tbuckley/cabot-search huggingface dataset:
Phase III trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC).
Authors: Ann-Lii Cheng, Richard S. Finn, Shukui Qin, Kwang-Hyub Han, Kenji Ikeda, Fabio Piscaglia, Ari David Baron, Joong-Won Park, Guohong Han, Jacek Jassem, Jean-Frédéric Blanc, Arndt Vogel, Dmitry Komov, T.R. Jeffry Evans, Carlos López-López, Corina E Dutcus, Min Ren, Silvija Kraljevic, Toshiyuki Tamai, Masatoshi Kudo
Journal: Journal of Clinical Oncology (2017)

4001 Background: SOR is the only approved agent in uHCC and new options are needed. LEN, an inhibitor of vascular endothelial growth factor receptors 1‒3, fibroblast growth factor receptors 1‒4, platelet derived growth factor receptor α, RET, and KIT, showed activity in uHCC in a phase II trial. We report a phase III trial of LEN vs SOR as first-line therapy for uHCC. Methods: In this randomized, open-label, noninferiority (NI) study, pts had uHCC, ≥ 1 measurable target lesion, Barcelona Clinic Liver Cancer stage B or C, Child-Pugh class A, ECOG PS ≤ 1, and no prior systemic therapy. Pts were randomized 1:1 to LEN (body weight ≥ 60 kg: 12 mg/day; &lt; 60 kg: 8 mg/day) or SOR 400 mg twice daily. The primary endpoint was overall survival (OS). The OS hazard ratio (HR) and its 95% CI were estimated with a stratified Cox proportional hazard model. The predefined NI margin was 1.08. Secondary efficacy endpoints were progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR) by modified RECIST. Type I error rates for secondary efficacy endpoints were controlled with a fixed sequence procedure at 2-sided α = 0.05 after OS NI was claimed. Results: 954 Pts enrolled (LEN: 478; SOR: 476). Efficacy outcomes are shown in the table. A similar number of pts in both arms had treatment-emergent adverse events (TEAEs). Most common LEN TEAEs were hypertension (42%), diarrhea (39%), decreased appetite (34%), decreased weight (31%), and fatigue (30%). Median (range) treatment duration was 5.7 mos (0−35.0) for LEN and 3.7 mos (0.1−38.7) for SOR. 13% Of LEN-treated and 9% of SOR-treated pts discontinued due to adverse events. 33% Of LEN-treated and 39% of SOR-treated pts received second-line therapy. Conclusions: LEN is noninferior in OS, and achieves statistically significant and clinically meaningful improvements in PFS, TTP, and ORR, as first line therapy for uHCC. TEAEs were consistent with the known LEN safety profile. Clinical trial information: NCT01761266. [Table: see text]
Biological effects and mechanisms of shortwave radiation: a review
Authors: Chao Yu, Rui-Yun Peng
Journal: Military Medical Research (2017)

With the increasing knowledge of shortwave radiation, it is widely used in wireless communications, radar observations, industrial manufacturing, and medical treatments. Despite of the benefits from shortwave, these wide applications expose humans to the risk of shortwave electromagnetic radiation, which is alleged to cause potential damage to biological systems. This review focused on the exposure to shortwave electromagnetic radiation, considering in vitro, in vivo and epidemiological results that have provided insight into the biological effects and mechanisms of shortwave. Additionally, some protective measures and suggestions are discussed here in the hope of obtaining more benefits from shortwave with fewer health risks.
The new radiolabelled somatostatin analogue 90Yttrium-dota-octreotate for the treatment of metastatic neuroendocrine tumors: Initial results and tolerability in a series of 47 patients
Authors: C. Toumpanakis, A. Quigley, R. Srirajaskanthan, A. Karpathakis, A. Krepska, A. Davidson, T. Meyer, J. Buscombe, M. E. Caplin
Journal: Gut (2007)
Prognostic and predictive role of circulating angiopoietin-2 in multiple solid tumors: An analysis of approximately 500 patients treated with lenvatinib across tumor types.
Authors: Ignace Vergote, Douglas Wilmot Ball, Masatoshi Kudo, Pallavi Sachdev, Mark Matijevic, Tadashi Kadowaki, Yasuhiro Funahashi, Keith Flaherty
Journal: Journal of Clinical Oncology (2014)

11061 Background: Lenvatinib is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT, and PDGFRα. Two phase 3 trials in differentiated thyroid cancer [DTC] and hepatocellular cancer [HCC] are ongoing. Baseline levels (BL) of circulating cytokines and angiogenic factors (CAFs) were evaluated across multiple phase 2 trials in 6 different types of solid tumors. Methods: BL serum or plasma samples from a total of approximately 500 patients were analyzed for about 50 CAFs using ELISA and multiplex assay platforms* in 5 phase 2 trials of lenvatinib for thyroid cancer (DTC and medullary thyroid cancer [MTC]), HCC, glioblastoma, endometrial cancer (EC), and melanoma (with or without BRAF V600E). Correlation with clinical outcomes (objective response rate [ORR], overall survival [OS]) was performed using Wilcoxon signed-rank test and univariate Cox proportional hazard model, respectively, whereas correlation with tumor size prior to lenvatinib treatment was performed using the Spearman's rank correlation test. Results: Among 50 CAFs, BL angiopoietin-2 (Ang-2) correlated with tumor size (p) in DTC (0.004), MTC (0.004), EC (<0.001), melanoma [WT (<0.001), MU (<0.001)] and HCC (0.046) among multiple phase 2 trials. BL Ang-2 levels showed consistent correlation with clinical outcomes per tumor types across trials and with OS (p/hazard ratio per standard deviation) in DTC (0.001/3.2), MTC (<0.001/3.2), EC (<0.001/1.8), and melanoma [WT (0.001/1.5), MU (<0.001/2.0)]. Correlation with ORR was observed only for a minor subset of analyzed CAFs; only BL Ang-2 levels correlated with ORR in >1 tumor type, specifically in DTC (0.034*), MTC (0.025) and EC (0.001). In EC, almost 50% of BL CAFs showed a significant correlation with tumor size, potentially suggestive of an EC-specific tumor micro-environment and the contribution of Ang-2 to tumor angiogenesis in EC. Conclusions: BL Ang-2 levels correlated with tumor size and OS across majority of solid tumors in multiple lenvatinib phase 2 trials. Only BL Ang-2 levels also correlated with ORR in a subset of tumors including EC. Clinical trial information: NCT00784303,NCT01111461,NCT01136967,NCT00946153,NCT01433991,.
Do depression and anxiety reduce the likelihood of remission in rheumatoid arthritis and psoriatic arthritis? Data from the prospective multicentre NOR-DMARD study
Authors: Brigitte Michelsen, Eirik Klami Kristianslund, Joseph Sexton, Hilde Berner Hammer, Karen Minde Fagerli, Elisabeth Lie, Ada Wierød, Synøve Kalstad, Erik Rødevand, Frode Krøll, Glenn Haugeberg, Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2017)

To investigate the predictive value of baseline depression/anxiety on the likelihood of achieving joint remission in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) as well as the associations between baseline depression/anxiety and the components of the remission criteria at follow-up.We included 1326 patients with RA and 728 patients with PsA from the prospective observational NOR-DMARD study starting first-time tumour necrosis factor inhibitors or methotrexate. The predictive value of depression/anxiety on remission was explored in prespecified logistic regression models and the associations between baseline depression/anxiety and the components of the remission criteria in prespecified multiple linear regression models.Baseline depression/anxiety according to EuroQoL-5D-3L, Short Form-36 (SF-36) Mental Health subscale ≤56 and SF-36 Mental Component Summary ≤38 negatively predicted 28-joint Disease Activity Score <2.6, Simplified Disease Activity Index ≤3.3, Clinical Disease Activity Index ≤2.8, ACR/EULAR Boolean and Disease Activity Index for Psoriatic Arthritis ≤4 remission after 3 and 6 months treatment in RA (p≤0.008) and partly in PsA (p from 0.001 to 0.73). Baseline depression/anxiety was associated with increased patient's and evaluator's global assessment, tender joint count and joint pain in RA at follow-up, but not with swollen joint count and acute phase reactants.Depression and anxiety may reduce likelihood of joint remission based on composite scores in RA and PsA and should be taken into account in individual patients when making a shared decision on a treatment target.
2-year outcomes with the Absorb bioresorbable scaffold for treatment of coronary artery disease: a systematic review and meta-analysis of seven randomised trials with an individual patient data substudy
Authors: Ziad A Ali, Patrick W Serruys, Takeshi Kimura, Runlin Gao, Stephen G Ellis, Dean J Kereiakes, Yoshinobu Onuma, Charles Simonton, Zhen Zhang, Gregg W Stone
Journal: The Lancet (2017)
Lung cancer characteristics in 762 never- and 6,246 ever-smoker patients: Study KBP-2010-CPHG.
Authors: Daniel Coëtmeur, Eric Briens, Christophe Perrin, Dragos Ciobanu, Olivier Leleu, Jean-Claude Mouries, Abderhamane Belmekki, Frederic Deniel, Jean-Pierre Di Mercurio, Etienne Leroy-Terquem, Veronique Tizon-Couetil, Jean-Michel Peloni, Didier Debieuvre, Charles Dayen, Francois Blanchon, Michel Grivaux
Journal: Journal of Clinical Oncology (2014)

1582 Background: In 2010, the French College of General Hospital Respiratory Physicians performed a prospective multicenter epidemiological study to describe the baseline characteristics and management of all new cases of primary lung cancer and evaluate survival. The present abstract compares characteristics according to smoking. Methods: 7,051 patients ≥18 years presenting with primary lung cancer, histologically or cytologically diagnosed between 1 January and 31 December 2010, and followed-up in the respiratory department of one of the 104 general hospitals participating in the study, were included. A standardized form was completed for each patient at diagnosis. A steering committee checked inclusion exhaustiveness. Results: 762 patients were never-smoker and 6,246 ever-smoker (43 missing data). Respectively, 222, 635, and 5,088 of ever-smokers claimed to consume or to have consumed 1-10, 11-20, and >20 pack-year; their median smoking duration was 40 years. Former-smokers stopped smoking 12 years ago (median). 158 never-smokers claimed to have been exposed to passive-smoking. At diagnosis, statistical significant differences between never- and ever-smoker patients (p<0.0001) were found for sex (women: 70%/19%); age (median: 73/64 years); stage of cancer (IV: 71%/59%); cancer type (adenocarcinoma: 69%/43%; small-cell lung cancer: 5%/14%; squamous-cell carcinoma: 8%/28%); EGFR mutation exploration (51%/28%) and positivity (37%/5%). For all these characteristics, significant trends (p<0.0001) were also observed when patients were graded according to consumption: e.g., percentage of adenocarcinoma was 63%, 54%, 50%, and 41% in the 0, 1-10, 11-20, and >20 pack-year groups, respectively. Conclusions: This study confirms the main differences between never-smokers and ever-smokers, in particular on histological type and EGFR-mutation, two characteristics that impact treatment.
Differential Outcome of Patients with Primary Refractory Vs. Relapsed Peripheral T-Cell Lymphoma: Analysis from a Prospective Multicenter US Cohort Study
Authors: Frederick Lansigan, Steven M Horwitz, Lauren C Pinter-Brown, Kenneth R Carson, Andrei R Shustov, Steven T. Rosen, Barbara Pro, Eric D. Hsi, Massimo Federico, Christian Gisselbrecht, Marc Schwartz, Lisa A Bellm, Mark Acosta, Francine M. Foss
Journal: Blood (2016)
Production of reactive persulfide species in chronic obstructive pulmonary disease
Authors: Tadahisa Numakura, Hisatoshi Sugiura, Takaaki Akaike, Tomoaki Ida, Shigemoto Fujii, Akira Koarai, Mitsuhiro Yamada, Katsuhiro Onodera, Yuichiro Hashimoto, Rie Tanaka, Kei Sato, Yutaka Shishikura, Taizou Hirano, Satoru Yanagisawa, Naoya Fujino, Tatsuma Okazaki, Tsutomu Tamada, Yasushi Hoshikawa, Yoshinori Okada, Masakazu Ichinose
Journal: Thorax (2017)

Oxidative stress is a major aetiological factor driving chronic obstructive pulmonary disease (COPD). Recently recognised as potent antioxidants, reactive persulfide and polysulfide species are biosynthesised by cystathionine β-synthase and cystathionine γ-lyase. The production of reactive persulfide and polysulfide species in the lungs of patients with COPD remain unknown.The aim of this study was to examine the production of reactive persulfides and polysulfides, such as glutathione persulfide (GSSH), cysteine persulfide (CysSSH) and glutathione trisulfide (GSSSH), in lung-resident cells and epithelial lining fluid (ELF) obtained from patients with mild to moderate COPD.Lung tissues, primary lung cells, ELF and sputum were obtained. The amounts of reactive persulfides and polysulfides in the cells and ELF were measured by liquid chromatography-tandem mass spectrometry with β-(4-hydroxyphenyl) ethyl iodoacetamide as a trapping agent for hydroper/polysulfides. The amounts of synthases in the lung tissues, sputum and primary cells were quantified.The amounts of GSSH, CysSSH and GSSSH were decreased in the lung cells and ELF from patients with COPD. The amounts of reactive persulfides and polysulfides in the lung cells had a positive correlation with the degree of airflow limitation. By contrast, the amounts of the synthases were increased in the lung tissues and sputum cells of patients with COPD.We have identified a decrease in reactive persulfide and polysulfide species in the lungs of patients with COPD. These data suggest that the newly detected antioxidants reactive persulfides and polysulfides could be associated with the redox balance in the lungs of patients with COPD.
Circulating tumor cell enumeration combined with gene expression analysis and clinical variables in castrate resistant prostate cancer
Authors: Mitchell Gross, David Agus, Yixin Wang, John Palma, John Jiang
Journal: Clinical Cancer Research (2008)

B33  Introduction: Enumeration of circulating tumor cells (CTCs) provides independent prognostic information in castrate resistant prostate cancer (CRPC). Expression of prostate cancer specific genes can be observed in peripheral blood cells following CTC-enrichment, and the molecular profiles of these cells has potential applications in predicting disease progression and in treatment selection. Serum prostate specific antigen (PSA) levels are regularly measured and reflect cancer growth and disease activity in castrate-resistant prostate cancer (CRPC). Here, we describe preliminary results of a pilot study to link CTC enumeration and targeted gene expression analysis with PSA and other clinical variables in CRPC. Methods: One 7.5ML volume of EDTA anti-coagulated bloodfor EpCAM-based immunomagnetic enrichment followed by QiagenRNA extraction and one 7.5ML volume of CellSaveTM preservedblood was collected for CTC enumeration and analysis was obtained from subjects prior to initiation of a cytotoxic chemotherapy (initial or salvage) for CRPC at time of disease progression. Clinical and pathological data including PSA is collected. RNA is analyzed by quantitative real-time RT-PCR. CTC enrichment and expression analysis from normal donors were performed in parallel as controls. Results: Data are available from the first 15 subjects enrolled. CTC elevation (≥1/ 7.5 ml blood) was found in 13 of 15 subjects and in 0 of 37 normal controls. Median (range) for CTCs was 17 (0-2362) cells/7.5 ml and for PSA was 261.4 (0.1-961.1) ng/ml. PSA doubling time could be calculated in 11 subjects with a median of 1.7 (0.2-5.3) months. Gene expression data are available for 11 subjects with CTC ≥ 5 and all normal controls. Elevated expression in subjects compared with controls was noted for several genes including: TACSTD (EpCAM; n=10); platelet-derived growth factor (PDEF; n=4); epidermal growth factor receptor (EGFR, n=2), human epidermal growth factor receptor - 2 (HER2, n=2); androgen receptor (AR; n=8); and PSA (n=9). Co-expression of EGFR/HER2 (n=2) and AR/PSA (n=8) was observed. Conclusion: CTCs can be isolated and analyzed for gene expression patterns from patients with progressive CRPC. Analysis of this data in conjunction with serum PSA and other clinical variables may provide greater biologic insight into the nature of CTCs and provide a non-invasive assay to direct and monitor therapy in CRPC.
Treatment of Cholesterol in 2017
Authors: Harlan M. Krumholz
Journal: JAMA (2017)

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Exosomes derived from gemcitabine-resistant cells transfer malignant phenotypic traits via delivery of miRNA-222-3p
Authors: Feng Wei, Chengyuan Ma, Tong Zhou, Xuechao Dong, Qinghua Luo, Li Geng, Lijuan Ding, Yandong Zhang, Li Zhang, Nan Li, Yang Li, Yan Liu
Journal: Molecular Cancer (2017)

Abstract Background Although gemcitabine-based chemotherapy has been established as a core multimodal therapy for non-small cell lung cancer (NSCLC) treatment, its clinical efficacy remains limited by the development of acquired resistance following tumor metastasis and relapse. In this study, we investigated how gemcitabine-resistant (GR) cells contribute to the development of NSCLC tumor malignancy via exosome-mediated transfer of microRNAs. Methods We first studied the mechanism of exosome internalization via PKH-67 staining and an immunofluorescence assay, then confirmed our finding by transmission electron microscopy and western blot analysis. Candidate miRNAs were identified through microarray analysis. Thereafter, RT-PCR, MTS, Transwell and soft agar assays were performed to assess the role of exosomic miR-222-3p in vitro. A 3’ untranslated region reporter assay was applied to identify the target of miR-222-3p. A lung metastasis mouse model was constructed to evaluate tumor growth and metastasis in vivo. Finally, clinical samples were used for correlation analysis between exosomic miR-222-3p levels and patients’ response to gemcitabine. Results A549-GR–derived exosomes were internalized by receipt cells via caveolin- and lipid raft-dependent endocytosis, which allowed the transfer of miR-222-3p. Exosomic miR-222-3p enhanced the proliferation, gemcitabine resistance, migration, invasion, and anti-anoikis of parental sensitive cells by directly targeting the promoter of SOCS3. In addition, a higher level of exosomic miR-222-3p in sera usually predicted worse prognosis in NSCLC patients. Conclusion Our data demonstrate that exosomic-miR-222-3p functions as a principal regulator of gemcitabine resistance and malignant characteristics by targeting SOCS3. The exosomic miR-222-3p level in sera may be a potential prognostic biomarker for predicting gemcitabine sensitivity in NSCLC patients.
A central venous catheter that revealed a vascular paradox
Authors: Savvoula Savvidou, Entela Koco, Matthew Tsagourias, Dimitrios Matamis
Journal: Thorax (2017)

A 60-year-old man with insignificant past medical history, was admitted to the intensive care unit with acute respiratory failure following community-acquired pneumonia. On admission, he was haemodynamically stable in sinus rhythm, febrile and neurologically intact with no focal neurological findings. Under mechanical ventilation, the ratio of arterial oxygen (PaO2) to fractional inspired oxygen concentration (FiO2) was 100. An antibiotic regime of ceftriaxone plus moxifloxacin was administered.

On day 6, a 3-lumen central venous catheter (CVC) (Arrow, 7 Fr x 20 cm, polyurethane radiopaque) was easily inserted into his left internal jugular vein using anatomical landmarks. Aspiration of blood from the distal tip of the catheter confirmed its intravascular placement; however, the sample’s bright red appearance strongly suggested it was ‘arterial’ in origin. Bedside B-mode ultrasonography excluded false cannulation of the carotid artery. Furthermore, connection of the CVC with a pressure transducer produced a venous waveform with low pressure. Blood gas analysis of the CVC sample returned a PaO …
What puts physicians and patients discussing cancer screening on the same page?
Authors: Danielle Seiden, Maureen Bezuhly, Gina Aharanoff, Kelly Cassano, Michael P. Osborne, Manjeet Chadha, James Austin Talcott
Journal: Journal of Clinical Oncology (2017)

1552 Background: Shared decision making requires effective provider-patient communication. We studied concordance in recalled discussions and factors that affected it. Methods: In a cluster-randomized trial of educational supports for providers (MDs), we are enrolling an age-(30-89 years) and sex-stratified sample of 216 patients (PTs) who underwent a physical examination at 2 urban hospitals, 18 for each of 12 primary care MDs. Screening guideline formatting (colorcoding) and academic detailing were randomly assigned in a 2x2 design. Immediate post encounter surveys recorded PT and MD recall of screening discussions. Results: The first 174 participants were diverse (63% white) and highly educated (77% college degree). PTs and MDs differed in recall of screening discussions, and the differences varied by screening test. When MDs reported a colorectal cancer (CRC) screening discussion, 21% of PTs did not; 20% of MDs disagreed when PTs reported the discussion. The discrepancies were greater for prostate specific antigen (PSA) screening, 29% and 29%, respectively, but much less for mammograms (MAM), 8% and 5%, respectively. Recall of the MD recommendation also differed: 15% of PTs disagreed when their MD reported it, and 33% of MDs when their PT reported it. For PSA, disagreement was 26% and 33%, respectively, and for MAM, disagreement was 17% and 10%, respectively. Overall, agreement between all PTs and MDs on whether screening was recommended was fair for CRC, PSA and MAM: kappa = 0.33, 0.34 and 0.29, respectively. For PTs &gt; 70 agreement was nonexistent on recalled CRC and PSA recommendations (kappa = -0.02 and -0.03, respectively) but preserved for MAM (kappa = 0.39). Sex did not affect CRC agreement. Recall concordance improved when SDM was recalled. For CRC, kappa rose from -0.12 to 0.52 if the MD recalled any MDM element. Conclusions: In a highly educated, diverse patient population, patients and physicians often disagreed on recalled cancer screening discussions. Discordance was greatest with PSA and least with MAM. Discordance was greater in older patients. If MDs recalled any shared decision making, agreement increased significantly. Communication varies by cancer screen, PT age and elements of shared decision making. Clinical trial information: NCT02430948.