tbuckley/cabot-search huggingface dataset:
Abstract 1701: Clinical significance of serum and tissue Dickkopf-1 in patients with gastric cancer
Authors: Kyoung Un Park, Do Joong Park, Hyung Ho Kim, Woo Ho Kim, Hye Seung Lee
Journal: Cancer Research (2012)

Abstract Background: Dickkopf-1 (DKK-1) is a secreted protein known as a negative regulator of the Wnt signaling pathway and involved in embryonic development and tumorigenesis. Clinical significance of serum DKK-1 and tissue DKK-1 expression in gastric cancer has not been clarified. Methods: Serum concentrations of DKK-1 were assessed by enzyme-linked immunosorbent assay in 153 gastric cancer patients and 33 healthy controls. We also obtained serum CEA (ng/mL) and CA19-9 (U/mL) values by chemiluminescence immunoassay. For tissue DKK-1, we performed immunohistochemical staining for DKK-1 in 144 cancer specimens of 153 patients and in additional 265 consecutive gastric cancer specimens. Results: Serum DKK-1 concentrations were significantly higher in gastric cancer patients (56.27 pg/mL) than in healthy controls (30.50 pg/mL, p=0.018). With 36.3150 pg/mL of cut-off value, sensitivity and specificity for gastric cancer diagnosis were 80.4% and 78.8%, respectively. Gastric cancer patients with a serum DKK-1 of 60.0 pg/mL or higher had a significantly diminished survival compared with patients whose serum DKK-1 were lower (p=0.033). By immunohistochemistry, DKK-1 overexpression in cancer specimens was significantly correlated with increased serum DKK-1 concentrations (correlation coefficient, 0.395; p&amp;lt;0.001). The cancer patients with DKK-1 overexpression had a significantly worse prognosis than the patients without DKK-1 expression in this cohort (p=0.004) and additional consecutive cases (p=0.030). By multivariate Cox regression model, DKK-1 expression status predicted patient prognosis independently of pTNM stage and histologic differentiation in consecutive cases (p=0.018). Conclusion: Increased serum DKK-1 concentrations and overexpression of DKK-1 in gastric cancer tissue may contribute to diagnosing gastric cancer and predicting cancer patient outcome. 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 1701. doi:1538-7445.AM2012-1701
The Appropriate Degree of Diagnostic Certainty
Authors: George E. Thibault
Journal: New England Journal of Medicine (1994)

A previously healthy 47-year-old man presented to the emergency room after the sudden onset of cough, shortness of breath, and tightness in his chest while climbing stairs.The first thing that occurs to me is that this man may be having acute myocardial ischemia. The chest tightness is especially suggestive of an ischemic episode. Shortness of breath and cough are not commonly major manifestations of an acute myocardial infarction, but they can be. Another diagnostic possibility is the sudden onset of a cardiac arrhythmia. Atrial fibrillation with a rapid ventricular rate or ventricular tachycardia could lead to acute . . .
LEPTIN-REGULATED MOLECULAR NETWORK IS ACTIVATED IN THE LUNG UNDER HEART FAILURE: THE CARDIO-ADIPO-PULMONARY AXIS
Authors: Kyung-Duk Min, Masanori Asakura, Kazuhiro Shindo, Hiroki Fukuda, Miki Imazu, Shin Ito, Masafumi Kitakaze
Journal: Journal of the American College of Cardiology (2016)
Phosphatidylinositol 3-kinase delta pathway: a novel therapeutic target for Sjögren’s syndrome
Authors: Saba Nayar, Joana Campos, Charlotte G Smith, Valentina Iannizzotto, David H Gardner, Serena Colafrancesco, Elena Pipi, Florian Kollert, Kelly J Hunter, Charlotte Brewer, Christopher Dominic Buckley, Simon J Bowman, Roberta Priori, Guido Valesini, Maria Juarez, William A Fahy, Benjamin A Fisher, Andrew Payne, Rodger A Allen, Francesca Barone
Journal: Annals of the Rheumatic Diseases (2018)

Background The phosphatidylinositol 3-kinase delta isoform (PI3Kδ) belongs to an intracellular lipid kinase family that regulate lymphocyte metabolism, survival, proliferation, apoptosis and migration and has been successfully targeted in B-cell malignancies. Primary Sjögren’s syndrome (pSS) is a chronic immune-mediated inflammatory disease characterised by exocrine gland lymphocytic infiltration and B-cell hyperactivation which results in systemic manifestations, autoantibody production and loss of glandular function. Given the central role of B cells in pSS pathogenesis, we investigated PI3Kδ pathway activation in pSS and the functional consequences of blocking PI3Kδ in a murine model of focal sialoadenitis that mimics some features of pSS. Methods and results Target validation assays showed significant expression of phosphorylated ribosomal protein S6 (pS6), a downstream mediator of the phosphatidylinositol 3-kinase delta (PI3Kδ) pathway, within pSS salivary glands. pS6 distribution was found to co-localise with T/B cell markers within pSS aggregates and the CD138+ plasma cells infiltrating the glands. In vivo blockade of PI3Kδ activity with seletalisib, a PI3Kδ-selective inhibitor, in a murine model of focal sialoadenitis decreased accumulation of lymphocytes and plasma cells within the glands of treated mice in the prophylactic and therapeutic regimes. Additionally, production of lymphoid chemokines and cytokines associated with ectopic lymphoneogenesis and, remarkably, saliva flow and autoantibody production, were significantly affected by treatment with seletalisib. Conclusion These data demonstrate activation of PI3Kδ pathway within the glands of patients with pSS and its contribution to disease pathogenesis in a model of disease, supporting the exploration of the therapeutic potential of PI3Kδ pathway inhibition in this condition.
Abstract C71: Inhibition of polyisoprenylated methylated protein methylesterase by anticancer drugs
Authors: Suzanne Schodlbauer, Randolph Duverna, Nazarius S. Lamango
Journal: Cancer Research (2009)

Abstract Polyisoprenylated methylated protein methylesterase (PMPMEase) is a little explored enzyme of the polyisoprenylation (isoprenylation) pathway (PP). Polyisoprenylation is a post-translational modification that is important for the function of such proteins as the heterotrimeric G proteins, Ras and Rab families of proteins. PMPMEase hydrolyzes a methyl ester formed by the S-adenosyl-L-methionine (SAM)-dependent enzyme, polyisoprenylated protein methyltransferase (PPMTase). PMPMEase's regulatory role is suggested by the fact it hydrolyzes the ester products of PPMTase. PMPMEase is a serine hydrolase, a class of hydrolytic enzymes that attack electron-deficient carbons of amide and ester bonds with the alkoxide ion of their catalytic serines. Because alkylating agents function through an aziridinium ion with an electron-deficient carbon atom, it is hypothesized that they may inhibit PMPMEase through active site adduct formation. Alkylating agents have been suspected of having other mechanisms of action against cells besides impeding replication via the cross-linking of DNA strands. The crystal structure of the human form of PMPMEase, human carboxylesterase 1, with tamoxifen bound to its active site has been solved, also suggesting its possible inhibition. Polyisoprenylated proteins are involved in processes that regulate cell viability. Mutations and overexpression of such proteins are implicated in about 30% of cancers. This study considers the possibility that the agents also reduce malignant cell growth by disrupting growth signaling pathways. Cyclophosphamide is an organophosphorous alkylating agent. Organophosphorous compounds irreversibly inhibit PMPMEase and other serine esterases. Busulfan, cyclophosphamide, mechlorethamine and tamoxifen were tested for porcine liver PMPMEase inhibition. At 1 mM concentrations, cyclophosphamide, mechlorethamine and tamoxifen inhibited 62, 35 and 55% of the PMPMEase activity. The results show that the anticancer drugs may owe part of their pharmacological activity to their modulation of oncogenic polyisoprenylated protein function through their inhibition of PMPMEase. Citation Information: Cancer Res 2009;69(23 Suppl):C71.
Abstract P5-02-01: FGFR Signalling Drives the Growth of Triple Negative and Basal-Like Breast Cancer Cell Lines Both In Vitro and In Vivo
Authors: N Turner, R Sharpe, D Johnson, A Pearson, A. Ashworth
Journal: Cancer Research (2010)

Abstract Background: Substantial evidence now links aberrant signalling by the fibroblast growth factor receptors (FGFRs) to the development of multiple different cancer types. The oncogenic drivers of triple negative and basal-like breast cancers are largely unknown and we examined for a potential role of FGFR signalling in the oncogenesis of triple negative breast cancer. Methods: We examined the sensitivity of a panel of 40 breast cancer cell lines to the selective fibroblast growth factor receptor (FGFR) inhibitor PD173074. Results: Triple negative (TN) breast cancer cell lines were more sensitive to PD173074 than comparator cell lines (p=0.0028), with half (8/16) of TN cell lines demonstrating significantly reduced growth. The majority of TN cell lines demonstrated only modest sensitivity to FGFR inhibition in two-dimensional growth, but were highly sensitive in anchorage independent conditions. PD173074 inhibited down stream MAPK signalling and induced cell cycle arrest and apoptosis. Basal-like breast cancer cell lines were found to express autocrine FGF2 ligand, and RNA interference targeting of FGF2 significantly reduced anchorage independent growth. Finally, PD173074 significantly reduced the growth of basal-like breast cancer cell line xenografts. Conclusion: Basal-like breast cancer cell lines express autocrine FGF2 and demonstrate substantial sensitivity to FGFR inhibitors, identifying a potential novel therapeutic approach for these cancers. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-02-01.
Imaging Calcific Concretions of Pulmonary Alveolar Microlithiasis With PET
Authors: Sandip Basu, Mehul Shah, J M Joshi, Sangita Lad
Journal: Clinical Nuclear Medicine (2012)

A case of 18F-FDG PET in pulmonary alveolar microlithiasis with bilateral reticulonodular opacities in the middle and lower zones on routine chest roentgenogram and calcification in the peribronchovascular interstitium, peribronchovascular and subpleural intralobular septal regions, and visceral pleura on high-resolution chest CT is presented. 18F-fluoride PET demonstrated intense tracer uptake in the lower zone of both lungs corresponding to CT findings. Minimal FDG activity in areas of dense calcification suggests minimal or no inflammation. This could account for the absence of symptoms in most cases despite remarkable imaging findings.
Abstract 4728: Fatostatin, a novel SREBP inhibitor, suppresses cell growth and induces apoptosis in prostate cancer
Authors: Xiangyan Li, Yi-Ting Chen, Leland W.K. Chung, Wen-Chin Huang
Journal: Cancer Research (2012)

Abstract Sterol regulatory element-binding proteins (SREBPs), SREBP-1 and SREBP-2, are transcription factors mainly controlling lipogenesis and cholesterogenesis via the regulation of genes related to fatty acid and cholesterol biosynthesis. We previously showed that SREBP-1 was highly elevated in clinical prostate cancer specimens compared with non-tumor prostate tissues. Also, SREBP-1 promoted cell viability and progression through alterations of the metabolic and signaling networks involving lipogenesis, androgen receptor (AR) and oxidative stress in prostate cancer cells. In the present study, we evaluated the therapeutic benefit of targeting the aberrant SREBP signaling in prostate cancer by using a novel SREBP inhibitor, fatostatin. Fatostatin significantly inhibited cell proliferation and suppressed anchorage-independent colony formation in soft agar in LNCaP and C4-2B prostate cancer cells. Fatostatin also reduced the abilities of in vitro migration and invasion in both cells. The results of flow cytometric analyses with annexin V/propidium iodide staining showed that fatostatin caused G2/M arrest and induced cell death. Additionally, apoptosis was observed by inducing caspase-3 and poly (ADP-ribose) polymerase cleavages and increasing caspase activities in fatostatin-treated prostate cancer cells. In the animal study, fatostatin significantly inhibited C4-2B xenograft tumor growth and markedly decreased serum PSA level compared to control group in immune-compromised mice. The results of fatostatin action in prostate cancer cells in vitro and in vivo are due to specific interruption of the proteolytic process of mature SREBP-1, -2 and their regulated gene expressions including HMG-CoA reductase, fatty acid synthase and further inhibition of lipid biosynthesis and AR signaling network. In summary, our study demonstrates for the first time that fatostatin will be developed as a novel anti-prostate cancer drug and provides new insights into cancer therapy by targeting SREBP. 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 4728. doi:1538-7445.AM2012-4728
Hepatitis C in the United States
Authors: Scott D. Holmberg, Philip R. Spradling, Anne C. Moorman, Maxine M. Denniston
Journal: New England Journal of Medicine (2013)

Recent analyses suggest that of the estimated 3.2 million people infected with hepatitis C virus, only about half have been tested and know their status, about a third have been referred for HCV care, and only 5 to 6% have been successfully treated.
Laparoscopic hysterectomy is an alternative
Authors: P. Kajanoja
Journal: BMJ (1995)

EDITOR,—We question S B Pinion and colleagues' recommendation for hysteroscopic endometrial ablation in dysfunctional uterine bleeding and believe that laparoscopic hysterectomy is an alternative with a high likelihood of success.1 In the analysis of their results the authors disregard the fact that 17 of …
Thrombectomy for Deep Thrombophlebitis of the Leg
Authors: J. Alex Haller
Journal: New England Journal of Medicine (1962)

Dissatisfaction with the high incidence of postphlebitic limb after massive deep thrombophlebitis has prompted the use of thrombectomy in an attempt to diminish this discouraging complication. In the belief that thrombectomy will not only remove a fresh clot that might become fragmented but also restore normal flow through undamaged valves 33 patients were operated upon in the acute phase of the disease. It is the purpose of this paper to report the results of this experience in the University of Louisville Hospitals.The conservative treatment of deep thrombophlebitis has been directed toward the prevention of two serious complications: fragmentation of . . .
SAT0589-HPR Body Mass Index and Its Relationship to Disease Activity in Early Rheumatoid Arthritis
Authors: C. Creaser, T. Harrison, L. Martin, C. Barnabe
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Obesity rates in Canada have increased 3% (to 25%) over the past 8 years. Obese patients develop more severe forms of many diseases and have more comorbidities develop over time. We are interested in determining if a relationship exists between the body mass index (BMI) of patients with early rheumatoid arthritis (ERA) in the first year of disease and their disease activity. This would support the need for lifestyle interventions in ERA patients to improve disease outcomes. <h3>Objectives</h3> 1) To determine whether BMI is related to disease activity in RA in the first year of disease; 2) To determine if overweight or obese (BMI ≥25) have worse disease activity, compared to normal or underweight status. <h3>Methods</h3> A multidisciplinary Early Inflammatory Arthritis Clinic is held at our tertiary care centre in Canada, with a catchment area of 1.5 million people. Criteria for the clinic include a referral for symmetric polyarthritis. A standardized data collection protocol captures clinical data including the DAS28, patient-reported outcomes, quality of life and function (HAQ). Patients are seen every 3 months for the first year, and are treated to a low disease activity target. Patients newly diagnosed with RA from 01/2009-12/2012 and with height and weight measurements at all visits (n=134) were included in this analysis. Patients were categorized as being normal weight (BMI 18.50-24.99), overweight (BMI 25.0-29.99) or obese (BMI ≥30). Ranked correlation tests were used to determine the relationship between BMI and HAQ, and BMI and DAS28, at each of 0, 6 and 12 months. Stratified analysis of HAQ and DAS28 scores by BMI category was performed. <h3>Results</h3> Our cohort included 93 females and 41 males with a mean age of 52 years. At baseline the mean tender joint count (28 joints) was 11 (SD ±6.56) and mean swollen joint count (28 joints) was 8 (SD ±5.91) with a HAQ of 1.18 (SD ±0.874) and DAS28 of 5.17 (SD ±1.31). Nearly 2/39s of the cohort was overweight or obese (n=89, 63%), with a baseline mean BMI of 27.7±5.47 and was 27.8±5.96 at 12 months. There was no relationship between BMI and HAQ at baseline (p=0.986), 6m (p=0.891) or 12 m (p=0.438). There was also no relationship found between BMI and DAS28 at each visit (p=0.892, 0.447, 0.381) respectively. Stratified analysis also did not find any differences in disease activity between BMI categories. <h3>Conclusions</h3> In our ERA cohort we did not find a relationship between BMI and disease activity at diagnosis or during the first year of treatment. A relationship may be seen with longer observation. Lifestyle modifications to reduce body weight are still important for minimizing the cardiovascular risks associated with obesity and cardiovascular disease. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4747
588 THE IL-6/GP130 SIGNALING PATHWAY IN MYELOID CELLS MODULATES THE INFLAMMATORY RESPONSE DURING SEPSIS
Authors: A. Mohs, S. Dutton Sackett, L.E. Sander, F.J. Cubero, S. Strauch, D. Kroy, K. Streetz, C. Trautwein
Journal: Journal of Hepatology (2013)
Abstract 2230: Quantitative expression of the hedgehog (Hh) signaling pathway in gastric carcinoma: A novel protocol to process RNA from paraffin-embedded tissue
Authors: Abebe Akalu, Leonard Liebes, Rulang Xu, Robert Schneider, Naoko Takebe,, Deirdre Cohen
Journal: Cancer Research (2011)

Abstract Background: The Hh pathway is an evolutionally highly conserved signaling cascade important in gastroesophageal embryonic pattern formation and stem cell response to tissue damage. Its aberrant activation has also been implicated in gastric cancer formation and progression. Multiple therapeutics targeting the Hh pathway have been developed and in order to test their activity and pharmacodynamic responses, routine and consistent gene expression measurement from clinical samples must be available. Aims and Methods: The aim of this work was to measure levels of Hh pathway expression in both gastric tumors and normal gastric tissue, using a novel protocol of processing RNA from formalin fixed, paraffin-embedded tissue (FFPET). Total RNA was extracted from FFPET using a combination of Qiagen and RecoverAllTM kits according to the manufacturer's protocol(s). cDNA was synthesized using the iScriptTMcDNA Synthesis Kit and then a minimum of 20 ng RNA was pre-amplified using an Applied Biosystems pre-amplification cDNA kit. The primers for the Shh and Gli1genes were then added to the pre-amplification reaction and TaqManPreAmp master mix, amplified for 14 cycles on a thermal cycler and then real time PCR carried out for 40 cycles in duplicate. The relative quantification of the Shh and Gli1 genes were compared to the reference gene succinate dehydrogenase complex subunit A (SDHA) where the ratio for the change in expression for the selected gene = 2−ΔΔCT. Results: The levels of gene expression in gastric adenocarcinomas for Shh and Gli1 were respectively 3.89 ± 0.49 (mean ± SEM, N = 11) and 4.57 ± 1.46. For 8 non-tumor gastric specimens, the CT values for Shh ranged from 30.24 to 35.81 and for Gli1 from 31.21 to 34.81 while for SDHA the mean CT was 18.4 ± 1.87. Based on these CT values, no expression of Shh and Gli1 was present in these non-tumor gastric tissues. Conclusion: Hh pathway signaling can be quantitatively measured using as little as 20ng of RNA obtained from FFPET, making this methodology valuable in the clinic where tissue acquisition is often limited, as for gastric tumors. Using our methodology we found that there is increased Hh pathway expression in gastric carcinomas as compared to normal tissue, a finding consistent with previous reports in the literature. Supported by NO1-CM-07103-74 RECOVERY – ACTNOW Clinical Trial 8376 and NCI 2P30 CA16087-23, Tissue Acquisition and Banking Core. 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 2230. doi:10.1158/1538-7445.AM2011-2230
Hyperendemic<i>Streptococcus pyogenes</i>Infection despite Prophylaxis with Penicillin G Benzathine
Authors: Gregory C. Gray, Joel Escamilla, Kenneth C. Hyams, Jeffery P. Struewing, Edward L. Kaplan, Alan K. Tupponce
Journal: New England Journal of Medicine (1991)

In closely confined populations, in which epidemics of Streptococcus pyogenes infection are common, penicillin G benzathine has long been used prophylactically to reduce morbidity from this pathogen. We report on our investigations of the effectiveness of penicillin G benzathine prophylaxis at a military recruit camp.
The Obesity Epidemic — Understanding the Disease and the Treatment
Authors: Caroline M. Apovian
Journal: New England Journal of Medicine (2016)

The prevalence of severe obesity in the United States has increased dramatically, not only among adults but also among children. The increase in childhood severe obesity, defined as 120% of the age-specific 95th percentile of body-mass index (BMI), has been alarming; the prevalence has risen from 4% during 1999–2004 to 6% during 2011–2012.1,2 Although the use of healthy lifestyle approaches to treat younger children with obesity can successfully reduce BMI, the implementation of these approaches among adolescents and adults is much less effective.3 Unfortunately, approximately 90% of children with severe obesity will become obese adults with a BMI (the . . .