tbuckley/cabot-search huggingface dataset:
Molecular profiling in the diagnosis of synchronous primary cancers of the endometrium and ovary
Authors: P. T. Soliman, J. Celestino, S. Finklelstein, R. Broaddus, S. Westin, K. M. Schmeler, K. H. Lu, R. L. Coleman
Journal: Journal of Clinical Oncology (2009)

e16500 Background: Synchronous primary cancers of the endometrium and ovary (SYNCH) have a better prognosis than either primary endometrial or ovarian cancer with metastasis (MET). Distinguishing SYNCH from MET can be a challenge when the neoplasms share similar histologic features. To date, histologic characteristics are used to make this distinction and guide treatment decisions. The purpose of this study was to determine if objective discrimination using an integrated molecular approach can assist in making this distinction. Methods: Paired tumor samples from 16 SYNCH and 11 MET were sent for mutational profiling. 13 samples were sent as blinded duplicates for internal validation. The mutational profile for each neoplasm was determined using PCR and quantitative genotyping for a panel of LOH markers targeting 1p,3p,5q,9p,10q,17p,17q,21q,22q and k-ras-2 exon 1 DNA sequencing for point mutational change. The paired samples were then re-defined as SYNCH versus MET based on the profile results. Survival was compared using Kaplan-Meier. Results: The results are in the table. All of the duplicate samples had the same molecular profile results. Median survival based on pathologic diagnosis was 106 months in SYNCH versus 37 months in MET (p=0.07). The median survival was 110 months in both groups based on molecular profiling results. For patients with a diagnosis of SYNCH by both pathology and molecular profiling median survival was 117 months. For those with a pathologic diagnosis of SYNCH but metastasis on molecular profiling survival was 129 months. Conclusions: Molecular profiling to distinguish synchronous primary cancers from either primary endometrial or ovarian cancer with metastasis, is currently being evaluated. In this study, the pathologic diagnosis was a better indicator of survival than a diagnosis based on molecular profiling alone. Further studies are being performed to determine the role of molecular profiling in women who are thought to have synchronous primary cancers of the endometrium and ovary. [Table: see text] [Table: see text]
Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry
Authors: Hanneke C. Kluin-Nelemans, Andreas Reiter, Anja Illerhaus, Bjorn van Anrooij, Karin Hartmann, Lambertus F. R. Span, Aleksandra Gorska, Marek Niedoszytko, Magdalena Lange, Luigi Scaffidi, Roberta Zanotti, Patrizia Bonadonna, Cecelia Perkins, Chiara Elena, Luca Malcovati, Khalid Shoumariyeh, Nikolas von Bubnoff, Roberta Parente, Massimo Triggiani, Juliana Schwaab, Mohamad Jawhar, Francesca Caroppo, Anna Belloni Fortina, Knut Brockow, Alexander Zink, David Fuchs, Alex Kilbertus, Akif Selim Yavuz, Michael Doubek, Mattias Mattsson, Hans Hagglund, Jens Panse, Vito Sabato, Elisabeth Aberer, Dietger Niederwieser, Christine Breynaert, Judit Várkonyi, Vanessa Kennedy, Olivier Lortholary, Thilo Jakob, Olivier Hermine, Julien Rossignol, Michel Arock, Jason Gotlib, Peter Valent, Wolfgang R. Sperr
Journal: Leukemia (2019)
Myocardial Strain Imaging by Echocardiography for the Prediction of Cardiotoxicity in Chemotherapy-Treated Patients
Authors: Lu Ye, Zhi-gang Yang, Joseph B. Selvanayagam, Hong Luo, Tai-zhu Yang, Rebecca Perry, Kai-yue Diao, Shan Huang, Meng-xi Yang, Pan Yang, Ya Jin, Ying-kun Guo
Journal: JACC. Cardiovascular imaging (2019)
Brentuximab Vedotin Plus Bendamustine: As Salvage Regimen for Relapsed or Refractory Hodgkin Lymphoma, King Abdulaziz Medical City - Jeddah - KSA Experience
Authors: Muteb Althomali, Ahmad Absi, Ihab El Hemaidi, Ashraf Warsi, Sameer AlAmoudi, Majed Alahmadi, Walaa Rajkhan, Sultan Almutairi, Saleem Eldadah, Manar Khalil, Muna Adam, Syed Adnaan Ali, Abdulrahman Alghamdi, Ahmad Alsaeed
Journal: Blood (2019)
Abstract 9763: Brain-targeted Intranasal Administration of Viral Inhibition Peptide of Toll-like Receptor 4 Improves Survival and Prevents Left Ventricular Remodeling Via Sympathoinhibition in Ischemia-induced Heart Failure
Authors: Takuya Kishi, Yoshitaka Hirooka, Kenji Sunagawa
Journal: Circulation (2012)

[Backgrounds] Abnormal sympathoexcitation causes left ventricular (LV) remodeling and worsen the prognosis of ischemia-induced heart failure (HF). Recent studies have suggested that inflammation in the brain induces sympathoexcitation in HF. We previously demonstrated that brain inflammatory cascade mediated by Toll-like receptor 4 (TLR4) is activated in HF associated with sympathoexcitation. However, brain-specific inhibitory agent of TLR4 has not been available. The aim of the present study was to investigate whether intranasal administration of viral inhibition peptide of TLR4 (VIPER) could inhibit brain-specific TLR4 or not, and whether the brain-targeted inhibition of TLR4 could improve survival rate and prevent LV remodeling via sympathoinhibition in ischemia-induced HF or not. [Methods and Results] Sprague-Dawley rats with HF by coronary artery ligation were initiated the treatment with a dairy intranasal administration of VIPER (VIP), dairy intraperitoneal administration of VIPER (IP) or vehicle (Veh) just after the operation. At day 1, the expressions of TLR4, MyD88 (second messenger of TLR4), and nuclear factor κB (NFκB) in the brain were already significantly lower in VIP than in IP and Veh. These effects in VIP group were confirmed continuously in terms of the treatments. At day 7, urinary norepinephrine excretion (UNE; parameter of sympathoexcitation) was significantly lower and LV end-systolic dimension (LVESD) were significantly smaller in VIP than in Veh (uNE; 1.6±0.2 μg/day vs. 2.5±0.2 μg/day, LVESD; 2.9±0.3 mm vs. 4.8±0.2 mm, n=15 for each, p&lt;0.05 for each). At day 30, the survival rate was significantly higher in VIP than in Veh (84 % vs 61 %, P&lt;0.05). All of these beneficial results in VIP group were not obtained in IP group. [Conclusion] Intranasal administration of viral inhibition peptide of TLR4 is able to inhibit brain-specific TLR4, and improves survival rate and prevents LV remodeling via sympathoinhibition in ischemia-induced HF. This method has a potential to be a novel treatment for ischemia-induced HF with sympathoinhibition.
Minorities Do Not Have Worse Outcomes for Diffuse Large B Cell Lymphoma (DLBCL) If Optimally Managed
Authors: Bei Hu, Tommy Chen, Danielle Boselli, Rupali Bose, James T. Symanowski, Derek Raghavan, Amy Soni, Steven I Park, Belinda R Avalos, Edward A Copelan, Ryan Jacobs, Nilanjan Ghosh
Journal: Blood (2019)
Identification of Novel Combination Therapies Active in BCL2 Inhibitor-Resistant Patient-Derived AML Models
Authors: Courtney L Andersen, Amanda L Christie, Alan Rosen, Kim Maratea, Maureen Hattersley, Jon Travers, Justin Cidado, Sai Pulukuri, Jamal Saeh, Edwin Clark, Corinne Reimer, Jerome Mettetal
Journal: Blood (2019)
Patient Characteristics and Outcomes in Adolescents and Young Adults (AYA) with Acute Myeloid Leukemia (AML): Princess Margaret Cancer Centre Experience
Authors: Muhned Alhumaid, Georgina S Daher-Reyes, Wilson Lam, Arjun Law, Tracy Murphy, Caroline J McNamara, Gil Yerushalmi, Aaron D Schimmer, Andre C. Schuh, Dawn Maze, Eshetu G Atenafu, Karen W.L. Yee, Mark D. Minden, Steven M Chan, Vikas Gupta, Hassan Sibai
Journal: Blood (2019)
Combination of NKTR-255, a Polymer Conjugated Human IL-15, with CD19 CAR T Cell Immunotherapy in a Preclinical Lymphoma Model
Authors: Cassie Chou, Simon Fraessle, Rachel Steinmetz, Reed M. Hawkins, Tinh-Doan Phi, Dirk Busch, Takahiro Miyazaki, Mario Q. Marcondes, Stanley R. Riddell, Cameron J. Turtle
Journal: Blood (2019)
Design and Characterization of FLT210, a Potent Next Generation AAV-hFVIII Vector Candidate
Authors: Azadeh Kia, Fabrizio Comper, Samantha Correia, Caterina Casari, Segen Negash, Maria Portillo, Jalpa Pandya, Tihomir Dodev, Andreas Schulze, Florian Sonntag, Renee Kober, Clement Cocita, Elisa Chisari, Rebecca Alade, Erald Shehu, Jey M Jeyakumar, Jaminder Khinder, Jonathan H. Foley, Allison Dane, Jenny McIntosh, Hattie Ollerton, Olivier Christophe, Cecile V. Denis, Romuald Corbau
Journal: Blood (2019)
Discrepancies in reported <i>versus</i> measured nicotine content of e-cigarette refill liquids across nine European countries before and after the implementation of the EU Tobacco Products Directive
Authors: Charis Girvalaki, Manolis Tzatzarakis, Alexander Vardavas, Christina N. Kyriakos, Katerina Nikitara, Polychronis Stivaktakis, Aristidis Tsatsakis, Constantine Vardavas
Journal: European Respiratory Journal (2019)

<b>Close monitoring of the nicotine concentration of e-cigarette refills in the EU is necessary, as discrepancies exist between the actual nicotine content in the vial as compared to that stated on the label, even after the implementation of the TPD</b>http://bit.ly/33kqMbZ
RTHP-05. CONTRIBUTION OF ATM MUTATION TO THE IMPROVED RADIO-SENSITIVITY: RETROSPECTIVE ANALYSIS USING NEXT-GENERATION SEQUENCING DATA
Authors: Hong In Yoon, Nalee Kim, Se Hoon Kim, Ju Hyung Moon, Seok-Gu Kang, Chang-Ok Suh, Jong Hee Chang
Journal: Neuro-Oncology (2019)

Abstract PURPOSE/OBJECTIVES To identify the association of somatic ATM mutation (mATM) with improved radiotherapy sensitivity, we retrospectively reviewed the next-generation sequencing (NGS) data from high grade glioma patients. MATERIALS/METHODS This analysis includes 48 consecutive individuals diagnosed with high grade glioma (diffuse astrocytoma IDH-wild type n=2, anaplastic astrocytoma n=18, and glioblastoma n=28) between June 2017 and October 2018. Patients who underwent subtotal (n=30, 62.5%), partial (n=17, 35.4%) removal or biopsy (n=1, 2.1%) were included in this analysis for interpreting radio-sensitivity of residual tumor. We investigated mATM by NGS of FFPE specimens with a TruSight Tumor 170 (TST-170) cancer panel. RESULTS Among 48 samples, mATM was detected in 17% of cases (n=8). There was no significant difference in patient or tumor characteristics. Among mATM patients, there were 5 patients with glioblastoma and 3 patients with anaplastic astrocytoma IDH-wildtype. Most mutation was missense mutation (n=7, 88%). Median variant allele frequency was 44.7% (Interquartile range, IQR, 10.5–59.9%). Median follow-up duration after radiotherapy was 11.4 (IQR, 8.0–15.8) months. Radiation-related change was observed in 34 patients (71%). Tumors with mATM were related to higher frequency of radiation-related change at 6 months than tumors without mATM, respectively (88% and 64%, p = 0.016). Cases with mATM exhibited significantly 1-year progression free survival (PFS, 100% vs. 54%, p = 0.036). On subgroup of IDH WT (n=39) known as poor prognostic molecular marker, patients with mATM showed significantly higher PFS than patients without mATM (p=0.016, 1yr PFS 100% vs 43%). On subgroup with sub-ventricular zone involvement (n=38) representative of aggressiveness, PFS of patients with mATM was significantly higher than others (p=0.026, 1yr PFS 100% vs 43.9%). CONCLUSIONS Our results demonstrated that mATM is involved in radio-sensitivity with immediate radiologic change after radiation therapy followed by favorable radiologic response and clinical outcome beyond the aggressive nature of high grade glioma.
Comprehensive Genomic Profiling of Pediatric Therapy-Related Myeloid Neoplasms Identifies Mecom Dysregulation to be Associated with Poor Outcome
Authors: Jason R Schwartz, Jing Ma, Michael P Walsh, Xiaolong Chen, Tamara Lamprecht, Jennifer Kamens, Scott Newman, Jinghui Zhang, Tanja A. Gruber, Xiaotu Ma, Jeffery M. Klco
Journal: Blood (2019)
P-Akt/SNF5 signaling interactions in rhabdoid tumors
Authors: Aubri L. Charboneau, Jingjing Chai, Bryan Betz, Bernard Weissman
Journal: Cancer Research (2005)

4544  Chromatin remodeling factors are important regulators of cell growth and differentiation. Alterations in these factors have been shown to lead to the development of human cancers. Expression of SNF5/Baf47, a member of the SWI/SNF (mating type switch/sucrose nonfermenting) complex, is lost in more than 80% of malignant rhabdoid tumors (MRT). Our lab previously demonstrated that re-introduction of SNF5 into A204 and TM87-16 MRT cell lines induces growth arrest. In A204 cells, SNF5 interacts directly at the p16 and p21 promoters to up-regulate expression. However, re-introduction of SNF5 does not induce a growth arrest in all SNF5 null rhabdoid tumor cell lines, including G401. Therefore we are investigating whether the SNF5 induced p21 response is functional in these cells. SNF5 does induce p21 expression in G401. However, transiently transfected p21 predominantly localizes in the cytoplasm of G401 as compared to solely localizing in the nucleus of A204. Because P-Akt has been shown to phosphorylate p21, causing its exclusion from the nucleus, we characterized Akt expression in these rhabdoid cell lines. We discovered high levels of P-Akt expression in G401 and TTC709 as compared to A204 and TM87-16 cells. As the growth inhibitory activity of p21 is associated with nuclear localization, we hypothesized that high levels of P-Akt and altered p21 localization may be responsible for impaired SNF5 sensitivity. In support of this model, we found that wild type p21 does not induce as great a growth arrest in G401 or TTC709 as compared to A204 or TM87-16 cells. In contrast, a p21 mutant incapable of being phosphorylated by P-Akt, induces a growth arrest in G401 and TTC709 similar to that found in A204 and TM87-16 cells. However, as p21 has some inhibitory effect on G401 and TTC709 cells, impaired p21 activity may not be solely responsible for lack of SNF5 induced growth arrest. We also generated stable control and dominant negative DN-Akt expressing G401 clones. We found DN-Akt G401 clones exhibit a 50% decrease in cellular proliferation and colony formation when transfected with SNF5 as compared to control. Therefore, blocking P-Akt allows SNF5 to induce a partial growth arrest in G401. These studies provide a more comprehensive approach to inhibiting rhabdoid tumor cell growth. Moreover, we also found that P-Akt expression is high in some human primary rhabdoid tumors in vivo. Therefore, this work may give insight into the development of rhabdoid tumors because their cellular origin remains unknown.
Daratumumab (DARA) Plus Lenalidomide Versus Lenalidomide Alone As Maintenance Treatment in Patients with Newly Diagnosed Multiple Myeloma (NDMM) after Frontline Autologous Stem Cell Transplant (ASCT): Use of Minimal Residual Disease (MRD) As a Novel Primary Endpoint in the Phase 3 Auriga Study
Authors: Nina D. Shah, Yana Lutska, Huiling Pei, Ming Qi, Maria Krevvata, Colleen Kane, Jon Ukropec, Thomas S. Lin, Shalaka Hampras
Journal: Blood (2019)
Effect of Radiation on Lymph and on Lymph Vessels
Journal: JAMA (1963)

I N SPITE of the fact that the majority of cancer deaths occur because of lymphatic metastasis, the effects of radiation upon the lymphatic vessels are still imperfectly known. Essentially the question is: Is it possible to seal the lymph vessels by irradiation? In an attempt to answer this question a number of experiments were conducted at the Radiological Institute of the University of Modena during the last five years with 200-kv radiation, a cobalt bomb, and by a 15-Mev betatron. Rabbits and guinea pigs were employed as experimental animals, and, in addition, 30 human uteri were examined following irradiation and hysterectomy for cancer. The technics of examination included injection of latex in the lymph vessels followed by maceration of the tissues. The circulating lymph was studied by phase contrast microscopy. For study of the circulating lymph 40 guinea pigs were given whole-body irradiation with a 1,500 curie cobalt bomb for a dose of 7,500 r at one sitting. Lymph specimens were studied five and twenty hours after irradiation (15 animals in each group). A few drops of Sky Blue dye were administered intratracheally, and the animals were killed under ether anesthesia. The lymph was aspirated from the prenodal pulmonary lymphatics, which were visualized by the dye, and placed on microscopic slides. Counts were then made of the normal and abnormal lymphocytes. The lymph of animals killed five hours following irradiation showed a constant diminution of the number of lymphocytes and a few abnormal cells. These changes were much more marked after twenty hours when a large number of lymphocytes had degenerated into cellular debris. The macrophages, on the other hand, were numerFig. 1. Lymph vessels of young female rabbit. A. Uterine network. B. Rectal network.
DDIS-32. MEK INHIBITORS INDUCES NEURONAL DIFFERENTIATION IN EGFR AMPLIFIED GLIOMA STEM LIKE CELLS
Authors: Veerakumar Balasubramaniyan, Soon Park, Yuji Piao, Emmanuel Martínez, Jianwen Dong, Sandeep Mittal, Sabbir Khan, Ze-yan Zhang, Erik Sulman, John DeGroot
Journal: Neuro-Oncology (2019)

Abstract The median survival for patients with glioblastoma (GBM) is 12–15 months highlighting the need for better therapeutic strategies for this deadly disease. Genomic and epigenomic sequencing analysis at the single cell level have identified multiple genomic aberrations as potential targets for therapeutic intervention in GBM. EGFR and PDGFR amplification are evident in nearly 40% and 12% of human GBM, respectively. Although the first and second-generation EGFR tyrosine kinase small molecule inhibitors failed to show long term therapeutic benefit in GBM patients, multiple factors such as incorrect patient selection, acquired resistance, and drug-target heterogeneity may all lead to clinical failure of targeted therapies. Although the multilevel genomic characterization of gliomas are increasing, the clinical translation of these findings is beginning to unravel. In this study, we attempted to correlate the genomic variations using an unbiased high throughput drug screen using primary glioma stem-like cell (GSCs) as our model system. An unbiased high-throughput screen utilizing our GSC models identified that glioblastoma cells harboring focal EGFR amplification are sensitive to mitogen-activated protein kinase (MEK) inhibitors. MEK inhibition induced apoptosis in EGFR amplified cells at low concentration. RNA sequence analysis of cells treated with MEK inhibitors revealed upregulation of genes related to neuronal differentiation and down regulation of MEK target genes in MEK sensitive glioma stem cells. Additionally, RNA sequencing of GSCs with acquired MEK inhibitor resistance demonstrated an upregulation of oncogenic transcription factor ETS Variant Gene 1 (ETV1) as a mediator of resistance. Overall our data suggest that the MEK inhibition in combination with ETV inhibitors could be a potential therapeutic target for a subset of GBM patients.
Muktwelve: A Randomized Phase II Trial of Selinexor, Cyclophosphamide and Prednisolone Vs Cyclophosphamide and Prednisolone in Relapsed or Refractory Multiple Myeloma (RRMM) Patients
Authors: Sarah R Brown, Andrew Hall, Jessica Kendall, Emma Ingleson, Louise Flanagan, Holger W Auner, Kevin Boyd, Mamta Garg, Martin F. Kaiser
Journal: Blood (2019)
Characteristics and Outcomes of Therapy Related Myeloid Neoplasms in Patients with Multiple Myeloma Following Autologous Stem Cell Transplantation
Authors: Kalyan Nadiminti, M Hasib Sidiqi, Kapil Meleveedu, Hassan B. Alkhateeb, Aref Al-Kali, William J Hogan, Mark Litzow, Shaji K. Kumar, Mrinal M Patnaik, Morie A. Gertz, Dong Chen, Mithun Vinod Shah
Journal: Blood (2019)
MCL-1 and PKA/AMPK Axis Fuel Venetoclax Resistance in Lymphoid Cancers
Authors: Vivian M. Liu, Romain Guièze, Daniel Rosebrock, Alexis A Jourdain, María Hernández-Sánchez, Aina Zurita Martinez, Elisa Ten Hacken, Philip A. Thompson, Julian Bryan Iorgulescu, Shuqiang Li, Matthew S. Davids, Jennifer R. Brown, Ana Lako, Zoe B. Ciantra, Matthew A. Lawlor, William G. Wierda, Anthony G. Letai, Donna S Neuberg, Christopher J. Ott, Ignaty Leshchiner, Vamsi Mootha, Gad Getz, Catherine J. Wu
Journal: Blood (2019)
A Novel Combination Regimen of BET and FLT3 Inhibition for FLT3-ITD Acute Myeloid Leukemia
Authors: Lauren Lee, Yoshiyuki Hizukuri, Paul Severson, Ben Powell, Chao Zhang, Yan Ma, Maiko Narahara, Hiroyuki Sumi, Gideon Bollag, Mark J. Levis
Journal: Blood (2019)
AB0568 How well are the asas/omeract core outcome sets for ankylosing spondylitis implemented in randomized clinical trials? a systematic literature review
Authors: W. Bautista-Molano, V. Navarro-Compán, R. Landewé, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The Assessment of SpondyloArthritis international Society (ASAS) has selected a core set of variables to include as standardized endpoints in clinical trials and clinical practice. These core sets received endorsement by OMERACT and specific measurement instruments to assess each of these domains have been chosen. The implementation of the ASAS/OMERACT core sets, though, has so far not been evaluated. The purpose of this systematic literature review, therefore, was to compare the usage of domains and instruments of the core-sets before and after the original publication. <h3>Objectives</h3> To investigate how well the ASAS/OMERACT core sets for the outcome of ankylosing spondylitis (AS) have been implemented in randomized controlled trials (RCTs) testing pharmacological and non-pharmacological interventions <h3>Methods</h3> A systematic literature search was performed in electronic databases up to January 2012 looking for RCTs in patients with AS. Domains of outcome, and instruments belonging to them, for disease controlling antirheumatic therapy (DC-ART) and symptom modifying antirheumatic drugs (SMARD) were extracted. Results are reported for clinical trials published before (control trials) in comparison to those published 2 years after the publication of the core set (1 April 2001, implementation trials). <h3>Results</h3> One hundred eight articles reporting results from 91 RCTs, and together including 11.174 patients, fulfilled the selection criteria for this project. Forty-seven RCTs were considered 'control trials' and 44 were considered 'implementation trials'. NSAID and conventional non-biological DMARD therapies were more often tested in the 'control' - than in the 'implementation trials'. Biological DMARDs and physical therapy were more often tested in the 'implementation trials'. The domains 'physical function', 'pain', 'stiffness', 'peripheral joint/entheses', 'acute phase reactants' and 'fatigue', as well as the instruments 'BASFI', 'BASMI', 'CRP' and 'spine radiograph' were more frequently addressed in the 'implementation trials'. <h3>Conclusions</h3> This systematic literature review suggests that the definition and dissemination of the core set measures for clinical trials in AS has indeed resulted in an improved usage of the endorsed domains and instruments. <h3>References</h3> van der Heijde D. J Rheumatol 1999;26:951-4, Sieper J. Ann Rheum Dis 2009;68:ii1-44 <h3>Disclosure of Interest</h3> None Declared
A Comparison of the Effect of Granulocyte-Colony Stimulating Factor (G-CSF) in Chemotherapy Versus Plerixafor for Hematopoietic Stem Sell Transplantation (HSCT) and Mobilization
Authors: Flavia zattar Piazera, Alexandre Nonino, Rafael De Sá Vasconcelos, Andre Luiz Soares Cunha, Jorge Vaz Pinto, Mariana Profiro
Journal: Blood (2019)