tbuckley/cabot-search huggingface dataset:
Decreased Expression of 14-3-3σ Is Associated with Advanced Disease in Human Epithelial Ovarian Cancer
Authors: Jun-ichi Akahira, Youko Sugihashi, Takashi Suzuki, Kiyoshi Ito, Hitoshi Niikura, Takuya Moriya, Makoto Nitta, Hitoshi Okamura, Satoshi Inoue, Hironobu Sasano, Kunihiro Okamura, Nobuo Yaegashi
Journal: Clinical Cancer Research (2004)

Abstract Purpose: In this study, we examined the promoter methylation status and expression of 14-3-3σ and evaluated its clinical significance in epithelial ovarian cancer. Experimental Design: Twelve ovarian cancer cell lines; 2 ovarian surface epithelial cell lines; and 8 normal, 8 benign, 12 borderline, and 102 ovarian cancer tissues were examined. Methylation-specific PCR, quantitative reverse transcription-PCR, and immunohistochemistry were used to evaluate methylation status and expression of 14-3-3σ gene and protein. Results: Among the 12 ovarian cancer cell lines, the presence of a methylated band was detected in seven cell lines. Median values of relative 14-3-3σ gene expression in cancers with methylation (3.27) were significantly lower than those without methylation (16.4; P &amp;lt; 0.001). Treatment of 5-aza-2′-deoxycitidine resulted in the demethylation of the promoter CpG islands and reexpression. All of the normal, benign, and borderline tissues were positive for 14-3-3σ protein, and in ovarian cancer tissues, 73.5% (75 of 102) were positive for 14-3-3σ protein and was almost consistent with methylation status. Negative immunoreactivity of 14-3-3σ was significantly correlated with high age and serous histology, high-grade, advanced-stage residual tumor of &amp;gt;2 cm, high serum CA125, high Ki-67 labeling index, and positive p53 immunoreactivity. 14-3-3σ immunoreactivity was significantly associated with overall survival (P = 0.0058). Conclusions: Our findings suggest that 14-3-3σ is inactivated mainly by aberrant DNA methylation and that it may play an important role in the pathogenesis of epithelial ovarian cancer.
Gene Expression Profiling of Papillary Thyroid Carcinoma Identifies Transcripts Correlated with <i>BRAF</i> Mutational Status and Lymph Node Metastasis
Authors: Gisele Oler, Cléber P. Camacho, Flávio C. Hojaij, Pedro Michaluart, Gregory J. Riggins, Janete M. Cerutti
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To identify papillary thyroid carcinoma (PTC)–associated transcripts, we compared the gene expression profiles of three Serial Analysis of Gene Expression libraries generated from thyroid tumors and a normal thyroid tissue. Experimental Design: Selected transcripts were validated in a panel of 57 thyroid tumors using quantitative PCR (qPCR). An independent set of 71 paraffin-embedded sections was used for validation using immunohistochemical analysis. To determine if PTC-associated gene expression could predict lymph node involvement, a separate cohort of 130 primary PTC (54 metastatic and 76 nonmetastatic) was investigated. The BRAFV600E mutational status was compared with qPCR data to identify genes that might be regulated by abnormal BRAF/MEK/extracellular signal-regulated kinase signaling. Results: We identified and validated new PTC-associated transcripts. Three genes (CST6, CXCL14, and DHRS3) are strongly associated with PTC. Immunohistochemical analysis of CXCL14 confirmed the qPCR data and showed protein expression in PTC epithelial cells. We also observed that CST6, CXCL14, DHRS3, and SPP1 were associated with PTC lymph node metastasis, with CST6, CXCL14, and SPP1 being positively correlated with metastasis and DHRS3 being negatively correlated. Finally, we found a strong correlation between CST6 and CXCL14 expression and BRAFV600E mutational status, suggesting that these genes may be induced subsequently to BRAF activation and therefore may be downstream in the BRAF/MEK/extracellular signal-regulated kinase signaling pathway. Conclusion: CST6, CXCL14, DHRS3, and SPP1 may play a role in PTC pathogenesis and progression and are possible molecular targets for PTC therapy.
Use of ipratropium bromide nasal spray in chronic treatment of nonallergic perennial rhinitis, alone and in combination with other perennial rhinitis medications
Authors: J GROSSMAN, C BANOV, P BOGGS, E BRONSKY, R DOCKHORN, H DRUCE, S FINDLAY, J GEORGITIS, F HAMPEL, H KAISER
Journal: Journal of Allergy and Clinical Immunology (1995)
Inhibition of Poly(ADP-Ribose) Polymerase Enhances Cell Death and Improves Tumor Growth Delay in Irradiated Lung Cancer Models
Authors: Jeffrey M. Albert, Carolyn Cao, Kwang Woon Kim, Christopher D. Willey, Ling Geng, Dakai Xiao, Hong Wang, Alan Sandler, David H. Johnson, Alexander D. Colevas, Jennifer Low, Mace L. Rothenberg, Bo Lu
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Poly(ADP-ribose) polymerase-1 (PARP-1) is the founding member of a family of enzymes that catalyze the addition of ADP-ribose units to proteins that mediate DNA repair pathways. Ionizing radiation induces DNA strand breaks, suggesting that PARP-1 inhibition may sensitize tumor cells to radiation. Experimental Design: We investigated the combination of PARP-1 inhibition with radiation in lung cancer models. ABT-888, a novel potent PARP-1 inhibitor, was used to explore the effects of PARP-1 inhibition on irradiated tumors and tumor vasculature. Results: ABT-888 reduced clonogenic survival in H460 lung cancer cells, and inhibited DNA repair as shown by enhanced expression of DNA strand break marker histone γ-H2AX. Both apoptosis and autophagy contributed to the mechanism of increased cell death. Additionally, ABT-888 increased tumor growth delay at well-tolerated doses in murine models. For a 5-fold increase in tumor volume, tumor growth delay was 1 day for ABT-888 alone, 7 days for radiation alone, and 13.5 days for combination treatment. Immunohistochemical staining of tumor sections revealed an increase in terminal deoxyribonucleotide transferase–mediated nick-end labeling apoptotic staining, and a decrease in Ki-67 proliferative staining after combination treatment. Matrigel assay showed a decrease in in vitro endothelial tubule formation with ABT-888/radiation combination treatment, and von Willebrand factor staining of tumor sections revealed decreased vessel formation in vivo, suggesting that this strategy may also target tumor angiogenesis. Conclusions: We conclude that PARP-1 inhibition shows promise as an effective means of enhancing tumor sensitivity to radiation, and future clinical studies are needed to determine the potential of ABT-888 as a radiation enhancer.
Methylation of Ribonucleic Acids of Liver and Other Organs in Different Species Treated With C&lt;sup&gt;14&lt;/sup&gt;- and H&lt;sup&gt;3&lt;/sup&gt;-Dimethylnitrosamines &lt;italic&gt;In Vivo&lt;/italic&gt;&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: K. Y. Lee, W. Lijinsky, P. N. Magee
Journal: JNCI Journal of the National Cancer Institute (1964)

When the carcinogen dimethylnitrosamine, labeled with radioactive carbon (C14-DMN), was injected into rats, mice, hamsters, and guinea pigs in doses sufficient to cause acute hepatic necrosis, radioactivity was found in the ribonucleic acid (RNA) of liver, kidney, spleen, and pancreas. Incorporation was greatest in liver and least in pancreas, with intermediate values in kidney and spleen that showed some species differences. Ion-exchange Chromatographic profiles of hydrolysates of the labeled liver RNA's confirmed previous work with the rat and showed similar patterns in the other species, which indicated that most of the radioactivity was present as 7-methylguanine and suggested that methylation of the RNA's had occurred in vivo. Tritiated dimethylnitrosamine (H3-DMN) was prepared by the Wilzbach exchange reaction, and its metabolic fate was compared with that of C14-DMN in rats and mice. The tritium was also incorporated into the RNA's of liver and other organs in both species, the distribution showing some similarities to and some dissimilarities to that observed with C14-DMN. Comparison of the ion-exchange Chromatographic profiles of hydrolysates of the labeled RNA's from different organs confirmed that incorporation probably occurs by two processes: 1) via normal “one-carbon” metabolic intermediates; 2) by methylation of the nucleic acids. Incorporation via normal intermediates was higher from C14-DMN than from H3-DMN. Calculations of the degree of methylation of the RNA's of different organs in rat and mouse were made. In both species the liver showed the highest degree of methylation, with the next highest in the kidney of the rat and lung of the mouse; the other organs showed low values. These results are discussed in relation to incidence and distribution of tumors in the different species and organs.
PD-L1 expression in nonclear-cell renal cell carcinoma
Authors: T.K. Choueiri, A.P. Fay, K.P. Gray, M. Callea, T.H. Ho, L. Albiges, J. Bellmunt, J. Song, I. Carvo, M. Lampron, M.L. Stanton, F.S. Hodi, D.F. McDermott, M.B. Atkins, G.J. Freeman, M.S. Hirsch, S. Signoretti
Journal: Annals of Oncology (2014)
Oncogenic Action of Secreted Phospholipase A2 in Prostate Cancer
Authors: Paul Sved, Kieran F. Scott, Duncan McLeod, Nicholas J. C. King, Jas Singh, Tania Tsatralis, Blagoy Nikolov, John Boulas, Laxman Nallan, Michael H. Gelb, Mila Sajinovic, Garry G. Graham, Pamela J. Russell, Qihan Dong
Journal: Cancer Research (2004)

Abstract Mortality from prostate cancer is associated with progression of tumors to androgen-independent growth and metastasis. Eicosanoid products of both the cyclooxygenase (COX) and lipoxygenase (LOX) pathways are important mediators of the proliferation of prostate cancer cells in culture and regulate tumor vascularization and metastasis in animal models. Pharmacologic agents that block either COX or LOX products effectively reduce the size of prostate cancer xenografts. Phospholipase A2 (PLA2) enzymes regulate the provision of arachidonic acid to both COX- and LOX-derived eicosanoids, and a secreted form of the enzyme (sPLA2-IIA) is elevated in prostate cancer tissues. Here, we show by immunohistochemistry, in patients receiving androgen ablation therapy, that sPLA2-IIA remains elevated in remaining cancer cells relative to benign glands after treatment. Furthermore, sPLA2-IIA expression seen in benign glands is substantially decreased after androgen depletion, whereas cytosolic PLA2-α (cPLA2-α) levels are unchanged. sPLA2-IIA mRNA expression is detectable and inducible by androgen (0.01–10 nmol/L) in the androgen-sensitive cell line LNCaP, and exogenous addition of sPLA2-IIA (1–100 nmol/L), but not an inactive sPLA2-IIA mutant (H48Q), results in a dose-dependent increase in cell numbers or the fraction of cells in G2-M phase, which is inhibited by sPLA2-IIA-selective inhibitors. The effect of exogenous sPLA2-IIA can also be blocked by inhibition of cPLA2-α, suggesting a role for cPLA2-α in mediating sPLA2-IIΑ action. sPLA2-IIA inhibitors suppressed basal proliferation in LNCaP cells and in the androgen-independent, sPLA2-positive cell line PC3 but not in the sPLA2-IIA-negative androgen-independent cell line DU145. Established PC3 xenograft tumors grew more slowly in mice treated with sPLA2-IIA inhibitors than those treated with saline only. The PLA2 enzymes, and sPLA2-IIA in particular, thus represent important targets for the treatment of sPLA2-IIA-positive androgen-independent prostate cancer.
Acute Coronary Insufficiency Due to Acute Hemorrhage: An Analysis of One Hundred and Three Cases
Authors: ARTHUR M. MASTER, SIMON DACK, HENRY HORN, BERNARD I. FREEDMAN, LEONARD E. FIELD
Journal: Circulation (1950)

The occurrence of 59 cases of acute coronary insufficiency among 103 patients with acute hemorrhage, chiefly from the gastrointestinal tract, emphasizes the frequency and gravity of this generally unrecognized complication of bleeding. Clinical, electrocardiographic and anatomic manifestations of myocardial ischemia and subendocardial necrosis are prone to appeal in previously diseased hearts, although they may develop in otherwise normal hearts. Consequently, prompt and adequate blood replacement is required in patients with coronary arteriosclerosis, enlarged hearts, valvular heart disease, etc. to prevent as well as to treat coronary insufficiency secondary to hemorrhage.
NADPH Oxidase Nox2 Is Required for Hypoxia-Induced Mobilization of Endothelial Progenitor Cells
Authors: Katrin Schröder, Andreas Kohnen, Alexandra Aicher, Elisa A. Liehn, Tom Büchse, Stefan Stein, Christian Weber, Stefanie Dimmeler, Ralf P. Brandes
Journal: Circulation Research (2009)

Rationale: Endothelial progenitor cells (EPCs, defined as sca-1 + flk-1 + lin − mononuclear blood cells) contribute to vascular repair. The role of hypoxia and reactive oxygen species (ROS) in mobilization and function of these cells is incompletely understood. Objective: We studied the contribution of the NADPH oxidase Nox2, an important vascular source of ROS in this context. Methods and Results: Hypoxia (10% oxygen) induced the mobilization of EPCs in wild-type (WT) and Nox1 but not in Nox2 knockout (Nox2 y/− ) mice. As erythropoietin (EPO) is known to induce EPC mobilization, we focused on this hormone. EPO induced the mobilization of EPCs in WT and Nox1 y/− but not Nox2 y/− animals. Transplantation of bone marrow from Nox2 y/− mice into WT-mice blocked mobilization in response to hypoxia and EPO, whereas transplantation of WT bone marrow into Nox2 y/− mice restored mobilization. Reendothelialization of the injured mouse carotid artery was enhanced by hypoxia as well as by EPO, and this effect was not observed in Nox2 y/− mice or after transplantation of Nox2 y/− bone marrow. In cultured EPCs from WT but not Nox2 y/− mice, EPO induced ROS production, migration, and proliferation. EPO signaling involves the STAT5 transcription factor. EPO-induced STAT5-dependent reporter gene expression was absent in Nox2-deficient cells. siRNA against the redox-sensitive phosphatase SHP-2 restored EPO-mediated STAT5 induction and inhibition of SHP-2 restored EPO-induced migration in Nox2-deficient cells Conclusions: We conclude that Nox2-derived ROS inactivate SHP-2 and thereby facilitate EPO signaling in EPCs to promote hypoxia-induced mobilization and vascular repair by these cells.
Architectural and functional asymmetry of the His–Purkinje system of the murine heart
Authors: L MIQUEROL, S MEYSEN, M MANGONI, P BOIS, H VANRIJEN, P ABRAN, H JONGSMA, J NARGEOT, D GROS
Journal: Cardiovascular Research (2004)

Journal Article Architectural and functional asymmetry of the His–Purkinje system of the murine heart Get access Lucile Miquerol, Lucile Miquerol * aLaboratoire de Génétique et Physiologie du Développement, UMR 6545, Institut de Biologie du Développement de Marseille, Université de la Méditerranée, Marseille, France *Corresponding author. Tel.: +33-4-9126-9734; fax: +33-4-9126-9726. Email address: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Sonia Meysen, Sonia Meysen aLaboratoire de Génétique et Physiologie du Développement, UMR 6545, Institut de Biologie du Développement de Marseille, Université de la Méditerranée, Marseille, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Matteo Mangoni, Matteo Mangoni bLaboratoire de Génomique Fonctionnelle, UPR 2580 Montpellier, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Patrick Bois, Patrick Bois cLaboratoire de Physiologie Générale, UMR 6558, Université de Poitiers, Poitiers, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold V.M van Rijen, Harold V.M van Rijen dDepartment of Medical Physiology, University Medical Center, Utrecht, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Patrice Abran, Patrice Abran aLaboratoire de Génétique et Physiologie du Développement, UMR 6545, Institut de Biologie du Développement de Marseille, Université de la Méditerranée, Marseille, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Habo Jongsma, Habo Jongsma dDepartment of Medical Physiology, University Medical Center, Utrecht, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Joël Nargeot, Joël Nargeot bLaboratoire de Génomique Fonctionnelle, UPR 2580 Montpellier, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniel Gros Daniel Gros aLaboratoire de Génétique et Physiologie du Développement, UMR 6545, Institut de Biologie du Développement de Marseille, Université de la Méditerranée, Marseille, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 63, Issue 1, July 2004, Pages 77–86, https://doi.org/10.1016/j.cardiores.2004.03.007 Published: 01 July 2004 Article history Received: 06 January 2004 Revision received: 19 February 2004 Accepted: 05 March 2004 Published: 01 July 2004
Respiratory resistance by the forced oscillation technique in asthmatic children and cystic fibrosis patients
Authors: P Lebecque, D Stanescu
Journal: European Respiratory Journal (1997)

Measurement of the total resistance of the respiratory system (Rrs) is an attractive alternative to measurement of forced expiratory volume in one second (FEV1) in young children because it requires minimal co-operation. The purpose of this study was to assess the ability of the forced oscillation technique (FOT) to detect airway obstruction in asthmatic children and in patients with cystic fibrosis (CF). Spirometry and Rrs were recorded in 45 asthmatic children (32 males and 13 females) and in 45 patients with CF (28 males and 17 females). Rrs was measured at 10 Hz with the Siregnost FD5 (Siemens, Germany). The asthmatic children were slightly younger than the patients with CF (10+/-3 vs 14+/-7 yrs), and had milder airway obstruction (FEV1 80+/-19 vs 66+/-27% of predicted). Rrs was significantly higher in the asthmatic children (6.6+/-1.7 cmH2O x L(-1) x s) than in the patients with CF (4.8+/-1.4 cmH2O x L(-1) x s). A normal FEV1 (&gt; or = mean -2SD) was associated with a normal Rrs (&lt; or = mean +2SD) in 17 of the 45 asthmatic children and in 13 of the 45 CF patients. By contrast, a low FEV1 (&lt; mean -2SD) was associated with an increased Rrs (&gt; mean +2SD) in 21 of the 45 asthmatic children, but in only 3 of the 45 CF patients. Thus, FEV1 and Rrs yielded concordant information in asthmatic children much more often (38 out of 45) than in CF patients (16 out of 45) (p &lt; 0.001). In CF, Rrs failed to detect even severe airways obstruction. These findings might be accounted for by the inability of Rrs to reflect peripheral obstruction. We conclude that total respiratory resistance is suitable to assess airways obstruction in asthmatic children but not in cystic fibrosis patients.
In Vitro Neutrophil Activation by Antibodies to Proteinase 3 and Myeloperoxidase from Patients with Crescentic Glomerulonephritis
Authors: Casper F. M. Franssen, Minke G. Huitema, Anneke C. Muller Kobold, Wia W. Oost-Kort, Pieter C. Limburg, Anton Tiebosch, Coen A. Stegeman, Cees G. M. Kallenberg, Jan W. Cohen Tervaert
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Previously, it was found that patients with necrotizing crescentic glomerulonephritis (NCGN) and anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against proteinase 3 (anti-PR3) had a faster deterioration of renal function and more active renal vasculitic lesions than patients with ANCA directed against myeloperoxidase (anti-MPO). Because ANCA-mediated neutrophil activation is thought to play an important role in the pathophysiology of this form of glomerulonephritis, this study was conducted to determine whether anti-PR3 are capable of inducing a more pronounced activation of neutrophils in vitro than anti-MPO. To test this hypothesis, the release of reactive oxygen radicals, as assessed by ferricytochrome c reduction and by dihydrorhodamine 123 oxidation, and the release of granule constituents from healthy donor neutrophils upon stimulation with IgG fractions were measured from 17 anti-PR3- and 14 anti-MPO-positive patients with active NCGN. Patients with anti-PR3 had a higher renal activity index ( P &lt; 0.05) compared with patients with anti-MPO. IgG fractions from anti-PR3-positive patients induced more oxygen radical release from tumor necrosis factor-α-primed neutrophils compared with IgG fractions from anti-MPO-positive patients, as assessed by ferricytochrome c reduction ( P &lt; 0.05) and dihydrorhodamine 123 oxidation ( P &lt; 0.01). In addition, IgG fractions from anti-PR3-positive patients generated more neutrophil degranulation of β-glucuronidase ( P &lt; 0.01) than IgG fractions from anti-MPO-positive patients. In conclusion, IgG fractions from anti-PR3-positive patients with NCGN are more potent activators of the respiratory burst and degranulation in vitro than IgG fractions from anti-MPO-positive patients. These observations may be relevant in view of the clinical differences between anti-PR3- and anti-MPO-positive patients with NCGN.
Cisplatin and Etoposide Versus Carboplatin and Paclitaxel With Concurrent Radiation for Stage III Non–Small-Cell Lung Cancer: Is There an Impact on Radiation Pneumonitis Rates?
Authors: David A. Palma, Suresh Senan, George Rodrigues
Journal: Journal of Clinical Oncology (2015)

TO THE EDITOR: The article by Santana-Davila et al compared etoposide and cisplatin (EP) with carboplatin and paclitaxel (CP) when delivered as part of concurrent chemoradiotherapy (CCRT) for stage III non–small-cell lung cancer (NSCLC). By using the Veterans’ Affairs (VA) Central Cancer Registry, the authors conducted a robust comparison of overall survival (OS) with EP versus CP, using a Cox proportional hazards model, propensity score techniques, and instrumental variable analysis. OS outcomes were not different between the two regimens, but EP was associated with higher rates of complications, including hospitalization, infection, acute renal disease/dehydration, and mucositis/esophagitis. The authors correctly point out that the findings are in contradistinction to a phase II randomized controlled trial (RCT) that had suggested superior OS with EP compared with CP. A potential concern with the use of CP as part of CCRT for stage III NSCLC has been the risk of radiation pneumonitis (RP). RP can adversely affect quality of life, and can uncommonly lead to long-term oxygen dependence or death. Taxanes are potent radiosensitizers, and an individual patient data meta-analysis identified CP use as a major risk factor for RP, with an odds ratio of 5.52 of developing symptomatic RP with CP compared with EP. The risk was highest in elderly patients (age 65 years) who received CP; such patients had an RP risk greater than 50%. Similarly, in the RCT noted above, the RP rate was 48.5% in the CP arm and 25% in the EP arm (P .09). In their study, Santana-Davila et al used International Classification of Diseases, 9th revision, codes to identify toxicities within the VA database but did not include RP (International Classification of Diseases, 9th revision, code 508.0) as one of the outcomes assessed. A comparison of RP rates with CP versus EP within the VA database would help to address this concern regarding pulmonary toxicity. The pathogenesis and risk of RP may differ depending on ethnicity, analogous to the increased risk of hematologic toxicity demonstrated in Asian versus non-Asian patients receiving CCRT for NSCLC. The meta-analysis and RCT contained many Asian patients, whereas the VA database contains mostly white male patients; therefore, the high risk of RP associated with CP in the two former studies may not generalize to the VA population. Could the authors provide additional data analysis comparing RP rates between the CP and EP groups in their study?