tbuckley/cabot-search huggingface dataset:
Activation of the human neutrophil nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase by protein kinase C.
Authors: J A Cox, A Y Jeng, N A Sharkey, P M Blumberg, A I Tauber
Journal: Journal of Clinical Investigation (1985)

A variety of phagocytosable and soluble agonists stimulate the human neutrophil respiratory burst enzyme, NADPH-oxidase, an activity required for normal microbicidal function. Of these agonists, the phorbol esters, which stimulate diverse systems by their ability to substitute for diacylglycerol to activate protein kinase C (the major phorbol ester receptor), have now been shown to directly stimulate NADPH-oxidase through this same receptor. Almost 90% of the specific receptors for phorbol 12,13-dibutyrate (PDBu) were found in the cytosol upon subcellular fractionation. The dissociation constant for [3H]PDBu was 1.2 nM. No significant difference was found in the distribution of the receptor between subcellular fractions from resting as compared with phorbol 12-myristate 13-acetate (PMA)-stimulated neutrophils. On the basis of these binding studies, we were able to establish a reconstituted system in which PMA activated dormant NADPH-oxidase in a light membrane fraction when cytosol, NADPH, phosphatidylserine, or phosphatidylinositol and ATP were added. The calcium chelator, EGTA, inhibited the activation, which suggested a requirement for calcium at low concentrations. The half-maximally effective PMA dose was 1.1 nM, as predicted from the receptor content in these preparations. Reconstitution of oxidase activity was rapid, peaking within 1 min of incubation. Purified protein kinase C was able to substitute for the cytosol fraction, and accounted for 80% of the cytosol activity. These studies demonstrate that phorbol esters stimulate the neutrophil respiratory burst through activation of cytosolic protein kinase C, which in turn activates either a regulatory constituent or the NADPH-oxidase directly in the plasma membrane to generate an active O-2-generating system.
Health-related quality of life in recurrent platinum-sensitive ovarian cancer—results from the CALYPSO trial
Authors: M. Brundage, M. Gropp, F. Mefti, K. Mann, B. Lund, V. Gebski, G. Wolfram, N. Reed, S. Pignata, A. Ferrero, C. Brown, E. Eisenhauer, E. Pujade-Lauraine
Journal: Annals of Oncology (2012)
Intensive treatment strategies may not provide superior outcomes in mantle cell lymphoma: overall survival exceeding 7 years with standard therapies
Authors: P. Martin, A. Chadburn, P. Christos, R. Furman, J. Ruan, M.A. Joyce, E. Fusco, P. Glynn, R. Elstrom, R. Niesvizky, E.J. Feldman, T.B. Shore, M.W. Schuster, S. Ely, D.M. Knowles, S. Chen-Kiang, M. Coleman, J.P. Leonard
Journal: Annals of Oncology (2008)
Differential Expression of Neuronal Genes Defines Subtypes of Disseminated Neuroblastoma with Favorable and Unfavorable Outcome
Authors: Matthias Fischer, André Oberthuer, Benedikt Brors, Yvonne Kahlert, Matthias Skowron, Harald Voth, Patrick Warnat, Karen Ernestus, Barbara Hero, Frank Berthold
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Identification of molecular characteristics of spontaneously regressing stage IVS and progressing stage IV neuroblastoma to improve discrimination of patients with metastatic disease following favorable and unfavorable clinical courses. Experimental Design: Serial analysis of gene expression profiles were generated from five stage IVS and three stage IV neuroblastoma. Differential expression of candidate genes was evaluated by real-time quantitative reverse transcription-PCR in 76 pretreatment tumor samples (stage IVS n = 27 and stage IV n = 49). Gene expression-based outcome prediction was determined by Prediction Analysis for Microarrays using 38 tumors as a training set and 38 tumors as a test set. Results: Comparison of serial analysis of gene expression profiles from stage IV and IVS neuroblastoma revealed ∼500 differentially expressed transcripts. Genes related to neuronal differentiation were observed more frequently in stage IVS tumors as determined by associating transcripts to Gene Ontology annotations. Forty-one candidate genes were evaluated by quantitative reverse transcription-PCR and 18 were confirmed to be differentially expressed (P ≤ 0.001). Classification of patients according to expression patterns of these 18 genes using Prediction Analysis for Microarrays discriminated two subgroups with significantly differing event-free survival (96 ± 6% versus 40 ± 8% at 3 years; P &amp;lt; 0.0001) and overall survival (100% versus 72 ± 7% at 3 years; P = 0.0003). This classifier was the only independent covariate marker in a multivariate analysis considering the variables stage, age, MYCN amplification, and gene signature. Conclusions: Spontaneously regressing and progressing metastatic neuroblastoma differ by specific gene expression patterns, indicating distinct levels of neuronal differentiation and allowing for an improved risk estimation of children with disseminated disease.
Polyethylenimine-based siRNA nanocomplexes reprogram tumor-associated dendritic cells via TLR5 to elicit therapeutic antitumor immunity
Authors: Juan R. Cubillos-Ruiz, Xavier Engle, Uciane K. Scarlett, Diana Martinez, Amorette Barber, Raul Elgueta, Li Wang,, Yolanda Nesbeth, Yvon Durant,, Andrew T. Gewirtz, Charles L. Sentman, Ross Kedl, Jose R. Conejo-Garcia
Journal: Journal of Clinical Investigation (2009)

The success of clinically relevant immunotherapies requires reversing tumor-induced immunosuppression. Here we demonstrated that linear polyethylenimine-based (PEI-based) nanoparticles encapsulating siRNA were preferentially and avidly engulfed by regulatory DCs expressing CD11c and programmed cell death 1-ligand 1 (PD-L1) at ovarian cancer locations in mice. PEI-siRNA uptake transformed these DCs from immunosuppressive cells to efficient antigen-presenting cells that activated tumor-reactive lymphocytes and exerted direct tumoricidal activity, both in vivo and in situ. PEI triggered robust and selective TLR5 activation in vitro and elicited the production of hallmark TLR5-inducible cytokines in WT mice, but not in Tlr5-/- littermates. Thus, PEI is a TLR5 agonist that, to our knowledge, was not previously recognized. In addition, PEI-complexed nontargeting siRNA oligonucleotides stimulated TLR3 and TLR7. The nonspecific activation of multiple TLRs (specifically, TLR5 and TLR7) reversed the tolerogenic phenotype of human and mouse ovarian tumor-associated DCs. In ovarian carcinoma-bearing mice, this induced T cell-mediated tumor regression and prolonged survival in a manner dependent upon myeloid differentiation primary response gene 88 (MyD88; i.e., independent of TLR3). Furthermore, gene-specific siRNA-PEI nanocomplexes that silenced immunosuppressive molecules on mouse tumor-associated DCs elicited discernibly superior antitumor immunity and enhanced therapeutic effects compared with nontargeting siRNA-PEI nanocomplexes. Our results demonstrate that the intrinsic TLR5 and TLR7 stimulation of siRNA-PEI nanoparticles synergizes with the gene-specific silencing activity of siRNA to transform tumor-infiltrating regulatory DCs into DCs capable of promoting therapeutic antitumor immunity.
HLA class II antigens associated with systemic lupus erythematosus in black South Africans.
Authors: M Rudwaleit, M Tikly, K Gibson, K Pile, P Wordsworth
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To assess the associations of HLA class II antigens with systemic lupus erythematosus (SLE) in black South Africans. METHODS--HLA-DRB1 genotype frequencies assigned by polymerase chain reaction (PCR) amplification and sequence specific oligonucleotide probes were compared between 49 black SLE patients from Baragwanath Hospital and 87 ethnically matched controls. HLA-DQA1 and -DQB1 genotypes were also assigned in 45 of the SLE patients and 74 controls by PCR using sequence specific primers. RESULTS--HLA-DRB1*02 was increased in the patients compared with controls (odds ratio = 3.67; 95% confidence interval = 1.49 to 9.02; p &lt; 0.005). HLA-DQB1*0201 was not associated with development of the disease itself, but was associated with the presence of Ro antibodies (p = 0.01). HLA-DRB1*03 was less strongly linked to DQB1*02 in this population than in white populations and was not associated with SLE. CONCLUSIONS--In black South Africans there is evidence for a locus on DR2 haplotypes contributing to SLE. Another gene, possibly HLA-DQB1*02, not linked to DR2 is involved in the subset of patients exhibiting Ro antibodies.
843 ADRENAL DYSFUNCTION IN CIRRHOSIS: PREVALENCE AND IMPACT ON SURVIVAL IN NONSEPTIC PATIENTS WITH ASCITES
Authors: C. Elia, C. Alessandria, A. Risso, L. Mezzabotta, S. Martini, A. Morgando, W. Debernardi-Venon, A. Marzano, M. Rizzetto
Journal: Journal of Hepatology (2010)
THE QT INTERVAL AND CARDIAC ARRHYTHMIAS
Authors: B Surawicz
Journal: Annual Review of Medicine (1987)

The relation between the QT interval, ventricular arrhythmias, and dispersion of ventricular repolarization is reviewed. Conditions associated with prolonged QT interval in clinical practice are listed and discussed briefly. There is no conclusive evidence that prolonged QT is an independent prognostic marker in patients with coronary and other types of heart disease.
Respiratory medications and risk of asthma death
Authors: S F Lanes
Journal: Thorax (2002)

The effect of respiratory medications on risk of asthma death in the UK was studied using the General Practice Research Database.A total of 96 258 individuals with a diagnosis of asthma were identified, 43 of whom had died as a result of their asthma. For each case 20 controls were selected. Relative risk (RR) estimates and 95% confidence intervals (CI) were computed for each respiratory drug category controlling for effects of age, sex, body mass index, smoking, frequency of visits to the GP, hospital admissions for asthma, and visits to a specialist.The strongest associations were found for at least 13 prescriptions of short acting beta agonists during the previous year (RR=51.6, 95% CI 7.9 to 345) and 7-12 prescriptions of short acting beta agonists (RR=16.2, 95% CI 2.6 to 101). Short acting beta agonists and inhaled steroids tended to be prescribed most frequently to the same patients. In patients who received more than one prescription per month of short acting beta agonists during the previous year, regular use of inhaled steroids was associated with a 60% reduced risk of asthma death (RR=0.4, 95% CI 0.2 to 1.0).Regular use of inhaled steroids is associated with a decreased risk of asthma death, and excessive use of short acting beta agonists is associated with a markedly increased risk of asthma death.
The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells.
Authors: D Vremec, M Zorbas, R Scollay, D J Saunders, C F Ardavin, L Wu, K Shortman
Journal: The Journal of Experimental Medicine (1992)

A new procedure for rapid isolation of dendritic cells (DC) was devised, involving collagenase digestion of tissues, dissociation of lymphoid-DC complexes, selection of light-density cells, then depletion of lymphocytes and other non-DC by treatment with a mixture of lineage-specific monoclonal antibodies (mAbs) and removal with anti-immunoglobulin-coupled magnetic beads. This enriched population (approximately 80% DC) was further purified when required by fluorescence-activated cell sorting for cells expressing high levels of class II major histocompatibility complex (MHC). The isolated DC were characterized by immunofluorescent staining using a panel of 30 mAbs. Thymic DC were surface positive for a number of markers characteristic of T cells, but they were distinct from T-lineage cells in expressing high levels of class II MHC, in lacking expression of the T cell receptor (TCR)-CD3 complex, and having TCR beta and gamma genes in germline state. Splenic DC shared many markers with thymic DC, but were negative for most T cell markers, with the exception of CD8. A substantial proportion of DC from both thymus and spleen expressed CD8 at high levels, comparable with that on T cells. This appeared to be authentic CD8, and was produced by the DC themselves, since they contained CD8 alpha mRNA. Thymic DC presented both the CD8 alpha and beta chains on the cell surface (Ly-2+3+), although the alpha chain was in excess; the splenic DC expressed only the CD8 alpha chain (Ly-2+3-). It is suggested that the expression of CD8 could endow certain antigen-presenting DC with a veto function.
IL-18–Primed Helper NK Cells Collaborate with Dendritic Cells to Promote Recruitment of Effector CD8+ T Cells to the Tumor Microenvironment
Authors: Jeffrey L. Wong, Erik Berk, Robert P. Edwards, Pawel Kalinski
Journal: Cancer Research (2013)

Abstract Chemokine-driven interactions of immune cells are essential for effective antitumor immunity. Human natural killer (NK) cells can be primed by the interleukin (IL)-1–related proinflammatory cytokine IL-18 for unique helper activity, which promotes dendritic cell (DC) activation and DC-mediated induction of type-1 immune responses against cancer. Here, we show that such IL-18–primed "helper" NK cells produce high levels of the immature DC (iDC)–attracting chemokines CCL3 and CCL4 upon exposure to tumor cells or the additional inflammatory signals IFN-α, IL-15, IL-12, or IL-2. These "helper" NK cells potently attract iDCs in a CCR5-dependent mechanism and induce high DC production of CXCR3 and CCR5 ligands (CXCL9, CXCL10, and CCL5), facilitating the subsequent recruitment of type-1 effector CD8+ T (Teff) cells. Using cells isolated from the malignant ascites of patients with advanced ovarian cancer, we show that "helper" NK cell-inducing factors can be used to enhance local production of Teff cell-recruiting chemokines. Our findings reveal the unique chemokine expression profile of "helper" NK cells and highlight the potential for using two-signal–activated NK cells to promote homing of type-1 immune effectors to the human tumor environment. Cancer Res; 73(15); 4653–62. ©2013 AACR.
<i>In Vivo</i> Cancer Targeting and Imaging-Guided Surgery with Near Infrared-Emitting Quantum Dot Bioconjugates
Authors: Yan Li, Zhe Li, Xiaohui Wang, Fengjun Liu, Yingsheng Cheng, Bingbo Zhang, Donglu Shi
Journal: Theranostics (2012)

Early detection and subsequent complete surgical resection are among the most efficient methods for treating cancer.However, low detection sensitivity and incomplete tumor resection are two challenging issues.Nanoparticle-based imaging-guided surgery has proven promising for cancer-targeted imaging and subsequent debulking surgery.Particularly, the use of near infrared (NIR) fluorescent probes such as NIR quantum dots (QDs) allows deep penetration and high sensitivity for tumor detection.In this study, NIR-emitting CdTe QDs (maximum fluorescence emission peak at 728 nm) were synthesized with a high quantum yield (QY) of 38%.The tumor-specific QD bioconjugates were obtained by attaching cyclic Arg-Gly-Asp peptide (cRGD) to the surface of synthesized QDs, and then injected into U87 MG tumor-bearing mice via tail veins for tumor-targeted imaging.The tumor and its margins were visualized and distinguished by NIR QD bioconjugates, and tumor resection was successfully accomplished via NIR guidance using a Fluobeam-700 NIR imaging system.Our work indicates that the synthesized tumor-specific NIR QDs hold great promise as a potential fluorescent indicator for intraoperative tumor imaging.
Pulmonary Surfactant Activity Is Impaired in Lung Transplant Recipients
Authors: JENS MICHAEL HOHLFELD, EZGI TIRYAKI, HINRICH HAMM, HEINZ GERD HOYMANN, NORBERT KRUG, AXEL HAVERICH, HELMUT FABEL
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Impaired graft function in the postoperative course after lung transplantation (LTx) may in part be due to alterations in pulmonary surfactant. Animal data provide increasing evidence for surfactant abnormalities in the early course after graft reperfusion. However, little is known about the integrity of the surfactant system in human lung transplant recipients. We therefore investigated surfactant properties in bronchoalveolar lavage fluid (BALF) of patients with lung transplants (n = 60) in comparison to that of healthy subjects (n = 10). The phospholipid concentrations of BALF and of surfactant subfractions were measured, and total protein was analyzed. Surface activity was measured with a pulsating bubble surfactometer (PBS). Minimum surface tension was 15.8 ± 1.1 mN/m in lung transplant recipients, whereas healthy subjects had minimum surface tensions of 3.4 ± 1.9 mN/m (p = 0.0004). As a marker for potential surfactant inhibition, protein-to-phospholipid (PL) ratios showed no significant differences in the two major study groups. The ratio of small surfactant aggregates to large surfactant aggregates was increased in patients with lung transplants (p = 0.043). Episodes of infection or rejection did not change surface activities, nor did they induce altered ratios of protein to PL or of small to large surfactant aggregates. Surfactant activity did not correlate with pulmonary-function data. Moreover, surface tension showed no correlation with the time after transplantation. Our results suggest a persistent impairment of biophysical surfactant properties after LTx, possibly due to type-II-cell malfunction.
Short-Term Neoadjuvant Androgen Deprivation Therapy and External-Beam Radiotherapy for Locally Advanced Prostate Cancer: Long-Term Results of RTOG 8610
Authors: Mack Roach, Kyounghwa Bae, Joycelyn Speight, Harvey B. Wolkov, Phillip Rubin, R. Jeffrey Lee, Colleen Lawton, Richard Valicenti, David Grignon, Miljenko V. Pilepich
Journal: Journal of Clinical Oncology (2008)

Radiation Therapy Oncology Group (RTOG) 8610 was the first phase III randomized trial to evaluate neoadjuvant androgen deprivation therapy (ADT) in combination with external-beam radiotherapy (EBRT) in men with locally advanced prostate cancer. This report summarizes long-term follow-up results.Between 1987 and 1991, 456 assessable patients (median age, 70 years) were enrolled. Eligible patients had bulky (5 x 5 cm) tumors (T2-4) with or without pelvic lymph node involvement according to the 1988 American Joint Committee on Cancer TNM staging system. Patients received combined ADT that consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg tid for 2 months before and concurrent with EBRT, or they received EBRT alone. Study end points included overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), disease-free survival (DFS), and biochemical failure (BF).Ten-year OS estimates (43% v 34%) and median survival times (8.7 v 7.3 years) favored ADT and EBRT, respectively; however, these differences did not reach statistical significance (P = .12). There was a statistically significant improvement in 10-year DSM (23% v 36%; P = .01), DM (35% v 47%; P = .006), DFS (11% v 3%; P < .0001), and BF (65% v 80%; P < .0001) with the addition of ADT, but no differences were observed in the risk of fatal cardiac events.The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events.
Identification of Altered Protein Expression and Post-Translational Modifications in Primary Colorectal Cancer by Using Agarose Two-Dimensional Gel Electrophoresis
Authors: Takeshi Tomonaga, Kazuyuki Matsushita, Seiko Yamaguchi, Masamichi Oh-Ishi, Yoshio Kodera, Tadakazu Maeda, Hideaki Shimada, Takenori Ochiai, Fumio Nomura
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Although numerous proteome studies have been performed recently to identify cancer-related changes in protein expression, only a limited display of relatively abundant proteins has been identified. The aim of this study is to identify novel proteins as potential tumor markers in primary colorectal cancer tissues using a high-resolution two-dimensional gel electrophoresis (2-DE). Experimental Design: 2-DE using an agarose gel for isoelectric focusing was used to compare protein profiling of 10 colorectal cancer tissues and adjacent normal mucosa. Altered expression and post-translational modification of several proteins were examined using Western blot analysis and immunohistochemistry. Results: Ninety-seven proteins of 107 spots (90.7%) that were differentially expressed between matched normal and tumor tissues were identified by mass spectrometry. Among them, 42 unique proteins (49 spots) significantly increased or decreased in the tumors. They include eukaryotic translation initiation factor 4H, inorganic pyrophosphatase, anterior gradient 2 homologue, aldolase A, and chloride intracellular channel 1, whose elevated expression in tumor tissues was confirmed by Western blot analysis and immunohistochemistry. Interestingly, only isoform 1 of two transcript variants of eukaryotic translation initiation factor 4H was greatly up-regulated in most of the tumor tissues. Moreover, post-translational modifications of the prolyl-4-hydroxylase β subunit and annexin A2 also were identified. Conclusions: We identified several novel proteins with altered expression in primary colorectal cancer using agarose 2-DE. This method is a powerful technique with which to search for not only quantitative but also qualitative changes in a biological process of interest and may contribute to the deeper understanding of underlying mechanisms of human cancer.
Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains.
Authors: B S Andrews, R A Eisenberg, A N Theofilopoulos, S Izui, C B Wilson, P J McConahey, E D Murphy, J B Roths, F J Dixon
Journal: The Journal of Experimental Medicine (1978)

MRL/1 and BXSB male mice have a systemic lupus erythematosus (SLE)-like disease similar to but more acute than that occurring in NZB X W mice. The common elements of lymphoid hyperplasia, B-cell hyperactivity, autoantibodies, circulating immune complex (IC), complement consumption, IC glomerulonephritis with gp70 deposition, and thymic atrophy were found in all three kinds of SLE mice. On the basis of these common elements, SLE seen in these mice can be considered a single disease in the same sense that human SLE is one disease. The differences in the SLE expressed in the different mice are no greater than those found in an unselected series of humans with SLE. However, the significant quantitative and qualitative variations in abnormal immunologic expression suggest that different constellations of factors, genetic and/or pathophysiologic, may operate in the three murine strains and that each constellation is capable of leading, via its particular abnormal immunologic consequences, to the activation of common immunopathologic effector mechanisms that cause quite similar SLE-like syndromes. From an experimental point of view, the availability of several inbred murine strains of commonplace histocompatibility types that express an SLE-like syndrome makes possible innumerable manipulations which should help to elucidate the nature and cause(s) of this disorder.