tbuckley/cabot-search huggingface dataset:
Abstract LB-462: Chemopreventive effects of freeze-dried strawberries in inflammation-associated mouse colon tumorigenesis
Authors: Fei Yan, Huaji Guan, Yongquan Wang, Xin Huang, Ronald G. Nines, Gary D. Stoner, Tong Chen
Journal: Cancer Research (2011)

Abstract Colorectal cancer (CRC) is one of the most common malignant neoplasms in the United States. The risk for CRC is associated with extent and duration of inflammatory bowel disease (IBD). Patients with IBD are at increased risk of developing CRC when compared to the general population. Therefore, primary cancer chemoprevention is an important strategy to reduce the risk of CRC in IBD patients and thus, this approach has recently received more attention. Our laboratory has conducted extensive research on cancer chemoprevention in GI tract. In our previous study, we found that dietary freeze-dried black raspberries significantly inhibited adenoma and adenocarcinoma formation and decreased the level of oxidative stress in an azoxymethane (AOM)-induced rat CRC model. In a carcinogen-induced rat esophageal cancer model, we found that dietary freeze-dried strawberries significantly inhibited tumor development. However, the effects of strawberries in inflammation-associated CRC have not been investigated as yet. The principal objective of this study is to investigate the inhibitory effects of dietary freeze-dried strawberries in AOM/Dextran Sodium Sulfate (DSS)-induced mouse colon carcinogenesis. At 4–5 weeks of age, male Crj: CD-1 mice were given a single intraperitoneal injection of AOM (10mg/kg body weight), followed by 2% DSS in their drinking water for seven days, starting one week after the AOM injection. After 3 weeks, animals were fed AIN-76A diet or AIN-76A diet containing 10% freeze-dried strawberries. At week 20, mice were sacrificed for histopathological examination. We found that strawberries significantly decreased tumor incidence from 100% in mice treated with AOM/DSS only to 44.4% in mice treated with AOM/DSS plus strawberries (55.6% reduction, P = 0.02). We also found that the average animal body weight was significantly higher (P = 0.036) in animals fed strawberries (41.9 ± 5.3 g) when compared to animals fed control diet (38.7 ± 3.7 g). A large-scale investigation of the inhibitory effects of strawberries on biomarkers associated with colon carcinogenesis is under way. (Supported by California Strawberry Commissions) 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 LB-462. doi:10.1158/1538-7445.AM2011-LB-462
Abstract 5666: DNA repair defects enhance tumor cell sensitivity to sapacitabine
Authors: Sheelagh Frame, Sian Armour, Daniella I. Zheleva, Simon R. Green, David G. Blake
Journal: Cancer Research (2012)

Abstract Sapacitabine, a novel, orally available, pro-drug of CNDAC (2′-C-cyano-2′-deoxy-1-β-D-arabino-pentofuranosylcytosine), is currently being evaluated in SEAMLESS, a pivotal Phase 3 trial in elderly patients with AML, and Phase 2 trials in AML, MDS, NSCLC, and CLL/SLL. CNDAC acts by a unique DNA-damaging mechanism. After CNDAC is incorporated into DNA, single-strand DNA breaks are generated via a β-elimination reaction. If unrepaired, these are subsequently converted to double-strand breaks during further replication. These DNA breaks can also activate the G2 checkpoint, leading to cell cycle arrest in G2. Parallel approaches have been utilized to identify further rational therapeutic development strategies for sapacitabine, particularly focusing on solid tumors. These approaches include synthetic lethality screening using focused siRNA libraries in CNDAC-treated cells, and screening for agents that could synergistically induce cell death when administered in combination with CNDAC. These have demonstrated that depletion or inhibition of components of the homologous recombination DNA repair (HRR) pathway (including ATM, BRCA1/2, Rad 51 and XRCC3) or disruption of the G2 checkpoint greatly sensitizes tumor cell lines to CNDAC-induced cell death. For example, cell lines in which BRCA1 or BRCA2 has been depleted through siRNA are significantly more sensitive to the compound than control cells. Moreover, inhibitors of the ATM or Chk1 kinases also sensitize cells to CNDAC, the latter through abrogation of the G2 checkpoint. These complementary approaches have underscored the potential clinical utility of sapacitabine in patients carrying homologous recombination DNA repair deficient (HRD) tumors, and have also highlighted promising combination strategies. Drug combination screening has also assessed the potential for combining sapacitabine with other agents active in HRD tumors, including platins and PARP inhibitors. Ongoing work is extending these findings to several solid tumor indications, including breast, ovarian and non-small cell lung cancers. Correlation of HRR status and CNDAC sensitivity will be reported for a panel encompassing cell lines derived from each of these target indications, in order to guide future clinical development of sapacitabine in solid tumors, and to aid development of biomarkers to identify suitable patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5666. doi:1538-7445.AM2012-5666
Exceptionally low rotavirus incidence in the Netherlands in 2013/14 in the absence of rotavirus vaccination
Authors: S Hahné, M Hooiveld, H Vennema, A van Ginkel, H de Melker, J Wallinga, W van Pelt, P Bruijning-Verhagen
Journal: Eurosurveillance (2014)

An unexpected drop in rotavirus (RV) detections was observed in the Netherlands in 2014, without RV vaccination. The estimated decrease in RV detections and gastroenteritis consultations in under five year-olds, in January-April 2014, compared to the same months in previous years, was 72% and 36%, respectively. The low birth rate, mild winter, high RV incidence in the previous year and the introduction of RV vaccination in neighbouring countries may have contributed to this decrease.
The Immotile-Cilia Syndrome
Authors: Rune Eliasson, Björn Mossberg, Per Camner, Björn A. Afzelius
Journal: New England Journal of Medicine (1977)

We investigated six men and a woman suspected of suffering from congenital immotility of cilia. All had chronic airway infections, and the men had immotile spermatozoa. The woman and three men had Kartagener's syndrome. The investigations included measurements of the mucociliary transport in the lower airways and ultrastructural studies of the sperm tails or respiratory cilia (or both). Mucociliary transport was significantly delayed. Sperm tails lacked dynein arms in five patients. Respiratory cilia from the women and two men lacked dynein arms and were irregularly oriented. The results support the hypothesis that a congenital defect in the cilia and sperm tails will cause chronic respiratory-tract infections and male sterility--the immotile-cilia syndrome. In about half these patients there will also be a situs inversus--i.e., Kartagener's syndrome.
Plasminogen fragment K1-5 improves survival in a murine hepatocellular carcinoma model
Authors: V. Schmitz, E. Raskopf, M. A. Gonzalez-Carmona, A. Vogt, C. Rabe, L. Leifeld, M. Kornek, T. Sauerbruch, W. H Caselmann
Journal: Gut (2006)

<b>Background:</b> The prognosis of patients with hepatocellular carcinoma (HCC) remains poor, and new alternative treatments are needed. <b>Aims:</b> To comparatively test the angiostatic and antitumour effects of adenoviral gene transfer of angiostatin (PlgK1–4, amino acids 1–440) and full kringles 1–5 (PlgK1–5, amino acids 1–546) in a model of subcutaneously transferred HCC in mice. <b>Methods:</b> PlgK1–4 and PlgK1–5 were generated from human WtPlg cDNA and used for adenovirus construction. Vector function and angiostatic effects were confirmed in vitro and in vivo. Antitumoral efficacies of intratumoral vector injections were studied in a model of subcutaneously transferred HCC model. <b>Results:</b> Cell supernatants containing PlgK1–4 and PlgK1–5 reduced endothelial tube formation in vitro by about 30%, whereas WtPlg exerted no inhibitory effect. Endothelial cell infiltration in vivo was decreased by about 60%, but not in AdWtPlg-treated animals. Intratumoral treatment of subcutaneous HCC tumours inhibited growth by 40% for AdPlgK1–4 and 63% for AdPlgK1–5 in surviving mice 12 days after initiation of treatment, whereas treatment with AdWtPlg even led to accelerated growth. Although PlgK1–4 and PlgK1–5 have similar inhibitory effects on intratumoral microvessels, PlgK1–5 markedly improved the survival time compared with PlgK1–4. <b>Conclusion:</b> PlgK1–5 and PlgK1–4 effectively inhibited HCC growth. As PlgK1–5 could also prolong the survival time, inducing complete tumour elimination in half of the AdPlgK1–5-treated mice, PlgK1–5 might be the most potential plasminogen fragment for treatment of experimental HCC.
AB1342 Impact of obesity and hyper-triglyceridemia on gout development with or without hyperuricemia –a prospective study in chinese
Authors: J.-H. Chen, C.-C. Hsu, P.-Y. Chen, W.-H. Pan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Hyperuricemia is the most important risk factor for gout development. However, not all patients with hyperuricemia develop gout. Meanwhile, patients during gout attack are not necessarily found hyperuricemia. <h3>Objectives</h3> To investigate the interaction between serum uric acid (sUA) and other potential metabolic co-morbidities to precipitate gout development (1). <h3>Methods</h3> A prospective study was conducted to link baseline metabolic profiles from the MJ Health Screening Center to gout outcomes extracted from Taiwan’s National Health Insurance database (2). A Cox proportional hazard model was used to assess the metabolic risks for incident gout stratified by hyperuricemia (sUA &gt;7mg/dL). <h3>Results</h3> During a mean follow-up of 6.45 years (261,500 PYs), 1,189 patients with clinical gout (898 men, 202 women aged &gt;50 years, and 88 women aged ≤50 years) were identified among 40,513 examinees. The multivariate adjusted hazard ratios (HR) of hyperuricemia for gouty arthritis were 5.80 (95% Confidence Interval, 4.93–6.81) in men and 4.37 (3.38–5.66) in women. Hyper-triglyceridemia (triglyceride &gt;150 mg/dL) was found an independent factor with HRs of 1.38 (1.18–1.60) in men with hyperuricemia and 1.40 (1.02–1.92) in those without. General obesity (body mass index &gt;27 kg/m<sup>2</sup>) was independently associated with gout in older women with HRs of 1.72 (1.15–2.56) in those with hyperuricemia and 2.19 (1.47–3.26) in those without. <h3>Conclusions</h3> Gout attack in patients with sUA below the saturation level was suspected due to a synergistic effect between sUA and triglyceride, or an enhanced effect between sUA and obesity to precipitate gout. Further investigation is needed. <h3>References</h3> Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2007;57(1):109-15. Chen JH, Yeh WT, Chuang SY, Wu YY, Pan WH. Gender-specific risk factors for incident gout: a prospective cohort study. Clin Rheumatol. 2012;31:239-45. <h3>Disclosure of Interest</h3> None Declared
Abstract 4115: PI3Kα/δ inhibition has greater efficacy compared to PI3Kδ-selective inhibition in NHL with activated NFkB pathway .
Authors: Ningshu Liu, Katja Haike, Juliane Paul, Isabelle Genvresse, Antje M. Wengner, Dirk Laurent, Damian O'Connell, Dominik Mumberg, Karl Ziegelbauer
Journal: Cancer Research (2013)

Abstract Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two of the most common Non-Hodgkin Lymphoma (NHL) wordwide. Although the introduction of anti-CD20 monoclonal antibodies has improved the outcome of patients with follicular lymphoma, a curative treatment or an improved treatment strategy for relapsed FL are still to be developed. DLBCL is an incurable, aggressive subtype of NHL with a high unmet medical need for effective therapeutics. Activation of the PI3K-AKT pathway by B cell receptor signaling and its role in the pathogenesis of FL and DLBCL have been highlighted in a number of studies, however, the relative importance of PI3K isoforms and effective application of PI3K inhibitors for the treatment of FL and DLBCL have not been fully addressed. To answer this question, we selected and characterized a panel of cell lines representing major subtypes (e.g. ABC and GCB) and frequent mutations (e.g. CD79, Bcl2, MyD88, CARD11, or EZH2) in FL and DLBCL. Analyzing the expression of PI3K isoforms indicated that not only PI3Kδ, an isoform known to be enriched in lymphocytes, but also PI3Kα is highly expressed in DLBCL and a subset of FL cell lines. Sensitivity profiling of the PI3Kα/δ inhibitor BAY 80-6946 (biochemical IC50=0.5 nM and 0.7 nM against PI3Kα and PI3Kδ, respectively) and the PI3Kδ-selective inhibitor CAL-101 confirmed that inhibition PI3Kα/δ is more effective than inhibition of PI3Kδ, particularly PI3Kα/δ inhibition showed a broader anti-tumor spectrum in the cell line panel. For example, unlike CAL-101, BAY 80-6946 revealed potent anti-tumor activity in NFκB activating MyD88 or CARD11 mutated DLBCL cell lines both in vitro and in vivo. Further analysis of mutation status and pathway inhibition discovered an unknown PI3K isoform-dependent crosstalk to the NFκB pathway in DLBCL. The detailed molecular mechanism and the strategy of developing PI3Kα/δ inhibitor as a single agent and rationale-based combination in FL and DLBCL will be discussed. Taken together, these findings provide further insights into the mechanism of action of BAY 80-6946 and support ongoing Phase I studies in FL and DLBCL patients (Lotze et al., J Clin Oncol 30, 2012, suppl, abstr 3019, data to be updated in the presentation). Citation Format: Ningshu Liu, Katja Haike, Juliane Paul, Isabelle Genvresse, Antje M. Wengner, Dirk Laurent, Damian O'Connell, Dominik Mumberg, Karl Ziegelbauer. PI3Kα/δ inhibition has greater efficacy compared to PI3Kδ-selective inhibition in NHL with activated NFkB pathway . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4115. doi:10.1158/1538-7445.AM2013-4115
Case 28-2004
Authors: Jeffrey M. Lipton, Sjirk Westra, Carrie E. Haverty, Drucilla Roberts, Nancy Lee Harris
Journal: New England Journal of Medicine (2004)

Newborn identical twin boys had thrombocytopenia, leukopenia, and hepatosplenomegaly. Platelet transfusions were ineffective. Screening for infections was negative. Bone marrow aspiration showed a single hemophagocytic histiocyte. Despite medical management, the patients' condition continued to worsen. A diagnostic procedure was performed.
AB0285 First real life experience with certolizumab pegol in rheumathoid arthritis (ra) in latinamerica
Authors: R. Guzman, G. Roa, W. Rodriguez, J. Cordoba, A. Villalba
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Certolizumab pegol (CZP) is a novel TNF inhibitor, consisting of a humanized Fab’ fragment fused to a 40-kd polyethylene glycol moiety with proved efficacy and safety in multiple RA clinical trials. Most pivotal clinical trials recruited patients from USA and Europe and therefore clinical experience in some developing countries including Latin America is limited. This is the first experience with CZP in daily clinical practice in Latin-American Country. <h3>Objectives</h3> To describe the evolution and characteristics of the first Latin-American patients receiving treatment with CZP in clinical practice. <h3>Methods</h3> 95 clinical records belonging to patients with active RA were reviewed; patients were treated with CZP in an autoimmune diseases specialized center in Colombia. Dosage scheme was 400 mg in weeks 0,2,4 followed by 400mg every 4 weeks. DAS28 score was recorded before treatment initiation with follow-ups at weeks 12 and 24. Mean change in DAS28 score, EULAR response and change in disease activity according to DAS28 score were calculated. Patients who discontinued treatment before week 24 were assigned to the non-responder group. <h3>Results</h3> 95 patients were included in the analysis 76 were women, aged 21 to 80 years old (mean ±SD 54.8 ±13.2). Patients had used an average of 2.3 Synthetic Disease Modifying Anti Rheumatic Drugs, 23 patients had received one or more biological agents previously (24.47%). Mean baseline DAS28 score was 5.33±0.64; after 12 and 24 weeks the DAS28 was 2.9±0.99 and 2.77±1.24, with a mean change of -2.43±0.96 and -2.55±1.25 respectively. In 82 patients (86.32%) the decrease (&gt;/=1.2 points) was clinically significant at week 24. At the end of the follow up period 69 participants (72.63%) showed a good EULAR (1) treatment response, 15 patients (15.79%) showed a moderate response and 11 were non-responders (11.58%). The Disease Activity changes are showed in table 1. Six adverse events were reported which included a serious one (a recurrent urinary tract infection that required hospitalization and iv antibiotics). <h3>Conclusions</h3> The first Latin-American patient’s clinical evolution suggests an adequate effectiveness and safety profile for CZP. Results are consistent with findings from randomized clinical trials. <h3>References</h3> Developmentand validationof the EuropeanLeagueAgainstRheumatismresponsecriteriafor rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International LeagueAgainstRheumatismCriteria. <h3>Disclosure of Interest</h3> None Declared
Assessment of Activity in Chronic Active Liver Disease
Authors: Melvyn G. Korman, Alan F. Hofmann, W. H. J. Summerskill
Journal: New England Journal of Medicine (1974)

Serum conjugates of cholic acid were determined by radioimmunoassay and compared with conventional tests in 38 patients during the course of chronic active liver disease that responded to treatment; 16 patients subsequently relapsed when treatment was discontinued. At the time of diagnosis, values for these bile acids were always significantly elevated. At biochemical resolution of conventional liver tests, the values were still elevated in 33 of 38 patients, and this finding correlated well with evidence of continuing histologic activity. At histologic remission of disease activity, these values were less than twice the upper limit of normal in all 22 patients who subsequently remained in remission without treatment, but were significantly higher in nine of 16 who later relapsed. During relapse, serial determinations showed that elevation of serum conjugates of cholic acid preceded an increased glutamic oxalacetic transaminase. Serum concentrations of these bile acids in chronic active liver disease during and after therapy appear to provide a more sensitive indication of active hepatitis than conventional liver tests. (N Engl J Med 290:1399–1402, 1974)
NATIONAL PATTERNS IN INTENSITY OF OUTPATIENT CARE FOR APPARENT TREATMENT RESISTANT HYPERTENSION
Authors: Sreekanth Vemulapalli, Luqin Deng, Manesh Patel, Meredith Kilgore, Lesley Curtis, Marguerite Irvin, Laura P. Svetkey, Daichi Shimbo, David Calhoun, Paul Muntner
Journal: Journal of the American College of Cardiology (2015)
Accidental Finding of Bladder Cancer in 99mTc Methylene Diphosphonate Whole-Body Bone Scan
Authors: Yin Lin, Yu Y. Lu, Hsin Y. Wang, Shih C. Tsai, Wan Y. Lin
Journal: Clinical Nuclear Medicine (2013)

A 53-year-old woman with a history of nasopharyngeal carcinoma underwent (99m)Tc methylene diphosphonate (MDP) whole-body scintigraphy for tumor staging. An MDP-avid lesion located in the urinary bladder was found. Computed tomography showed a protruding mass with calcific surface in the left inferolateral wall of the urinary bladder. A biopsy was conducted and the pathological report confirmed the diagnosis of transitional cell carcinoma. The patient received transurethral resection and Bacillus Calmette-Guérin intravesical therapy. Four months later, she underwent an (18)F-FDG PET/CT scan. Unfortunately, tumor recurrence in the bladder cancer was diagnosed by the (18)F-FDG PET/CT scan.
AB0900 The prevalence of daytime sleepiness in axial spondyloartritis
Authors: O. Karadag, N. Yılmaz, L. Kılıc, A. Akdogan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Sleep-disordered breathing causes fatigue and daytime sleepiness. Since cervical and thoracic involvement, it is suspected as sleep disordered breathing is frequent in Ankylosing spondylitis (AS) and axial spondyloartritis (SpA). But there are limited studies on this subject. This study is aimed to investigate daytime sleepiness in SpA patients. <h3>Methods</h3> Totally 143 SpA patients (F/M: 46/97) fulfilling ASAS-EULAR 2009 criteria and 135 healthy subjects (F/M: 45/90) were included into the study. Daytime sleepiness investigated with Epworth test. In addition to routine laboratory tests, metrological measures, BASDAI and BASFI were done. <h3>Results</h3> There was no difference between patients and controls regarding ages (respectively 36.2±11.5 vs. 34.8±9.2 years, p=0.29). Median disease duration was 5 (IQR: 3-10) years. Epworth scores was not statistically different between groups [respectively 3 (IQR: 1-7) vs. 3 (IQR: 2-5), p=0.86]. Although number of patients needed for further polysomnographic examination was higher in AS patients, it was not statistically different [12 (8.4%) vs. 6 (6%), p=0.41]. Epworth scores was positively correlated with BASDAI and BASFI (respectively r<sup>2</sup>=0.246, p=0.003 and r<sup>2=</sup>0.225, p=0.007). <h3>Conclusions</h3> Day-time sleepiness was not different between SpA patients and controls. But patients with higher Epworth scores had high disease activity. Daytime sleepiness could be kept in mind especially in SpA patients with active disease. <h3>Disclosure of Interest</h3> None Declared