tbuckley/cabot-search huggingface dataset:
Abstract 921: Carvacrol Protects Against Diabetes-induced Hypercontractility in the Aorta Through Activating Pi3k/akt Pathway
Authors: Yun Liu, Kai-Ting Ma, Jie Wei, Yun-Pei Mai, Xiao-Xia Qiu, Han Wei, Ning Hou, Jian-Dong Luo
Journal: Circulation Research (2019)

Vascular complications induced by diabetes constitute the principal cause of morbidity and mortality in diabetic patients. It’s reported that carvacrol (CAR) possess a wide range of biological activities. The effect of CAR on diabetes-induced vasculopathy remains unknown. In this study, diabetic mice were created by intraperitoneal injection of streptozotocin to investigate whether CAR provided a protective effect against diabetes-induced vasculopathy and the underlying mechanisms. We found that CAR decreased blood glucose level of diabetic mice. Moreover, CAR ameliorated diabetes-induced aorta morphological alteration, evidenced by increased thickness of intima-media width and increased number of vascular smooth muscle cell (VSMC) layer. Further studies revealed that CAR inhibited the hypercontractility in the aorta of diabetic mice and VSMC in response to hyperglycemia, evidenced by decreased expression of smooth muscle (SM)-α-actin, and increased expression of Ki67 and PCNA. Furthermore, PI3K/Akt signal pathway was inhibited in the aorta of diabetic mice and VSMC in response to hyperglycemia, while CAR treatment activated PI3K/Akt signaling pathway. In conclusion, our results strongly suggested that CAR played a protective role in diabetes-induced aorta hypercontractility, possibly by activating PI3K/Akt signaling pathway. CAR is a potential drug for the treatment of diabetic vasculopathy.
Poor Prognosis of Adult Acute Myeloid Leukemia (AML) with High Level of Evi1 and BAALC Transcript.
Authors: Valeria Biggio, Selim Corm, Hugues Leroy, Stephane De Botton, Christophe Roumier, Stephane Depil, Nathalie Philippe, Jean-Luc Lai, Francis Bauters, Pierre Fenaux, Claude Preudhomme
Journal: Blood (2004)
Robust Detection Of Minimal Residual Disease In Unselected Patients With B-Cell Precursor Acute Lymphoblastic Leukemia By High-Throughput Sequencing Of IGH
Authors: David Wu, Ryan O Emerson, Anna Sherwood, Mignon L. Loh, Anne Angiolillo, Ilan Kirsch, Christopher S Carlson, David Williamson, Brent L. Wood, Harlan Robins
Journal: Blood (2013)
Quality improvement pilot to engage rural Kentucky frontline against lung cancer death.
Authors: Laura Lee Hall, Joseph Weigel, Grace Libby Campbell, Will Miller, J'Aimee Louis, Gregory A Hood
Journal: Journal of Clinical Oncology (2019)

164 Background: Kentucky is the epicenter of smoking and lung cancer in the U.S.: over half the population is a current or former smoker (second only to WV); and it has the highest annual lung cancer incidence—89.6 per 100,000 population—according to the most recent CDC data. While offering a significant, double-digit death benefit due to early recognition and improved therapies, LDCT lung cancer screening of at-risk individuals remains extremely low. Helping primary care practices identify their at-risk patients, promote reduced tobacco use, and refer for screening is critical. Methods: In this pilot, family practice and internal medicine practices, residency programs, and federally qualified health centers (FQHCs) were recruited in rural regions of Eastern Kentucky with populations at highest risk. The Sustainable Healthy Communities Quality Improvement Education (SHC-QIE) model—which engages multidisciplinary practice leaders, rapid cycle improvement or a PDSA approach to QI, geoanalytics, and community engagement support—was implemented to promote better screening while enhancing clinician satisfaction. Results: Each practice significantly improved their identification of smokers and patients qualifying for lung cancer screening in the Medicare program as well as screening referrals by nearly 2-fold. For example, in one FQHC, accurate reporting of tobacco history data in the medical record increased from 34.6% to 56.9%. Another example showed referrals for LDCTs increased from 230 in 2017 to 412 in 2018, with a 71% increase over baseline. While survey data from the participating clinics conceded challenges in implementing a QI initiative, significant satisfaction with the initiative, ongoing plans for activities building on the program, and community engagement were found as well. Pre-, post-survey data also revealed significant improvement in screening, tobacco counseling, and LDCT referral. Conclusions: In spite of EMR barriers, significant increases in smoking history taking, counseling for tobacco cessation, and referral for lung cancer screening was achieved over the course of 9 months.
Abstract 738: Comparative Cardiotoxicity of Tyrosine Kinase Inhibitors Ponatinib and PF114
Authors: Anand P Singh, Prachi Umbarkar, Michael S Glennon, Qinkun Zhang, Ghermes Chilov, Jason R Becker, Hind Lal
Journal: Circulation Research (2019)

Background: The advent of tyrosine kinase inhibitor (TKI) targeted therapy revolutionized the treatment of chronic myelogenous leukemia (CML) patients, leading to a significant impact on remission rates and overall survival. However, cardiotoxicity associated with these targeted therapies put the cancer survivors at greater risk. Ponatinib is an example shown unexpected wide spectrum of cardiotoxic complications which limits its clinical applications. A newly designed 4 th -generation tyrosine kinase inhibitor PF114 having better target spectra in CML, could be a potential alternative to ponatinib. But the cardiotoxic potential of PF114 is not yet fully understood. Objectives: The objectives of the present study were to compare cardiotoxicity of ponatinib with PF114. Methods: In this study, we employed zebrafish transgenic BNP reporter line that expresses luciferase under control of the nppb promoter ( nppb : F-Luciferase) to compare cardiotoxic potential of TKIs. We also exploited NRVMs to explore cardiotoxic mechanism associated with ponatinib and PF114. Results: We observed that increasing dose of PF114 showed minimal induction of the BNP reporter compared to ponatinib. PF114 did not reduce the ventricular fractional shortening in zebrafish as compared to ponatinib. Consistently, in cultured rat cardiomyocytes, PF114 could not reiterate the same cardiotoxic effect of ponatinib as depicted by cell viability and TUNEL assay. Mechanistically, PF114 has shown no effects on essential prosurvival AKT and ERK signaling pathway while ponatinib is known to exerts its cardiotoxic effects by their inhibition. Additionally, the allosteric tyrosine kinase inhibitor ABL001(Asciminib) in combination with PF114 depicts less pronounced cardiotoxic effects than ponatinib in similar settings. Conclusions: This study provides further rationale to utilize zebrafish for the prediction of cardiotoxicity of anticancer drugs. The comparative cardiotoxicity of ponatinib and PF114 suggest that PF114 is a significantly less cardiotoxic analogue and safer treatment option than ponatinib for CML patients harboring BCR/ABL-T315I “gatekeeper” mutation.
Clinical research adds billions to UK economy, analysis shows
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Clinical research backed by England’s national funder, the National Institute for Health Research (NIHR), contributed an estimated £2.7bn (€3.1bn; $3.4bn) to the UK economy and supported over 47 000 jobs last year, an analysis has shown.1

NIHR’s Clinical Research Network works to ensure that research funded by the institute delivers high quality studies. The network commissioned an economic …
Abstract 411: Surface Engineering Strategies to Study Diseases of Heart and Skeletal Muscle
Authors: Aditi Jain, Venkatraman Ravi, Jafar Hasan, Manisha Behera, Kaushik Chatterjee, Nagalingam Ravi Sundaresan
Journal: Circulation Research (2019)

There is an increasing need to develop simplified in vitro platforms that mimic the tissue environment to understand cardiovascular and musculoskeletal diseases. Towards this objective, we first explored different surface engineering strategies for culturing cardiomyocytes, which could be used for investigating disease conditions like cardiac hypertrophy. Firstly, we investigated the possibility of using human hair derived keratin as a simple, efficient and cost-effective substrate for culturing cardiomyocytes. Cardiomyocytes grown on keratin expressed cardiac specific markers and displayed spontaneous contraction. We further evaluated the development of cardiomyocyte hypertrophy upon treatment with the agonist, phenylephrine. We observed the induction of hypertrophy at the transcriptional as well as signaling level. We also observed a marked increase in protein synthesis in these cells indicating the development of hypertrophy. Next, we employed microscale topography to confine cardiomyocytes along ridges which closely resembles mammalian heart. Cardiomyocytes grown on micro-ridges showed global alignment and elliptical nuclear morphology. Calcium currents traversed the cardiomyocytes in a directional manner and were also responsive to hypertrophic stimuli. Like cardiomyocytes, we also investigated the effect of aligned topography on primary myoblasts using nanofibers. These nanofibers retained the myotubes in culture for longer duration as compared to myotubes formed on flat surfaces. Recently, we have seen that once the myoblasts grown on flat surfaces become confluent they spontaneously differentiate to form myotubes even in the absence of differentiation cues. However, myoblasts grown on aligned fibers remain in their undifferentiated state and differentiate only upon induction with differentiation media. These results highlight the suitability of using keratin for cardiomyocyte culture and also emphasize the importance of topography in assessing cardiac and musculoskeletal function. We propose that studies which take into account the morphology of the cells offer greater potential towards clinical translation.
Cure With Interferon‐Free Direct‐Acting Antiviral Is Associated With Increased Survival in Patients With Hepatitis C Virus‐Related Hepatocellular Carcinoma From Both East and West
Authors: Hansen Dang, Yee Hui Yeo, Satoshi Yasuda, Chung‐Feng Huang, Etsuko Iio, Charles Landis, Dae Won Jun, Masaru Enomoto, Eiichi Ogawa, Pei‐Chien Tsai, An Le, Matthew Liu, Mayumi Maeda, Brian Nguyen, Nathan Ramrakhiani, Linda Henry, Ramsey Cheung, Akihiro Tamori, Takashi Kumada, Yasuhito Tanaka, Ming‐Lung Yu, Hidenori Toyoda, Mindie H. Nguyen
Journal: Hepatology (2019)

Background and Aims Survival data among patients with hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC) after achieving sustained virologic response (SVR) with interferon‐free direct‐acting antivirals (DAAs) in both Asian and western countries are limited. Survival rates were compared between patients with HCV‐related HCC who were untreated for HCV and those who achieved SVR. Approach and Results Using data from two U.S. and six Asian centers from 2005 to 2017, we categorized 1,676 patients who were mono‐infected with HCV‐related HCC into patients untreated for HCV (untreated group) and DAA‐treated patients with SVR (SVR group) and matched by propensity score matching (PSM); multivariable Cox regression with HCV treatment status as a time‐varying covariate was used to determine mortality risk and landmark analysis to avoid immortal time bias. There were 1,239 untreated patients and 437 patients with SVR. After PSM, background risks of the 321 pairs of matched patients were balanced (all P &gt; 0.05). After time‐varying adjustment for HCV treatment initiation compared with untreated patients, patients with SVR had significantly higher 5‐year overall survival (87.78% vs. 66.05%, P &lt; 0.001). Multivariable Cox regression showed that SVR was independently associated with a 63% lower risk of 5‐year all‐cause mortality (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.16‐0.83; P = 0.016) and 66% lower risk of 5‐year liver‐related mortality (HR, 0.34; 95% CI, 0.13‐0.88; P = 0.026) with similar trends after removing patients with liver transplants. Landmark analysis at 90, 180, and 360 days showed consistent results (HRs ranged 0.22 to 0.44, all P &lt; 0.05). Conclusion In this multinational consortium, patients with HCV‐related HCC who obtained SVR achieved a 60%‐70% improvement in 5‐year survival (both all‐cause and liver related) compared with patients untreated for HCV. Patients eligible for HCC therapy should also be considered for DAA therapy.
Targeting autophagy-related protein kinases for potential therapeutic purpose
Authors: Honggang Xiang, Jifa Zhang, Congcong Lin, Lan Zhang, Bo Liu, Liang Ouyang
Journal: Acta Pharmaceutica Sinica B (2019)

Autophagy, defined as a scavenging process of protein aggregates and damaged organelles mediated by lysosomes, plays a significant role in the quality control of macromolecules and organelles. Since protein kinases are integral to the autophagy process, it is critically important to understand the role of kinases in autophagic regulation. At present, intervention of autophagic processes by small-molecule modulators targeting specific kinases has becoming a reasonable and prevalent strategy for treating several varieties of human disease, especially cancer. In this review, we describe the role of some autophagy-related kinase targets and kinase-mediated phosphorylation mechanisms in autophagy regulation. We also summarize the small-molecule kinase inhibitors/activators of these targets, highlighting the opportunities of these new therapeutic agents.
Evi-1 Is a Direct Target of MLL Oncoproteins in Hematopoietic Stem Cells
Authors: Shunya Arai, Susumu Goyama, Munetake Shimabe, Motoshi Ichikawa, Yoichi Imai, Tsuyoshi Takahashi, Akira Hangaishi, Mineo Kurokawa
Journal: Blood (2008)
Decision Analysis of Allogeneic Stem Cell Transplantation in Patients with Myelodysplastic Syndrome Stratified According to the Who Classification-Based Prognostic Scoring System (WPSS)
Authors: Emilio Paolo Alessandrino, Matteo G Della Porta, Luca Malcovati, Christopher H Jackson, Cristiana Pascutto, Andrea Bacigalupo, Maria Teresa van Lint, Michele Falda, Massimo Bernardi, Francesco Onida, Stefano Guidi, Anna Paola Iori, Raffaella Cerretti, Paola Marenco, Pietro Pioltelli, Emanuele Angelucci, Rosi Oneto, Alessandro Rambaldi, Alberto Bosi, Mario Cazzola
Journal: Blood (2011)
Polymeric nanobiotics as a novel treatment for mycobacterial infections
Authors: Iris L. Batalha, Audrey Bernut, Mark Schiebler, Myriam M. Ouberai, Charlotte Passemar, Catherine Klapholz, Sonja Kinna, Sarah Michel, Kasim Sader, Pablo Castro-Hartmann, Stephen A. Renshaw, Mark E. Welland, R. Andres Floto
Journal: Journal of Controlled Release (2019)

Mycobacterium tuberculosis (Mtb) remains a major challenge to global health, made worse by the spread of multi-drug resistance. Currently, the efficacy and safety of treatment is limited by difficulties in achieving and sustaining adequate tissue antibiotic concentrations while limiting systemic drug exposure to tolerable levels. Here we show that nanoparticles generated from a polymer-antibiotic conjugate ('nanobiotics') deliver sustained release of active drug upon hydrolysis in acidic environments, found within Mtb-infected macrophages and granulomas, and can, by encapsulation of a second antibiotic, provide a mechanism of synchronous drug delivery. Nanobiotics are avidly taken up by infected macrophages, enhance killing of intracellular Mtb, and are efficiently delivered to granulomas and extracellular mycobacterial cords in vivo in an infected zebrafish model. We demonstrate that isoniazid (INH)-derived nanobiotics, alone or with additional encapsulation of clofazimine (CFZ), enhance killing of mycobacteria in vitro and in infected zebrafish, supporting the use of nanobiotics for Mtb therapy and indicating that nanoparticles generated from polymer-small molecule conjugates might provide a more general solution to delivering co-ordinated combination chemotherapy.
Improving the survivorship care plan process across an academic and community cancer center.
Authors: Robert Stuver, Jennifer Faig, Gerry Abrahamian, Matthew M. Cadorette, William M. Decaneas, Irving D. Kaplan, Michael S. Kent, Christine Van De Wege, Jessica A. Zerillo
Journal: Journal of Clinical Oncology (2019)

184 Background: The goal of a survivorship care plan (SCP) is to improve provider coordination and engage patients in their care. Despite requirements from professional societies, implementation of SCPs is challenging. From April to July 2018, 36% of eligible patients received an SCP at our institution. We aimed to identify barriers to SCP completion and implement interventions to increase their delivery for all cancer types at our academic and community cancer sites. Methods: We created a survey to assess physician, nursing and trainee perceptions and identify barriers to SCP completion. The survey was sent to providers within our medical, surgical, and radiation oncology departments. Providers were asked to rate their satisfaction with our current SCP process and identify obstacles and solutions to achieve SCP completion. In response, we held meetings between oncology attendings, trainees, tumor registry staff, and health information management personnel to design an improvement plan. Results: Of 178 providers, 74 (41.6%) responded. Four percent were satisfied with our current process. The most frequently cited barriers were time (62.1%), lack of clarity regarding who completes the SCP (52%), and insufficient personnel (47.3%). The most frequently cited solutions were dedicated personnel (84.9%), disease-specific templates (61.6%), and education regarding SCPs (48.1%). Based on these results, we: (1) Streamlined our SCP process by entering a partially-templated SCP into an eligible patient’s electronic medical record by our tumor registrar; (2) Asked for disease-specific recommendations that can be included in the template; (3) Asked providers to identify additional team members who assist with SCP completion so that SCPs can be appropriately queued; and (4) Designed an online educational module. Conclusions: We identified multiple barriers to SCP completion at our institution. In response, we implemented a multifaceted improvement plan across our academic and community cancer sites. An analysis of its effects are forthcoming.
Myd88/CD40 Costimulation to Enhance the Antitumor Activity of CD123-ENG T-Cells for the Immunotherapy of AML
Authors: Erin Doherty, Abishek Vaidya, Xiya Wu, Challice L. Bonifant, Melinda Mata, Ann M. Leen, Stephen Gottschalk, Mireya P. Velasquez
Journal: Blood (2018)
Abstract 278: Reduced HtrA2 Protein Levels in Mitochondria but Elevated Levels in Cytosol of Left Ventricular Myocardium of Dogs with Chronic Heart Failure
Authors: Ramesh C Gupta, Vinita Singh-Gupta, Hani N Sabbah
Journal: Circulation Research (2019)

Background: The high-temperature requirement serine peptidase 2 (HtrA2) is a pro-apoptotic mitochondrial serine protease involved in caspase-dependent as well as caspase-independent programmed cell death. When HtrA2 protein is tightly associated with mitochondria (MITO), its protease activity is masked. In contrast, once the protein is released from MITO into the cytosol (CS), its protease activity is exposed. Once active HtrA2 activates caspase-3, a pro-apoptotic enzyme, by degrading the caspase-3 inhibitor XIAP (x-linked inhibitor of apoptosis protein. Recent studies have shown that translocation of HtrA2 protein from the MITO to the CS occurs in mice hearts during experimental myocardial ischemic and reperfusion. Hypothesis: In this study we examined if translocation of HtrA2 from MITO to CS occurs in LV myocardium of dogs with chronic stable heart failure (HF). Methods: LV tissue from 7 dogs with chronic HF produced by multiple sequential intracoronary micro-embolizations (LV ejection fraction &lt;35%) and 7 normal (NL) dogs was used to prepare crude homogenate (HG) and to isolate MITO and CS fractions. Using primary antibodies, HtrA2 protein was determined in HG, MITO and CS fractions by Western blotting coupled with chemiluminescence. GAPDH was used as an internal loading control for both HG and CS fractions. Porin was used as an internal loading control for MITO fractions. HtrA2 band intensity was normalized to GAPDH for HG and CS and to porin for MITO. Results: GAPDH and porin protein levels were unchanged between NL and HF dogs. Compared to NL, HtrA2 protein levels in dogs with HF were unchanged in HG (0.76 ± 0.04 vs. 0.73 ± 0.08), significantly reduced in MITO (0.17 ± 0.02 vs. 0.40 ± 0.05, p&lt;0.05) and significantly increased in CS (0.90 ± 0.07 vs. 0.36 ± 0.05, p&lt;0.05). Conclusions: Compared to NL dogs, HtrA2 protein levels are significantly reduced in MITO but increased in cytosol fractions from LV myocardium of dogs with chronic stable HF; a maladaptations that promotes cardiomyocyte apoptosis and progressive LV dysfunction. Inhibiting the translocation of HtrA2 from MITO to CS may have therapeutic potential for the preventing progressive dysfunction of the failing heart.
The Evolution of Malignant and Reactive γδ+T Cell Clones in Relapse T-ALL After Allogeneic Stem Cell Transplantation
Authors: Shaohua Chen, Xin Huang, Haitao Zheng, Suxia Geng, Junyan Hu, Fan Zhang, Lijian Yang, Jianyu Weng, Xin Du, Yangqiu Li
Journal: Blood (2012)
Nelarabine Is Safe and Effective In Adult Relapsed or Refractory T Cell Acute Lymphoblastic Leukemia (T-ALL) and Lymphoblastic Lymphoma (T-LBL): The Bologna Experience
Authors: Cristina Papayannidis, Ilaria Iacobucci, Mariachiara Abbenante, Annalisa Lonetti, Viviana Guadagnuolo, Anna Ferrari, Emanuela Ottaviani, Nicoletta Testoni, Carmen Baldazzi, Antonio Curti, Sarah Parisi, Cristina Clissa, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2011)
Eculizumab Is An Effective Long-Term Treatment In Patients with Atypical Hemolytic Uremic Syndrome (aHUS) Resistant to Plasma Exchange/Infusion (PE/PI): Results of An Extension Study
Authors: Larry Greenbaum, Sunil Babu, Richard R. Furman, Neil Sheerin, David Cohen, Osama Gaber, Frank Eitner, Yahsou Delmas, Chantal Loirat, Camille L Bedrosian, Christophe Legendre
Journal: Blood (2011)
IL3 Induces Osteoclastogenesis In Vivo and Is Modulated By Bone Marrow Monocyte / Macrophage Derived Activin A
Authors: Rebecca Silbermann, Marina Bolzoni, Paola Storti, Daniela Guasco, Judith Anderson, Jolene J. Windle, G. David Roodman, Nicola Giuliani
Journal: Blood (2013)
Correction to: Polatuzumab Vedotin: First Global Approval
Authors: Emma D. Deeks
Journal: Drugs (2019)

The article Polatuzumab Vedotin: First Global Approval, written by Emma D. Deeks, was originally published Online First without Open Access. After publication in volume 79, issue 13, pages 1467-1475 Roche/GCC requested that the article be Open Choice to make the article an open access publication. Post-publication open access was funded by Roche/GCC. The article is forthwith distributed under the terms of the Creative Commons Attribution-NonCommercial.
Proteomic Analysis of the Role of STAT5A in the Apoptosis of Human Pre-B Cells : Evidence for a Connection to Daxx and the Oxidative Stress
Authors: Eric Cholez, Veronique Debuysscher, Roland Charlionet, Francois Tron, Fabrice Gouilleux, Kaiss Lassoued, Valerie Gouilleux-Gruart
Journal: Blood (2008)
Single-Centre Validation Of a Disease Risk Index For Estimating Survival and Relapse In Allogeneic Hematopoietic Stem Cell Transplant Recipients: Sample Size, Adequate Follow-Up, and Use Of Local Data Are Vital Considerations
Authors: Andrew B M Lim, Andrew W. Roberts, Kate Mason, Ashish R. Bajel, Jeffrey Szer, David Ritchie
Journal: Blood (2013)
Platelet Dysfunction and Cellular Microparticles May be Involved in the Hipercoagulable State Observed in Obstructive Sleep Apnea Syndrome
Authors: Ihosvany Fernandez-Bello, Raul Justo Sanz, Elena Monzón Manzano, Francisco García Río, Carolina Cubillos, Cristina Balbás-García, Teresa Álvarez-Roman, Mónica Martín, María Isabel Rivas Pollmar, Miguel A. Canales, Victor Jimenez-Yuste, Nora Butta
Journal: Blood (2018)