tbuckley/cabot-search huggingface dataset:
TarO-specific inhibitors of wall teichoic acid biosynthesis restore β-lactam efficacy against methicillin-resistant staphylococci
Authors: Sang Ho Lee, Hao Wang, Marc Labroli, Sandra Koseoglu, Paul Zuck, Todd Mayhood, Charles Gill, Paul Mann, Xinwei Sher, Sookhee Ha, Shu-Wei Yang, Mihir Mandal, Christine Yang, Lianzhu Liang, Zheng Tan, Paul Tawa, Yan Hou, Reshma Kuvelkar, Kristine DeVito, Xiujuan Wen, Jing Xiao, Michelle Batchlett, Carl J. Balibar, Jenny Liu, Jianying Xiao, Nicholas Murgolo, Charles G. Garlisi, Payal R. Sheth, Amy Flattery, Jing Su, Christopher Tan, Terry Roemer
Journal: Science Translational Medicine (2016)

New inhibitors of wall teichoic acid biosynthesis restore susceptibility of drug-resistant staphylococci to β-lactam antibiotics.
Phototherapy: Ruthenium‐Containing Block Copolymer Assemblies: Red‐Light‐Responsive Metallopolymers with Tunable Nanostructures for Enhanced Cellular Uptake and Anticancer Phototherapy (Adv. Healthcare Mater. 4/2016)
Authors: Wen Sun, Maria Parowatkin, Werner Steffen, Hans‐Jürgen Butt, Volker Mailänder, Si Wu
Journal: Advanced Healthcare Materials (2016)

On Page 467, S. Wu and co-workers demonstrate a novel photo-controlled drug delivery system based on Ru-containing block copolymers. The Ru-containing block copolymers self-assemble into nanostructures that can enter cancer cells. Red light can penetrate into tissue deeply, activate the Ru-containing block copolymers, and inhibit the growth of cancer cells.
IMPS-33THE EXTRACELLULAR MATRIX OF GLIOMA TUMORS INFLUENCES MACROPHAGE ACTIVITY
Authors: Michelle Previtera, Amitahba Sengupta, Rajat Patel, Poonit Mehta, Kimberly Peterman, Mason Hui, Stephen Bloomfield, Joseph Landolfi, C. Alexander Ewing
Journal: Neuro-Oncology (2015)

Glioblastoma (GB) is the most common and aggressive form of malignant primary brain tumors in adults. Immunotherapeutics are a promising avenue of treatment, but their effectiveness can improve if we further understand the immune system's role in tumor progression. The tumor extracellular matrix (ECM) and tumor-associated macrophages promote tumor growth and invasion, but the effect of the tumor ECM on macrophage activity is unknown. We hypothesize that the physical and biological properties of the tumor ECM drive macrophage phenotypes that promote tumor growth. In this study, we investigated the ECM-macrophage interface from both a biological and physical perspective. We found that tumor ECM stiffness and composition promoted the proinflammatory activity of macrophages in short-term cultures. This is surprising considering most investigators have found that macrophages have anti-inflammatory activity in mouse tumors. We also examined whether proinflammatory mediators were present in GB tumors. We found that TNF-alpha, a proinflammatory cytokine, was present in 7 out of 7 tumors of patients with GB. Also, we found that IL-10, an anti-inflammatory cytokine, was present in 6 out of 6 tumors of patients with GB. Our results show a need to clinically define the inflammatory activity in the tumor microenvironment and identify the mechanisms that drive inflammation.
Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia
Authors: J.-H. Yoon, H.-Y. Yhim, J.-Y. Kwak, J.-S. Ahn, D.-H. Yang, J.-J. Lee, S.-J. Kim, J.-S. Kim, S.J. Park, C.W. Choi, H.-S. Eom, S.-K. Park, S.-Y. Choi, S.-H. Kim, D.-W. Kim, S. Lee
Journal: Annals of Oncology (2016)
Changing Incidence of Thyroid Cancer
Authors: W Weiss
Journal: JNCI Journal of the National Cancer Institute (1979)

The Incidence of thyroid cancer was examined temporally and geographically by age and sex from data provided by tumor registries in the United States and abroad. The temporal trends in Connecticut showed an increase in annual incidence after 1945, with an especially sudden increase in incidence in females. The increase occurred predominantly in older males and younger females. The increase in young females was confirmed by cohort analysis. The rates rose with age in both sexes, but recently females have developed a secondary peak in the fourth decade of life. The same phenomenon was observed in other U.S. data but not as clearly in data from ten foreign registries. These observations are consistent with the hypothesis that X-radiation therapy for benign conditions of the head and neck in childhood was a factor in the increased incidence of thyroid cancer in U.S. females, but some other etiologic or modifying factor should be sought to explain the increased incidence in U.S. males.
Abstract 13658: Comparison of Complications Between Transradial Approach and Transfemoral Approach for Patients With St-segment Elevation Myocardial Infarction
Authors: Ryuma Ishihara, Atsushi Tosaka, Toshio Katagiri, Yuriko Sato, Taisuke Mizumura, Toshitake Tamamura, Youichi Sugimura, Masakazu Tsutsumi, Naoto Hashizume, Naoyuki Abe, Takashi Miura
Journal: Circulation (2013)

Introduction: Some trials have suggested that transradial intervention (TRI) reduces vascular complications and bleeding compared with transfemoral intervention (TFI).In this study,we aimed to asse...
Targeting DNA-PK and ATM Increases Sensitivity to Chlorambucil and Fludarabine in Chemoresistant and p53-Defective B-CLL Cells.
Authors: Elaine Willmore, Geoffrey P. Summerfield, Tryfonia Mainou-Fowler, Graham H. Jackson, Anthony Carter, Andrew R. Pettitt, Barbara W. Durkacz
Journal: Blood (2006)
Phase I study of CNTO 95, a fully human monoclonal antibody (mAb) to α<sub>v</sub> integrins, in patients with solid tumors
Authors: G. C. Jayson, S. Mullamitha, C. Ton, J. Valle, A. Jackson, P. Julyan, M. C. Munteanu, H. M. Davis, Z. Lang, R. A. Beckman
Journal: Journal of Clinical Oncology (2005)

3113 CNTO 95 is a fully human anti-αvintegrin antibody that inhibits the growth of human melanoma xenografts in nude mice and rats by ∼80% and >99%, respectively. The objective of this phase I dose-escalating study was to assess the safety and pharmacokinetics of CNTO 95 in patients with advanced refractory solid tumors. CNTO 95 was infused on days 0, 28, 35 and 42 and standard clinical assessments, DCE-MRI, and FDG-PET were performed. Twenty four patients were enrolled at 0.1, 0.3, 1, 3 and 10 mg/kg. Tumor types included ovarian (6), colorectal (9), angiosarcoma (2), ureteric (1), PNET (1), pseudomyxoma peritonei (1), endometrial (1), metastatic melanoma (1), renal cell carcinoma (1), and carcinosarcoma (1). CNTO95 was associated with one episode of grade III and several episodes of grade II infusion-related fever, which were controllable with acetaminophen. One patient with cutaneous angiosarcoma dosed at 10 mg/kg had a partial response that is ongoing after 2 months on extended treatment (10 mg/kg). A lesion in a patient with ovarian carcinosarcoma and stable disease (10mg/kg) was undetectable on FDG-PET at day 49. Exploratory DCE-MRI analysis indicated a non-dose dependent decrease in area under the gadolinium curve in some patients. Preliminary PK data indicated that drug exposure increased in a greater than dose propor tional manner with dose dependent half-life ranging from 0.19 to 11.81 days over the doses 0.1–10 mg/kg. The initial rapid clearance is probably due to tissue binding at low doses (< 3 mg/kg). At higher doses slower drug clearance could indicate saturation of tissue sites. In conclusion, CNTO 95, a fully human mAb to αv integrins, is well tolerated up to weekly doses of 10 mg/kg. Six patients had extended therapy including one with angiosarcoma who has a partial response. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centocor Centocor Centocor
Syndecan-1 Attenuates Lung Injury during Influenza Infection by Potentiating c-Met Signaling to Suppress Epithelial Apoptosis
Authors: Rena Brauer, Lingyin Ge, Saundra Y. Schlesinger, Timothy P. Birkland, Ying Huang, Tanyalak Parimon, Vivian Lee, Bonnie L. McKinney, John K. McGuire, William C. Parks, Peter Chen
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Syndecan-1 is a cell surface heparan sulfate proteoglycan primarily expressed in the lung epithelium. Because the influenza virus is tropic to the airway epithelium, we investigated the role of syndecan-1 in influenza infection.Objectives: To determine the mechanism by which syndecan-1 regulates the lung mucosal response to influenza infection.Methods: Wild-type (WT) and Sdc1−/− mice were infected with a H1N1 virus (PR8) as an experimental model of influenza infection. Human and murine airway epithelial cell cultures were also infected with PR8 to study the mechanism by which syndecan-1 regulates the inflammatory response.Measurement and Main Results: We found worsened outcomes and lung injury in Sdc1−/− mice compared with WT mice after influenza infection. Our data demonstrated that syndecan-1 suppresses bronchial epithelial apoptosis during influenza infection to limit widespread lung inflammation. Furthermore, we determined that syndecan-1 attenuated apoptosis by crosstalking with c-Met to potentiate its cytoprotective signals in airway epithelial cells during influenza infection.Conclusions: Our work shows that cell-associated syndecan-1 has an important role in regulating lung injury. Our findings demonstrate a novel mechanism in which cell membrane–associated syndecan-1 regulates the innate immune response to influenza infection by facilitating cytoprotective signals through c-Met signaling to limit bronchial epithelial apoptosis, thereby attenuating lung injury and inflammation.
Abstract 14717: A Meta-Analysis of Prognostic Effects of Calcium Channel Blockers in Patients with Vasospastic Angina
Authors: Kazuhiko Nishigaki, Yukiko Inoue, Yoshio Yamanouchi, Yoshihiro Fukumoto, Satoshi Yasuda, Shozo Sueda, Hidenori Urata, Hiroaki Shimokawa, Shinya Minatoguchi
Journal: Circulation (2010)

Background: Although calcium channel blockers (CCBs) are highly effective for suppression of vasospastic angina (VSA) attacks, their prognostic effects in VSA patients remain to be examined in a la...
Translational Research for Tuberculosis Elimination: Priorities, Challenges, and Actions
Authors: Christian Lienhardt, Knut Lönnroth, Dick Menzies, Manica Balasegaram, Jeremiah Chakaya, Frank Cobelens, Jennifer Cohn, Claudia M. Denkinger, Thomas G. Evans, Gunilla Källenius, Gilla Kaplan, Ajay M. V. Kumar, Line Matthiessen, Charles S. Mgone, Valerie Mizrahi, Ya-diul Mukadi, Viet Nhung Nguyen, Anders Nordström, Christine F. Sizemore, Melvin Spigelman, S. Bertel Squire, Soumya Swaminathan, Paul D. Van Helden, Alimuddin Zumla, Karin Weyer, Diana Weil, Mario Raviglione
Journal: PLoS Medicine (2016)

Competing Interests: CMD is employed by FIND, a nonprofit organization that collaborates with industry partners for the development, evaluation and demonstration of new diagnostic tests
Effects of Carcinogen Dosage on Experimental Colonic Carcinogenesis by Azoxymethane: An Ultrastructural Study of Grossly Normal Colonic Mucosa&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Q Pan, S R Hamilton, J Hyland, J K Boitnott
Journal: JNCI Journal of the National Cancer Institute (1985)

The transmission electron microscopic features of grossly normal colonic mucosa in the azoxymethane [(AOM) CAS: 25843-45-2]-treated rat model of colonic carcinogenesis were studied by the method of concomitant variation. Ten-week-old male F344 rats were given 10 weekly sc injections of AOM at doses of 3, 7, or 14 mg/kg body weight and were killed 1 week or 15 weeks after the last AOM dose. Grossly normal distal left colon was examined using transmission electron microscopy. Three transient dose-dependent features of colonic epithelial cells were identified: a) mitochondrial injury, b) nuclear pleomorphism and loss of polarity, and c) increased numbers of mitotic figures in the lower third of the crypts. Because these dose-dependent features were present only shortly after AOM administration, they appeared to be manifestations of carcinogen toxicity and associated reactive, regenerative epithelial changes. By contrast, four persistent dose-dependent features were identified: a) increased numbers of epithelial cells with enlarged nucleoli, b) increased numbers of mitotic figures in the middle third of crypts, c) reduced numbers of goblet cells, and d) reduced numbers of apical cytoplasmic vacuoles in the upper third of the crypts. Because these features persisted in a dose-dependent manner for many weeks after the last dose of AOM and were present after the latent period to tumor formation, they appear to be morphologic precursors to colonic carcinogenesis in the model.
Use of high-flow nasal cannula oxygenation in ICU adults: a narrative review
Authors: Laurent Papazian, Amanda Corley, Dean Hess, John F. Fraser, Jean-Pierre Frat, Christophe Guitton, Samir Jaber, Salvatore M. Maggiore, Stefano Nava, Jordi Rello, Jean-Damien Ricard, François Stephan, Rocco Trisolini, Elie Azoulay
Journal: Intensive Care Medicine (2016)
Abstract 65: Racial Disparities in Outcomes Following Nonshockable In-Hospital Cardiac Arrest
Authors: Rabia R Razi, Matthew M Churpek, Trevor C Yuen, Monica E Peek, Dana P Edelson
Journal: Circulation (2012)

Background: Black patients have previously been shown to have worse outcomes from ventricular arrhythmias. This discrepancy was largely explained by individual patient characteristics and racial clustering by hospital. However, the vast majority of in-hospital cardiac arrests are due to pulseless electrical activity (PEA) and asystole and little is known about the relationship between race and outcomes in this patient group. Methods: We analyzed PEA and asystolic in-hospital cardiac arrests in the Get With The Guidelines-Resuscitation (GWTG-R) database from 2000 to 2009. A generalized estimating equation model was used to estimate the average survival difference between black and white patients in the study population. Multilevel conditional fixed effects logistic regression models were then used to estimate the relationship between race and survival to discharge and ROSC, sequentially controlling for hospital, patient demographics, comorbidities, arrest characteristic, process measures and interventions in place at the time of arrest. Results: We identified 76,385 eligible index arrests with a presenting rhythm of PEA or asystole, of which 19,236 (25%) were black. Black patients were younger on average (63 vs 71 years, p&lt;0.001) and had more comorbidities than their white counterparts. Survival to discharge was 13% for white patients and 10% for black patients (unadjusted OR 0.83; 95% CI 0.78-0.88). This effect remained nearly constant after controlling for hospital, patient, and event-specific confounders (adjusted OR 0.85; 95% CI 0.79-0.92). Similar results were shown for ROSC (adjusted OR 0.88; 95% CI 0.84-0.92). Conclusion: Black patients have significantly lower survival rates after in-hospital PEA and asystolic arrests. Hospital, patient demographics, event characteristics, and co-morbidities as measured in the GWTG-R database failed to explain this discrepancy. Furthermore, the consistency between the outcomes differences in ROSC and survival to discharge suggest that there are unmeasured intra-arrest and/or pre-arrest racial differences present. This is in contrast to shockable cardiac arrests in the same database, in which the disparity was greatly reduced after accounting for measured confounders.
Testosterone and components of aggressive and sexual behavior in man
Authors: P M Monti, W A Brown, D P Corriveau
Journal: American Journal of Psychiatry (1977)

The combined intake of social (moderate) doses of alcohol and marijuana resulted in a significant incidence of severe nausea, vomiting, autonomic nervous system lability, behavioral impairment, and intense psychological distress in our subjects. Although this syndrome is self-limiting, it could be dangerous for some individuals under certain conditions, e.g. , in the presence of cardiac or central nervous system disorders. The “self-titration” of marijuana is not always safe, even with moderate doses ofalcohol. The mechanism of this interaction is not known and no treatment for the adverse reaction is available at the present time.
How Do Cancer Cells Die?
Authors: Susan E. Bates
Journal: Clinical Cancer Research (2015)

How do cancer cells die and how can we increase the fraction of cells that die after cancer treatment? This question has been a puzzle for almost 75 years, from the first i.v. administration in 1942 of a cancer chemotherapeutic to a patient, as described later by Fenn and Udelsman (1). We repeat the question when the tumor in one patient shrinks, while that in another patient grows. That cells would die after a chemotherapeutic interfered with DNA or with the cytoskeleton seems intuitive. But cancer cells also die from withdrawal of a hormone such as estrogen or androgen, blockade of a growth factor such as EGFR, loss of cellular attachment, interference with intracellular signaling, amino acid starvation, viral infection, and immune activation. Unequal triggers to be sure—some active, some passive—but, regardless of the trigger, the same outcome. Clearly, cell death is a complex event, and much less is known about how cells die than about the array of triggers. Several defined and distinct mechanisms are accepted: apoptosis, autophagy, and necroptosis. Work in this field is the subject of this section of CCR Focus with Guest Editor Anthony Letai, who has assembled a series of experts in the field. Two articles look at agents in the clinic that directly promote intrinsic apoptosis: Christopher Gibson and Matthew Davids on BCL-2 antagonists and Simone Fulda on SMAC mimetics. Eileen White and colleagues explain autophagy and its potential in the clinic. Finally, Luis Martínez-Lostao and colleagues ask what happens after immune activation—how do cancer cells die?Successful drug therapy for a cancer requires distribution of the drug to the cancer cell, interaction or interference with the cellular target, and triggering and following the final common pathway to cell death. We know a lot about hitting the target, and we have many agents for that. At last, we may be able to treat the cell death pathways as therapeutic targets and leverage them in combination therapies.Susan E. BatesDeputy Editor, CCR FocusColumbia University Medical CenterSee all articles in this CCR Focus section, “Cell Death and Cancer Therapy.”Publication of the first report of nitrogen mustard therapy for cancer (2). Copyright © 1946 American Medical Association. All rights reserved.
Natural Antibodies to Human Lymphocytes in Murine Strains 2 3
Authors: S. Ferrone, M. A. Pellegrino, K. K. Mittal
Journal: JNCI Journal of the National Cancer Institute (1976)

Murine strains vary greatly in their content of natural antibodies to human lymphocytes; sera from NZB, B10.BR/Sn, DBA/J, and B10.S mice reacted with more than 90% of the panel of human lymphocytes, yet those from other strains did not react. These levels of natural antibodies to human lymphocytes did not correlate with the H-2 type of mice, but appeared to be a dominant character with incomplete penetrance. Since sera from germfree mice also contained natural antibodies to human lymphocytes, their formation was not influenced substantially by bacteria.
Health-related quality of life in patients with advanced prostate cancer undergoing treatment with TRIPTOrelin Pamoate SIX month formulation: Results of the non-interventional TRIPTOSIX study.
Authors: Andreas Eisenhardt, Tim Schneider, Karl Scheithe, Christiane Colling, Axel Heidenreich
Journal: Journal of Clinical Oncology (2015)

287 Background: Preserving quality of life (QoL) is an important therapeutic aim in advanced prostate cancer (PCa). The effects of treatment on QoL were studied in a non-interventional study performed from 2010 until 2012 evaluating 1 year of treatment with a LHRH agonist, triptorelin pamoate 6-month depot (TP 6M). Methods: Data of 564 patients with advanced PCa treates in 129 German urology outpatient clinics were analysed. Data on QoL were collected by EORTC questionnaires (QLQ-C30 and -PR25) at baseline, 6 months and 12 months. The QLQ-C30 assesses functional QoL, global health and symptoms of disease, the QLQ-PR25 covers PCa specific symptoms and sexual activity. A clinically relevant improvement, i.e. increase of ≥10 points in the QLQ-C30 global health status/QoL scale, defined treatment responders. Response at month 6 compared to baseline was the primary study endpoint. Results: GlobalHealth Related (HR) QoL was similar over the 1 year follow-up period with a mean (± SD) score of 60.9 (±21.8) at baseline and 61.7 (±22.2) at 12 months. Within the first 6 months, 24.0% of patients were identified as responders (i.e. a clinically relevant improvement in this parameter of ≥10 points). The responder rate was maintained at 12 months of treatment (25.5%). This trend in QoL was also seen in the QLQ-C30 subscales, which were generally similar over the study period. QLQ-PR25 scores were also found to be similar over 1 year, although some deterioration was reported by sexually active patients, as expected. Subgroup analyses on response rates identified age, risk group, pretreatment for PCa and baseline QoL scores as predictors of change in QoL. Conclusions: Treatment with TP 6M over 12 months is associated with few changes in HRQoL and might lead in some patients to clinically meaningful improvements of HRQoL.
NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 4.2016
Authors: David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Thomas J. Dilling, M. Chris Dobelbower, Ramaswamy Govindan, Mark Hennon, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, Neelesh Sharma, James Stevenson, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2016)

These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC; Versions 1–4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies). Nivolumab and pembrolizumab are preferred based on improved overall survival rates, higher response rates, longer duration of response, and fewer adverse events when compared with docetaxel therapy.
Feasibility of the association of mitotane with etoposide, adriamycin and cisplatin combination chemotherapy in advanced adrenocortical cancer patients. Report on 7 cases
Authors: A. Pia, A. Berruti, M. Terzolo, P. Paccotti, C. Letizia, L. Dogliotti, A. Angeli
Journal: Annals of Oncology (1995)
An autonomous CEBPA enhancer specific for myeloid-lineage priming and neutrophilic differentiation
Authors: Roberto Avellino, Marije Havermans, Claudia Erpelinck, Mathijs A. Sanders, Remco Hoogenboezem, Harmen J. G. van de Werken, Elwin Rombouts, Kirsten van Lom, Paulina M. H. van Strien, Claudia Gebhard, Michael Rehli, John Pimanda, Dominik Beck, Stefan Erkeland, Thijs Kuiken, Hans de Looper, Stefan Gröschel, Ivo Touw, Eric Bindels, Ruud Delwel
Journal: Blood (2016)