tbuckley/cabot-search huggingface dataset:
Improvement of Antigen-Specific CTL Persistence By Transduction of Novel Artificial Adapter Molecule
Authors: Kotaro Miyao, Seitaro Terakura, Keisuke Watanabe, Reona Sakemura, Jakrawadee Julamanee, Shingo Okuno, Sonoko Kamoshita, Erina Takagi, Daisuke Koyama, Tatsunori Goto, Ryo Hanajiri, Tetsuya Nishida, Makoto Murata, Hitoshi Kiyoi
Journal: Blood (2016)
A cohort pilot study on therapeutic vaccination of advanced melanoma patients with dendritic cells loaded with multiple peptides or electroporated with mRNA
Authors: B. Neyns, J. Corthals, J. De Grève, C. De Greef, P. G. Coulie, K. Thielemans
Journal: Journal of Clinical Oncology (2006)

18011 Background: Therapeutic vaccination of melanoma patients with tumor specific antigenic peptides has been associated with increased frequency of anti-vaccine CTL precursor frequencies in peripheral blood and objective tumor regression in a low percentage of patients. Methods: We investigated the safety and activity of two autologous dendritic cell-based vaccines in 2 sequential cohorts of advanced melanoma patients. Patients first underwent a leucapheresis. Following enrichment in a semi-closed culture system using Cell Factories (Nunc), adherent cells were cultured in RPMI 1640 medium supplemented with 1% heat-inactivated autologous plasma, 500U/ml IL-4 and 1000 U/ml GM-CSF for 6 days and cryo-preserved. Upon thawing, DC were pulsed with 8 peptides or electroporated with synthetic mRNA encoding 7 antigens. Dendritic cell vaccines were administered by intradermal and subcutaneous biweekly injections for a total of 6 times (= cycle 1). Thereafter vaccination was repeated every 6w until clinical deterioration or patient refusal. Frequencies of blood anti-vaccine CTL were estimated by in vitro restimulation in limiting dilution conditions followed by detection with tetramer assay. Results: Fifteen patients were recruited (9M/6F; median age was 49 y, range 28–81). Seven HLA-A2 patients were treated with peptide pulsed DC (cohort A) and 7 patients (4 HLA-A2 and 3 HLA-A1) with mRNA electroporated DC (cohort B). One patient was sequentially treated with both vaccines. Five patients in cohort A and 3 patients in cohort B completed the first treatment cycle of 6 bi-weekly vaccinations (cycle 1 is ongoing in 3 patients of cohort B). Toxicity was limited to grade 1 or 2 local skin reactions at the vaccine administration sites in all patients. In cohort B one patient qualified for stable disease and 2 other patients with progressive disease displayed regression of individual metastases. A &gt;10-fold increase in CTL precursor frequency was observed in 2 out of 3 patients of cohort A that have been analyzed at present. Conclusions: Vaccination of melanoma patients with peptide pulsed or mRNA electroporated autologous DC vaccines was found to be feasible and safe. Updated results will be presented at the meeting. [Table: see text]
QUANTITATIVE DIFFERENTIATION OF LV MYOCARDIUM WITH AND WITHOUT LAYER-SPECIFIC FIBROSIS ON CMR IN HYPERTROPHIC CARDIOMYOPATHY USING LAYER-SPECIFIC STRAIN TTE ANALYSIS
Authors: Nobusada Funabashi, Hiroyuki Takaoka, Koya Ozawa, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2017)
PROGNOSTIC IMPACT OF ALKALINE PHOSPHATASE MEASURED AT THE TIME OF PRESENTATION IN PATIENTS UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Pyung Chun Oh, Woong Chol Kang, Minsu Kim, Jeonggeun Moon, Kyounghoon Lee, Eak Kyun Shin, Jon Suh, Hyun Woo Park, Ho-Jun Jang, Tae-Hoon Kim, Sang-Don Park, Sung Woo Kwon
Journal: Journal of the American College of Cardiology (2017)
ANATOMIC VERSUS ISCHEMIC BURDEN IN PREDICTING OUTCOMES OF CORONARY ARTERY DISEASE: DATA FROM IRIS-FFR REGISTRY
Authors: Doyoon Kang, Jung-Min Ahn, Ungjeong Do, Osung Kwon, Kyusup Lee, Jung Ae Hong, Se Hun Kang, Pil Hyung Lee, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2017)
PORTRAITS OF ANDREAS VESALIUS
Authors: M. H. Spielmann
Journal: BMJ (1919)

ENGLAND AND WALES).SR,-We 'desire to thank the registered practitioners of England and Wales for their support in the eletion of direct representatives on the General Medical Council.It will be our duty and pleasure to take a full share in the work of the Council.In the general interest, that of the practitioner no less than that of the public, we shall wsaoh carefully the conditions under which medical service to the community is given, and we shall help to direct the traikig of the student so that it may con- form to the needs of social and scientific progress.-
Cyclophosphamide Kinetics Influences Toxicity and Outcome of Bone Marrow Transplantation in Patients with β-Thalassemia Major.
Authors: Alok Srivastava, Balasubramanian Poonkuzhali, Desire Salamun, Biju George, Vikram Mathews, Rajagopal Krishnamoorthy, Mammen Chandy
Journal: Blood (2004)
Extracellular Vesicles as Potential Biomarker for Acute Graft-Versus-Host-Disease
Authors: Giuseppe Lia, Lucia Brunello, Paola Omedè, Monica Astolfi, Daniela Drandi, Luisa Giaccone, Moreno Festuccia, Enrico Maffini, Sara Butera, Giovannino Ciccone, Andrea Evangelista, Andrea Carpanetto, Stefania Bruno, Laura Tosti, Fabio Cattelino, Giovanni Camussi, Mario Boccadoro, Benedetto Bruno
Journal: Blood (2016)
Symptom Burden As Primary Driver for Therapy in Patients with Myelofibrosis: An Analysis By MPN International Quality of Life Study Group
Authors: Robyn M. Scherber, Holly Geyer, Amylou Constance Dueck, Heidi E. Kosiorek, Jean-Jacques Kiladjian, Stefanie Slot, Sonja Zweegman, Peter Te Boekhorst, Suzan Commandeur, Harry C. Schouten, Federico Sackmann, Ana Kerguelen Fuentes, Dolores Hernandez-Maraver, Heike L Pahl, Martin Griesshammer, Frank Stegelmann, Konstanze Doehner, Thomas Lehmann, Karen Bonatz, Andreas Reiter, Francoise Boyer, Gabriel Etienne, Jean Christophe Ianotto, Dana Ranta, Lydia Roy, Jean-Yves Cahn, Claire N. Harrison, Deepti Radia, Pablo J. Muxi, Norman I Maldonado, Carlos Besses, Francisco Cervantes, Peter L. Johansson, Tiziano Barbui, Giovanni Barosi, Alessandro M. Vannucchi, Bjorn Andreasson, Maria Ferarri, Alessandro Rambaldi, Jan Samuelsson, Gunnar Birgegard, Keith Cannon, Xuijuan Sun, Junqing Xu, Peihong Zhang, Zefeng Xu, Ruben A. Mesa
Journal: Blood (2016)
Polymorhism of the neuronal nitric oxide synthase gene (NOS1) in allergic diseases
Authors: Lydie Izakovičová Hollá, Marcel Schüller, Dana Bučková, Jiří Vácha
Journal: Allergy (2003)

Although no significant differences were found for the C/T polymorphism in exon 29 of the NOS1 gene between patients with IgE-mediated allergic diseases and healthy subjects, the T allele of this common polymorphism showed a significant association with high total serum IgE levels.
Association between baseline tumor dimensions and survival in advanced non-small cell lung cancer (NSCLC).
Authors: Daniel H. Ahn, Suzanne Eleanor Dahlberg, Alan Sandler, Michael C. Perry, Joan H. Schiller, Julie R. Brahmer, David H. Johnson, David E. Gerber
Journal: Journal of Clinical Oncology (2013)

8046 Background: It is not known to what extent radiographic tumor burden is associated with survival in patients with advanced NSCLC. The purpose of this study is to assess whether baseline tumor dimensions are associated with patient survival in advanced NSCLC. Methods: Data were derived from the Eastern Cooperative Oncology Group (ECOG) 4599 trial of carboplatin-paclitaxel (CP) ± bevacizumab (B) for advanced nonsquamous NSCLC. Associations between the Response Evaluation Criteria in Solid Tumors (RECIST) baseline sum longest diameter (BSLD) and progression-free survival (PFS) and overall survival (OS) were evaluated using univariate and multivariable Cox regression models. Results: 759 of 850 patients (89%) enrolled in E4599 had measurable disease and were included in the analysis. 76% of patients were age &lt; 70 years, 46% were female, and 86% were white. Median number of target lesions was 2; median BSLD was 7.5 cm. In univariate Cox models, BSLD predicted OS (HR 1.41; P&lt;0.001) and had a trend toward association with PFS (HR 1.14; P=0.08). OS was 12.6 months (mos) for BSLD &lt; 7.5 cm, compared to 9.5 mos for BSLD ≥ 7.5 cm. This association persisted across both treatment groups (CP: median OS 11.5 vs 8.5 mos; CP+B: median OS 14.1 vs 10.7 mos), when BSLD was categorized according to quartile (median OS: 13.3, 11.5, 11.6, and 8.3 mos; P&lt;0.001), and in a multivariable model controlling for prognostic factors and the presence and site of extrathoracic disease (OS HR 1.24; P=0.01). Conclusions: Radiographic disease burden, as determined by RECIST BSLD, is associated with survival in the E4599 trial. If validated in other populations, this parameter merits consideration in the stratification of patients for clinical trials and may provide important prognostic information for patients and clinicians.
IMPACT OF STATIN INTOLERANCE RATES ON NEED FOR EZETIMIBE AND/OR PCSK9 INHIBITORS FOR MEETING LOW-DENSITY LIPOPROTEIN GOALS IN A REAL-WORLD COHORT WITH ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
Authors: Christopher P. Cannon, Irfan Khan, Alexa Klimchak, Robert Sanchez, William Sasiela, Matthew Reynolds
Journal: Journal of the American College of Cardiology (2017)
CORONARY ARTERY BYPASS GRAFT SURGERY AFTER ACUTE ST ELEVATION MYOCARDIAL INFARCTION: HOW EARLY IS TOO EARLY?
Authors: Gbolahan Ogunbayo, Odunayo Olorunfemi, Ayman Elbadawi, Deola Saheed, Adrian Messerli
Journal: Journal of the American College of Cardiology (2017)
Homoharringtonine (HHT) with Imatinib in Chronic, Accelerated, and Blast Phase Chronic Myeloid Leukemia (CML)
Authors: Abhishek Maiti, Hagop M. Kantarjian, Alessandra Ferrajoli, Zeev Estrov, Gautam Borthakur, Guillermo Garcia-Manero, Elias J. Jabbour, Farhad Ravandi, Susan M. O'Brien, Jorge E. Cortes
Journal: Blood (2016)
Long-term follow-up of a phase I/II trial of radioimmunotherapy (RIT) with yttrium 90 (<sup>90</sup>Y) ibritumomab tiuxetan for CD20+ B-cell non-Hodgkin's lymphoma (NHL)
Authors: L. I. Gordon, A. Molina, C. Emmanouilides, A. Raubitschek, M. Darif, R. J. Schilder, G. A. Wiseman, C. A. White, T. E. Witzig
Journal: Journal of Clinical Oncology (2004)

6574 Background: Updated time to disease progression (TTP) and duration of response (DR) are reported for responders from a multicenter phase I/II dose-escalation trial of 90Y ibritumomab tiuxetan (Zevalin®) in 51 patients (pts) with relapsed or refractory CD20+ B-cell NHL. Methods: 5 pts were treated at a dose of 0.2 mCi/kg, 15 at 0.3 mCi/kg, and 30 at 0.4 mCi/kg; 1 pt was not treated. Maximum tolerated dose (MTD) was 0.4 mCi/kg for pts with baseline platelets (plts) ≥ 150,000/μL (0.3 mCi/kg for plts 100,000–149,000/μL). Maximum dose for all pts was 32 mCi. Median age was 60 years (yrs) (range, 24–82). Median time from diagnosis to treatment was 3.8 yrs (range, 0.7–33.1). Median number of prior chemotherapy regimens was 2 (range, 1–7); 47 pts (92%) had received an anthracycline. 10 pts (20%) were resistant to prior chemotherapy. At study entry, 59% of pts had ≥ 1 tumor mass ≥ 5 cm; 43% had bone marrow involvement. Results: TTP and DR in responders were updated, response rates (RR) reported at all dose levels by International Workshop Response Criteria. Complete response (CR), CR unconfirmed (CRu), and partial response (PR) rates were 29%, 22%, and 22%, respectively, for an overall RR (ORR) of 73% (51% CR/CRu). ORR in pts with follicular lymphoma (FL) was 85% (58% CR/CRu, 27% PR). TTP and DR in all responders were 12.6 months (mos) and 11.7 mos, respectively. At MTD, TTP and DR in complete responders (CR/CRu) were 28.3 and 27.5 mos, respectively. 9 pts (24% of responders) had TTP >3 yrs; 5 had FL and 4 had diffuse large cell lymphoma (DLCL). 5 pts (FL, 3; DLCL, 2) are still in CR (range, 60+-74+ mos). Conclusions: 90Y ibritumomab tiuxetan produces high RRs and durable responses in pts with relapsed or refractory B-cell NHL. Durable responses >5 years have been seen in FL and DLCL. Because most relapses in DLCL occur early, the 2 DLCL pts with durable remissions might be cured. This observation provides the basis for further studies to define the efficacy of 90Y ibritumomab tiuxetan in relapsed DLCL. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biogen/IDEC Biogen/IDEC Biogen/IDEC Biogen/IDEC
Randomized trial effect of an oral nutritional supplement with eicosapentaenoic acid on nutritional and inflammatory parameters, response and toxicity to chemotherapy, quality of life, and survival in treatment-naive patients with advanced non-small lung cancer.
Authors: Karla Sanchez-Lara, Jenny Turcott, Eva Juarez, Martha de la Torre, Geraldine Villanueva, Dan Green, Oscar Arrieta
Journal: Journal of Clinical Oncology (2012)

e19594 Background: Nutritional interventions have shown increased of energy intake but the effect of improvement in health related quality of life (HRQL) in non small cell lung cancer (NSCLC) patients is controversial. Eicosapentaenoic acid has been proposed to have anti-inflammatory, anticachectic and possibly could have antitumoral effects. Methods: Patients with advanced NSCLC naive to treatment were included and randomly assigned to receive diet and oral nutritional supplement enriched with EPA or only isocaloric diet. All patients received paclitaxel and cisplatin-carboplatin treatment. Weight, body composition measured with bioelectrical impedance analysis, dietary ingestion, inflammatory parameters and HRQL were assessed at baseline and after 1 st and 2 nd cycle. Response to chemotherapy and survival were evaluated. Results: Ninety-two patients were analyzed, (46 EPA, 46 control group). No basal differences between groups were found. Experimental group present significantly increased albumin levels, energy, proteins, lipids and carbohydrate intake, and reduced serum CPR, TNF-α and Neutrophyls/Lymphocytes index. Patients in experimental group presented minor prevalence of weight loss and increased 1.6 kg of lean body mass (LBM) compared with controls. In HRQL, experimental group presented an improvement in global and physical scale and anorexia, and regarding toxicity, fatigue and neuropathy diminished. There was no difference in response rate, progression free survival and overall survival between groups. Conclusions: EPA enriched supplementation provided a therapeutic advantage by increasing LBM and nutrients intake, improving HRQL, and reduce several toxicity parameters in NSCLC patients under chemotherapy. The study was registered with ClinicalTrials.gov, number NCT01048970.
Coadministration of Canagliflozin and Phentermine for Weight Management in Overweight and Obese Individuals Without Diabetes: A Randomized Clinical Trial
Authors: Priscilla Hollander, Harold E. Bays, Julio Rosenstock, Mary Ellen Frustaci, Albert Fung, Frank Vercruysse, Ngozi Erondu
Journal: Diabetes Care (2017)

OBJECTIVE To assess the efficacy and safety of coadministration of canagliflozin (CANA) and phentermine (PHEN) compared with placebo (PBO) and CANA or PHEN monotherapies in individuals who were overweight and obese without type 2 diabetes. RESEARCH DESIGN AND METHODS This 26-week, phase 2a, randomized, double-blind, PBO-controlled, multicenter, parallel-group study enrolled individuals who were obese or overweight without type 2 diabetes (N = 335, aged 18–65 years, BMI ≥30 to &amp;lt;50 kg/m2 or BMI ≥27 to &amp;lt;50 kg/m2 with hypertension and/or dyslipidemia). Participants were randomized (1:1:1:1) to receive PBO, CANA 300 mg, PHEN 15 mg, or coadministration of CANA 300 mg and PHEN 15 mg (CANA/PHEN) orally once daily. The primary end point was percent change in body weight from baseline to week 26; key secondary end points were the proportion of participants achieving weight loss ≥5% and change from baseline in systolic blood pressure. RESULTS CANA/PHEN provided statistically superior weight loss from baseline versus PBO at week 26 (least squares mean difference –6.9% [95% CI –8.6 to –5.2]; P &amp;lt; 0.001). CANA/PHEN also provided statistically superior achievement of weight loss ≥5% and reduction in systolic blood pressure compared with PBO. CANA/PHEN was generally well tolerated, with a safety and tolerability profile consistent with that of the individual components. CONCLUSIONS CANA/PHEN produced meaningful reductions in body weight and was generally well tolerated in individuals who were overweight or obese without type 2 diabetes. Further studies are warranted to evaluate potential use of this combination for long-term weight management.
Cirugía resectiva vs. prótesis como tratamiento inicial en pacientes con cáncer de colon obstructivo en estadío IV
Authors: A Raga, E O'Callaghan, A Alvarez Marco, F Riu, M Dedeu Josep, L Barranco, F Enriquez Carlos, E Saperas, F Bory, A Seoane
Journal: Endoscopy (2015)

La clínica obstructiva en el cáncer colorrectal (CCR) en estadio paliativo obliga a un tratamiento sintomático. La prótesis de colon (PC) es actualmente el tratamiento de elección si bien es un tema en discusión que la cirugía resectiva (CR) pueda aumentar la supervivencia en éstos pacientes.
CLOSURE OF A VENTRICULAR SEPTAL DEFECT COMPLICATED BY HEMOLYSIS REQUIRING TRANSCATHETER RETRIEVAL OF AMPLATZER OCCLUDER
Authors: Akanksha Thakkar, Ponraj Chinnadurai, Maan Malahfji, Gary Monteiro, John Breinholt, C. Huie Lin
Journal: Journal of the American College of Cardiology (2017)
A phase I/II study of AZD6244 in combination with sorafenib in advanced hepatocellular carcinoma.
Authors: Su Pin Choo, Quan Sing Ng, Wallace Jian Jun Chen, Chee Kian Tham, Wei-Peng Yong, Ling Zhi Wang, Tong San Koh, Boon C. Goh, Choon Hua Thng, Hung The Huynh, Ying Kiat Zee, Li shan Low, Han Chong Toh
Journal: Journal of Clinical Oncology (2012)

4100^ Background: Preclinical studies have shown that pharmacological inhibition of the MEK/ERK pathway by AZD6244 enhanced the anti-tumor effect of sorafenib in both orthotopic and ectopic models of HCC. We conducted this study to determine tolerability, pharmacokinetics, and pharmacodynamics of AZD6244 when combined with sorafenib in advanced HCC. Methods: Patients with biopsy-proven unresectable BCLC B/C hepatocellular carcinoma were recruited. Only those with Childs-Pugh A or B (7) liver cirrhosis and without prior systemic therapy were included. Sorafenib at 400mg bd was given 1 week before initiation of AZD6244 which was escalated in subsequent cohorts from 75mg om based on 3+3 design. PK and PD studies and QOL assessments were performed. DCE-MRI imaging was performed to assess tumor vascularity in response to treatment. Results: Fourteen patients were recruited (including 2 replaced). 11 had evaluable disease. Characteristics: all male, all Chinese, 12 were BCLC C stage. Two DLTs were seen out of 6 patients at dose level 1 (AZD6244 at 50mg bd) which were grade 3 fatigue and grade 3 abdominal pain with elevated transaminases. When an additional dose level 1A was added (ADZ6244 at 100mg om), 2 out of 3 patients had DLTs of grade 3 raised aspartate transaminase and grade 3 diarrhea. Thus, the MTD was determined to be AZD6244 at 75mg om when combined with sorafenib 400mg bd. Common toxicities were diarrhea (83%), rash (58%), fatigue (50%), hypertension (42%), anorexia/vomiting/thrombocytopenia (25%). Two patients had reversible LVEF dysfunction and there were no eye toxicities. PK of AZD6244 showed oral clearance of 11.2 + 6.8 L/h and terminal half-life of 6.0 +2.0 h.Objective responses were 3 PR, 6 SD and 2 PD.DCE-MRI measurements demonstrated significant reductions in permeability surface area product (PS, ml/100ml/min) and fractional intravascular blood volume (v1, ml/100ml) seven days after starting sorafenib. No additional antivascular activity was observed when AZD6244 was added to sorafenib. Conclusions: The recommended phase II dose for AZD6244 is 75mg om when combined with sorafenib 400mg bd for advanced HCC patients. This combination is feasible, shows activity and warrants further investigation.
Activated TAFI Promotes the Development of Chronic Thromboembolic Pulmonary Hypertension
Authors: Taijyu Satoh, Kimio Satoh, Nobuhiro Yaoita, Nobuhiro Kikuchi, Junichi Omura, Ryo Kurosawa, Kazuhiko Numano, Elias Al-Mamun, Mohammad Abdul Hai Siddique, Shinichiro Sunamura, Masamichi Nogi, Kota Suzuki, Satoshi Miyata, John Morser, Hiroaki Shimokawa
Journal: Circulation Research (2017)

Pulmonary hypertension is a fatal disease; however, its pathogenesis still remains to be elucidated. Thrombin-activatable fibrinolysis inhibitor (TAFI) is synthesized by the liver and inhibits fibrinolysis. Plasma TAFI levels are significantly increased in chronic thromboembolic pulmonary hypertension (CTEPH) patients.To determine the role of activated TAFI (TAFIa) in the development of CTEPH.Immunostaining showed that TAFI and its binding partner thrombomodulin (TM) were highly expressed in the pulmonary arteries (PAs) and thrombus in patients with CTEPH. Moreover, plasma levels of TAFIa were increased 10-fold in CTEPH patients compared with controls. In mice, chronic hypoxia caused a 25-fold increase in plasma levels of TAFIa with increased plasma levels of thrombin and TM, which led to thrombus formation in PA, vascular remodeling, and pulmonary hypertension. Consistently, plasma clot lysis time was positively correlated with plasma TAFIa levels in mice. Additionally, overexpression of TAFIa caused organized thrombus with multiple obstruction of PA flow and reduced survival rate under hypoxia in mice. Bone marrow transplantation showed that circulating plasma TAFI from the liver, not in the bone marrow, was activated locally in PA endothelial cells through interactions with thrombin and TM. Mechanistic experiments demonstrated that TAFIa increased PA endothelial permeability, smooth muscle cell proliferation, and monocyte/macrophage activation. Importantly, TAFIa inhibitor and peroxisome proliferator-activated receptor-α agonists significantly reduced TAFIa and ameliorated animal models of pulmonary hypertension in mice and rats.These results indicate that TAFIa could be a novel biomarker and realistic therapeutic target of CTEPH.