tbuckley/cabot-search huggingface dataset:
Hypofractionated Radiotherapy for Patients with Early-Stage Glottic Cancer: Patterns of Care and Survival
Authors: Trevor J. Bledsoe, Henry S. Park, John M. Stahl, Wendell G. Yarbrough, Barbara A. Burtness, Roy H. Decker, Zain A. Husain
Journal: JNCI Journal of the National Cancer Institute (2017)

Radiotherapy alone is often used to treat early-stage glottic cancer (ESGC); however, the optimal radiation treatment schedule remains unknown. The National Comprehensive Cancer Network (NCCN) guidelines recommend both hypofractionated radiotherapy (HFX) and conventionally fractionated radiotherapy (CFX). We compared overall survival (OS) and treatment patterns among patients treated with HFX vs CFX for ESGC using a large national database.We identified patients diagnosed with stage I-II (cT1-2N0M0) glottic cancer from 2004 to 2013 within the National Cancer Data Base who were treated with either HFX (2.25 Gy/fraction to 63-65.25 Gy) or CFX (2.0 Gy/fraction to 66-70 Gy). The overall survival of patients receiving HFX vs CFX was compared using the log-rank test, multivariable Cox proportional hazards regression, and propensity score matching. All statistical tests were two-sided.Among 10 212 included patients, 4030 patients (39.5%) received HFX and 6182 patients (60.5%) received CFX. Predictors for receipt of HFX included clinical T1 disease, recent year of diagnosis, and treatment at academic and higher-volume centers (all P < .001). Patients treated with HFX increased from 22.1% in 2004 to 58.0% in 2013. HFX was associated with improved OS compared with CFX on univariate (five-year OS = 77.1%, 95% CI = 75.2% to 78.8%, vs 73.5%, 95% CI = 72.1% to 74.8%, respectively, log-rank P < .001) and multivariable analysis (HR = 0.89, 95% CI = 0.81 to 0.98, P = .02), a finding confirmed on propensity score matching.HFX is associated with improved survival compared with CFX among patients treated with definitive radiotherapy for ESGC, particularly among patients with cT2 disease. HFX utilization increased over the study period; however, 40% of patients in our cohort did not receive HFX in the most recent year of our analysis.
Use of nebulized antimicrobials for the treatment of respiratory infections in invasively mechanically ventilated adults: a position paper from the European Society of Clinical Microbiology and Infectious Diseases
Authors: J. Rello, C. Solé-Lleonart, J.-J. Rouby, J. Chastre, S. Blot, G. Poulakou, C.-E. Luyt, J. Riera, L.B. Palmer, J.M. Pereira, T. Felton, J. Dhanani, M. Bassetti, T. Welte, J.A. Roberts
Journal: Clinical Microbiology and Infection (2017)
The influence of somatic and depression comorbidity on physical functioning over eleven years in patients with rhematoid arthritis (FRI0116)
Authors: J. Hoek, L.D. Roorda, H.C. Boshuizen, J. Dekker, J. van Hees, I. Rupp, G. Tijhuis, G.A. van den Bos
Journal: Annals of the Rheumatic Diseases (2012)
Phase I study of rilotumumab (AMG 102), an HGF inhibitor, and erlotinib in patients with advanced non-small cell lung cancer (NSCLC).
Authors: Phu Tran, William E. Gooding, Liza Cosca Villaruz, Timothy Francis Burns, Mark A. Socinski, Ahmad A. Tarhini
Journal: Journal of Clinical Oncology (2014)

e19065 Background: MET is frequently overexpressed in NSCLC and amplification of MET and its ligand, hepatic growth factor (HGF), are mechanisms of resistance to epidermal growth factor receptor (EGFR) inhibitors. Rilotumumab is a fully human monoclonal antibody (IgG2) that binds to HGF with high affinity and inhibits activation of the MET pathway. This phase I trial was conducted to evaluate the safety and recommended phase 2 dose (RP2D) of rilotumumab and erlotinib in pts with recurrent or progressive, advanced NSCLC. Methods: A dose de-escalation design was adopted with rilotumumab starting at 15 mg/kg IV every 3 weeks and erlotinib at 150 mg PO daily (dose level 0). If dose de-escalation was needed it would proceed according to a Narayana k-in-a-row design and the selected dose was to be estimated by isotonic regression. For this trial k was set to 3. RP2D was the maximum dose below the dose associated with a 25% dose-limiting toxicity (DLT) rate. In the absence of the need for de-escalation per protocol specified decision rules among the first 8 patients the RP2D would be dose level 0. Enrollment criteria included stage IV NSCLC pts with ECOG performance status 1 or less who failed 1-2 prior chemotherapy regimens. Pts were assessed clinically every cycle of 3 weeks and radiologically every 6 weeks. Results: Eight pts with NSCLC (4 squamous cell; 4 adenocarcinoma) were enrolled. There were no DLTs. One pt had Grade 3 rash that did not meet criteria for DLT. Grade 2 toxicities were rash (n=4), diarrhea (1), fatigue (1), hypertension (1), and edema (1). Grade 1 toxicities included rash (4), diarrhea (2), edema (2), paronychia (2), fatigue (1), abdominal pain (1), lymphopenia (1), elevated bilirubin (1), elevated alkaline phosphatase (1), proteinuria (1), muscle spasm (1), and alopecia (1). Three pts had partial tumor response (one with EGFR p.L858R exon 21 mutation), 3 had stable disease, and 2 had progressive disease by RECIST. Conclusions: In the absence of DLTs among the first 8 pts on the study, dose level 0 (Rilotumumab 15 mg/kg IV every 3 weeks and erlotinib 150 mg PO daily) was the RP2D. A phase II study in NSCLC is ongoing. Clinical trial information: NCT01233687.
Transparent and Gas‐Permeable Liquid Marbles for Culturing and Drug Sensitivity Test of Tumor Spheroids
Authors: Hualin Li, Peng Liu, Guneet Kaur, Xi Yao, Mengsu Yang
Journal: Advanced Healthcare Materials (2017)

Transparent nanoparticle-based liquid marbles with high gas-permeability are prepared to culture tumor spheroids in 3D without the need of supplementary growth factor. The culturing process of spheroids from a population of cancer cells or a single cell in the transparent liquid marbles can be optically recorded continuously. Compared to monolayer cells and spheroids generated in multiwell plate, tumor spheroids cultured in the liquid marbles show enhanced viability under the treatment of chemotherapeutic drugs and small interfering RNA.
Semaphorin 4D inhibits neutrophil activation and is involved in the pathogenesis of neutrophil-mediated autoimmune vasculitis
Authors: Masayuki Nishide, Satoshi Nojima, Daisuke Ito, Hyota Takamatsu, Shohei Koyama, Sujin Kang, Tetsuya Kimura, Keiko Morimoto, Takashi Hosokawa, Yoshitomo Hayama, Yuhei Kinehara, Yasuhiro Kato, Takeshi Nakatani, Yoshimitsu Nakanishi, Takeshi Tsuda, Jeong Hoon Park, Toru Hirano, Yoshihito Shima, Masashi Narazaki, Eiichi Morii, Atsushi Kumanogoh
Journal: Annals of the Rheumatic Diseases (2017)

Inappropriate activation of neutrophils plays a pathological role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The aim of this study was to investigate the functions of semaphorin 4D (SEMA4D) in regulation of neutrophil activation, and its involvement in AAV pathogenesis.Serum levels of soluble SEMA4D were evaluated by ELISA. Blood cell-surface expression of membrane SEMA4D was evaluated by flow cytometry. To determine the functional interactions between neutrophil membrane SEMA4D and endothelial plexin B2, wild-type and SEMA4D-/- mice neutrophils were cultured with an endothelial cell line (MS1) stained with SYTOX green, and subjected to neutrophil extracellular trap (NET) formation assays. The efficacy of treating human neutrophils with recombinant plexin B2 was assessed by measuring the kinetic oxidative burst and NET formation assays.Serum levels of soluble SEMA4D were elevated in patients with AAV and correlated with disease activity scores. Cell-surface expression of SEMA4D was downregulated in neutrophils from patients with AAV, a consequence of proteolytic cleavage of membrane SEMA4D. Soluble SEMA4D exerted pro-inflammatory effects on endothelial cells. Membranous SEMA4D on neutrophils bound to plexin B2 on endothelial cells, and this interaction decreased NET formation. Recombinant plexin B2 suppressed neutrophil Rac1 activation through SEMA4D's intracellular domain, and inhibited pathogen-induced or ANCA-induced oxidative burst and NET formation.Neutrophil surface SEMA4D functions as a negative regulator of neutrophil activation. Proteolytic cleavage of SEMA4D as observed in patients with AAV may amplify neutrophil-mediated inflammatory responses. SEMA4D is a promising biomarker and potential therapeutic target for AAV.
Targeting Levels, Aberrant Localization or Oligomerization of Mutant Nucleophosmin Induces Differentiation and Loss of Survival of Human AML Cells with Mutant NPM1.
Authors: Ramesh Balusu, Warren C. Fiskus, Rekha Rao, Kathleen M. Buckley, Yongchao Wang, Atul Joshi, Sanjay Koul, Anand Jillella, Celalettin Ustun, Susan Sunay, H. Jean Khoury, Kapil N. Bhalla
Journal: Blood (2009)
Netrin1 Produced by Neural Progenitors, Not Floor Plate Cells, Is Required for Axon Guidance in the Spinal Cord
Authors: Supraja G. Varadarajan, Jennifer H. Kong, Keith D. Phan, Tzu-Jen Kao, S. Carmen Panaitof, Julie Cardin, Holger Eltzschig, Artur Kania, Bennett G. Novitch, Samantha J. Butler
Journal: Neuron (2017)
Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia
Authors: Sebastian Mohr, Carmen Doebele, Federico Comoglio, Tobias Berg, Julia Beck, Hanibal Bohnenberger, Gabriela Alexe, Jasmin Corso, Philipp Ströbel, Astrid Wachter, Tim Beissbarth, Frank Schnütgen, Anjali Cremer, Nadine Haetscher, Stefanie Göllner, Arefeh Rouhi, Lars Palmqvist, Michael A. Rieger, Timm Schroeder, Halvard Bönig, Carsten Müller-Tidow, Florian Kuchenbauer, Ekkehard Schütz, Anthony R. Green, Henning Urlaub, Kimberly Stegmaier, R. Keith Humphries, Hubert Serve, Thomas Oellerich
Journal: Cancer Cell (2017)

The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
TCTAP C-084 Application of Bioresorbable Vascular Scaffolds and Drug Eluting Stent with T-STENTING and Small Protrusion (TAP) Technique in Bifurcation Lesion
Authors: Tse-Husan Yang, Wei-Chun Huang, Chin-Chang Cheng, Cheng-Hung Chiang, Feng Yu Kuo, Guang-Yuan Mar, Chun-Peng Liu
Journal: Journal of the American College of Cardiology (2017)
Neonatal signs after in utero exposure to selective serotonin reuptake inhibitors [4] (multiple letters)
Authors: Bennett A. Kaye, Judith Weinstein, Bennett Lavenstein, Eydie L. Moses-Kolko, Debra Bogen, James Perel, Katherine L. Wisner, Amy Bregar, Kathleen Uhl, Bob Levin
Journal: JAMA (2005)
Use of Echocardiography for Guiding Percutaneous Tricuspid Valve Procedures
Authors: Eustachio Agricola, Francesco Ancona, Stefano Stella, Isabella Rosa, Claudia Marini, Marco Spartera, Paolo Denti, Alberto Margonato, Rebecca T. Hahn, Ottavio Alfieri, Antonio Colombo, Azeem Latib
Journal: JACC. Cardiovascular imaging (2017)
A simple risk stratification model to predict one-year postoperative mortality rate in patients with solid-organ cancer.
Authors: Wen-Chi Chou, Yu-Fan Cheng, Miao-Fen Chen, CHENG-Hsu Wang, Yung-Chang Lin, Ta-Sen Yeh
Journal: Journal of Clinical Oncology (2015)

e17706 Background: Comprehensive preoperative assessment and accurate prediction of surgery-related risks are vital in ensuring better patient selection and improved surgical outcoms in the management of solid organ cancers. This study aim to develop a scoring system that predicts one-year postoperative mortality for patients with solid organ cancers. Methods: A total of 20,632 patients who had a curative resection for primary solid organ cancers between 2007 and 2012 at Chang Gung Memorial Hospital Linkou Medical Center were included in the derivation cohort. Multivariate logistic regression analysis was performed to develop a risk model that predicted one-year postoperative mortality. Patients were then stratified into four risk groups (low, intermediate, high and very high-risk) according to the total score (0-34) for mortality risk analysis. An independent cohort of 16,656 patients who underwent curative cancer surgeries at three other hospitals during the same study period (validation cohort) was enrolled to verify the risk model. Results: Age, gender, cancer site, history of previous cancer, Charlson comorbidity index, American Society of Anesthesiologist score, admission type, and Eastern Cooperative Oncology Group performance status were independently predictive of one-year postoperative mortality. The one-year postoperative mortality rates were 1.7%, 6.1%, 12.2% and 24.2%, respectively, among the four risk groups in the derivation cohort (c-statistics, 0.73), compared to 2.2%, 7.0%, 13.0% and 23.9%, respectively, in the validation cohort (c-statistics, 0.70). The risk stratification model also demonstrated good discrimination of long-term survival outcome of the four-tier risk groups (p < 0.01 for both cohorts). Conclusions: The risk stratification model, developed exclusively from the preoperative data, not only predicts one-year postoperative mortality but also differentiates long-term survival outcome between the risk groups.
EZH2 alterations in follicular lymphoma: biological and clinical correlations
Authors: S Huet, L Xerri, B Tesson, S Mareschal, S Taix, L Mescam-Mancini, E Sohier, M Carrère, J Lazarovici, O Casasnovas, L Tonon, S Boyault, S Hayette, C Haioun, B Fabiani, A Viari, F Jardin, G Salles
Journal: Blood Cancer Journal (2017)

The histone methyltransferase EZH2 has an essential role in the development of follicular lymphoma (FL). Recurrent gain-of-function mutations in EZH2 have been described in 25% of FL patients and induce aberrant methylation of histone H3 lysine 27 (H3K27). We evaluated the role of EZH2 genomic gains in FL biology. Using RNA sequencing, Sanger sequencing and SNP-arrays, the mutation status, copy-number and gene-expression profiles of EZH2 were assessed in a cohort of 159 FL patients from the PRIMA trial. Immunohistochemical (IHC) EZH2 expression (n=55) and H3K27 methylation (n=63) profiles were also evaluated. In total, 37% of patients (59/159) harbored an alteration in the EZH2 gene (mutation n=46, gain n=23). Both types of alterations were associated with highly similar transcriptional changes, with increased proliferation programs. An H3K27me3/me2 IHC score fully distinguished mutated from wild-type samples, showing its applicability as surrogate for EZH2 mutation analysis. However, this score did not predict the presence of gains at the EZH2 locus. The presence of an EZH2 genetic alteration was an independent factor associated with a longer progression-free survival (hazard ratio 0.58, 95% confidence interval 0.36-0.93, P=0.025). We propose that the copy-number status of EZH2 should also be considered when evaluating patient stratification and selecting patients for EZH2 inhibitor-targeted therapies.
Hepatitis B virus reactivation during hepatitis C direct-acting antiviral therapy in patients with previous HBV infection
Authors: Naoki Kawagishi, Goki Suda, Masahiro Onozawa, Megumi Kimura, Osamu Maehara, Jun Ito, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
Journal: Journal of Hepatology (2017)
The use of immunotherapy in the treatment of melanoma
Authors: Tala Achkar, Ahmad A. Tarhini
Journal: Journal of Hematology & Oncology (2017)

Patients with advanced melanoma have a compromised anti-tumor immune response leading to tumor immune tolerance and a tumor microenvironment conducive to disease progression. Immunotherapy that successfully overcomes this tumor-mediated immune suppression has made the greatest impact in the management of this disease over the past few years. This progress through immunotherapy builds upon earlier successes that interferon-α had in the treatment of melanoma in the adjuvant setting, as well as that of high-dose interleukin-2 in advanced melanoma. The development of immune checkpoint inhibitors has led to dramatic clinical activity in advanced melanoma. In particular, anti-CTLA4 and anti-PD1 monoclonal antibodies have taken us forward into the realm of longer survival and durable responses with the possibility of cure in a continuously increasing proportion of patients. Combination immunotherapeutic strategies and novel immunotherapeutic agents are being tested at an accelerated pace where the outlook for long-term survival benefits for the majority of patients appears brighter than ever.
Abstract #2316: Anti-tumor effects of on the combination of photodynamic therapy with arsenic compound in TC-1 cells implanted C57BL/6 mice
Authors: Eun Kyung Oh, Su Mi Bae, Lanying Wen, Yong Wook Kim, Young-Jae Kim, Jung-Sik Kim, Woong Shick Ahn
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Objective: We studied the effects of As4O6 as adjuvant on photodynamic therapy of TC-1 cells in order to provide higher efficiency and explored the mechanisms underlying these effects. As4O6 is considered to have anticancer activity via several biological actions such as free radical producing and inhibition of VEGF expression. Methods and Materials : The present study was consisted of two part. In vitro experiments, cell proliferation and morphology was determined by MTT assay, when TC-1 cells, which overexpressed the HPV16-E6/E7, were exposed to either photodynamic therapy or As4O6 alone, or vehicle alone. Also, quantitative PCR array was performed to assay the signal transduction regulation. Additionally, this study was supported by the finding that combination of photodynamic therapy and As4O6 shows a inhibition effect of tumor growth in C57BL/6 mice with TC-1 cells xenographs in vivo . Results and conclusions; Cell proliferation was first estimated using an MTT assay after TC-1 cells were treated with either Radachlorin or As4O6 at various concentrations. Radachlorin and As4O6 significantly inhibited TC-1 cell proliferation in a dose-dependent manner (P<0.05). Antiproliferative effect of combination treatment was significantly higher than those of TC-1 cells treated with either photodynamic therapy or As4O6 (62.4 and 52.5% decrease, respectively, compared to photodynamic therapy or As4O6 alone, P <0.05). In addition, cell proliferation in combination of photodynamic therapy and As4O6 treatment significantly decreased by 77.4% compared to vehicle-only treated TC-1 cells (P<0.05). This inhibition in turn led to induce the apoptotic morphological features such as cell shrinkage and blebbing. Cell survival pathway (Naip1, Tert and Aip1) and p53-dependent pathway (Bax, p21Cip1, Fas, Gadd45, IGFBP-3 and Mdm-2) were markedly increased by combination treatment of photodynamic therapy and As4O6. Besides, the immunology response NEAT pathway (Ly-12, CD178 and IL-2) also modulated after combination treatment of photodynamic therapy and As4O6. This combination effect apparently shows a same pattern in vivo model. These findings suggest the benefit of the combination treatment of photodynamic therapy and As4O6 for the inhibition of cervical cancer growth

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2316.
Plasma viral DNA as a marker of tumor response in EBV(+) Hodgkin lymphoma in a phase III study (E2496).
Authors: Jennifer Ann Kanakry, Hailun Li, Lan L. Gellert, M. Victor Lemas, Wen Son Hsieh, King L. Tan, Randy D. Gascoyne, Leo I. Gordon, Sandra J. Horning, Brad S. Kahl, Richard F. Ambinder
Journal: Journal of Clinical Oncology (2012)

8003 Background: Epstein-Barr virus (EBV) is associated with Hodgkin lymphoma (HL) and can be detected by in situ hybridization (ISH) of viral nucleic acid (EBER) in tumor cells. Studies have suggested a correlation in HL between plasma EBV DNA and EBER ISH. We previously studied the DNase sensitivity of plasma EBV DNA and found plasma EBV of patients with EBV(+) HL was not protected from DNase digestion, consistent with tumor-derived DNA, while plasma EBV of patients with HIV without EBV(+) tumors was protected from DNase digestion, consistent with virion DNA. We sought to determine whether plasma EBV could serve as a surrogate for EBER ISH and whether reappearance of plasma EBV predicts treatment failure. Methods: Specimens from a Cancer Cooperative Intergroup Trial (E2496/Stanford V versus ABVD for HL) were used to compare pretreatment plasma EBV DNA copy number, assessed by real-time quantitative PCR, with EBV status by EBER ISH. An ROC analysis was performed using patients with both pretreatment plasma EBV and EBER results (n=121), identifying a cutoff of 60 viral copies/100 µL plasma (95% concordance, 92% sensitivity, 96% specificity for EBV status by EBER). Using this cutoff, pretreatment plasma specimens (n=274) were designated EBV(+) (n=54) or EBV(-) (n=220), as were serial follow-up specimens. Cox proportional hazard models were constructed to evaluate plasma EBV as a prognostic factor for failure-free survival (FFS). FFS was estimated by the Kaplan-Meier method. Results: Pretreatment EBV(+) plasma was associated with treatment failure with a hazard ratio of 2.1 (95% CI 1.2-3.6, p=0.01) after adjusting for International Prognostic Score, treatment arm, and histology. Of the EBV(+) patients with follow-up specimens (n=45), patients with EBV(+) plasma beyond 1 month of therapy (n=9) had inferior FFS compared to those who cleared their plasma of EBV (n=36), (3-year FFS 44% versus 69%, respectively; log rank p=0.03). Conclusions: HL patients with EBV(+) plasma at baseline have inferior FFS compared to others. Among patients with EBV(+) plasma at baseline, those in whom plasma EBV persists or reappears after initiation of therapy have inferior FFS. Such patients may benefit from experimental or intensified therapies.
TCTAP A-108 Comparison of Procedural Time of Endomyocardial Biopsy to Jugular Vein Versus Femoral Vein Access
Authors: Yusuke Nakano, Tomofumi Mizuno, Kentaro Mukai, Toru Niwa, Hirokazu Wakabayashi, Atsushi Watanabe, Hirohiko Ando, Hiroaki Takashima, Katsuhisa Waseda, Tetsuya Amano
Journal: Journal of the American College of Cardiology (2017)
Stress Perfusion CMR in Patients With Known and Suspected CAD
Authors: Gabriella Vincenti, Pier Giorgio Masci, Pierre Monney, Tobias Rutz, Sarah Hugelshofer, Mirdita Gaxherri, Olivier Muller, Juan F Iglesias, Eric Eeckhout, Valentina Lorenzoni, Cyril Pellaton, Christophe Sierro, Juerg Schwitter
Journal: JACC. Cardiovascular imaging (2017)
Location in the spleen dictates the function of murine neutrophils
Authors: Patrizia Scapini, Marco A. Cassatella
Journal: The Journal of Experimental Medicine (2017)

In this issue of JEM, Deniset et al. (https://doi.org/10.1084/jem.20161621) provide new data that extend our knowledge on the mechanisms whereby Streptococcus pneumoniae is cleared by the spleen. The authors identify novel populations of murine splenic neutrophils that localize in the red pulp and the marginal zone. During the acute phases of S. pneumoniae infection, these populations of splenic neutrophils act in concert with specialized macrophage and B cell populations to provide very rapid innate immune protection.