tbuckley/cabot-search huggingface dataset:
Immunotherapy of Tumors with Protein Vaccine Based on Chicken Homologous Tie-2
Authors: Yan Luo, Yan-Jun Wen, Zhen-Yu Ding, Chun-Hua Fu, Yang Wu, Ji-Yan Liu, Qiu Li, Qiu-Ming He, Xia Zhao, Yu Jiang, Jiong Li, Hong-Xin Deng, Bin Kang, Yong-Qiu Mao, Yu-Quan Wei
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Tie-2 is an endothelium-specific receptor tyrosine kinase known to play a key role in tumor angiogenesis. The present study explores the feasibility of immunotherapy of tumors by using a protein vaccine based on chicken Tie-2 as a model antigen to break the immune tolerance against Tie-2 in a cross-reaction between the xenogeneic homologous and self-Tie-2. Experimental Design and Results: In this study, a chicken homologous Tie-2 protein vaccine (chTie-2) and a corresponding mouse Tie-2 vaccine as a control were prepared and the antitumor effect of these vaccines was tested in two tumor models (murine B16F10 melanoma and murine H22 hepatoma). Immunotherapy with chTie-2 was found effective in two tumor models. Autoantibodies against mouse Tie-2 were detected in sera of mice immunized with chTie-2 through Western blot analysis and ELISA assay. Anti-Tie-2 antibody-producing B cells were detectable by ELISPOT. Histologic examination revealed that autoantibodies were deposited on the endothelial cells of tumor tissues. Purified immunoglobulins from chTie-2-immunized mice could induce the apoptosis of human umbilical vein endothelial cells in vitro. Importantly, adoptive transfer of purified immunoglobulins led to antitumor effect in vivo; apparently, angiogenesis was significantly inhibited in these tumors. Furthermore, the antitumor activity and production of autoantibodies could be abrogated by depletion of CD4+ T lymphocytes. Conclusions: Our findings may provide a vaccine strategy for cancer therapy and show the potential utilization of interference with Tie-2 pathway.
Platelet Redox Balance in Diabetic Patients With Hypertension Improved by n-3 Fatty Acids
Authors: Denise M. McDonald, Fiona O’Kane, Maeve McConville, Adrian B. Devine, Gary E. McVeigh
Journal: Diabetes Care (2012)

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease, largely as a result of defective production of cardioprotective nitric oxide and a concomitant rise in oxidative stress. Dietary interventions that could reverse this trend would be extremely beneficial. Here we investigated whether dietary n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation positively affected platelet nitroso-redox imbalance.
Musculoskeletal pain in recreational runners prior to race participation: a cross-sectional survey in 1049 runners
Authors: A D Lopes, B T Saragiotto, T P Yamato, F Adami, L O P Costa
Journal: British Journal of Sports Medicine (2011)

Background We know that high-performance sports place high stress in the musculoskeletal system, often resulting in injury, pain, or other complaints. It is not unusual for athletes to decide to participate in important competitions, despite an ongoing disability or injury. However, we are unaware of any study that has presented any clear information about this issue in recreational runners. Objective The aims of this study were to calculate the prevalence of presence of musculoskeletal pain in amateur runners immediately before a race and to identify possible factors that could be associated with presence of musculoskeletal pain in this population. Design This is a cross-sectional survey study. Setting These runners were recreational athletes that participated in different races in São Paulo (Brazil), the distance of these races ranged from 5.000/10.000 meters. Participants A convenience sample of 1049 runners, 24.1% women (n=253) and 75.9% men (n=796). Assessment of risk factors This questionnaire contained information on presence of musculoskeletal pain, demographic characteristics, weight, body mass index, running experience, running mileage/week, number of training sessions/week, predominant training surface and coaching utilisation. We used logistic regression analysis to indentify associations between possible factors and presence of musculoskeletal pain (p&lt;0.05). The data were collected 1–2 h prior to the races. Main outcome measurements Presence of musculoskeletal pain. Results The prevalence of presence of musculoskeletal pain was 20% and 26.9% for men and women respectively. Running experience (OR=2.97, 95% CI 1.59 to 5.56) and weekly running distance (OR=1.88, 95% CI 1.02 to 3.48) were associated with presence of musculoskeletal pain in men prior to the race. Conclusion The prevalence of presence of musculoskeletal pain in amateur runners prior to the race was high. We have observed higher experience in running (ie, more than 10 years) and high training volumes (ie, more than 50 Km/week) were associated with presence of musculoskeletal pain.
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Authors: Kaori Sakuishi, Lionel Apetoh, Jenna M. Sullivan, Bruce R. Blazar, Vijay K. Kuchroo, Ana C. Anderson
Journal: The Journal of Experimental Medicine (2010)

The immune response plays an important role in staving off cancer; however, mechanisms of immunosuppression hinder productive anti-tumor immunity. T cell dysfunction or exhaustion in tumor-bearing hosts is one such mechanism. PD-1 has been identified as a marker of exhausted T cells in chronic disease states, and blockade of PD-1–PD-1L interactions has been shown to partially restore T cell function. We have found that T cell immunoglobulin mucin (Tim) 3 is expressed on CD8+ tumor-infiltrating lymphocytes (TILs) in mice bearing solid tumors. All Tim-3+ TILs coexpress PD-1, and Tim-3+PD-1+ TILs represent the predominant fraction of T cells infiltrating tumors. Tim-3+PD-1+ TILs exhibit the most severe exhausted phenotype as defined by failure to proliferate and produce IL-2, TNF, and IFN-γ. We further find that combined targeting of the Tim-3 and PD-1 pathways is more effective in controlling tumor growth than targeting either pathway alone.
Mechanism of Prolongation of the R-R Interval with Electrical Stimulation of the Carotid Sinus Nerves in Man
Authors: DWAIN L. ECKBERG, GERALD F. FLETCHER, EUGENE BRAUNWALD
Journal: Circulation Research (1972)

To elucidate the mechanism by which stimulation of the carotid sinus nerves prolongs the R-R interval, the effects of activating an implanted carotid sinus nerve stimulator were studied in eight patients at varying levels of background autonomic activity and with varying types of efferent autonomic blockade. Beta-receptor blockade was induced with intravenous propranolol, 0.20 mg/kg, and parasympathetic blockade with intravenous atropine, 0.04 mg/kg. In the supine position, average prolongation of the R-R interval due to stimulation of the carotid sinus nerves was 269 ± 56 msec prior to autonomic blocking drugs, 442 ± 214 msec after propranolol (NS), and 44 ± 13 msec after propranolol and atropine ( P &lt; 0.025). Comparable changes were produced in the standing position. With moderate treadmill exercise, stimulation of the carotid sinus nerves prolonged the R-R interval by only 40 ± 30 msec prior to blocking drugs, 62 ± 19 msec after propranolol, and 40 ± 30 msec after propranolol and atropine. It is concluded that the prolongation of the R-R interval produced by stimulation of the carotid sinus nerves is secondary to augmented parasympathetic activity, and the attenuation of this response during erect exercise appears to be due to a centrally mediated reduction in the responsiveness of the parasympathetic nervous system to baroreceptor stimuli.
Propagation Velocities and Voltage Magnitudes in Local Segments of Dog Myocardium
Authors: R. H. SELVESTER, W. L. KIRK, R. B. PEARSON
Journal: Circulation Research (1970)

Propagation velocities and differential voltages of the electromotive surface in the left ventricle were measured in dogs by multipoint bipolar intramyocardial electrodes. The average velocity of propagation in the inner 4 mm of the ventricular wall of dogs was 2.0 mm/msec, which is considerably greater than that in the middle (0.70 mm/msec) or the outer 4 mm (0.40 mm/msec). The average voltage was less in the inner levels of the ventricular wall than in the outer, but significantly different from zero. This fact indicates a definite but lesser contribution per unit volume than from the outer levels. The propagation of the electromotive surface through the ventricular wall was consistently from endocardium to epicardium with no significant areas propagated in the reverse direction. These data disagree with the hypothesis that certain levels in the wall of the heart and certain regions of the heart are electrocardiographically silent. In dogs, and to a greater degree in humans, small infarcts anywhere in the heart can be expected to produce significant and discernible changes in surface ECGs. The task remains to refine and validate criteria for the diagnosis of infarct in these areas. When viewed from within the myocardium, the waveforms observed in bipolar intramyocardial electrodes are inconsistent with the dipole layer hypothesis as a model of the electromotive surface of ventricular depolarization in the heart.
Phosphoproteomics Identifies Driver Tyrosine Kinases in Sarcoma Cell Lines and Tumors
Authors: Yun Bai, Jiannong Li, Bin Fang, Arthur Edwards, Guolin Zhang, Marilyn Bui, Steven Eschrich, Soner Altiok, John Koomen, Eric B. Haura
Journal: Cancer Research (2012)

Abstract Driver tyrosine kinase mutations are rare in sarcomas, and patterns of tyrosine phosphorylation are poorly understood. To better understand the signaling pathways active in sarcoma, we examined global tyrosine phosphorylation in sarcoma cell lines and human tumor samples. Anti-phosphotyrosine antibodies were used to purify tyrosine phosphorylated peptides, which were then identified by liquid chromatography and tandem mass spectrometry. The findings were validated with RNA interference, rescue, and small-molecule tyrosine kinase inhibitors. We identified 1,936 unique tyrosine phosphorylated peptides, corresponding to 844 unique phosphotyrosine proteins. In sarcoma cells alone, peptides corresponding to 39 tyrosine kinases were found. Four of 10 cell lines showed dependence on tyrosine kinases for growth and/or survival, including platelet-derived growth factor receptor (PDGFR)α, MET, insulin receptor/insulin-like growth factor receptor signaling, and SRC family kinase signaling. Rhabdomyosarcoma samples showed overexpression of PDGFRα in 13% of examined cases, and sarcomas showed abundant tyrosine phosphorylation and expression of a number of tyrosine phosphorylated tyrosine kinases, including DDR2, EphB4, TYR2, AXL, SRC, LYN, and FAK. Together, our findings suggest that integrating global phosphoproteomics with functional analyses with kinase inhibitors can identify drivers of sarcoma growth and survival. Cancer Res; 72(10); 2501–11. ©2012 AACR.
GoIFISH: a system for the quantification of single cell heterogeneity from IFISH images
Authors: Anne Trinh, Inga H Rye, Vanessa Almendro, Åslaug Helland, Hege G Russnes, Florian Markowetz
Journal: Genome biology (2014)

Molecular analysis has revealed extensive intra-tumor heterogeneity in human cancer samples, but cannot identify cell-to-cell variations within the tissue microenvironment. In contrast, in situ analysis can identify genetic aberrations in phenotypically defined cell subpopulations while preserving tissue-context specificity. GoIFISHGoIFISH is a widely applicable, user-friendly system tailored for the objective and semi-automated visualization, detection and quantification of genomic alterations and protein expression obtained from fluorescence in situ analysis. In a sample set of HER2-positive breast cancers GoIFISHGoIFISH is highly robust in visual analysis and its accuracy compares favorably to other leading image analysis methods. GoIFISHGoIFISH is freely available at www.sourceforge.net/projects/goifish/.
Randomized, controlled trial with interferon-alpha (IFN-alpha) combined with ribavirin with and without amantadine sulfate in primary IFN-alpha nonresponsive patients with chronic hepatitis C
Authors: G. Teuber, T. Berg, M. Lafrenz, H. Weidenbach, J. Schoelmerich, P. Wietzke-Braun, J. Pausch, R. Arnold, G. Lock, U. Hopf, S. Zeuzem
Journal: Journal of Hepatology (2001)
Health Care Vouchers — A Proposal for Universal Coverage
Authors: Ezekiel J. Emanuel, Victor R. Fuchs
Journal: New England Journal of Medicine (2005)

Emanuel and Fuchs outline their proposal for a universal health care voucher system. Americans would receive vouchers to purchase coverage from their choice of private health plans. The system would replace Medicaid, Medicare, and employer-based insurance. The authors propose funding vouchers with a national value-added tax and argue that this would control costs, because increases in health care spending would require public approval of tax increases.
Response to Letters Regarding Article, “Randomized Comparison of Sevoflurane Versus Propofol to Reduce Perioperative Myocardial Ischemia in Patients Undergoing Noncardiac Surgery”
Authors: Giovanna A.L. Lurati Buse, Philippe Schumacher, Esther Seeberger, Wolfgang Studer, Regina M. Schuman, Jens Fassl, Jorge Kasper, Miodrag Filipovic, Daniel Bolliger, Manfred D. Seeberger
Journal: Circulation (2013)

eg, opioids), and (4) inclusion of patients undergoing orthopedic surgery.
Correlation between galactomannan antigen levels in serum and neutrophil counts in haematological patients with invasive aspergillosis
Authors: C. Cordonnier, F. Botterel, R. Ben Amor, C. Pautas, S. Maury, M. Kuentz, Y. Hicheri, S. Bastuji-Garin, S. Bretagne
Journal: Clinical Microbiology and Infection (2008)
Imaging Transgenic Animals
Authors: T. F. Budinger, D. A. Benaron, A. P. Koretsky
Journal: Annual Review of Biomedical Engineering (1999)

Transgenic and eugenic animals as small as 30 g can be studied non-invasively by radionuclides with resolutions of 1-2 mm, by MRI with resolution of 100 microns and by light fluorescence and bioluminescence with high sensitivities. The technologies of radionuclide emission, magnetic resonance imaging, magnetic resonance spectroscopy, optical tomography, optical fluorescence and optical bioluminescence are currently being applied to small-animal studies. These technologies and examples of their applications are reviewed in this chapter.
Age and Clinical Decision Making in Oncology Patients
Authors: S. B. Yellen, D. F. Cella, W. T. Leslie
Journal: JNCI Journal of the National Cancer Institute (1994)

Background: Ageism is a cultural bias that might inappropriately steer oncologists away from recommending aggressive treatments for older patients. The extent to which older patients might prefer less aggressive cancer therapies is unknown. Our lack of knowledge about patients' personal preferences for therapy may perpetuate this bias. Purpose: We conducted a study to determine 1) if age influences patient acceptance of cancer therapy and 2) if the older patients would be more or less likely to trade increased survival for maintaining quality of life than their younger counterparts. Methods: Using an interview format, 244 cancer patients of all ages treated at a tertiary care cancer center read two sets of hypothetical vignettes. The first set consisted of four vignettes that varied in terms of stage of disease and treatment toxicity. Patients were asked to make hypothetical decisions about treatment given with respect to varying levels of either increasing cure or extending survival. The second set of vignettes presumed acceptance of cancer therapy. Within each vignette, two hypothetical treatments (mild versus severe) with different probabilities of 1-year survival were contrasted. The point at which patients shifted preferences from a treatment with mild versus severe side effects was the dependent measure. Mixed analysis of variance (ANOVA) procedures (F test) assessed the impact of age (<65 years versus ≥65 years) and patient disease stage (early versus advanced) on hypothetical decisions about treatment. All P values are two sided. Results: In the treatment-preference vignettes, there was no effect of either age [F(l,239) = 2.14; P = .14] or patient stage [F(l,239) = .40; P = .53] on treatment acceptance. Older adults were as likely as their younger counterparts to agree to chemotherapy for both curative and control purposes. In the switch-point vignettes, younger adults switched to a more toxic treatment to gain survival advantage at an earlier point than the older patients in both the early-disease vignette [F(l,232) = 3.88; P = .05] and the advanced-disease vignette [F(l,232) = 4.43; P = .036]. There was neither an effect of disease stage on treatment decisions nor an interaction between disease stage and age. Conclusions and Implications: In a tertiary care setting, older adults do not differ from their younger counterparts in terms of acceptance of chemotherapy. However, when treatment is presumed, they differ in terms of willingness to trade survival for current quality of life. Generalization of findings is limited by the relatively small sample of older adults (n = 43) and the referral population from which the sample was drawn. Replication with a larger older adult sample in a community setting is needed. [J Natl Cancer Inst 86:1766–1770, 1994]
Quality-of-Life Impact of Primary Treatments for Localized Prostate Cancer in Patients Without Hormonal Treatment
Authors: Yolanda Pardo, Ferran Guedea, Ferrán Aguiló, Pablo Fernández, Víctor Macías, Alfonso Mariño, Asunción Hervás, Ismael Herruzo, María José Ortiz, Javier Ponce de León, Jordi Craven-Bratle, José Francisco Suárez, Ana Boladeras, Àngels Pont, Adriana Ayala, Gemma Sancho, Evelyn Martínez, Jordi Alonso, Montserrat Ferrer
Journal: Journal of Clinical Oncology (2010)

Earlier studies evaluating the effect on quality of life (QoL) of localized prostate cancer interventions included patients receiving adjuvant hormone therapy, which could have affected their outcomes. Our objective was to compare the QoL impact of the three most common primary treatments on patients who were not receiving adjuvant hormonal treatment.This was a prospective study of 435 patients treated with radical prostatectomy, external-beam radiotherapy, or brachytherapy. QoL was assessed before and after treatment with the Short Form-36 and the Expanded Prostate Cancer Index Composite. Differences between groups were tested by analysis of variance. Distribution of outcome at 3 years was examined by stratifying according to baseline status. Generalized estimating equation models were constructed to assess the effect of treatment over time.Compared with the brachytherapy group, the prostatectomy group showed greater deterioration on urinary incontinence and sexual scores but better urinary irritative-obstructive results (-18.22, -13.19, and +6.38, respectively, at 3 years; P < .001). In patients with urinary irritative-obstructive symptoms at baseline, improvement was observed in 64% of those treated with nerve-sparing radical prostatectomy. Higher bowel worsening (-2.87, P = .04) was observed in the external radiotherapy group, with 20% of patients reporting bowel symptoms.Radical prostatectomy caused urinary incontinence and sexual dysfunction but improved pre-existing urinary irritative-obstructive symptoms. External radiotherapy and brachytherapy caused urinary irritative-obstructive adverse effects and some sexual dysfunction. External radiotherapy also caused bowel adverse effects. Relevant differences between treatment groups persisted for up to 3 years of follow-up, although the difference in sexual adverse effects between brachytherapy and prostatectomy tended to decline over long-term follow-up. These results provide valuable information for clinical decision making.
Epirubicin and docetaxel with or without capecitabine as neoadjuvant treatment for early breast cancer: final results of a randomized phase III study (ABCSG-24)
Authors: G.G. Steger, R. Greil, A. Lang, M. Rudas, F. Fitzal, B. Mlineritsch, B.L. Hartmann, R. Bartsch, E. Melbinger, M. Hubalek, H. Stoeger, P. Dubsky, S. Ressler, A.L. Petzer, C.F. Singer, C. Muss, R. Jakesz, S.P. Gampenrieder, C.C. Zielinski, C. Fesl, M. Gnant
Journal: Annals of Oncology (2013)
PD-1/PD-L1 Interactions Contribute to Functional T-Cell Impairment in Patients Who Relapse with Cancer After Allogeneic Stem Cell Transplantation
Authors: Wieger J. Norde, Frans Maas, Willemijn Hobo, Alan Korman, Michael Quigley, Michel G.D. Kester, Konnie Hebeda, J.H. Frederik Falkenburg, Nicolaas Schaap, Theo M. de Witte, Robbert van der Voort, Harry Dolstra
Journal: Cancer Research (2011)

Abstract Tumor relapses remain a serious problem after allogeneic stem cell transplantation (alloSCT), despite the long-term persistence of minor histocompatibility antigen (MiHA)-specific memory CD8+ T cells specific for the tumor. We hypothesized that these memory T cells may lose their function over time in transplanted patients. Here, we offer functional and mechanistic support for this hypothesis, based on immune inhibition by programmed death-1 (PD-1) expressed on MiHA-specific CD8+ T cells and the associated role of the PD-1 ligand PD-L1 on myeloid leukemia cells, especially under inflammatory conditions. PD-L1 was highly upregulated on immature human leukemic progenitor cells, whereas costimulatory molecules such as CD80 and CD86 were not expressed. Thus, immature leukemic progenitor cells seemed to evade the immune system by inhibiting T-cell function via the PD-1/PD-L1 pathway. Blocking PD-1 signaling using human antibodies led to elevated proliferation and IFN-γ production of MiHA-specific T cells cocultured with PD-L1–expressing leukemia cells. Moreover, patients with relapsed leukemia after initial MiHA-specific T-cell responses displayed high PD-L1 expression on CD34+ leukemia cells and increased PD-1 levels on MiHA-specific CD8+ T cells. Importantly, blocking PD-1/PD-L1 interactions augment proliferation of MiHA-specific CD8+ memory T cells from relapsed patients. Taken together, our findings indicate that the PD-1/PD-L pathway can be hijacked as an immune escape mechanism in hematological malignancies. Furthermore, they suggest that blocking the PD-1 immune checkpoint offers an appealing immunotherapeutic strategy following alloSCT in patients with recurrent or relapsed disease. Cancer Res; 71(15); 5111–22. ©2011 AACR.