tbuckley/cabot-search huggingface dataset:
Abstract 1895: Phytochemicals inhibit proliferation and promote death through NADPH oxidase and G6PD
Authors: Mouad Edderkaoui, Hongxiang Hui, Gang Li, Jun Xu, Wai-Nang Lee, Vay Liang W. Go, Stephen J. Pandol
Journal: Cancer Research (2010)

Abstract Background &amp; Aims: Pancreatic cancer is a very aggressive disease that is resistant to therapy. Evidence from population studies indicates a protective effect of fruits and vegetables in the diet on cancer including pancreatic cancer. In vitro and in vivo studies, including our own, suggest that several phytochemicals, such as ellagic acid and lycopene may be involved in this beneficial effect. In this study we investigated the effect of these phytochemicals, alone and in combination, on apoptosis and proliferation of pancreatic cancer cells in vitro, and we analyzed their mechanism of action. Methods: We measured the effect of ellagic acid and lycopene on DNA fragmentation using Cell Death Detection ELISA and on proliferation using 3H-thymidine incorporation into DNA in pancreatic cancer cell line MIA PaCa-2. Molecular signaling mechanisms were evaluated with Western. NF-kB activity was measured using electromobility shift assay. Metabolic phenotype of the cells was analyzed using mass spectrometry and the glucose molecule labeled with stable isotope D-glucose (1,2-13C2). Results: Both lycopene and ellagic acid at doses from 0.1 to 30 μM induced increases in DNA fragmentation and inhibited proliferation in pancreatic cancer cells. Combinations of ellagic acid with lycopene at low doses (1 µM) induced a synergistic effect on DNA fragmentation and proliferation. Ellagic acid induced apoptosis by decreasing NF-kB activity in pancreatic cancer cells. Lycopene decreased NADPH oxidase activity. Combined compounds had a synergistic effect on the inhibition of glucose-6-phosphate dehydrogenase (G6PD) activity as measured by mass spectrometry leading to a synergistic inhibition of DNA synthesis. Conclusions: Combination of ellagic acid and lycopene induced a synergistic effect on apoptosis and proliferation in pancreatic cancer cells. The synergistic effect is due to different mechanisms of action of these phytochemicals leading to the inhibition of G6PD activity, a key step in DNA synthesis. Our study suggests a potentially beneficial role for combinations of ellagic acid and lycopene in prevention and treatment strategies of pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1895.
Residential proximity to traffic and adverse birth outcomes in Los Angeles county, California, 1994-1996.
Authors: Michelle Wilhelm, Beate Ritz
Journal: Environmental Health Perspectives (2002)

We reported previously that increases in ambient air pollution in the Los Angeles basin increased the risk of low weight and premature birth. However, ambient concentrations measured at monitoring stations may not take into account differential exposure to pollutants found in elevated concentrations near heavy-traffic roadways. Therefore, we used an epidemiologic case-control study design to examine whether residential proximity to heavy-traffic roadways influenced the occurrence of low birth weight (LBW) and/or preterm birth in Los Angeles County between 1994 and 1996. We mapped subject home locations at birth and estimated exposure to traffic-related air pollution using a distance-weighted traffic density (DWTD) measure. This measure takes into account residential proximity to and level of traffic on roadways surrounding homes. We calculated odds ratios (ORs) and risk ratios (RRs) for being LBW and/or preterm per quintile of DWTD. The clearest exposure-response pattern was observed for preterm birth, with an RR of 1.08 [95% confidence interval (CI), 1.01-1.15] for infants in the highest DWTD quintile. Although higher risks were observed for LBW infants, exposure-response relations were less consistent. Examining the influence of season, we found elevated risks primarily for women whose third trimester fell during fall/winter months (OR(term LBW) = 1.39; 95% CI, 1.16-1.67; OR(preterm and LBW) = 1.24; 95% CI = 1.03-1.48; RR(all preterm) = 1.15; 95% CI, 1.05-1.26), and exposure-response relations were stronger for all outcomes. This result is consistent with elevated pollution in proximity to sources during more stagnant air conditions present in winter months. Our previous research and these latest results suggest exposure to traffic-related pollutants may be important.
South Korean funding helps North Korea improve health care
Authors: J. Zarocostas
Journal: BMJ (2010)

<h3>SUMMARY</h3> Successful vaccines rely on activating a functional humoral response that results from generating class-switched high affinity immunoglobulins (Igs) with a superior capacity to neutralize infection. Key to this process is the germinal center (GC) reaction, in which B cells are selected in their search for antigen and T cell help. A major hurdle to understanding the mechanisms of B cell:T cell cooperation has been the lack of an <i>in vitro</i> system to recreate GCs in an antigen-specific manner. Here we report the generation of functional antigen-specific high affinity Igs of different isotypes in simple 2-cell type cultures of naïve B and T cells. It is crucial for this process for B cells to take up antigen by a phagocytic mechanism, which results in stronger and more sustained BCR signals compared to stimulation with a soluble antigen. We also show the applicability of the system to generate antibodies of potential clinical interest.
Salvage Radiotherapy After High-Intensity Focussed Ultrasound for Recurrent Localised Prostate Cancer
Authors: Julien Riviere, Jean-Christophe Bernhard, Grégoire Robert, Hervé Wallerand, Edouard Deti, Sylvie Maurice-Tison, Jean-Michel Ardiet, Jean-Philippe Maire, Pierre Richaud, Jean-Marie Ferriere, Philippe Ballanger, Albert Gelet, Gilles Pasticier
Journal: European Urology (2010)
Therapeutic Status–Dependent Thymic Changes on 18F-FDG PET/CT in an Adult Patient With Lymphoma Who Underwent 2 Phases of Chemotherapy
Authors: Qiuping Fan, Minggang Su, Lin Li, Fanglan Li, Rong Tian
Journal: Clinical Nuclear Medicine (2013)

A 31-year-old woman who underwent 2 phases of chemotherapy for Hodgkin lymphoma subsequently underwent 8 F-FDG PET/CT scans for staging and treatment response evaluation. The images revealed that the Hounsfield unit and SUV of the thymus changed with the therapeutic status; both decreased to the lowest level 0.5 months after chemotherapy and increased to the highest level 8 to 12 months after the end of treatment. Interestingly, we found a positive correlation between the thymic Hounsfield unit and SUV, with a Spearman correlation coefficient of 0.946 (P < 0.001).
Physicians' attitudes toward evidence based obstetric practice: a questionnaire survey
Authors: O. A Olatunbosun, L. Edouard, R. A Pierson
Journal: BMJ (1998)

general practitioners to implement evidence based general practice.They should refocus their efforts on promoting and improving access to summaries of evidence.They should also encourage local general practitioners working in localities or commissioning groups, who are themselves skilled in accessing and interpreting evidence, to develop local evidence based guidelines and advice.This may be a more effective approach to harness the interest and welcoming attitude of general practitioners towards evidence based medicine than trying to teach all general practitioners skills in search and critical appraisal.We thank the Wessex general practitioners who took part in this survey.
Leukocytosis: The mysteries within
Authors: Javier Munoz, Yue Guo
Journal: American Journal of Hematology (2011)

67-year-old male was referred to our clinic for evaluation of progressive lymphocytosis and was diagnosed with chronic lymphocytic leukemia (CLL) by peripheral blood flow cytometry. On top of lymphocytosis (30.8 K/μL), other abnormalities were seen on the complete blood count and differential as basophilia (13.2 K/μL), eosinophilia (9.5 K/μL), monocytosis (2.3 K/μL), and neutrophilia (49.8 K/μL), hence a bone marrow aspirate (Image 1 Panel A) and biopsy (Image 1 Panel B) were performed showing myeloid hyperplasia. Fluorescent in-situ hybridization (FISH) showed 74% t(9;22) confirming a diagnosis of concurrent chronic myelogenous leukemia (CML) and CLL. The patient achieved complete hematological, cytogenetic and molecular remission 6 months after starting imatinib mesylate for CML. The follow-up bone marrow biopsy, molecular studies, and peripheral blood smear showing smudge cells (Image 1 Panel C) were all compatible with CLL with no evidence of CML.
Abstract 144: microRNA-107 regulates PKCepsilon and functions as a tumor suppressor miR in head and neck squamous cell carcinoma
Authors: Jharna Datta, Ashley Smith, James Lang, Mozaffarul Islam, Theodoros N. Teknos, Quintin Pan
Journal: Cancer Research (2011)

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The 5-year survival rate of HNSCC has remained stagnant despite advances in the clinical management of this disease. Understanding the molecular pathways that lead to aggressive HNSCC is crucial to identify new “druggable” targets for anti-cancer drug development. Protein kinase Cepsilon (PKCε) is elevated in HNSCC and regulates cell invasion and motility thorough activation of Rho GTPases. Our laboratory and others provide evidence that PKCε is a transforming oncogene that phosphorylates and modulates a cascade of signal transduction pathways, including Akt, EGFR, Rho GTPases, and Stat3. Thus, targeting PKCε may be an attractive therapeutic approach to dampen multiple hyper-active signaling pathways in concert. At this time, the molecular mechanism of PKCε dysregulation in HNSCC remains to be elucidated. In silico analysis with TargetScan, MiRBase, and miRanda identified numerous putative microRNA (miR) binding sites in the 3’-UTR region of PKCε. We screened a panel of miRs using qPCR and miR-107 was identified to have an inverse association with PKCε in HNSCC cell lines with high endogenous PKCε. Ectopic expression of miR-107 in several HNSCC cell lines significantly reduced PKCε mRNA expression and protein levels. The expression of a luciferase reporter construct containing the 3’-UTR of PKCε was down-regulated by miR-107 and deletion/mutation of the three cognate miR-107 binding sites completely abolished the regulation by miR-107. These observations confirm PKCε as a validated target of miR-107. Ectopic expression of miR-107 in HNSCC cell lines significantly inhibited cell proliferation, DNA replication, clonogenic survival, invasion and migration. Tumor take and tumor growth of HNSCC cells was suppressed by miR-107 in a pre-clinical nude mouse model of HNSCC. Lastly, miR-107 was significantly reduced and showed an inverse expression relationship with PKCε in human primary HNSCC tumors. These results indicate that miR-107 regulates PKCε levels to control the tumorigenicity of HNSCC cells. Taken together, our data substantiate the potential application of miR-107 as a novel anti-cancer therapeutic for HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 144. doi:10.1158/1538-7445.AM2011-144
Chromosomal Deletion and Retinoblastoma
Authors: Alfred G. Knudson, Anna T. Meadows, Warren W. Nichols, Rosina Hill
Journal: New England Journal of Medicine (1976)

Retinoblastoma occurs at a very high rate among two groups of genetically predisposed persons: those who inherit the tumor potential with a dominant mode of transmission, and those who bear a deletion of the long arm of chromosome 13 in all their somatic cells. The latter group is particularly important because it is the only instance in animal or man in which a specific chromosomal abnormality can occur prezygotically and consistently predispose to a specific tumor. We report below a new case of this deletion and consider its relation to previously reported cases and the relation between the two genetic . . .
Treatment of aggressive periodontitis
Authors: Wim Teughels, Rutger Dhondt, Christel Dekeyser, Marc Quirynen
Journal: Periodontology 2000 (2014)

Abstract Despite etiological differences between aggressive and chronic periodontitis, the treatment concept for aggressive periodontitis is largely similar to that for chronic periodontitis. The goal of treatment is to create a clinical condition that is conducive to retaining as many teeth as possible for as long as possible. When a diagnosis has been made and risk factors have been identified, active treatment is commenced. The initial phase of active treatment consists of mechanical debridement, either alone or supplemented with antimicrobial drugs. Scaling and root planing has been shown to be effective in improving clinical indices, but does not always guarantee long‐term stability. Antimicrobials can play a significant role in controlling aggressive periodontitis. Few studies have been published on this subject for localized aggressive periodontitis, but generalized aggressive periodontitis has been subject to more scrutiny. Studies have demonstrated that systemic antibiotics as an adjuvant to scaling and root planing are more effective in controlling disease compared with scaling and root planing alone or with supplemental application of local antibiotics or antiseptics. It has also become apparent that antibiotics ought to be administered with, or just after, mechanical debridement. Several studies have shown that regimens of amoxicillin combined with metronidazole or regimens of clindamycin are the most effective and are preferable to regimens containing doxycycline. Azithromycin has been shown to be a valid alternative to the regimen of amoxicillin plus metronidazole. A limited number of studies have been published on surgical treatment in patients with aggressive periodontitis, but the studies available show that the effect can be comparable with the effect on patients with chronic periodontitis, provided that proper oral hygiene is maintained, a strict maintenance program is followed and modifiable risk factors are controlled. Both access surgery and regenerative techniques have shown good results in patients with aggressive periodontitis. Once good periodontal health has been obtained, patients must be enrolled in a strict maintenance program that is directed toward controlling risk factors for disease recurrence and tooth loss. The most significant risk factors are noncompliance with regular maintenance care, smoking, high gingival bleeding index and poor plaque control. There is no evidence to suggest that daily use of antiseptic agents should be part of the supportive periodontal therapy for aggressive periodontitis.
Aerosolized interferon gamma for Mycobacterium avium-complex lung disease.
Authors: G Chatte, G Panteix, M Perrin-Fayolle, Y Pacheco
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

It has recently been shown that human alveolar macrophages can be selectively activated without systemic effect by the use of aerosolized interferon-gamma (IFN gamma), a cytokine that enhances macrophage oxidative and antimicrobial activity. We report the case of a 38-yr-old man negative for human immunodeficiency virus (HIV), with silicosis and advanced cavitary lung disease due to Mycobacterium avium intracellulare (MAI), who failed to improve despite 3 yr of continuous medical therapy with three or more drugs. He received three courses of aerosolized IFN gamma (500 micrograms 3 d per week for 5 wk in two courses and 200 micrograms 3 d a week for 5 wk after a short single trial of subcutaneous IFN gamma). The numbers of MAI decreased in the sputum during therapy, but cultures of the organism remained positive at the same level for the first two treatment periods. The patients sputum became AFB smear negative and the number of colonies decreased significantly after the third course of IFN gamma therapy. Cessation of IFN gamma was associated with a rapid increase in the numbers of MAI in the sputum. Aerosolized IFN gamma can be considered as an adjuvant to conventional drug therapy, with a good tolerance, in cases of lung disease caused by resistant MAI.
Experiences in the first year of an "open door" x-ray department.
Authors: P. L. Cook
Journal: BMJ (1966)

In 1946 the Annual Representative Meeting of the British Medical Association recommended that, wherever possible, hospital departments of pathology and radiology should give direct-access facilities to general practitioners, and this policy has repeatedly been urged at meetings of the Radiologists Group.In spite of this, the "open door" department, as it has come to be known, has been slow to find favour.This is due, in the main, to difficulties in accommodation and staffing, both secretarial and technical, but no doubt also in part to resistance by radiologists and clinicians.In February 1964 it was decided that the diagnostic x-ray department at the Middlesex Hospital should give direct access to general practitioners, and a letter was sent to 200 doctors in the area.At first the department was open only for limited radiological investigations, but in September 1964 the service was extended, in response to a considerable demand, to include all investigations suitable for out-patients with the exception of barium-enema examinations, where it was felt that the difficulties involved in adequate preparation of the patient were too great.Copies of the instruction sheets normally given to out-patients were sent to the same doctors. Material and MethodsA total of 2,621 examinations were carried out in the first 12 months on 2,400 patients, and the demand is increasing (Table I).TABLE I.
TCT-212 Percutaneous intervention of circumflex chronic total occlusions is associated with worse procedural outcomes: insights from a multicenter US registry
Authors: Georgios Christopoulos, Dimitri Karmpaliotis, R. Michael Wyman, Khaldoon Alaswad, James M. McCabe, William Lombardi, J. Aaron Grantham, Steven Marso, Anna Kotsia, Bavana V. Rangan, Santiago Garcia, Nicholas Lembo, David Kandzari, James Lee, Kalynych Anna, Harold Carlson, Craig Thompson, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2014)
Health Benefits from Large-Scale Ozone Reduction in the United States
Authors: Jesse D. Berman, Neal Fann, John W. Hollingsworth, Kent E. Pinkerton, William N. Rom, Anthony M. Szema, Patrick N. Breysse, Ronald H. White, Frank C. Curriero
Journal: Environmental Health Perspectives (2012)

Background: Exposure to ozone has been associated with adverse health effects, including premature mortality and cardiopulmonary and respiratory morbidity. In 2008, the U.S. Environmental Protection Agency (EPA) lowered the primary (health-based) National Ambient Air Quality Standard (NAAQS) for ozone to 75 ppb, expressed as the fourth-highest daily maximum 8-hr average over a 24-hr period. Based on recent monitoring data, U.S. ozone levels still exceed this standard in numerous locations, resulting in avoidable adverse health consequences.Objectives: We sought to quantify the potential human health benefits from achieving the current primary NAAQS standard of 75 ppb and two alternative standard levels, 70 and 60 ppb, which represent the range recommended by the U.S. EPA Clean Air Scientific Advisory Committee (CASAC).Methods: We applied health impact assessment methodology to estimate numbers of deaths and other adverse health outcomes that would have been avoided during 2005, 2006, and 2007 if the current (or lower) NAAQS ozone standards had been met. Estimated reductions in ozone concentrations were interpolated according to geographic area and year, and concentration–response functions were obtained or derived from the epidemiological literature.Results: We estimated that annual numbers of avoided ozone-related premature deaths would have ranged from 1,410 to 2,480 at 75 ppb to 2,450 to 4,130 at 70 ppb, and 5,210 to 7,990 at 60 ppb. Acute respiratory symptoms would have been reduced by 3 million cases and school-loss days by 1 million cases annually if the current 75-ppb standard had been attained. Substantially greater health benefits would have resulted if the CASAC-recommended range of standards (70–60 ppb) had been met.Conclusions: Attaining a more stringent primary ozone standard would significantly reduce ozone-related premature mortality and morbidity.
Abstract 3932: Loss of PTEN sensitizes cells to DNA damaging agents in a RAD51-independent manner
Authors: Michael E. Fraser, Helen Zhao, Cecilia Lundin, Andrew Evans, Thomas Helleday, Robert G. Bristow
Journal: Cancer Research (2010)

Abstract The PTEN tumor suppressor gene is frequently mutated or deleted in many cancers. While the role of PTEN as an inhibitor of the PI3K/Akt signaling pathway via its intrinsic lipid phosphatase activity has been well-studied, recent data suggest that loss of PTEN contributes to genomic instability through a PI3K/Akt-independent pathway via down-regulation of E2F1-dependent transactivation of Rad51, a key mediator of homologous recombination (HR). Cells with dysfunctional HR are sensitive to inhibitors of Poly(ADP)Ribose Polymerase (PARP) and therefore PTEN loss could sensitize cells to PARP inhibitors in a RAD51-dependent manner. Using PTEN-isogenic cell lines, cells treated with siRNA to PTEN and human prostate cancer cell lines with disparate PTEN status, we assessed whether PTEN loss is associated with altered expression of RAD51 protein. We also evaluated the effects of PTEN loss on sensitivity to PARP inhibition and various DNA damaging agents which sensitize cells based on deficiency in DNA double- and single-strand break repair, nucleotide excision repair and base excision repair (i.e. ionizing radiation (IR), camptothecin (CPT), Mitomycin C, cisplatin, ultraviolet radiation (UV), H2O2 and MMS). We observed that PTEN status did not predict RAD51 expression in PTEN−/− (PC3), PTEN+/− (DU145), and PTEN+/+ (22RV1) prostate cancer cells or xenografts in vitro or in vivo. Using a dedicated tissue microarray of localized prostate cancer, PTEN status (based on FISH) did not predict for RAD51 expression. Furthermore, we observed no difference in RAD51 mRNA or protein expression nor in E2F1 binding to the RAD51 promoter in PTEN-deficient HCT116 colorectal cancer cells or H1299 lung carcinoma cells treated with siRNA to PTEN. PTEN expression also did not alter RAD51 localization to IR-induced nuclear foci or UV microirradiation-induced DNA DSBs. However, using clonogenic assays, we observed that loss of PTEN did miminally sensitize cells to PARP inhibition with increased sensitization to MMC, cisplatin, UV, and IR. PTEN loss did not sensitize tumour cells to MMS, CPT or paclitaxel. Taken together, these data suggest that PTEN influences sensitivity to certain DNA damaging agents in a RAD51-independent manner. To understand this sensitivity, we are documenting gene expression changes in 200 DNA repair and replication genes using NanoString technology. A better understanding of the influence of PTEN on cellular sensitivity to chemo- and radiotherapy may ultimately help to guide treatment options for patients based on PTEN status (Sponsored by CCSRI, PCC and the Terry Fox Foundation). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3932.