tbuckley/cabot-search huggingface dataset:
First use of Amplatzer device for bronchopleural fistula after lung transplantation
Authors: Antolina Gómez López, Ricardo García Luján, Alicia De Pablo Gafas, Felipe Hernández Hernández, Victoria Villena Garrido, Arschang Valipour, Jose Carlos Meneses Pardo, Eduardo De Miguel Poch
Journal: Thorax (2017)

Lung transplant recipients have a higher morbidity and mortality when compared with other solid organ transplants.

Particularly vascular complications can compromise the function of the transplanted lung and increase mortality. While vascular anastomotic stenosis is less common than central airways complications, it is associated with a high mortality rate if left untreated.

Here we describe a non-surgical treatment for a bronchopleural fistula due to a vascular complication after lobectomy.

A 49-year-old woman with emphysema secondary to α-1 antitrypsin deficiency was admitted for evaluation of lung transplantation, due to progressive worsening of disease despite optimal medical management, including monthly intravenous prolastin therapy, maximum bronchodilator therapy and oxygen.

Based on the hospital protocol and consistent with recommended guidelines double lung transplantation was performed in June 2010. Surgery was complicated by an intraoperative injury of the left pulmonary artery, which required a cardiopulmonary bypass for 4 hours. During the following 48 hours the patient required vasoactive drugs (norepinephrine 0.2 μg/kg/min and dobutamine 2 μg/kg/min) and mechanical ventilation for 7 days (tracheostomy was performed on the 3rd day). Twenty-four hours after lung transplantation a chest radiograph showed a right basal infiltrate. On computed axial tomography an oedema and congestion in the right lower lobe was diagnosed. A subsequent transoesophageal echocardiogram demonstrated absence of flow in the right inferior pulmonary vein without evidence of a thrombotic occlusion. The decision of immediate right lower lobectomy (RLL) was made, followed by an uneventful immediate postoperative course.

A week after lobectomy (9th day after transplantation) a bronchopleural fistula was diagnosed clinically and confirmed endoscopically.

Bronchoscopy revealed a 9 mm dehiscence in the stump of the right lower lobe (figure 1), the transplantation sutures were intact. …
Analysis of Toxicity and Efficacy of Subcutaneous Cladribine at Reduced or Standard Doses (Five Versus Seven Consecutive Days) In Patients with Hairy Cell Leukemia (HCL) In the ICGHCL2004 Protocol by the Italian Cooperative Group on Hcl
Authors: Francesco Forconi, Emanuele Cencini, Francesco Zaja, Tamara Intermesoli, Francesca Fiore, Benedetta Puccini, Caterina Stelitano, Renato Cantaffa, Alessandro Pulsoni, Alfonso Zaccaria, Pier Luigi Zinzani, Andrea Piccin, Filippo Gherlinzoni, Alessandro Levis, Giovanni Martinelli, Sara Barulli, Fortunato Morabito, Ivana Pierri, Miriana Ruggeri, Alessandra Caremani, Luciano Masini, Giuseppe Polimeno, Angelo Guerrasio, Elisa Sozzi, Davide Rossi, Piero Galieni, Marco Gobbi, Sergio Cortelazzo, Luigi Rigacci, Andrea Gallamini, Robin Foà, Francesco Lauria
Journal: Blood (2010)
Dose-Dependent Role of the Cohesin Complex in Normal and Malignant Hematopoiesis
Authors: Aaron D. Viny, Christopher J. Ott, Barbara Spitzer, Martin A Rivas, Cem Meydan, Efthymia Papalexi, Dana Yelin, Kaitlyn Shank, Jaime Reyes, April Chiu, Swapna Thota, Jaroslaw P Maciejewski, Ari Melnick, James E. Bradner, Ross L. Levine
Journal: Blood (2015)
629. Preclinical Evaluation of Prodrug Activator Gene Therapy by Retroviral Replicating Vectors (RRV) in Experimental Models of Breast Cancer CNS Metastasis
Authors: Akihito Inagaki, Kei Hiraoka, Shuichi Kamijima, Joan M. Robbins, Douglas J. Jolly, Harry E. Gruber, Noriyuki Kasahara
Journal: Molecular Therapy (2015)

Retroviral replicating vectors (RRV) are capable of highly efficient replication in cancer cells in vitro and in vivo. In a variety of cancer models this is associated with high levels of tumor-selective gene transfer and significantly enhanced survival benefit when employed for prodrug activator gene therapy. An RRV encoding a modified yeast cytosine deaminase (CD) prodrug activator gene (Toca 511) in combination with extended-release flucytosine (Toca FC) is under investigation in multi-center ascending-dose trials in patients with recurrent high grade glioma. In the present study, our goal is to establish the feasibility of also applying this novel gene therapy strategy to secondary brain tumors arising from metastasis of systemic cancers. In particular, brain metastases of breast cancer frequently arise from highly aggressive, treatment-refractory, "triple-negative" (ER(-), PR(-), HER2(-)) cells, and are associated with a dismal prognosis of 4-6 months survival. First, RRV encoding GFP (AC3-emd, RRV-GFP) showed robust replication activity in the human breast cancer tumor cell lines MDA-MB-231-BR and JC over time at both MOI = 0.01 and 0.1, resulting in high levels of transduction within 1-2 weeks. Next, we tested in vitro cytotoxicity after 5-FC treatment of MDA-MB-231BR and JC cells infected with an RRV expressing CD (AC3-yCD2, Toca 511). In both of the AC3-yCD2-transduced cell lines, cell viability was reduced approximately 70-85% after exposure to 12.9 mg/mL 5-FC and complete cell killing was observed with 129 mg/mL 5-FC (6 days 5-FC treatment for 231-BR; 4 days for JC). In a 231-BR intracranial xenograft model, intratumoral injection of 10^6 Transducing Units of RRV-GFP resulted in >80% transduction efficiency on Day 10 post-virus injection. In survival studies, animals treated with Toca 511 and 5-FC showed statistically significant (p<0.0001) survival benefit. These preclinical data support the advancement of RRV gene therapy towards clinical investigation in patients with CNS-metastatic breast cancer.
The Reduced Intensity Cvd Regimen: A Good Option with Well Balanced Efficacy/Toxicity Ratio for Elderly Patients with Poor Status Performance
Authors: Roman Hajek, Lenka Zahradova, Evzen Gregora, Miroslava Schutzova, Vladimir Koza, Petr Pavlicek, Ludek Pour, Marta Krejci, Viera Sandecka, Andrea Krivanova, Mohammed Al Sahmani, Dana Kralova, Zdenek Adam
Journal: Blood (2008)
MicroRNA Profiling in Low-Grade Ocular MALT and Diffuse Large B-Cell Lymphoma: A Role for MYC and NFKB1 Mediated Dysregulation of MicroRNA Expression in Aggressive Disease
Authors: Christoffer Hother, Peter Kristian Rasmussen, Tejal Joshi, Ditte Reker, Ulrik Ralfkiaer, Christopher Workman, Peter De Nully Brown, Steffen Heegaard, Elisabeth Ralfkiaer, Kirsten Grønbæk
Journal: Blood (2012)
Abstract 2451: The nuclear-targeted gold nanoparticles inhibit the tumor growth in mouse model as potential anticancer agents
Authors: Xianghong Peng, Megan A. Macke, Hyung Ju C Shin, Sreenivas Nannapaneni, Nelson Chen, Sungjin Kim, Zhuo (Georgia) Chen, Mostafa A El-Sayed, Dong Shin
Journal: Cancer Research (2015)

Abstract The use of gold nanoparticles (AuNPs) as chemotherapeutic agents, based on their intrinsic antineoplastic properties is becoming an increasingly exciting possibility for the treatment of cancer. The specific targeting of AuNPs to the nucleus of malignant cells can be achieved via peptide functionalization of the nanoparticle surface, resulting in DNA damage and subsequent apoptosis. Here, we utilized these novel AuNPs for systemic delivery in vivo and determined their efficacy as chemotherapeutic agents. In addition, we assessed their effects on overall health in order to characterize their systemic toxicity. AuNPs (30 nm in diameter) were functionalized with an Arg-Gly-Asp (RGD) peptide sequence, providing tumor cell specific targeting, as well as a Lys-Lys-Lys-Arg-Lys nuclear localization sequence (NLS) peptide. These novel nuclear-targeting AuNPs were delivered via tail vein injection in nude mice bearing Tu212 tumors. Their in vivo therapeutic efficacy was evaluated, along with assessing their systemic toxicity. The AuNPs, specifically targeted to the tumor cell nucleus, exhibit circulation half-life of 4.1 h, which is exceptionally greater than common chemotherapeutic agents and, although they exhibit uptake by organs of the reticuloendothelial system (RES) (e.g. liver and spleen), they also accumulate in the tumor. In addition, when systemically delivered at low doses (5 nM AuNPs) these novel targeted AuNPs show significant tumor regression (via DNA damage and subsequent apoptosis) when compared to their non-targeting counterparts (P = 0.004), with no observed toxicity in terms of hepatic function, renal function, or body weight. In conclusion, by delivering AuNPs to the nucleus of tumor cells, at low doses in vivo, high therapeutic efficacy is achieved with minimal side effects, indicating the potential for the use of these novel nuclear-targeted AuNPs as chemotherapeutic agents. Citation Format: Xianghong Peng, Megan A. Macke, Hyung Ju C Shin, Sreenivas Nannapaneni, Nelson Chen, Sungjin Kim, Zhuo (Georgia) Chen, Mostafa A El-Sayed, Dong Shin. The nuclear-targeted gold nanoparticles inhibit the tumor growth in mouse model as potential anticancer agents. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2451. doi:10.1158/1538-7445.AM2015-2451
Imatinib Inhibits Both CD4+ T Regulatory Cells and CD8+ T Lymphocytes Specifically Directed Against the Leukemia-Associated Antigen RHAMM/CD168.
Authors: Jinfei Chen, Anita Schmitt, Baoan Chen, Markus Rojewski, Jochen Greiner, Philippe Guillaume, Hartmut Dohner, Donald Bunjes, Michael Schmitt
Journal: Blood (2006)
Clues for Novel Pathways in Leukemogenesis: Global Gene Expression Profiling in Acute Myeloid Leukemia Patients Negative for a Comprehensive Series of Molecular Alterations.
Authors: Peter Hokland, Charlotte Guldborg Nyvold, Caroline Juhl Christensen, Anita Rethmeier, Torben Ørntoft, Thomas Thykjær Andersen
Journal: Blood (2004)
138. Microencapsulated Aptamer Sensors for Digital Quantification of Blood Biomarkers
Authors: Weian Zhao
Journal: Molecular Therapy (2015)

Analysis and quantification of blood biomarkers including proteins, nucleic acids and circulating cells becomes an emerging approach to detect, predict and monitor diseases including blood inflection and cancer. Unfortunately, existing methods of biomarker detection (e.g., PCR, ELISA, and flow cytometry) often suffer from 1) poor sensitivity given that many biomarkers exist in low numbers in blood, and 2) large preanalytical variability due to lengthy sample processing required by those assays. Here we present a new technology termed "Integrated Comprehensive Droplet Digital Detection (IC 3D)" that is able to selectively detect a variety of biomarkers including cells and miRNA directly from blood at a single-cell (or single-molecule) sensitivity in a one-step process within 1-3 hours. The IC 3D integrates target-sensing aptamer biosensors, droplet microencapsulation and a high throughput 3D particle counter system. Fluorogenic aptamer sensors used here are short catalytic oligonucleotides that are identified by in vitro evolution to specifically react with specific marker(s), leading to a rapid, real-time fluorescence signal. For instance, we demonstrate that the IC 3D can provide absolute quantification of target bacteria or cancer miRNA from patient samples with a broad range of extremely low concentration from 10 to 10,000 copies(or cells)/mL with exceptional robustness. Our IC 3D system as a platform technology has the potential to introduce a new paradigm for rapid detection, in particular of biological markers that are in low quantity, in other diseases as well.
Socioeconomic position and delays in lung cancer diagnosis: should we target the more deprived?
Authors: David R Baldwin
Journal: Thorax (2016)

Lung cancer incidence and mortality increase with all measures of socioeconomic deprivation primarily because of the fact that smoking rates also increase with the same measures. This powerful association means that we see double the number of people with lung cancer in the most deprived quintile compared with the least deprived. Socioeconomic deprivation is associated with reduced survival, more early deaths (within 30 or 90 days) and lower treatment rates.1–3 Possible explanations include a failure to present and seek help from doctors early and less effective primary healthcare in deprived communities, both factors postulated to result in delays in diagnosis and later stage at presentation. The systematic review and meta-analysis by Forrest et al 4 concludes that there is no association between socioeconomic position (SEP) and either stage at diagnosis or time intervals on the lung cancer pathway. More deprived patients were more likely to present as emergencies. The most important limitation, acknowledged by the authors, is the potential for masking of the effect of SEP on delays in the pathway by the ‘sicker quicker’ effect. This refers to the finding that sicker patients progress more quickly through the pathway, thus potentially cancelling an effect of SEP on late presentation. This factor was not accounted for in the included studies. They also raise concerns about whether all studies that contain information about the factors studied have been included. Despite these important limitations, the authors say that the implication of their findings for policy is that early diagnosis campaigns do not need to be targeted to the more deprived and that these should be applied irrespective of SEP. Back-tracking somewhat, they also say it may be prudent to target the more deprived groups purely because of the increased incidence of lung cancer. So, do we target the more deprived or not? …
Early Post-Transplant Administration of Recombinant Erythropoietin Decreases Transfusion Needs and Hastens Haemoglobin Reconstitution in Reduced Intensity Conditioned (RIC) Allogeneic Stem Cell Transplantation (ASCT) for Non-Myeloid Malignancies.
Authors: Vadim Ivanov, Catherine Faucher, Patrick Ladaique, Sabine Furst, Mohamad Mothy, Jean El Cheikh, Thomas Prebet, Diane Coso, Jean-Marc Schiano, Frederic Viret, Christian Chabannon, Didier Blaise
Journal: Blood (2007)
Abstract SY35-04: Arming tumor-targeting antibodies with cytokine payloads: Emerging clinical results
Authors: Dario Neri
Journal: Cancer Research (2015)

Abstract Antibodies can be used to deliver bioactive molecules (drugs, cytokines, photosensitizers, radionuclides, etc.) to the tumor environment, thus sparing normal tissues. Pharmacodelivery strategies targeting certain modified extracellular matrix components, associated with the tumor neo-vasculature, is particularly attractive, because of: (i) the abundance and stability of these antigens (e.g., splice isoforms of fibronectin and tenascin-C); (ii) the dependence of cancer on new blood vessels; (iii) the accessibility of neo-vascular structures for therapeutic agents coming from the blood-stream; (iv) the fact that some extracellular matrix components are very abundant in many different cancer types, while being virtually undetectable in most normal adult tissues [Refs. 1-8]. In this lecture, I will present our experience (at a preclinical and clinical level) in the development and clinical applications of antibody-cytokine fusion proteins (“immunocytokines”) for cancer therapy applications. In particular, I will focus on pro-inflammatory immunocytokines specific to the alternatively-spliced EDA and EDB domains of fibronectin, or A1 domain of tenascin-C, used either as single agents or in combination. Immunocytokines based on IL2 or TNF as payloads are able to dramatically increase the density of certain leukocytes (e.g., T cells and NK cells) at the neoplastic site in various types of malignancies. References: 1. Neri, D. &amp; Bicknell, R.. Nature Rev. Cancer. 2005, 5, 436-446 2. Neri, D. &amp; Supuran, C. Nature Rev. Drug Discov., 2011, 10, 767-777 3. Neri, D. &amp; Pasche N. Drug Discov. Today, 2012, 17, 583-590 4. Gutbrodt, K. et al. Sci. Transl. Med., 2013, 5, 201ra118 5. Hemmerle, T. et al. Br. J. Cancer, 2013, 109, 1206-1213 6. Schwager K. et al. J. Invest. Dermatol., 2013, 133, 751-758 7. Schliemann C. et al. Blood, 2009, 113, 2275-2283 8. Halin C. et al. Nat. Biotechnol., 2002, 20, 264-269 Citation Format: Dario Neri. Arming tumor-targeting antibodies with cytokine payloads: Emerging clinical results. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY35-04. doi:10.1158/1538-7445.AM2015-SY35-04
Investigating Personal and Treatment Related Factors Associated with Adherence Behavior in Patients with Chronic Myeloid Leukemia Receiving Long Term Imatinib Therapy
Authors: Fabio Efficace, Michele Baccarani, Massimo Breccia, Giuliana Alimena, Gianantonio Rosti, Francesco Cottone, Fausto Castagnetti, Giorgio Lambertenghi Deliliers, Antonella Russo Rossi, Simonetta Pardini, Filippo Gherlinzoni, Marzia Salvucci, Mario Tiribelli, Marco Vignetti, Franco Mandelli
Journal: Blood (2011)
Leveraging Statistical Methods to Improve Validity and Reproducibility of Research Findings
Authors: Jennifer Urbano Blackford
Journal: JAMA Psychiatry (2016)

Scientific discoveries have the profound opportunity to impact the lives of patients.They can lead to advances in medical decision making when the findings are correct, or mislead when not.We owe it to our peers, funding sources, and patients to take every precaution against false conclusions, and to communicate our discoveries with accuracy, precision, and clarity.With the National Institutes of Health's new focus on rigor and reproducibility, scientists are returning attention to the ideas of validity and reliability.At JAMA Psychiatry, we seek to publish science that leverages the power of statistics and contributes discoveries that are reproducible and valid.Toward that end, I provide guidelines for using statistical methods: the essentials, good practices, and advanced methods.
Pulmonary microvascular architecture in hereditary haemorrhagic telangiectasia
Authors: Maximilian Ackermann, Steven J Mentzer, Wilfried Roth, Urban Geisthoff, Erich Stoelben
Journal: Thorax (2017)

A 24-year-old Caucasian man was admitted with a known hereditary haemorrhagic telangiectasia (HHT) and heterozygous mutation of factor V Leiden following episodes of cerebral infarctions in occipital lobes, cerebellum and brainstem.In his case history, the patient underwent several interventional embolisation of arteriovenous (AV) malformations in the middle and lower lobes (figure 1).However, those were not completely successful as the malformations were diffuse.We performed
A phase I study of MEK inhibitor MEK162 (ARRY-438162) in patients with biliary tract cancer.
Authors: Richard S. Finn, Milind M. Javle, Benjamin R. Tan, Colin D. Weekes, Johanna C. Bendell, Amita Patnaik, Gazala Naaz Khan, Dan Laheru, Lisa Anderson, Janna Lynn Christy-Bittel, Emma Barrett, Kari Guthrie, Kevin S. Litwiler, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2012)

220 Background: The RAS/RAF/MEK/ERK pathway plays a major role in cell growth and survival and is aberrantly activated in many cancers. MEK162 (ARRY-438162) is a potent, selective, ATP-uncompetitive inhibitor of MEK1/2. The objectives of this Phase 1 expansion study were to characterize the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of MEK162 in patients (pts) with biliary tract cancer (BTC). Methods: Pts with unresectable, locally advanced or metastatic BTC who had received ≤ 1 prior systemic therapy received oral MEK162 at 60 mg twice daily (BID). Mutation status of RAS, BRAF and other relevant genes were assessed from tumor samples. Tumor response was assessed every 6 weeks. Results: Twenty-eight pts, median age 64 years (range 30-86) with gallbladder (7), intrahepatic (14) or extrahepatic (7) cholangiocarcinoma (CC) were enrolled. All pts were ECOG 0-1 and 43% received previous first-line therapy (primarily gemcitabine combinations). Of the 23 tumors assessed, 17 were wild type (WT) on all loci tested and 6 had mutations (1 MET, 1 PIK3CA, 2 KRAS, 2 PTEN null). The most common treatment-related AEs were rash, nausea, vomiting, diarrhea, peripheral edema, fatigue and central serous-like retinopathy, and most were Grade (G) 1 or 2. G3/4 treatment-related AEs were anasarca, hypokalemia, hyponatremia, upper/lower gastrointestinal hemorrhage and mucositis (1 each). Thirteen pts were dose reduced for AEs, of which, G1/2 central serous-like retinopathy was the most frequently reported event (6). Three pts were discontinued for treatment-related AEs (G2 central serous-like retinopathy, G1 nausea, G4 anasarca). Of the 26 pts evaluable for response, 1 CR, 1 PR and 11 SD (≥ 6 weeks) were observed. Of note, both responders were WT on all loci tested and had extrahepatic CC. The PK in this population was equivalent to that observed in prior studies. A consistent mean reduction (40-60%) of circulating TNFα was observed. Conclusions: MEK162 has an acceptable safety profile and desirable PK properties at 60 mg BID and RECIST responses were observed in pts with BTC. Additional expansion cohorts are ongoing in pts with KRAS- or BRAF-mutant metastatic colorectal cancer.
EXTH-27. FLAG-003 AS A SMALL MOLECULE ORAL THERAPY FOR THE TREATMENT OF GLIOMA
Authors: Frank Sorgi, Aleem Gangjee
Journal: Neuro-Oncology (2016)

FLAG-003 is a novel NCE that was created to be a dual-acting compound for the treatment of highly vascularized tumors. This new class of compounds combines the therapeutic effects of an anti-angiogenic agent and an anti-tubulin to create the AA/AT platform. They are the product of years of molecular modeling and structure activity relationship (SAR) optimization culminating in a series of small molecules that are (1) easy to synthesize, (2) cost effective, (3) orally active, and (4) highly efficacious in treating a variety of highly vascularized tumors ranging from breast to lung to brain cancer. FLAG-003 is one specific AA/AT compound which is being developed for the treatment of brain cancer. FLAG-003 is unique in that it is a small molecule (MW = 283) that was originally being developed as a treatment for breast cancer but researchers noted that it crossed the blood brain barrier (BBB) and was therefore discarded as a breast cancer candidate. FLAG Therapeutics is therefore developing FLAG-003 as an oral treatment for gliomas. FLAG-003 is one of the few small molecules for the treatment of GBM that is not an alkylating agent. As an antitubulin, it binds to the colchicine-binding site on tubulin and interferes in microtubule processing. This is significant in that FLAG-003 is not affected by the MGMT status, unlike temozolomide (TMZ) and other alkylating agents and has been shown to be effective regardless of MGMT status. Further, FLAG-003’s efficacy was tested by the Tisch Brain Cancer Center at Duke University in two of their proprietary PDX GBM models and demonstrated highly statistical increases in survival in their aggressive models. These findings and our preclinical development package is the basis for Duke agreeing to test FLAG-003 as an oral agent in an upcoming Phase I and II clinical trials for the treatment of glioma.
Effect of Thalidomide and Revlimid on the Gene Expression That Reveals Molecular Circuitries Involved in T Cell Co-Activation.
Authors: Rao Prabhala, Puneet Cheema, Masood A. Shammas, Weihua Song, Elizabeth Blanchard, Dharminder Chauhan, Paola Neri, Pierfrancesco Tassone, David Stirling, Kenneth Anderson, Nikhil C. Munshi
Journal: Blood (2004)
Novel Small Molecule Inhibitors Of The Gas6/TAM Signaling Pathway Inhibit Platelet Aggregation In Vitro and Protect Mice From Arterial and Venous Thrombosis In Vivo
Authors: Gilbert Acevedo, Brian R. Branchford, Christine Brzezinski, Susan Sather, Gary Brodsky, Deborah DeRyckere, Weihe Zhang, Jing Liu, H. Shelton Earp, Xiaodong Wang, Stephen V Frye, Douglas K. Graham, Jorge Di Paola
Journal: Blood (2013)