tbuckley/cabot-search huggingface dataset:
Co-clinical assessment identifies patterns of BRAF inhibitor resistance in melanoma
Authors: Lawrence N. Kwong, Genevieve M. Boland, Dennie T. Frederick, Timothy L. Helms, Ahmad T. Akid, John P. Miller, Shan Jiang, Zachary A. Cooper, Xingzhi Song, Sahil Seth, Jennifer Kamara, Alexei Protopopov, Gordon B. Mills, Keith T. Flaherty, Jennifer A. Wargo, Lynda Chin
Journal: Journal of Clinical Investigation (2015)

Multiple mechanisms have been described that confer BRAF inhibitor resistance to melanomas, yet the basis of this resistance remains undefined in a sizable portion of patient samples. Here, we characterized samples from a set of patients with melanoma that included individuals at baseline diagnosis, on BRAF inhibitor treatment, and with resistant tumors at both the protein and RNA levels. Using RNA and DNA sequencing, we identified known resistance-conferring mutations in 50% (6 of 12) of the resistant samples. In parallel, targeted proteomic analysis by protein array categorized the resistant samples into 3 stable groups, 2 of which were characterized by reactivation of MAPK signaling to different levels and 1 that was MAPK independent. The molecular relevance of these classifications identified in patients was supported by both mutation data and the similarity of resistance patterns that emerged during a co-clinical trial in a genetically engineered mouse (GEM) model of melanoma that recapitulates the development of BRAF inhibitor resistance. Additionally, we defined candidate biomarkers in pre- and early-treatment patient samples that have potential for predicting clinical responses. On the basis of these observations, we suggest that BRAF inhibitor-resistant melanomas can be actionably classified using protein expression patterns, even without identification of the underlying genetic alteration.
Angiopoietin 2 Induces Glioma Cell Invasion by Stimulating Matrix Metalloprotease 2 Expression through the αvβ1 Integrin and Focal Adhesion Kinase Signaling Pathway
Authors: Bo Hu, Michael J. Jarzynka, Ping Guo, Yorihisha Imanishi, David D. Schlaepfer, Shi-Yuan Cheng
Journal: Cancer Research (2006)

Abstract Accumulating evidence reveals a significant correlation between angiopoietin 2 (Ang2) expression and tumor invasion and metastasis in various human cancers, but the major focus of recent studies has been on the angiogenic effects of Ang2. We recently reported that Ang2-stimulated glioma cell invasion results from the up-regulation and activation of matrix metalloprotease 2 (MMP-2) in tumor cells. In this study, we identify a novel mechanism by which Ang2 stimulates MMP-2 expression leading to glioma cell invasion. We show that Ang2 interacts with αvβ1 integrin in Tie2-deficient human glioma cells, activating focal adhesion kinase (FAK), p130Cas, extracellular signal–regulated protein kinase (ERK) 1/2, and c-jun NH2-terminal kinase (JNK) and substantially enhancing MMP-2 expression and secretion. The Ang2/αvβ1 integrin signaling pathway was attenuated by functional inhibition of β1 and αv integrins, FAK, p130Cas, ERK1/2, and JNK. Furthermore, expression of a negative regulator of FAK, FAK-related nonkinase, by U87MG/Ang2–expressing glioma xenografts suppressed Ang2-induced MMP-2 expression and glioma cell infiltration in the murine brain. These data establish a functional link between Ang2 interaction with αvβ1 integrin and glioma cell invasion through the FAK/p130Cas/ERK1/2 and JNK-mediated signaling pathway. (Cancer Res 2006; 66(2): 775-83)
Coadministration of a Herpes Simplex Virus-2–Based Oncolytic Virus and Cyclophosphamide Produces a Synergistic Antitumor Effect and Enhances Tumor-Specific Immune Responses
Authors: Hongtao Li, Zihua Zeng, Xinping Fu, Xiaoliu Zhang
Journal: Cancer Research (2007)

Abstract Despite their unique property of selective replication and propagation in tumor tissues, oncolytic viruses have had only limited antitumor effects in cancer patients. One of the major reasons is probably the host's immune defense mechanisms, which can restrict the ability of the virus to replicate and spread within tumors. The innate immune system, which can be rapidly activated during virus infection, likely plays a more pivotal antiviral role than does acquired immunity, as the antitumor effect of an oncolytic virus is mainly generated during the acute phase of virus replication. To exploit the potential of cyclophosphamide, a cancer chemotherapeutic drug that also inhibits innate immune responses, to enhance the activity of oncolytic viruses, we evaluated the effect of coadministration of this drug with a herpes simplex virus-2–based oncolytic virus (FusOn-H2) against Lewis lung carcinoma, which is only semipermissive to infection with FusOn-H2. This strategy synergistically enhanced the antitumor effect against lung carcinoma growing in mice. It also potentiated the ability of FusOn-H2 to induce tumor-specific immune responses. Together, our results suggest that coadministration of FusOn-H2 with cyclophosphamide would be a feasible way to enhance the antitumor effects of this oncolytic virus in future clinical trials. [Cancer Res 2007;67(16):7850–5]
Troponin I levels in unstable angina/non-Q wave myocardial infarction patients treated with tirofiban, a glycoprotein IIb/IIIa antagonist
Authors: S.S. Hahn, C. Chae, R. Giugliano, K. Lewandrowski, P. Theroux, I.-K. Jang
Journal: Journal of the American College of Cardiology (1998)
A canine model of coronary artery thrombosis with superimposed high grade stenosis for the investigation of rethrombosis after thrombolysis
Authors: Tsunehiro Yasuda, Herman K. Gold, John T. Fallon, Robert C. Leinbach, Harry D. Garabedian, J.Luis Guerrero, Desire Collen
Journal: Journal of the American College of Cardiology (1989)
Maximizing Local Control and Organ Preservation in Stage IV Squamous Cell Head and Neck Cancer With Hyperfractionated Radiation and Concurrent Chemotherapy
Authors: David J. Adelstein, Jerrold P. Saxton, Pierre Lavertu, Lisa A. Rybicki, Ramon M. Esclamado, Benjamin G. Wood, Marshall Strome, Marjorie A. Carroll
Journal: Journal of Clinical Oncology (2002)

Results are reported from an aggressive chemoradiotherapy protocol for advanced squamous cell head and neck cancer.Patients with advanced squamous cell head and neck cancer were treated with hyperfractionated radiation therapy (72 Gy at 1.2 Gy twice per day) and two courses of concurrent chemotherapy with fluorouracil (1,000 mg/m(2)/d) and cisplatin (20 mg/m(2)/d), both given as 96-hour continuous intravenous infusions during weeks 1 and 4 of radiation therapy. Primary-site resection was reserved for residual or recurrent primary-site disease after chemoradiotherapy. Neck dissection was considered for N2 or greater disease, irrespective of clinical response, and for residual or recurrent neck disease after nonoperative treatment.Forty-one patients with stage IV disease were treated. Toxicity was significant, with grade 3 to 4 mucositis in 98%, dysphagia in 88%, and skin reaction in 85%. Neutropenic fever requiring hospitalization occurred in 51%. Despite feeding tube placement in 35 patients (85%), the mean weight loss during chemoradiotherapy was 13.3% of initial body weight. One patient died during treatment as a result of a pulmonary embolus. At a median follow-up period of 30 months, the 3-year Kaplan-Meier projected overall survival was 59%, disease-specific survival 69%, likelihood of local control without surgical resection 91%, and local control with surgical resection 97%. The likelihood of distant disease control at 3 years was 74%, and distant metastases were present in eight of 13 patients who died.This chemoradiotherapy schedule produces considerable but manageable toxicity. Survival and organ preservation are excellent for this poor-prognosis patient cohort. Distant metastases are the most common cause of treatment failure.
COMMON CARRIERS AS DISSEMINATORS OF CONTAGION.Read in the Section on State Medicine, at the Forty-fifth Annual Meeting of the American Medical Association, held at San Francisco, June 5-8, 1894.
Authors: S. S. HERRICK
Journal: JAMA (1894)

It is not necessary here to consider the part played by sea-going craft, for this, as a factor in spreading disease, is practically eliminated. The ancient method of detention for a definite period has been superseded by inspection and exclusion of infected persons and things at the port of departure and repeated inspection, with disinfection if needed, at the port of arrival. Neither is it necessary to speak of the modern methods of inland quarantine, in which inspection with cleansing and disinfection have obviated all serious interruption of traffic. In both the measures used are reasonably efficient for the protection of the public, and at the same time generally satisfactory to carriers. There is, however, a source of danger which so far, has attracted little attention, and no measures have been put in operation to counteract it. This is the disposal of the excretions of travelers on inland waters and
Results of the arterial switch operation for transposition of the great arteries with ventricular septal defect. Surgical considerations and midterm follow-up data.
Authors: R M Di Donato, G Wernovsky, E P Walsh, S D Colan, P Lang, D L Wessel, R A Jonas, J E Mayer, A R Castañeda
Journal: Circulation (1989)

Between January 1983 and December 1987, 62 patients underwent an arterial switch operation for transposition of the great arteries with ventricular septal defect or double outlet right or left ventricle. There were three hospital deaths (4.8%), and no deaths occurred in neonates (less than 1 month of age, n = 18). There were three late deaths, one due to coronary obstruction and two due to pulmonary vascular obstructive disease. One child has been lost to follow-up. We have prospectively evaluated the remaining 55 survivors by clinical evaluation, echocardiography, cardiac catheterization, ambulatory electrocardiographic monitoring, and limited electrophysiologic studies. The mean length of follow-up has been 27 +/- 16 months since surgery. One child has required reoperation for a residual ventricular septal defect; no child has undergone reoperation for supravalvar pulmonary or aortic stenosis. Aortic regurgitation was identified in 12 children (22%), which was mild in 11 and moderate in one. One child has asymptomatic occlusion of the left main coronary artery, one child has a tiny right coronary artery-to-pulmonary artery fistula, and one child has abnormal left ventricular wall motion according to follow-up angiography. No other abnormalities of systemic (left) ventricular function have been identified at late follow-up. In addition to the two late deaths due to pulmonary vascular obstructive disease, three children, all of whom were repaired at more than 6 months of age, have elevated pulmonary vascular resistance. Notable postoperative arrhythmias include complete heart block in four patients and nonsustained supraventricular or ventricular tachycardia early after surgery in eight patients (all resolved without medication at later follow-up). Only two patients have evidence of sinus node dysfunction and have not required treatment. The low hospital mortality and encouraging early follow-up data represent a significant improvement over atrial level repairs, supporting the arterial switch operation as the procedure of choice for children who have transposition of the great arteries with ventricular septal defect or double outlet ventricle. Because of the potential for the development of early pulmonary vascular obstructive disease in these patients, repair is recommended within the first 2 months of life.
Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-γ and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway
Authors: Jizhong Liu, Abdelbasset Hamrouni, Darius Wolowiec, Valérie Coiteux, Kazimierz Kuliczkowski, Dominique Hetuin, Aurore Saudemont, Bruno Quesnel
Journal: Blood (2007)
Comparison of Static Mechanical Properties of the Passive Pharynx between Normal Children and Children with Sleep-disordered Breathing
Authors: SHIROH ISONO, AKIKO SHIMADA, MAKOTO UTSUGI, AKIYOSHI KONNO, TAKASHI NISHINO
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Collapsibility of the active pharynx, where active contraction of the upper airway muscles is evident, was previously reported to be higher in children with obstructive sleep apnea (OSA) than in those with primary snoring during sleep. Contribution of neuromuscular and anatomic factors to the increased collapsibility, however, was not estimated. We therefore evaluated collapsibility of the passive pharynx, in which upper airway muscle activities were eliminated. Our aim in the present study was to test the hypothesis that children with sleep-disordered breathing (SDB) have a structurally narrowed and a more collapsible pharynx compared with normal children. The static pressure/area relationship of the passive pharynx was endoscopically quantified in 14 children with SDB and in 13 normal children under general anesthesia with complete paralysis. The majority of children with SDB primarily closed their airways at levels of enlarged adenoids and tonsils with positive closing pressure (Pclose) (3.5 ± 4.3 cm H2O), whereas half of the normal children closed their airways at the soft palate edges and the other half at the tongue bases with subatmospheric Pclose ( − 7.4 ± 4.9 cm H2O). Cross-sectional area of the narrowest segment was significantly smaller in SDB children than in normal children. Interestingly, collapsibility of the retropalatal and retroglossal segments significantly increased in SDB children, compared with the normal subjects. We conclude that anatomic factors play a significant role in the pathogenesis of pediatric OSA and that predisposing structural abnormalities of the entire pharynx are likely to contribute to manifestation of OSA in addition to enlarged adenoids and tonsils.
Long-Term Benefit of Primary Angioplasty as Compared with Thrombolytic Therapy for Acute Myocardial Infarction
Authors: Felix Zijlstra, Jan C.A. Hoorntje, Menko-Jan de Boer, Stoffer Reiffers, Kor Miedema, Jan Paul Ottervanger, Arnoud W.J. van 't Hof, Harry Suryapranata
Journal: New England Journal of Medicine (1999)

As compared with thrombolytic therapy, primary coronary angioplasty results in a higher rate of patency of the infarct-related coronary artery, lower rates of stroke and reinfarction, and higher in-hospital or 30-day survival rates. However, the comparative long-term efficacy of these two approaches has not been carefully studied.We randomly assigned a total of 395 patients with acute myocardial infarction to treatment with angioplasty or intravenous streptokinase. Clinical information was collected for a mean (+/-SD) of 5+/-2 years, and medical charges associated with the two treatments were compared.A total of 194 patients were assigned to undergo primary angioplasty, and 201 to receive streptokinase. Mortality was 13 percent in the angioplasty group, as compared with 24 percent in the streptokinase group (relative risk, 0.54; 95 percent confidence interval, 0.36 to 0.87). Nonfatal reinfarction occurred in 6 percent and 22 percent of the two groups, respectively (relative risk, 0.27; 95 percent confidence interval, 0.15 to 0.52). The combined incidence of death and nonfatal reinfarction was also lower among patients assigned to angioplasty than among those assigned to streptokinase, with a relative risk of 0.13 (95 percent confidence interval, 0.05 to 0.37) for early events (within the first 30 days) and a relative risk of 0.62 (95 percent confidence interval, 0.43 to 0.91) for late events (after 30 days). The rates of readmission for heart failure and ischemia were also lower among patients in the angioplasty group than among patients in the streptokinase group. Total medical charges per patient were lower in the angioplasty group (16,090 dollars) than in the streptokinase group (16,813 dollars, P=0.05).During five years of follow-up, primary coronary angioplasty for acute myocardial infarction was associated with lower rates of early and late death and nonfatal reinfarction, fewer hospital readmissions for ischemia or heart failure, and lower total medical charges than treatment with intravenous streptokinase.
Effect of insulin on myocardial contractility during canine endotoxin shock
Authors: W. R LAW, M. P McLANE, R. M RAYMOND
Journal: Cardiovascular Research (1988)

During endotoxin shock the heart becomes less responsive to the stimulatory effect of insulin on glucose uptake. In the present study we sought to determine if the heart was also less responsive to the positive inotropic effect of insulin during non-cardiogenic endotoxin shock. Responses of the heart to insulin were assessed under conditions of hyperinsulinaemic (4U·min−1), euglycaemic clamp (INS). Adult mongrel dogs, weighing 20-25 kg, were anaesthetised and instrumented to measure differences in substrate concentrations between arterial and coronary sinus blood, circumflex artery blood flow (using electromagnetic flow probe), haemodynamic variables, and left ventricular posterior wall thickness (using sonomicrometry). The first derivative of left ventricular pressure with respect to time was measured and its maximal value (LV dP/dtmax) used as an index of cardiac performance. Myocardial contractility was measured using the end systolic pressure-dimension relationship. Endotoxin shock was induced by Salmonella typhimurium (1 mg·kg−1 intravenously), and resulted in depression of myocardial performance but increased contractility. INS caused a twofold elevation in myocardial glucose uptake in control animals while in endotoxin shocked dogs it was unable to elevate glucose uptake above the pre-endotoxin level. In control animals INS caused both increased cardiac contractility and performance. In the endotoxin shock group INS was unable to increase LVdP/dtmax above the basal, pre-endotoxin level and did not cause any significant change in myocardial contractility. We suggest that the heart becomes less responsive to the positive inotropic as well as metabolic effects of insulin during endotoxin shock. Changes in LV dP/dtmax can be attributed to the changing loading conditions that occur during endotoxin shock.
Pure Red-Cell Aplasia and Antierythropoietin Antibodies in Patients Treated with Recombinant Erythropoietin
Authors: Nicole Casadevall, Joelle Nataf, Béatrice Viron, Amir Kolta, Jean-Jacques Kiladjian, Philippe Martin-Dupont, Patrick Michaud, Thomas Papo, Valérie Ugo, Irène Teyssandier, Bruno Varet, Patrick Mayeux
Journal: New England Journal of Medicine (2002)

Within a period of three years, we identified 13 patients in whom pure red-cell aplasia developed during treatment with recombinant human erythropoietin (epoetin). We investigated whether there was an immunologic basis for the anemia in these patients.
Opiate Use in London
Authors: Herbert H. Blumberg
Journal: JAMA (1975)

BRITISH opiate users appear to be more gainfully employed, stably housed, and socially involved than might be commonly expected. As part of an ongoing prospective study, the present sample consisted of people who had approached any of the 16 ordinary outpatient drug clinics in Greater London between mid-November 1970 and mid November 1972, provided that they had "fixed" (injected drugs in a nonmedical context), were seen by a doctor at the clinic, and were "new" to the clinic system. Three of four new attenders were interviewed in the first year of the study (210 subjects, a response rate of more than 90% of the 230 people eligible) and one of four newly attending in the second year (68 subjects, 86% of 79 people eligible). Social and psychological findings from the first year of this study have previously been reported.<sup>1,2</sup>The London drug clinics (for outpatient treatment under the National Health
CLASSIFICATION MISMATCH BETWEEN FRACTIONAL FLOW RESERVE AND INSTANTANEOUS WAVE-FREE RATIO FOR DETECTING ISCHEMIA CAUSING STENOSIS: THE INFLUENCE OF CORONARY FLOW RESERVE
Authors: Yoshiaki Kawase, Hitoshi Matsuo, Jun Kikuchi, Taiji Miyake, Tatsuya Saigusa, Hiroki Kondoh, Munenori Ohkubo, Kunihiko Tsuchiya, Junko Hone, Katsumi Ueno, Takahiko Suzuki
Journal: Journal of the American College of Cardiology (2014)
Expression of ST2 in Helper T Lymphocytes of Malignant Pleural Effusions
Authors: Katsuhisa Oshikawa, Ken Yanagisawa, Shoji Ohno, Shin-Ichi Tominaga, Yukihiko Sugiyama
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The objective of this study was to test the hypothesis that accumulated helper T lymphocytes in malignant pleural effusions may shift to T-helper type 2 (Th2) and produce soluble ST2 protein. We took samples of serum and pleural effusions (p-) from patients with carcinomatous pleurisy (CA, n = 17), tuberculous pleurisy (TB, n = 8), and congestive heart failure (HF, n = 5) and compared the concentration of cytokines or ST2. Ex vivo production of interleukin (IL)-4 and IL-10, though not that of interferon (IFN)- γ or IL-12, from CD4+ T cells isolated from pleural effusions was higher in the CA group than in the TB or HF group. The p-ST2 concentrations were significantly higher in the CA group than in the TB or HF group, positively correlated with the percentage of pleural effusion CD4+ T cells (r = 0.432, p = 0.016) and inversely correlated with p-IFN- γ concentrations (r = − 0.423, p = 0.019). Furthermore, mRNA expression of ST2 in CD4+ T cells isolated from group CA was upregulated, compared with that in those isolated from the TB group. These results suggest that CD4+ T cells in CA shift to Th2, which can produce soluble ST2 protein, resulting in increased concentrations of p-ST2 in malignant pleural effusion.
Glucosamine and Chondroitin for Treating Symptoms of Osteoarthritis
Authors: Tanveer E. Towheed, Tassos P. Anastassiades
Journal: JAMA (2000)

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Optical coherence tomography detects characteristic retinal nerve fiber layer thickness corresponding to band atrophy of the optic discs
Authors: Akiyasu Kanamori, Makoto Nakamura, Noriko Matsui, Azusa Nagai, Yoriko Nakanishi, Sentaro Kusuhara, Yuko Yamada, Akira Negi
Journal: Ophthalmology (2004)
PRELIMINARY RESULTS OF THE SVELTE TRIAL: FIRST-IN-MAN ASSESSMENT OF THE NOVEL ACROBAT™ SOAW (STENT-ON-A-WIRE) CORONARY SYSTEM
Authors: José de Ribamar Costa, Alexandre Abizaid, Pieter R. Stella, Andres Fernandez, Juan Granada, Fausto Feres, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2011)