tbuckley/cabot-search huggingface dataset:
Octreotide Acetate in Prevention of Chemoradiation-Induced Diarrhea in Anorectal Cancer: Randomized RTOG Trial 0315
Authors: Babu Zachariah, Clement K. Gwede, Jennifer James, Jaffer Ajani, Lisa J. Chin, David Donath, Seth A. Rosenthal, Brent L. Kane, Marvin Rotman, Lawrence Berk, Lisa A. Kachnic
Journal: JNCI Journal of the National Cancer Institute (2010)

In anorectal cancer patients, an acute side effect of chemoradiotherapy is gastrointestinal toxicity, which often impedes treatment delivery. Based on previous trials, octreotide acetate is widely recommended for the control of chemotherapy-induced diarrhea. However, the effectiveness of octreotide in preventing or controlling radiation- and chemoradiation-induced diarrhea is not known.A randomized, double-blinded, placebo-controlled trial was designed to determine the efficacy of long-acting octreotide acetate (LAO) in preventing the onset of acute diarrhea in patients undergoing chemoradiation therapy for rectal or anal cancer. Between 4 and 7 days before the start of radiation therapy, patients received a 30-mg dose of LAO (109 patients) or placebo (106 patients) via intramuscular injection. A second dose was given on day 22 (+/-3 days) of radiation treatment. A total of 215 patients were included in the final analysis. The primary endpoint was the incidence of grade 2-4 acute diarrhea; secondary endpoints included treatment compliance, medical resource utilization, patient-reported bowel function, and quality of life (QoL). Statistical tests were one- or two-sided, as specified.After a median follow-up time of 9.64 months, incidence rates of grades 2-4 acute diarrhea were similar in both groups (49% placebo vs 44% LAO; P = .21). No statistically significant treatment differences in chemotherapy or radiation delivery, medical resource utilization, patient-reported bowel function, or QoL were observed.In this study, the prophylactic use of LAO did not prevent the incidence or reduce the severity of diarrhea and had no notable impact on patient-reported bowel function or QoL.
Anti-angiogenic treatment strategies for the therapy of endometriosis
Authors: M.W. Laschke, M.D. Menger
Journal: Human Reproduction Update (2012)

Angiogenesis, i.e. the development of new blood vessels from pre-existing ones, represents an integral part in the pathogenesis of endometriosis. During the last decade, an increasing number of studies have therefore focused on the anti-angiogenic treatment of the disease. The present review provides a systematic overview of these studies and critically discusses the future role of anti-angiogenic therapy in the multimodal management of endometriosis. Literature searches were performed in PubMed, MEDLINE and ISI Web of Knowledge for original articles published before the end of March 2012, written in the English language and focusing on anti-angiogenic approaches for the therapy of endometriosis. The searches included both animal and human studies. Numerous compounds of different substance groups have been shown to exert anti-angiogenic effects on endometriotic lesions under experimental in vitro and in vivo conditions. These include growth factor inhibitors, endogenous angiogenesis inhibitors, fumagillin analogues, statins, cyclo-oxygenase-2 inhibitors, phytochemical compounds, immunomodulators, dopamine agonists, peroxisome proliferator-activated receptor agonists, progestins, danazol and gonadotropin-releasing hormone (GnRH) agonists. However, clinical evidence for their efficacy in anti-angiogenic endometriosis therapy is still lacking. Anti-angiogenic compounds hold great promise for the future treatment of endometriosis because they may inhibit the establishment of new endometriotic lesions in early stages of the disease or after surgical treatment. Further experimental studies, controlled clinical trials in particular, are required now to clarify which compounds fulfil these expectations without inducing severe side effects in patients with endometriosis.
Circulating Interleukin (IL)-8, IL-2R, IL-12, and IL-15 Levels Are Independently Prognostic in Primary Myelofibrosis: A Comprehensive Cytokine Profiling Study
Authors: Ayalew Tefferi, Rakhee Vaidya, Domenica Caramazza, Christy Finke, Terra Lasho, Animesh Pardanani
Journal: Journal of Clinical Oncology (2011)

Purpose Abnormal cytokine expression accompanies myelofibrosis and might be a therapeutic target for Janus-associated kinase (JAK) inhibitor drugs. This study describes the spectrum of plasma cytokine abnormalities in primary myelofibrosis (PMF) and examines their phenotypic correlates and prognostic significance. Patients and Methods Patients included in this study were required to have archived plasma, bone marrow biopsy, and cytogenetic information available at the time of first referral to the Mayo Clinic. Multiplex biometric sandwich immunoassay was used to measure plasma levels of 30 cytokines. Results In total, 127 PMF patients were studied; comparison with normal controls (n = 35) revealed significantly increased interleukin-1β (IL-1β), IL-1RA, IL-2R, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, tumor necrosis factor α (TNF-α), granulocyte colony-stimulating factor (G-CSF), interferon alfa (IFN-α), macrophage inflammatory protein 1α (MIP-1α), MIP-1β, hepatocyte growth factor (HGF), IFN-γ–inducible protein 10 (IP-10), monokine induced by IFN-γ (MIG), monocyte chemotactic protein 1 (MCP-1), and vascular endothelial growth factor (VEGF) levels and decreased IFN-γ levels. In treatment-naive patients (n = 90), increased levels of IL-8 (P &lt; .001), IL-2R (P &lt; .001), IL-12 (P &lt; .001), IL-15 (P = .001), and IP-10 (P = .003) were independently predictive of inferior survival. A similar multivariable analysis that included all 127 study patients confirmed the prognostic value of these five cytokines, and IL-8, IL-2R, IL-12, and IL-15 remained significant when risk stratification, according to the recently revised Dynamic International Prognostic Scoring System (DIPSS plus), was added to the multivariable model. Leukemia-free survival was predicted by IL-8, which was also the only cytokine associated with ≥ 1% circulating blasts. Other cytokine-phenotype associations included increased IL-8 and constitutional symptoms; IL-2R, IL-12, and transfusion need; IL-2R, IL-8, and leukocytosis; IP-10 and thrombocytopenia; HGF, MIG, IL-1RA, and marked splenomegaly; and IL-1RA, IL-2R, IP-10, MIP-1β, and JAK2V617F. A two-cytokine (IL-8/IL-2R) –based risk categorization delineated prognostically different groups within specific DIPSS plus risk categories. Conclusion This study signifies the presence of specific cytokine-phenotype associations in PMF and a prognostically relevant plasma cytokine signature that might prove useful as a laboratory tool for predicting and monitoring treatment response.
Induction of Heme Oxygenase-1 Suppresses Venular Leukocyte Adhesion Elicited by Oxidative Stress
Authors: Shinobu Hayashi, Rina Takamiya, Tokio Yamaguchi, Kenji Matsumoto, Shinichiro J. Tojo, Takuya Tamatani, Masaki Kitajima, Nobuya Makino, Yuzuru Ishimura, Makoto Suematsu
Journal: Circulation Research (1999)

Abstract —This study aimed to examine whether an elevated activity of heme oxygenase (HO)-1 in the tissue attenuates endothelial cell–leukocyte interactions microvessels in vivo. When rats were pretreated with an intraperitoneal injection of hemin, an HO-1 inducer, mesenteric tissues, including their microvessels, displayed a marked induction of HO-1 concurrent with an increase in plasma concentrations of bilirubin-IXα, the product of HO-catalyzed degradation of protoheme IX. In these rats, oxidative stress such as superfusion with H 2 O 2 and ischemia-reperfusion of the tissues neither induced rolling nor exhibited adherent responses of leukocytes in venules. In contrast, the oxidative stresses evoked marked rolling and adhesion of leukocytes in the control rats without HO-1 induction. The HO-1 induction also downregulated leukocyte adhesion elicited by other pro-oxidant stimuli such as N ω -nitro- l -arginine methyl ester. The decreases in the oxidant-elicited leukocyte adhesive responses under HO-1–inducing conditions were restored by perfusion with zinc protoporphyrin-IX, an HO inhibitor, but not with copper protoporphyrin-IX, which did not inhibit the enzyme. Furthermore, the effects of zinc protoporphyrin-IX were repressed by superfusion with bilirubin or biliverdin at the micromolar level, but not by the same concentration of carbon monoxide, another product of HO. These results indicate that induction of the HO-1 activity serves as a potential stratagem to prevent oxidant-induced microvascular leukocyte adhesion through the action of bilirubin, a product of HO reaction.
Use of HbA1c in Predicting Progression to Diabetes in French Men and Women
Authors: Celine Droumaguet, Beverley Balkau, Dominique Simon, Emile Caces, Jean Tichet, Marie Aline Charles, Eveline Eschwege
Journal: Diabetes Care (2006)

Early identification of subjects at high risk for diabetes is essential, and random HbA(1c) (A1C) may be more practical than fasting plasma glucose (FPG). The predictive value of A1C, in comparison to FPG, is evaluated for 6-year incident diabetes.From the French cohort study Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR), 1,383 men and 1,437 women, aged 30-65 years, were volunteers for a routine health check-up. Incident diabetes was defined by FPG >or=7.0 mmol/l or treatment by antidiabetic drugs. Multivariate logistic regression models were used to predict diabetes at 6 years. Receiver operating characteristic curves compared the predictive values of A1C and FPG.At 6 years, 30 women (2.1%) and 60 men (4.3%) had developed diabetes. Diabetes risk increased exponentially with A1C in both sexes (P < 0.001). After stratifying on FPG, A1C predicted diabetes only in subjects with impaired fasting glucose (IFG) (FPG >or=6.10 mmol/l): the odds ratio (95% CI) for a 1% increase in A1C was 7.20 (3.00-17.00). In these subjects, an A1C of 5.9% gave an optimal sensitivity of 64% and specificity of 77% to predict diabetes.A1C predicted diabetes, even though the diagnosis of diabetes was based on FPG, but it was less sensitive and specific than FPG. It could be used as a test if fasting blood sampling was not available or in association with FPG. In subjects with IFG, A1C is better than glucose to evaluate diabetes risk, and it could be used to select subjects for intensive early intervention.
Epicardial Mapping of Chronic Atrial Fibrillation in Patients
Authors: Jayakumar Sahadevan, Kyungmoo Ryu, Leora Peltz, Celeen M. Khrestian, Robert W. Stewart, Alan H. Markowitz, Albert L. Waldo
Journal: Circulation (2004)

The mechanisms of chronic atrial fibrillation (AF) are not well understood. We performed epicardial mapping of chronic AF in patients undergoing open heart surgery to test the hypothesis that chronic AF is due to a left atrial "driver" with a regular, short cycle length, resulting in fibrillatory conduction to the rest of the atria.Nine patients with chronic AF (1 month to >15 years' duration) were studied at open heart surgery, 8 before and 1 during cardiopulmonary bypass. During AF, atrial electrograms (AEGs) were recorded for 1 to 5 minutes from 404 epicardial electrodes arranged in bipoles along with ECG lead II or ventricular electrogram. Four-second segments of each bipolar AEG were also subjected to fast Fourier transform analysis. Two patterns of atrial activation were present during AF. In pattern 1 (7/9 patients), AEGs from parts of the atria demonstrated a short, regular cycle length with identical beat-to-beat morphology, and the rest of the atria were activated irregularly, and AEGs that demonstrated constant morphology and cycle length were localized to parts of the left atria (5/7), the right atria (1/7), or both atria (1/7). In pattern 2 (2/9 patients), AEGs showed no evidence of regular activation or constant morphology.In 9 patients with chronic AF, the commonest recorded AEG pattern showed an area of regular, rapid rhythm, consistent with the possibility that a driver causing fibrillatory conduction is one mechanism of AF in these patients.
IMPAIRED GLOBAL RIGHT VENTRICULAR LONGITUDINAL STRAIN PREDICTS LONG-TERM ADVERSE OUTCOMES IN PATIENTS WITH PRIMARY PULMONARY HYPERTENSION
Authors: Jae-Hyeong Park, Margaret Park, Samar Farha, Jacqueline Sharp, Erika Lundgrin, Suzy Comhair, Wai Hong Tang, Serpil C. Erzurum, James Thomas
Journal: Journal of the American College of Cardiology (2012)
Nondiabetic patients with either subclinical Cushing's or nonfunctional adrenal incidentalomas have lower insulin sensitivity than healthy controls: Clinical implications
Authors: Miomira Ivović, Ljiljana V. Marina, Svetlana Vujović, Milina Tančić-Gajić, Miloš Stojanović, Nevena V. Radonjić, Milan Gajić, Ivan Soldatović, Dragan Micić
Journal: Metabolism (2013)
Lipopolysaccharide induces prostaglandin H synthase-2 protein and mRNA in human alveolar macrophages and blood monocytes.
Authors: S L Hempel, M M Monick, G W Hunninghake
Journal: Journal of Clinical Investigation (1994)

We and others have previously demonstrated that human alveolar macrophages produce more PGE2 in response to lipopolysaccharide (LPS) than do blood monocytes. We hypothesized that this observation was due to a greater increase in prostaglandin H synthase-2 (PGHS-2) enzyme mass in the macrophage compared to the monocyte. To evaluate this hypothesis, alveolar macrophages and blood monocytes were obtained from healthy nonsmoking volunteers. The cells were cultured in the presence of 0 to 10 micrograms/ml LPS. LPS induced the synthesis of large amounts of a new 75-kD protein in human alveolar macrophages, and a lesser amount in monocytes. Synthesis of this protein required more than 6 h and peaked in 24 to 48 h; the protein reacted with an anti-PGHS-2 antibody prepared against mouse PGHS-2. Associated with synthesis of the protein was a marked increase in LPS-stimulated and arachidonic acid-stimulated synthesis of PGE2 by alveolar macrophages compared to monocytes. Cells not exposed to LPS contained only PGHS-1 and synthesized very little PGE2 during culture or in response to exogenous arachidonic acid. An LPS-induced mRNA, which hybridized to a human cDNA probe for PGHS-2 mRNA, was produced in parallel with production of this new protein and was produced in much greater amounts by alveolar macrophages compared to blood monocytes. This mRNA was not detectable in cells not exposed to LPS. In contrast, both types of cells contain mRNA, which hybridizes to a cDNA probe for PGHS-1. This mRNA did not increase in response to LPS. LPS also had no effect on PGHS-1 protein. These data demonstrate that PGE2 synthesis in human alveolar macrophages and blood monocytes correlates to the mass of PGHS-2 in the cell. We conclude that the greater ability of the macrophage to synthesize PGE2 in response to LPS is due to greater synthesis of PGHS-2 by the macrophage.
The Combination of the Rexinoid, LG100268, and a Selective Estrogen Receptor Modulator, Either Arzoxifene or Acolbifene, Synergizes in the Prevention and Treatment of Mammary Tumors in an Estrogen Receptor–Negative Model of Breast Cancer
Authors: Karen Liby, Mara Rendi, Nanjoo Suh, Darlene B. Royce, Renee Risingsong, Charlotte R. Williams, William Lamph, Fernand Labrie, Stan Krajewski, Xiaochun Xu, Heetae Kim, Powel Brown, Michael B. Sporn
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We tested whether a selective estrogen receptor modulator (SERM) and a rexinoid are active for prevention and treatment in the mouse mammary tumor virus-neu mouse model of estrogen receptor–negative breast cancer. Experimental Design: For prevention, mice were fed a powdered control diet, the SERM arzoxifene (Arz, 20 mg/kg diet), the rexinoid LG100268 (268, 30 mg/kg diet), or the combination for 60 weeks. In a second prevention study, mice were fed Arz (6 mg/kg diet), 268 (30 mg/kg diet), the combination of Arz and 268, the SERM acolbifene (Acol, 3 mg/kg diet), or the combination of Acol and 268 for 52 weeks. For the treatment studies, mice with tumors were fed combinations of a SERM and 268 for 4 weeks. Results: The rexinoid 268 and the SERMs Arz and Acol, as individual drugs, delayed the development of estrogen receptor–negative tumors. Moreover, the combination of a SERM and 268 was strikingly synergistic, as no tumors developed in any mouse fed the combination of 268 and a SERM. Moreover, this drug combination also induced significant tumor regression when used therapeutically. These drugs did not inhibit transgene expression in vitro or in vivo, and the combination of Arz and 268 inhibited proliferation and induced apoptosis in the tumors. Conclusion: The combination of a rexinoid and SERM should be considered for future clinical trials.
Resistance exercise does not affect the serum concentrations of cell adhesion molecules * Commentary
Authors: Anatoli Petridou, Athanasios Chatzinikolaou, Ioannis Fatouros, George Mastorakos, Asimina Mitrakou, Helen Chandrinou, Ioannis Papassotiriou, Vassilis Mougios
Journal: British Journal of Sports Medicine (2006)

Cell adhesion molecules are proteins expressed on the surface of a variety of cells and mediate the leucocyte response to inflammation. Some of these molecules are released to the plasma as soluble forms, whose presence indicates the degree of vascular endothelial activation or dysfunction. Increased concentrations of soluble adhesion molecules are thought to hamper the immune response and mediate the atherosclerotic inflammatory process. Studies on the effect of exercise on the concentrations of soluble adhesion molecules have almost exclusively used aerobic exercise.To assess the effect of resistance exercise on the serum concentrations of five cell adhesion molecules during and immediately after 30 min of exercise in lean and obese participants.Fourteen healthy young men (eight lean and six obese) performed 3 sets of 10 resistance exercises with 10-12 repetitions at 70-75% of one repetition maximum in a circuit training fashion. Venous blood samples were drawn at baseline and at the end of the first, second and third sets. The serum concentrations of vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, E-selectin, P-selectin and L-selectin were measured in a biochip array analyser.No significant changes were observed in the concentrations of these cell adhesion molecules during exercise, or between lean and obese participants.Our data indicate that resistance exercise of moderate to high intensity does not affect the serum concentrations of cell adhesion molecules in healthy young lean or obese men, suggesting no considerable negative effect on immune function.
Noninvasive Imaging and Quantification of Epidermal Growth Factor Receptor Kinase Activation <i>In vivo</i>
Authors: Wenrong Li, Fang Li, Qian Huang, Barbara Frederick, Shideng Bao, Chuan-Yuan Li
Journal: Cancer Research (2008)

Abstract Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) critical in tumor growth and a major target for anticancer drug development. However, thus far, there is no effective system to monitor its activities in vivo. Here, we report a novel approach to monitor EGFR activation based on the bifragment luciferase reconstitution system. The EGFR receptor and its interacting partner proteins (EGFR, growth factor receptor binding protein 2, and Src homology 2 domain-containing) were fused to NH2 terminal and COOH terminal fragments of the firefly luciferase. After establishing tumor xenograft from cells transduced with the reporter genes, we show that the activation of EGFR and its downstream factors could be quantified through optical imaging of reconstituted luciferase. Changes in EGFR activation could be visualized after radiotherapy or EGFR inhibitor treatment. Rapid and sustained radiation-induced EGFR activation and inhibitor-mediated signal suppression were observed in the same xenograft tumors over a period of weeks. Our data therefore suggest a new methodology where activities of RTKs can be imaged and quantified optically in mice. This approach should be generally applicable to study biological regulation of RTK, as well as to develop and evaluate novel RTK-targeted therapeutics. [Cancer Res 2008;68(13):4990–7]
Single-agent high-dose melphalan salvage therapy for Hodgkin's disease: Cost, safety, and long-term efficacy
Authors: D.A. Stewart, D. Guo, J.A. Sutherland, B.A. Ruether, A.R. Jones, M.-C. Poon, C. deMetz, J. Klassen, A. Chaudhry, C.B. Brown, J.A. Russell
Journal: Annals of Oncology (1997)
Immune response of peripheral blood mononuclear cells to HBx-antigen of hepatitis B virus
Authors: Maria-Christina Jung, Marietta Stemler, Thomas Weimer, Ulrich Spengler, Jutta Döhrmann, Robert Hoffmann, Dieter Eichenlaub, Josef Eisenburg, Gustav Paumgartner, Gert Riethmüller, Hans Will, Gerd R. Pape
Journal: Hepatology (1991)

The hepatitis B virus genome encodes a transcriptional transactivator protein designated HBxAg. We have investigated whether this antigen is a target structure for human T-lymphocytes. Using recombinant HBxAg protein, we found HBxAg-specific stimulation of peripheral blood mononuclear cells in patients with acute hepatitis B virus infection (6 of 6) and chronic hepatitis B virus infection (6 of 17) but not in healthy individuals. With HBxAg-specific synthetic polypeptides, several T-cell epitopes were identified. Most were located in the carboxyterminal half of the HBxAg protein. Five T-cell clones specific for a T-cell epitope located at the carboxyterminal region of HBxAg were established and found to belong to the CD2/CD4-positive, CD8-negative subtype. These data establish for the first time HBxAg as an antigen in the cellular immune response.
The fine-scale architecture of defibrillation
Authors: A HOLDEN
Journal: Cardiovascular Research (2004)

See article by Sharifov et al. (pages 448–456) in this issue 

Ventricular fibrillation is fatal, unless it self-terminates or is terminated by an intervention. It probably is partially responsible for most non-violent deaths and is the immediate cause of death in most sudden cardiac deaths, which form up to a fifth of adult premature deaths in the developed world [1]. The only effective treatment is prompt defibrillation by a brief, large-amplitude electrical shock that produces a field of more than 5 V/cm in the myocardium. Since DC cardiac defibrillation/cardioversion was pioneered by Lown [2] in the 1960s, there have been substantial improvements in the engineering of defibrillators, leading to implantable devices for high-risk patients and public access automatic defibrillators in public areas [1,3]. However, the cellular and tissue electrophysiological mechanisms that underlie defibrillation remain poorly understood and controversial. Improvement in the spatial resolution of optical recording of the spatio-temporal pattern of activity across the ventricular wall produced by electrical shocks has helped to clarify these mechanisms.

Fibrillation is produced by irregular, self-sustained propagation of activation wave fronts through the ventricle. The wave front will propagate into tissue that has recovered its excitability (the excitable gap), with a velocity that depends on both its local curvature and the relative refractoriness of the tissue (determined by the time since the previous activation, or the rate of activity). During normal sinus rhythm, the ventricular activation wave front forms a continuous surface, propagating from the sub-endocardial Purkinje fibers towards the epicardium. At a line break in the activation surface, produced by some heterogeneity, propagation may curl back on itself and … 

*Tel.: +44 113 343 4251; fax: +44 113 343 4230. Email address: arun{at}cbiol.leeds.ac.uk