tbuckley/cabot-search huggingface dataset:
Randomized phase II study of capecitabine with or without ramucirumab (IMC-1121B) or IMC-18F1 in patients with unresectable, locally advanced or metastatic breast cancer (mBC) previously treated with anthracycline and taxane therapy (CP20-0903/NCT01234402).
Authors: L. T. Vahdat, K. Miller, J. A. Sparano, H. Youssoufian, J. D. Schwartz, S. Nanda, W. Wang, L. Abad, A. Dontabhaktuni, M. D. Rutstein
Journal: Journal of Clinical Oncology (2011)

TPS151 Background: Ramucirumab is a fully human IgG1 monoclonal antibody (MAb) that targets the VEGFR‐2, blocks the interaction of VEGF and VEGFR‐2 and neutralizes VEGF-induced mitogenesis of human endothelial cells. Treatment with DC101 (MAb targeting murine VEGFR-2) impairs vascular function and increases tumor hypoxia in the MDA-MB-231 breast cancer xenograft model (Cancer Res. 2006;66:3639-48) and inhibits tumor growth in cytotoxic therapy-resistant breast cancer xenograft models (Clin Cancer Research. 2002;8:221–32). IMC-18F1 is a fully human IgG1 MAb which targets human VEGFR-1 (Flt-1). IMC‐18F1 binds to VEGFR-1 and blocks receptor binding of VEGF-A, VEGF-B, and PlGF, and inhibits subsequent signaling. IMC-18F1 and MF1 (MAb targeting murine VEGFR-1) treatment with 5-FU/LV, cyclophosphamide, or doxorubicin resulted in enhanced antitumor efficacy compared with cytotoxic monotherapy in MD-MBA-231 tumor xenografts (Clin Cancer Res.2006;12:6573-84). Methods: This 3-arm study opened for accrual in 11/2010. Enrollment of 150 patients (pts) with unresectable, locally advanced or mBC, previously treated with anthracycline and taxane therapy, will occur at 30 US centers. The primary objective is PFS. Secondary objectives include tumor response, safety, PK, and immunogenicity. Association between clinical outcome and genetic polymorphisms, levels of plasma angiogenic proteins, and levels of VEGFR-1 positive circulating tumor cells and hematopoietic precursor cells will be assessed. Pts will be randomized in a 1:1:1 ratio to 1 of 3 arms in 21-day cycles as follows: capecitabine (1000 mg/m2 po BID for 14 days) plus ramucirumab (10 mg/kg) on Day 1 (Arm A); capecitabine plus IMC-18F1 (12 mg/kg) on Day 1 and Day 8 (Arm B); or capecitabine (Arm C). Pts in Arm C will be eligible to receive either MAb with capecitabine, after disease progression on capecitabine. Randomization will be stratified by triple-negative receptor status and prior antiangiogenic therapy. Pts will be treated until disease progression or other withdrawal criteria are met.
P1.06-041 Overall Survival and Intermediate Outcomes among Scandinavian Non-Small Cell Lung Cancer Patients: The SCAN-LEAF Study
Authors: Simon Ekman, Jens Benn Sørensen, Julia Rockberg, Martin Sandelin, Melinda Daumont, Patrik Sobocki, Peter Klint, Han-Yao Huang, Jenny Svärd, Oana Chirita, Leif Jørgensen, Maria Planck
Journal: Journal of Thoracic Oncology (2017)
P3.03-004 Genome-Wide Copy Number Aberrations in Mesothelioma and Its Correlation with Tumor Microenvironment including PD-L1 Expression
Authors: Bibhusal Thapa, Marzena Walkeiwicz, Carmel Murone, Malaka Ameratunga, Khashyar Asadi, Siddhartha Deb, Stephen Barnett, Simon Knight, Xihui Lin, Adriana Salcedo, Paul Mitchell, Paul Boutros, Neil Watkins, Thomas John
Journal: Journal of Thoracic Oncology (2017)
Clonal Dasatinib Large Granular Expansion Is Associated with Suboptimal and Optimal Leukemia Net Response Criteria in Chronic Myelogenous Leukemia
Authors: Flávia Dias Xavier, Fernanda Salles Seguro, Marcela Cavalcante de Andrade Silva, Daniel Salas Steinbaum, Mariana Serpa, Gracia Aparecida Martinez, Carla Rosa Teixeira de Godoy, Graciela Aparecida Aparecida Brocardo, Lis Vilela de Almeida, Debora Levy, Fernanda Fava, Claudia Bitti Barroso, Israel Bendit, Juliana Pereira, Pedro E Dorlhiac Llacer
Journal: Blood (2011)
Impact of CRi on the Outcome of Elderly Patients with Untreated Acute Myeloid Leukemia (AML)
Authors: Anne Etienne, Aude Charbonnier, Thomas Prebet, Diane Coso, Evelyne D’Incan, Marie-Francoise Doglio, Daniele Sainty, Marie-Joelle Mozziconacci, Jerome Rey, Norbert Vey
Journal: Blood (2008)
P1.07-040 Prognostic Factors in Extensive Disease (ED) Small Cell Lung Cancer (SCLC): An ELCWP Phase III Randomized Trial
Authors: Thierry Berghmans, Jean-Jacques Lafitte, Anne-Pascale Meert, Arnaud Scherpereel, Marianne Paesmans, Nathalie Leclercq, Jean-Paul Sculier
Journal: Journal of Thoracic Oncology (2017)
A dual-modality approach of endobiliary radiofrequency ablation and self-expandable metal stent placement to control malignant hemobilia
Authors: Christopher Linz, Rohan Modi, Somashekar Krishna
Journal: Endoscopy (2017)

A 69-year-old man with a history of metastatic pancreatic cancer involving the head of the pancreas and previous placement of an uncovered self-expandable metal stent (SEMS) for malignant biliary obstruction presented to the hospital with new-onset jaundice, melena, and a drop in hemoglobin from 11.0 to 5.6 g/dL over 2 weeks. Given his clinical picture, an urgent upper endoscopy and endoscopic retrograde cholangiopancreatography (ERCP) were performed ([Video 1]).
Low Molecular Weight Heparin in Sufficient Dose of ≥70 IU/kg as an Effective and Safe Thromboprophylaxis in Patients with Newly Diagnosed Multiple Myeloma during Conventional VAD Induction Therapy.
Authors: Ludek Pour, Petr Kessler, Evzen Gregora, Marketa Zemanova, Miroslav Penka, Jaromir Gumulec, Zdenek Adam, Bacovsky Jaroslav, Hana Frankova, Kamila Havlikova, Frantisek Lehanka, Vladimir Maisnar, Ivana Meluzinova, Yvetta Stavarova, Jan Straub, Adam Svobodnik, Vlastimil Scudla, Elena Sumna, Lenka Walterova, Roman Hajek
Journal: Blood (2007)
Improved Outcomes with Class I and II DNA-Based HLA Typing for Matched Unrelated Donor (MUD) Allogeneic Bone Marrow Transplant (ABMT) in Hematologic Diseases.
Authors: Ronald Sobecks, Edward J. Ball, Lisa Rybicki, Elizabeth Kuczkowski, Matt Kalaycio, Brad Pohlman, Steven Andresen, Karen Sands, Jennifer Kosar, Mary Serafin, Jennifer Bates, Christy Lalli, Brian Bolwell
Journal: Blood (2004)
Macrophages and Mast Cells Infiltration Are Biomarkers of Primary Refractory Hodgkin's Lymphoma
Authors: Deau Benedicte, Bachy Emmanuel, Ribrag Vincent, Delarue Richard, Rubio Marie-Therese, Bosq Jacques, Vassiliu Viorel, Varet Bruno, Brousse Nicole, Hermine Olivier, Canioni Danielle
Journal: Blood (2010)
Appearance of Monoclonal Plasma Cell Diseases in Whole Body MRI in 544 Patients and Correlation with Parameters of Disease Activity
Authors: Jens Hillengass, Kerstin Kilk, Karin Listl, Thomas Hielscher, Kai Neben, Dirk Hose, Anthony D. Ho, Marc-André Weber, Ola Landgren, Hartmut Goldschmidt
Journal: Blood (2012)
P64 Multiple dimensions of excessive daytime sleepiness
Authors: SKS Smith, J Steier, Y Serry, A Sekaran
Journal: Thorax (2016)

<h3>Introduction</h3> Sleepiness is a subjective symptom, often reported by patients with sleep disorders. We investigated subjective measures of sleepiness, as measured by the Epworth Sleepiness Scale (ESS), and correlated this to objective observations, as recorded by the mean sleep latency (MSL). We related our findings to affect, fatigue, emotion, mood, and quality of life. <h3>Patients and methods</h3> Patients referred to a tertiary referral centre for sleep disorders were assessed regarding their sleep complaint, excessive daytime sleepiness (EDS), sleep routine and night-time symptoms. Age, gender and BMI were recorded. The ESS (0–24 points), the Stanford Sleepiness Scale (SSS; 0–8 points), the Samn-Perrelli fatigue scale (SPS; 0–7 points), the Global Vigour and Affect Scale (GVS and GAS 0–10 points, respectively), the Hospital Anxiety and Depression Scale (HADS-A and HADS-D 0–21 points, respectively), and the Positive and Negative Affect Schedule (PAS and NAS 10–50 points, respectively) were recorded. Patients underwent polysomnography (PSG) and multiple sleep latency tests (MSLT). <h3>Results</h3> 9 patients (5 male/4 female, age 44.1 (14.6) years, BMI 30.5 (6.7) kg/m<sup>2</sup>; obstructive sleep apnoea (OSA, n = 4), narcolepsy (n = 2), idiopathic hypersomnia (n = 1), insomnia (n = 1), no sleep disorder (n = 1)) were studied. The PSG results showed a short total sleep time (TST 360.1 (69.7) min) with a slightly reduced sleep efficiency (SE 79.6 (11.4)%), there were no relevant periodic limb movements (PLM index 7.3 (4.3)/h) but mild-moderate OSA (apnoea-hypopnoea index (AHI) median 6.4(interquartile range 0.2–30.5)/h). The ESS was 13.9 (7.2) points, the MSL was 7.6 (5.9) min, the SSS was 3.0 (1.3) points and the SPS was 4.0 (1.3) points. The GVS was 5.6 (2.2) points and the GAS was 4.8 (1.6) points, the HADS-A was 8.7 (6.2) points and the HADS-D was 8.9 (5.9) points, the PAS was 23.9 (10.7) and the NAS was 25.6 (8.0) points. There was a positive correlation between the ESS and the SPS, but no other significant correlations (Table 1). <h3>Conclusion</h3> The ESS and the MSL did not correlate well, nor did they relate to measures of affect, emotion, mood, or quality of life. Conversely, there was an interaction between measures of fatigue and the ESS. These findings emphasise the need to develop better scores to characterise EDS, other than the ESS.
Remote ischemic conditioning: the enigmatic transfer of protection
Authors: Gerd Heusch
Journal: Cardiovascular Research (2016)

This editorial refers to ‘Glucagon-like peptide-1 (GLP-1) mediates cardioprotection by remote ischaemic conditioning’ by Basalay et al. , doi: 10.1093/cvr/cvw216. 

Remote ischemic conditioning is the systemic response to brief non-lethal ischemia/reperfusion in various tissues or organs which provides protection to a number of target tissues or organs over a distance. These target organs, including brain, heart, liver, lungs, intestine, kidneys, skeletal muscle, and skin, are then more resistant to sustained ischemia/reperfusion.1

Remote ischemic conditioning can be elicited prior (pre-), during (per-) and following (post-conditioning) the sustained ischemia. The peripheral stimulus appears to involve the activation of sensory nerve fibers and/or vascular shear stress, and the protective signal transduction in the target organs, notably in the heart, is very similar to that of local ischemic pre- and post-conditioning. The most fascinating feature of remote ischemic conditioning, however, is the transfer of a protective signal over a larger distance. This transfer appears to mechanistically involve both humoral and neuronal pathways but is largely enigmatic in its details.1,2 On the other hand, just this transfer of protection from the periphery to central organs such as brain, heart, and kidneys has attracted clinical interest for potential translation. A number of studies in patients undergoing cardiovascular surgery have …
Membrane Derived Micorvesicles - Underappreciated Components of the Tumor Microenvironment That Modulate Tumor Growth, Vascularization and Metastasis.
Authors: Marcin Wysoczynski, Fadhi Hayek, Janina Ratajczak, Anna Janowska-Wieczorek, Mariusz Z. Ratajczak
Journal: Blood (2005)
P2.01-094 Stromal Antigen 1 (SA-1), a Cohesin, is a Novel Proto-Oncogene Regulating Chromatin in Non-Small Cell Lung Cancer (NSCLC)
Authors: Sanjib Chowdhury, Navneet Momi, Mart Dela Cruz, Vadim Backman, Hemant Roy
Journal: Journal of Thoracic Oncology (2017)
Microarray gene expression patterns recapitulated on a clinically tractable diagnostic platform using breast and lung cancer formalin-fixed paraffin-embedded tissues.
Authors: J. Ruiz, J. Chou, K. R. Geisinger, C. H. Schoppe, A. A. Miller, M. C. Willingham, W. J. Petty, B. H. Bolemon, L. D. Miller
Journal: Journal of Clinical Oncology (2011)

e21027 Background: In Vitro Diagnostic Multivariate Index Assays (IVDMIA) are diagnostic tools that produce a diagnostic, prognostic and predictive index. The development of a gene expression (GE)-based IVDMIA require investigation of devices that integrate accurate, rapid and cost-effective multi-GE analysis with conventional protocols for tissue processing. We evaluated the Panomics’ QuantiGene Plex 2.0 expression analysis system (QGS). The QGS is a nucleic acid hybridization-based assay that allows direct quantification of mRNA transcripts from formalin-fixed, paraffin-embedded (FFPE) tissue sections. In this study, we evaluate this method to investigate its utility in diagnostic GE analysis. Methods: We analyzed 16 FFPE breast and 24 FFPE non-small cell lung cancer (NSCLC) samples using the QGS. There was pathologic confirmation of tumor cellularity in all specimens, estrogen receptor (ER) status and proliferative capacity in breast cancer, and histology of NSCLC tumors. In the breast cancer tumors, we focused on genes discovered by microarray analysis that distinguish ER+ and ER- breast tumors as well as tumors with low and high proliferation rates (the “Genetic Grade Signature”, GGS). In the NSCLC tumor set, we focused on genes that correlated with pathologic histology (the “A/S” panel). QuantiGene probes for each of the target genes were designed against corresponding Affymetrix probe set target sequences. Resultant GE profiles were normalized to housekeeping genes and evaluated for correlations. Results: Each of the 8 genes of the ER status panel was correlated with tumor ER status (p<0.05). In unsupervised cluster analysis, the GE profiles of these genes accurately segregated ER+ and ER- tumors. The GGS genes, transformed to a single metagene, showed a robust association with IHC-derived KI67 scores, consistent with involvement in a larger proliferation signature. Finally, in the NSCLC tumors, the “A/S” signature genes showed a marked ability to distinguish NSCLC adenocarcinomas from squamous cell carcinomas. Conclusions: The QGS method may be a used as a diagnostic platform for multi-gene diagnostics.
Outcome of Allogeneic Stem Cell Transplantation in Patients with Low Ventricular Ejection Fraction
Authors: Ziad U. Khan, Rima M Saliba, Suhail Qureshi, Chitra Hosing, Sergio A Giralt, M. J De Lima, S. W Yusuf, Uday R Popat, Richard E Champlin, Muzaffar H. Qazilbash
Journal: Blood (2008)
Using Nontraditional Risk Factors in Coronary Heart Disease Risk Assessment: U.S. Preventive Services Task Force Recommendation Statement
Journal: Annals of Internal Medicine (2009)

Description: New recommendation from the U.S. Preventive Services Task Force (USPSTF) on the use of nontraditional, or novel, risk factors in assessing the coronary heart disease (CHD) risk of asymptomatic persons. Methods: Systematic reviews were conducted of literature since 1996 on 9 proposed nontraditional markers of CHD risk: high-sensitivity C-reactive protein, ankle–brachial index, leukocyte count, fasting blood glucose, periodontal disease, carotid intima–media thickness, coronary artery calcification score on electron-beam computed tomography, homocysteine, and lipoprotein(a). The reviews followed a hierarchical approach aimed at determining which factors could practically and definitively reassign persons assessed as intermediate-risk according to their Framingham score to either a high-risk or low-risk strata, and thereby improve outcomes by means of aggressive risk-factor modification in those newly assigned to the high-risk stratum. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of using the nontraditional risk factors studied to screen asymptomatic men and women with no history of CHD to prevent CHD events. (I statement).
P1.08-039 Systematic Review and Updated Meta-Analysis of Uniportal versus Multiportal Video-Assisted Thoracoscopic Surgery for Lung Cancer
Authors: Mariusz Kowalewski, Maciej Dancewicz, Mariusz Bella, Tomasz Szczęsny, Przemysław Bławat, Marzena Lewandowska, Aleksandra Chrzastek, Janusz Kowalewski
Journal: Journal of Thoracic Oncology (2017)
P1.07-033 Trastuzumab Emtansine (T-DM1) Suppresses the Growth of HER2-Positive Small-Cell Lung Cancer in Preclinical Models
Authors: Osamu Morimura, Toshiyuki Minami, Takashi Kijima, Shohei Koyama, Tomoyuki Otsuka, Yuhei Kinehara, Akio Osa, Masayoshi Higashiguchi, Kotaro Miyake, Izumi Nagatomo, Haruhiko Hirata, Kota Iwahori, Takayuki Takimoto, Yoshito Takeda, Hiroshi Kida, Atsushi Kumanogoh
Journal: Journal of Thoracic Oncology (2017)
P3.01-009 A Prospective Study of ‘Spread through a Knife Surface' (STAKS) in Non-Small Cell Lung Cancer Resection Specimens
Authors: Hans Blaauwgeers, Douglas Flieder, Arne Warth, Kim Monkhorst, Teh Ying Chou, Birgit Witte, Erik Thunnissen
Journal: Journal of Thoracic Oncology (2017)
GCSF-Primed Allo-BMT Following Reduced Intensity Conditioning Regimen In Children with AML- Good Outcome In Patients In 1 st Complete Remission with Rapid Neutrophil Engraftment and Low Incidence of Chronic Gvhd.
Authors: Fabiana Ostronoff, Mauricio Ostronoff, ANA Patricia Souto Maior, Rodolfo Calixto, Monique Martins, Mariana Coutinho, Alexandre Sucupira, Luis Fabio Botelho, Rodrigo Florencio
Journal: Blood (2010)
Discontinuation of Warfarin Therapy for Patients With Atrial Fibrillation
Authors: Geoffrey D. Barnes, Scott Kaatz, Alexis Lopez, Xiaokui Gu, Jay Kozlowski, Gregory D. Krol, James B. Froehlich
Journal: JAMA Cardiology (2017)

This study finds that most patients undergoing warfarin therapy for atrial fibrillation discontinue it within the first year, particularly those who have scheduled electrical cardioversion or radiofrequency ablation.
Purinergic Signaling in the Cardiovascular System
Authors: Geoffrey Burnstock
Journal: Circulation Research (2017)

There is nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory-motor nerves, as well as in intracardiac neurons. Centers in the brain control heart activities and vagal cardiovascular reflexes involve purines. Adenine nucleotides and nucleosides act on purinoceptors on cardiomyocytes, AV and SA nodes, cardiac fibroblasts, and coronary blood vessels. Vascular tone is controlled by a dual mechanism. ATP, released from perivascular sympathetic nerves, causes vasoconstriction largely via P2X1 receptors. Endothelial cells release ATP in response to changes in blood flow (via shear stress) or hypoxia, to act on P2 receptors on endothelial cells to produce nitric oxide, endothelium-derived hyperpolarizing factor, or prostaglandins to cause vasodilation. ATP is also released from sensory-motor nerves during antidromic reflex activity, to produce relaxation of some blood vessels. Purinergic signaling is involved in the physiology of erythrocytes, platelets, and leukocytes. ATP is released from erythrocytes and platelets, and purinoceptors and ectonucleotidases are expressed by these cells. P1, P2Y1, P2Y12, and P2X1 receptors are expressed on platelets, which mediate platelet aggregation and shape change. Long-term (trophic) actions of purine and pyrimidine nucleosides and nucleotides promote migration and proliferation of vascular smooth muscle and endothelial cells via P1 and P2Y receptors during angiogenesis, vessel remodeling during restenosis after angioplasty and atherosclerosis. The involvement of purinergic signaling in cardiovascular pathophysiology and its therapeutic potential are discussed, including heart failure, infarction, arrhythmias, syncope, cardiomyopathy, angina, heart transplantation and coronary bypass grafts, coronary artery disease, diabetic cardiomyopathy, hypertension, ischemia, thrombosis, diabetes mellitus, and migraine.
Very High Risk CLL Characterized by a “Double Hit” Clone with Both 11q22 and 17p13 Deletion.
Authors: Patricia T. Greipp, Stephanie A. Smoley, David S. Viswanatha, Lori S. Frederick, Ruchi G. Sharma, Kari G. Rabe, Susan L Slager, Daniel L. Van Dyke, Neil E. Kay, Tait D. Shanafelt, Clive S. Zent
Journal: Blood (2012)
Clinical and Laboratory Evaluation of Patients with Familial Hemophagocytic Lymphohistiocytosis in a Single Center; Striking the Importance of Central Nervous System and Hepatic Involvement
Authors: Burcin Beken, Selin Aytac, Barýs Kuskonmaz, Gunay Balta, Mualla Cetin, Aytemiz Gurgey, Duygu Uckan Cetinkaya, Fatma Gumruk
Journal: Blood (2014)
Drug Metabolism Gene Polymorphisms and the Risk of Hepatic Sinusoidal Obstruction Syndrome in Children with Inherited Diseases Receiving Haematopoietic Stem Cell Transplantation.
Authors: Juliana F. Fernandes, Vanderson Rocha, Raphael Porcher, Benedicte Neven, Christophe Hue, Marli Tavela, Alain Fischer, Marco Antonio Zago, Marina Cavazzana-Calvo
Journal: Blood (2007)
Significant Impact of IL-17A Gene Polymorphism On Transplant Outcomes After HLA-Fully-Matched Unrelated Bone Marrow Transplantation.
Authors: Akiyoshi Takami, J. Luis Espinoza, Makoto Onizuka, Takakazu Kawase, Takamasa Katagiri, Shigeki Ohtake, Yasuo Morishima, Takahiro Fukuda, Yoshihisa Kodera, Shinji Nakao
Journal: Blood (2009)
Treatment of Primary CNS Lymphoma in the Elderly with High-Dose Methotrexate Containing Chemotherapy Followed Radiotherapy or Chemotherapy Alone Plus Deferred Radiotherapy: Evaluation of Modification of Treatment Modalities in Leon Berard Cancer Center.
Authors: Hervé Ghesquières, Agathe Bajard, Gilles Albrand, Khaoula Alaoui-Slimani, Philippe Rey, Catherine Sebban, Marie Pierre Sunyack, Emmanuel Jouanneau, Francois Ducray, Catherine Chassagne-Clement, Pierre Biron, Jean-Yves Blay
Journal: Blood (2009)
P2.05-042 Development of Thoracic Magnetic Resonance Imaging (MRI) for Radiotherapy Planning
Authors: Hannah Bainbridge, Andreas Wetscherek, Cynthia Eccles, David Collins, Erica Scurr, Martin Leach, Dow-Mu Koh, Fiona Mcdonald
Journal: Journal of Thoracic Oncology (2017)
NY-ESO-1 Vaccination in Combination with Decitabine for Patients with MDS Induces CD4+ and CD8+ T-Cell Responses
Authors: Pragya Srivastava, Junko Matsuzaki, Benjamin E. Paluch, Zachary Brumberger, Stephanie Kaufman, Adam R. Karpf, Kunle Odunsi, Austin Miller, Justin Kocent, Eunice S. Wang, Michael J. Nemeth, Elizabeth A. Griffiths
Journal: Blood (2015)
Somatic Mutations in E3 Ubiquitin Ligase Deltex 1 Are Associated with Survival in Diffuse Large B-Cell Lymphoma
Authors: Minna Taskinen, Leo Meriranta, Annika Pasanen, Riku Louhimo, Alejandra Cervera, Marja-Liisa Karjalainen-Lindsberg, Harald Holte, Jan Delabie, Rainer Lehtonen, Sampsa Hautaniemi, Sirpa Leppä
Journal: Blood (2014)
The Relationship Between the Right Ventricle and its Load in Pulmonary Hypertension
Authors: Anton Vonk Noordegraaf, Berend E. Westerhof, Nico Westerhof
Journal: Journal of the American College of Cardiology (2017)

In pulmonary hypertension, the right ventricle adapts to the increasing vascular load by enhancing contractility ("coupling") to maintain flow. Ventriculoarterial coupling implies that stroke volume changes little while preserving ventricular efficiency. Ultimately, a phase develops where ventricular dilation occurs in an attempt to limit the reduction in stroke volume, with uncoupling and increased wall stress as a consequence. With pressure-volume analysis, we separately describe the changing properties of the pulmonary vascular system and the right ventricle, as well as their coupling, as important concepts for understanding the changes that occur in pulmonary hypertension. On the basis of the unique properties of the pulmonary circulation, we show how all relevant physiological parameters can be derived using an integrative approach. Because coupling is maintained by hypertrophy until the end stage of the disease, when progressive dilation begins, right ventricular volume is the essential parameter to measure in follow-up of patients with pulmonary hypertension.
Pharmacodynamic Biomarkers in the Phase 1 Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia
Authors: Michael Andreeff, Kensuke Kojima, Vivian Ruvolo, Anas Younes, Wei Wei, Marina Konopleva, Seshagiri Duvvuri, Xuelin Huang, Lin Wu, Lori Jukofsky, Lyubomir Vassilev, Jianguo Zhi, David Geho, Gwen Nichols
Journal: Blood (2011)
Targeting Epigenetic Operations with HDAC Inhibitor and Hypomethylating Drugs in Combination Exhibit Synergy in Preclinical and Clinical Experiences in Drug Resistant T-Cell Lymphoma (TCL): A Translational Focus on Doublet Development
Authors: Owen A. O'Connor, Kelly Zullo, Enrica Marchi, Changchun Deng, Ahmed Sawas, Donald Steven Colbourn, Celeste Rojas, Renee Lichtenstein, Ellen Neylon, Emily Lichtenstein, Michael Smith, Luigi Scotto, Jennifer E Amengual
Journal: Blood (2015)