. Process measures included correct test ordering, number of Hepatology referrals was a balancing measure. Results were analysed with statistical process control charts. Results: From April 2017-Feb 2019, 5604 pts commenced systemic therapy. Interventions were modified iteratively as the project progressed. HBV screening rate improved from 43 to 79% (84% improvement). Incidence of chronic HBV was routinely above the Canadian average ( &gt; 2%). The percent of correctly ordered screening tests fell from 48 to 33% (31% worsening), while the volume of Hepatology referrals remained manageable (1.5 pts/week). Conclusions: Our Quality Improvement project led to a significant improvement in HBV screening prior to systemic therapy. Further interventions are planned to achieve our target improvement of 100%.
Leukemia-Associated Mutations Of DNMT3A Inhibit Differentiation Of Hematopoietic Stem Cells and Promote Leukemic Transformation Through Abberant Recruitment Of Bmi1
Authors: Junji Koya, Keisuke Kataoka, Takako Tsuruta-Kishino, Hiroshi Kobayashi, Kensuke Narukawa, Tomohiko Sato, Mineo Kurokawa
Journal: Blood (2013)
Assessment Of Human Equilibrative Nucleoside Transporter 1 (hENT1) – Expression By Flow Cytometry In Acute Myeloid Leukemia and Myelodysplastic Syndromes and Correlation To Clinical Outcome In Acute Myeloid Leukemia Patients Treated With Intensive Chemotherapy
Authors: Frauke Bellos, Bruce H. Davis, Naomi B. Culp, Birgitte Booij, Susanne Schnittger, Claudia Haferlach, Torsten Haferlach, Wolfgang Kern
Journal: Blood (2013)
Platelet-Dependent Thrombin Generation Induced By ADP or Activated Factor X Does Not Contribute to Increased In Vivo Thrombin Formation in Myeloproliferative Neoplasms
Authors: Christina Berens, Heiko Rühl, Jens Müller, Johannes Oldenburg, Peter Brossart, Dominik Wolf, Bernd Pötzsch
Journal: Blood (2018)
Proportion of immune suppressive cells in peripheral blood of patients with Gynecologic cancer.
Authors: Ha-Young Lee, Shin Wha Lee, Yong-Man Kim, Hae-Kyeong Yoon, Ji Hye Yoo, Hyun Ok Yang, Seung Tae Lee, Chi Heum Cho, Young-Tak Kim, Joo-Hyun Nam, Jung-Eun Mok
Journal: Cancer Research (2008)

243  Background: Development of tumor occurs through over the growth of cells which have imbalance of growth signals and rapid growth with suppression of immune response by diverse methods. In spite of treating cancer patients with immunotherapy by using diverse immune cells, many cases did not respond due to immune suppression and tolerance. Myeloid-derived suppressor cells (MDSCs), which has been known as immature myeloid cells, facilitate tumor progression and are found in patients whose T cell function does not work efficiently. There is a study reported that the depletion of the MDSCs restores interferon-gamma production and T cell proliferation. Regulatory T lymphocytes (Tregs) constitute an active and dominant mechanism of immunological tolerance and can be defined as a T cell population that functionally suppresses an immune response. Generally, Tregs express CD4 and CD25 on the surface of cells and have Forkhead box P3 (FoxP3) as a transcription factor in cytosol. Many studies have indicated that MDSCs and Tregs play a major roll in the immune response when the immunotherapy is suppressed. However, it is not clear what conditions occurred to the immune suppressor cells of the gynecologic cancer patients. To improve immunotherapy, we need to find out the features of immune system. In this study, therefore, we need to investigate the proportion of MDSCs and Tregs in gynecologic cancer patients.  Materials and methods: Peripheral blood was sampled from 40 with gynecologic cancer patients who were treated in Asan medical center from July to October 2007 and from 9 healthy women as controls and the samples were contained in heparin tubes. We obtained the peripheral blood mononuclear cells by the Ficoll-Hypaque gradient density centrifuge method and analyzed the phenotype with flow cytometry by using anti-CD11b and anti-CD33 antibodies for MDSCs and anti-CD4, anti-CD25 and FoxP3 antibodies for Tregs.  Results: The immune suppressor cells were highly found in the patient group compared with the healthy group. The proportion of CD11b+CD33+ MDSCs was significantly increased in the patient group as 23.44±13.81% whereas the healthy group indicated 15.13±7.88%, (p
Treatment Outcome of Brazilian Patients with Acute Myeloid Leukemia According to the New European LeukemiaNet Recommendations
Authors: Mariana Tereza Lira Benício, Ana Flávia Leonardi Tibúrcio Ribeiro, Antonio R Lucena-Araujo, Ana Beatriz Firmato Glória, Fabio Morato Oliveira, Silvana Maria Eloi Santos, Roberto P. Falcao, Evandro Fagundes, Eduardo M. Rego
Journal: Blood (2011)
More Intensive Fludarabine/Busulfan (Flu/Bu) Conditioning Regimens Result in Similar Outcomes without Adding Serious Toxicity When Compared to Fludarabine/Melphalan (Flu/Mel) in Patients Undergoing Allogeneic Hematopoietic Cell Transplant (Allo-HCT)
Authors: Jeremy Pappacena, Valkal Bhatt, Gunjan L. Shah, Patrick Hilden, Molly Maloy, Larry W Buie, Sergio A. Giralt, Michael Scordo
Journal: Blood (2017)
Abstract 844: β <sub>IV</sub> -spectrin Regulates Cardiac Fibroblast Phenotype, Fibrosis, and Cardiac Function
Authors: Nehal J Patel, Drew M Nassal, Benjamin W Scandling, Amara D Greer-Short, Sathya D Unudurthi, Xianyao Xu, Peter J Mohler, Keith J Gooch, Thomas J Hund
Journal: Circulation Research (2019)

Increased fibrosis is associated with cardiac dysfunction and arrhythmias. Activation of quiescent cardiac fibroblasts (CFs) occurs in response to injury although the underlying mechanistic pathways remain unclear. The cytoskeletal protein β IV -spectrin has been shown to control targeting and activity of the multifunctional transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) for maladaptive remodeling. The mechanism linking spectrin dysfunction to altered STAT3 signaling, fibrosis, and function remains unknown. The objective of this study was to investigate the role of stress-induced disruption of β IV -spectrin/STAT3 complex in modulating CF phenotype, fibrosis, and cardiac function. Cardiac function (echocardiography) and fibrosis (Masson’s trichrome) were evaluated in adult wildtype (WT) and qv 4J mice expressing truncated β IV -spectrin lacking STAT3 interaction. A subset of WT mice were subjected to 6 wks of transaortic constriction (TAC) to induce heart failure. From these groups, CFs were isolated from ventricles and analyzed for STAT3 localization, gene expression, and activity. CFs were treated with selective STAT3 inhibitor S3I-201 (100μM) or transfected for 72 hrs with β IV -spectrin fragment from repeat 10 to C-terminus (β IV,10-C , contains STAT3 binding motif). Ejection fraction was decreased in qv 4J and WT TAC relative to WT baseline (49.5±0.85% vs 34.9±2.2% vs 63.2±0.60% respectively, p&lt;0.05, N=5. Ventricular fibrosis was augmented in qv 4J and WT TAC compared to WT baseline (2.4±0.09% vs 3.2±0.25% vs 0.48±0.01% respectively, p&lt;0.05, N=5). qv 4J CFs showed STAT3 mislocalization (49.7±10.7% nuclear accumulation vs 5.3±.1.8% in WT, p&lt;0.05, N=5) with higher STAT3 transcriptional activity (2.6±0.17-fold increase over WT, p&lt;0.05, N=9). In parallel, qv 4J CFs displayed elevated expression of fibrotic genes associated with CF activation. At the functional level, qv 4J CFs showed increased proliferation (1.9±0.19-fold increase over WT at 24 hrs, p&lt;0.05, N=4). STAT3 inhibition with S31-201 or transfection with β IV,10-C normalized gene expression and proliferation in qv 4J CFs compared to WT. These studies identify a requirement of β IV -spectrin for normal STAT3 signaling and quiescent phenotype in CFs.
Exercise is medicine in oncology: Engaging clinicians to help patients move through cancer
Authors: Kathryn H. Schmitz, Anna M. Campbell, Martijn M. Stuiver, Bernardine M. Pinto, Anna L. Schwartz, G. Stephen Morris, Jennifer A. Ligibel, Andrea Cheville, Daniel A. Galvão, Catherine M. Alfano, Alpa V. Patel, Trisha Hue, Lynn H. Gerber, Robert Sallis, Niraj J. Gusani, Nicole L. Stout, Leighton Chan, Fiona Flowers, Colleen Doyle, Susan Helmrich, William Bain, Jonas Sokolof, Kerri M. Winters‐Stone, Kristin L. Campbell, Charles E. Matthews
Journal: CA A Cancer Journal for Clinicians (2019)

Multiple organizations around the world have issued evidence‐based exercise guidance for patients with cancer and cancer survivors. Recently, the American College of Sports Medicine has updated its exercise guidance for cancer prevention as well as for the prevention and treatment of a variety of cancer health‐related outcomes (eg, fatigue, anxiety, depression, function, and quality of life). Despite these guidelines, the majority of people living with and beyond cancer are not regularly physically active. Among the reasons for this is a lack of clarity on the part of those who work in oncology clinical settings of their role in assessing, advising, and referring patients to exercise. The authors propose using the American College of Sports Medicine's Exercise Is Medicine initiative to address this practice gap. The simple proposal is for clinicians to assess, advise, and refer patients to either home‐based or community‐based exercise or for further evaluation and intervention in outpatient rehabilitation. To do this will require care coordination with appropriate professionals as well as change in the behaviors of clinicians, patients, and those who deliver the rehabilitation and exercise programming. Behavior change is one of many challenges to enacting the proposed practice changes. Other implementation challenges include capacity for triage and referral, the need for a program registry, costs and compensation, and workforce development. In conclusion, there is a call to action for key stakeholders to create the infrastructure and cultural adaptations needed so that all people living with and beyond cancer can be as active as is possible for them.
Factors Associated with Bleeding Events in Patients Receiving Rivaroxaban for Venous Thromboembolism: A Real World Experience
Authors: Ankit Mangla, Muhammad Umair Mushtaq, Koosha Paydary, Hashim Mann, Jiaxiang Liu, Jayasree Krishnan, Tauseef Akhtar, Jishanth Mattumpuram, Aakash Putta, Alok Uprety, Yanting Wang, Barbra Yim, Thomas Lad
Journal: Blood (2018)
Transduction of Human CD34+ Derived NSG Repopulating Cells with An Insulated SIN Lentiviral Vector for SCID-X1 From a Stable Producer Cell Line At Clinical Scale
Authors: Michael R. Greene, Timothy Lockey, John T. Gray, Paul W. Eldridge, Yoon-Sang Kim, Perdeep K. Mehta, Brian P. Sorrentino
Journal: Blood (2011)
Beyond mRNAs and Mirnas: Unraveling the Full-Spectrum of the Normal Human Platelet Transcriptome Through Next-Generation Sequencing
Authors: Eric R. Londin, Eleftheria Hatzimichael, Phillipe Loher, Yue Zhao, Yi Jing, Huang Chen, Leonard C. Edelstein, Srikanth Nagalla, Kathleen Delgrosso, Adam Ertel, Joan Kupper, Paolo M. Fortina, Steven E. McKenzie, Paul F. Bray, Isidore Rigoutsos
Journal: Blood (2012)