tbuckley/cabot-search huggingface dataset:
Abstract 5397: MYC-driven glutamine metabolism promotes antiestrogen resistance in breast cancer.
Authors: Ayesha N. Shajahan, Katherine L. Cook, Jessica L. Schwartz-Roberts, Ahreej E. Eltayeb, Diane M. Demas, Anni Warri, Leena Hilakivi-Clarke, Steven Metallo, Robert Clarke
Journal: Cancer Research (2013)

Abstract About 70% of newly diagnosed cases of invasive breast cancer in the U.S. will be estrogen receptor alpha positive (ER+). Endocrine therapy is the least toxic and most effective means to manage the hormone-dependent breast cancer, administered as an antiestrogen, e.g., Tamoxifen (TAM) or Faslodex (FAS; Fulvestrant; ICI 182,780) or an aromatase inhibitor (AI), e.g., Letrozole (LET). However, advanced ER+ breast cancer that has become resistant to endocrine therapy remains a significant clinical problem. Here we show that in breast cancer cells and rat tumors with acquired antiestrogen resistance, MYC, a oncogenic transcription factor, is overexpressed. Inhibition of MYC with small molecule inhibitor or siRNA resensitizes resistant cells to antiestorgens by inducing apoptosis. MYC inhibition in resistant cells also inhibited glutamine uptake and decreased levels of ASCT2/SLC1A5, a glutamine transporter. Resistant cells showed significant increase in cell proliferation in response to glutamine than sensitive cells. Moreover, resistant cells showed increased sensitivity to an inhibitor of glutaminase, GLS, an enzyme that hydrolysis of glutamine to glutamate. Thus, MYC promotes increased dependence on glutamine in antiestrogen resistant cells, and targeting glutamine metabolism could help circumvent antiestrogen resistance. Overreaching goal of this study is to and to identify effective therapies to treat endocrine resistant breast cancer. Citation Format: Ayesha N. Shajahan, Katherine L. Cook, Jessica L. Schwartz-Roberts, Ahreej E. Eltayeb, Diane M. Demas, Anni Warri, Leena Hilakivi-Clarke, Steven Metallo, Robert Clarke. MYC-driven glutamine metabolism promotes antiestrogen resistance in breast cancer. [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 5397. doi:10.1158/1538-7445.AM2013-5397
DUAL LIPID-LOWERING WITH EZETIMIBE/STATIN AS A PROMISING ANTI-ATHEROSCLEROTIC STRATEGY
Authors: Kenichi Tsujita, Kenshi Yamanaga, Naohiro Komura, Hideki Shimomura, Masaharu Ishihara, Koichi Kaikita, Seiji Hokimoto, Hisao Ogawa
Journal: Journal of the American College of Cardiology (2016)
Abstract 4097: Sorafenib sensitizes solid tumors to TRAIL or TRAIL receptor agonist antibodies
Authors: Junaid Abdulghani, Joshua E. Allen, David T. Dicker, Charles D. Smith, Robin C. Humphreys, Wafik S. El-Deiry
Journal: Cancer Research (2011)

Abstract Solid carcinomas display considerable resistance to chemotherapeutic drugs and tumor cell apoptosis-inducing agents such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death. A phase III clinical trial with the multi-kinase inhibitor sorafenib (Nexavar) in Hepatoceullular carcinoma (HCC) was completed leading to the first FDA-approved drug therapy for liver cancer in 2007. Phase I/II trials have been completed with a fully-human anti-TRAIL death receptor 1 (DR4) agonist antibody (mapatumumab) in non small-cell lung carcinoma and non-Hodgkin's lymphoma and phase I trials with an anti-TRAIL-R2 (DR5) monoclonal antibody (lexatumumab) in advanced cancers. We hypothesized that sorafenib and TRAIL or sorafenib and TRAIL receptor agonist antibodies (mapatumumab or lexatumumab) may overcome resistance to apoptosis in a panel of TRAIL-resistant solid carcinoma cell lines. We observed that sorafenib induces apoptosis of HepG2 and Hep3B cells in a dose-dependent manner. In addition, sorafenib is a potent sensitizer of HCC cell lines to TRAIL. We have also found that single agent lexatumumab causes cell death in HepG2, Hep3B and SNU449 cells whereas mapatumumab does not. The combination of sorafenib with TRAIL or either TRAIL receptor agonist antibody enhances apoptosis in HCC cell lines. We found that in other solid tumor types including prostate, breast and colon cancer there is a synergistic interaction between sorafenib and TRAIL or TRAIL receptor agonist antibodies. Furthermore, these combinations prevent the growth of tumors in vivo. Sorafenib downregulates the expression of Mcl-1 protein, a member of the Bcl-2 family that has been previously found to be overexpressed in about 50% of HCC patient samples. Sorafenib was also found to inhibit Stat3 activation by Jak2 kinases. These findings suggest a molecular rationale for combining these agents in therapy of solid tumors in clinical trials. 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 4097. doi:10.1158/1538-7445.AM2011-4097
PREVALENCE AND MANAGEMENT OF ASPIRIN ALLERGY IN AN AMBULATORY CARDIOLOGY PRACTICE AND IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION
Authors: Gabriela Orgeron, Marc Mugmon, Candice Crichlow, Laura S. Miller, Robabeh Mohammadzadeh, John Wang, Sudhir Sekhsaria
Journal: Journal of the American College of Cardiology (2016)
Drug Promotion for an Unlabeled Indication -- The Case of Topical Tretinoin
Authors: Robert S. Stern
Journal: New England Journal of Medicine (1994)

In 1972, topical tretinoin (Retin-A, Ortho Pharmaceutical) was approved for the treatment of acne. Today this remains the only medical indication for its use approved by the Food and Drug Administration (FDA). In 1988 a highly publicized study reported that topical tretinoin improves the appearance of “photoaged” skin1. Since then, the manufacturer of topical tretinoin has conducted an active, controversial multimedia effort to ensure that the general public and the medical profession are aware of the “unlabeled” use of tretinoin to treat benign cutaneous changes, such as wrinkles and brown spots, that may be annoying to patients because of . . .
THU0289 Nutritional Status and Diet in Systemic Lupus Erythematosus
Authors: A. Abou-Raya, S. Abou-Raya, M. Helmii
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Nutritional status and intake of selected food may influence systemic lupus erythematosus (SLE) course and activity. SLE patients may have nutritional changes triggered by disease or treatment and this may influence the course of the disease. <h3>Objectives</h3> To assess the nutritional status and diet of SLE patients and the association with disease activity. <h3>Methods</h3> 121 consecutive SLE patients (98 females, 23 males), mean age 42.5 years and mean disease duration 7.5 years diagnosed according to the American College of Rheumatology (ACR) criteria for SLE were assessed. Nutritional status was determined by body mass index (BMI) and subjective global assessment. Dietary intake at baseline was assessed by a semiquantitative food frequency questionnaire (FFQ). All patients were interrogated about medication usage and sociodemographic factors. Disease activity was assessed using the SLE disease activity index (SLE-DAI). <h3>Results</h3> BMI assessment revealed that 43% of SLE patients were overweight, 28.9% were obese, 10% were malnourished and 18.1% were of normal weight. The FFQ revealed a decreased consumption of fresh fruit, vegetables, milk and other dairy products and an increased intake of fats and oils. Low intake of iron, calcium and zinc was found in 30%, 57% and 87% respectively. Increased BMI correlated with lower socioeconomic status, lower level of education, increased disease activity (SLE-DAI), higher dosages of corticosteroid intake and decreased physical activity. <h3>Conclusions</h3> Abnormalities in nutritional status is common among SLE patients with excessive intake of lipids and low intake of vitamins and trace elements. As nutritional status may influence disease activity in SLE patients, proper attention should be paid to the diet and nutritional assessment should be included in the comprehensive management of these patients. <h3>Disclosure of Interest</h3> None Declared
SP0109 Twisting pathogenic T cell memory
Authors: A. Radbruch
Journal: Annals of the Rheumatic Diseases (2013)

Proinflammatory T helper (Th) lymphocytes initiate and presumably also drive chronic inflammation. It is unclear, however, how they escape physiological and therapeutic immunregulation, persist and adapt to the inflammatory environment. To understand the molecular mechanisms underlying the transition of an acute self-limiting T cell response to a chronic pathogenic effector/memory response, the genes regulating these processes have to be identified. To this end, and with the rationale that Th cells driving chronic inflammation have a history of repeated encounter with (self)antigen, the global gene expression signature of Th cells of the Th1, Th2 and Th17 lineages was compared, activated just once or repeatedly reactivated. The genes <i>Twist1</i> and <i>Hopx</i> are upregulated selectively in proinflammatory Th1 cells upon repeated restimulation. <i>Twist1</i> encodes an E-box binding transcription factor and is highly expressed in Th cells of inflamed tissue of patients with rheumatic or gastrointestinal inflammation. Knock-down of <i>Twist1</i> in Th1 cells of murine models of arthritis exacerbates chronic inflammation, but also regulates genes controlling survival and apoptosis. <i>Hopx</i> promotes the survival of Th1 cells. ShRNA-mediated downregulation of <i>Hopx</i> in Th1 cells reduces their ability to persist <i>in vivo,</i> following adoptive transfer. Th1 cells lacking <i>Hopx</i> do not induce inflammation in experimental colitis or arthritis. Thus, <i>Twist1</i> and <i>Hopx</i> qualify as markers of Th1 cells in chronic inflammation, reflect molecular adaptation to chronicity, regulate function and persistence of Th1 cells, and may allow to target therapies selectively to pathogenic versus protective Th cells. <h3>Disclosure of Interest</h3> None Declared
AB0133 New evidence linking the in vivo implication of 4-hydroxynonenal in osteoarthritis pathogenesis
Authors: Q. Shi, H. Fahmi, J.C. Fernandes, M. Benderdour
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> 4-Hydroxynonenal (HNE) is one of the most abundant and reactive aldehydes of lipid peroxidation products and exerts various effects on intracellular and extracellular signalling cascades [1]. We have previously shown that HNE at low concentrations could be considered as an important mediator of catabolic and inflammatory processes in osteoarthritis (OA) [2,3]. <h3>Objectives</h3> To demonstrate the <i>in vivo</i> involvement of HNE in OA pathogenesis using experimental dog model of this disease. <h3>Methods</h3> <i>Protocol 1</i> - OA was induced by anterior cruciate ligament transection of the right knee in crossbred dogs. There were two experimental groups (n=4 dogs/group): placebo and carnosine (an HNE-trapping drug, 50 mg/kg/day) given orally for 8 weeks. <i>Protocol 2</i> - Vehicle or pathophysiological dose of HNE (100 μM) were injected weekly into the right knee joint of crossbred dogs (n=4 dogs/group) for the entire duration of the study (16 weeks). We conducted macroscopic and histomorphological analyses of cartilage of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage explants for the following antigens: HNE, agrecannase-2, and matrix metalloproteinase -13 (MMP-13). <h3>Results</h3> In the protocol 1, treatment with carnosine reduced the severity and histopathological score of OA cartilage lesions as well as the levels of HNE, MMP-13 and agrecannase-2 in cartilage explants. In the protocol 2, the intraarticular injection of HNE induced cartilage lesions on the tibial plateaus and femoral condyles with prominent osteophytes on lateral condyles. The expression of both MMP-13 and agrecannase-2 increased in cartilage explants from HNE-treated dogs. <h3>Conclusions</h3> This is the first in vivo study to demonstrate the pathophysiological role of HNE in OA. The fact that carnosine abolishes HNE production and a number of factors known to be involved in OA pathogenesis renders it a clinically valuable agent in the prevention of this disease. <h3>References</h3> Poli et al. Med Res Rev. 2008; 28:569-631. Morquette et al. Arthritis &amp; Rheum 2006; 54(1):271-81. Vaillancourt et al. J Cell Biochem. 2007; 100(5):1217-31. <h3>Disclosure of Interest</h3> None Declared
Long-term remission of an EBV-positive B cell lymphoproliferative disorder associated with rheumatoid arthritis under methotrexate with anti-CD20 monoclonal antibody (Rituximab) monotherapy
Authors: C Kelaïdi, M Tulliez, C Lecoq-Lafon, X-V Pham, A Kahan, F Dreyfus, D Bouscary
Journal: Leukemia (2002)
SP0086 Does Self Management save Costs in Health Care for People with RMDS?
Authors: J. Dekker
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> The increasing prevalence of rheumatic and musculoskeletal diseases (RMDs) and other chronic diseases constitute a major challenge to sustainable health care. Self management is frequently seen as a cost-effective substitute for health care. Self management is expected to be effective, and to save costs. Empirical studies provide a sobering perspective. Reviews and meta-analyses often show small to moderate effects of self management on health and quality of life, some reduction of health care use, while few studies show a reduction of health care costs. Chronic illness is associated with a range of self management tasks [1]: – Monitoring health status and making associated care decisions – Interacting with health care providers – Engaging in activities to promote physical and psychological health – Managing the impact of the illness on physical, psychological and social functioning. It will be argued to some self management activities could substitute health care, leading to cost savings (e.g. monitoring health status). Other self management activities are of major importance, but are less likely to lead to substitution of care and cost savings (e.g. managing the impact of the illness on psychological and social functioning). People with RMDs differ in their self management needs and preferences. Tailoring of self management to these needs and preferences is of utmost importance [2]. Comorbidity is a major issue to consider in this respect. For example, comorbid cardiovascular disease is a major barrier to exercise, while exercise has been shown to be effective in many RMDs. Exercise needs to be adapted to comorbid disease [3,4]. More generally, needs and preferences need to be taken into account in developing effective approaches towards self management. Self management is crucial for health and wellbeing of people with RMDs. Self management activities need to be tailored to personal needs and preferences of people with RMDs. This approach is expected to improve the effectiveness of self management, while the impact on saving costs remains to be seen. <h3>References</h3> Bayliss EA, Steiner JF, Fernald DH, Crane LA, Main DS. Descriptions of barriers to self-care by persons with comorbid chronic diseases. Ann Fam Med 2003 May;1(1):15-21. Trappenburg J, Jonkman N, Jaarsma T, van Os-Medendorp H, Kort H, de WN et al. Self-management: one size does not fit all. Patient Educ Couns 2013 July;92(1):134-7. de Rooij M, van der Leeden M., Avezaat E, Hakkinen A, Klaver R, Maas T et al. Development of comorbidity-adapted exercise protocols for patients with knee osteoarthritis. Clinical Interventions in Aging (in press) 2014. de Rooij M, Steultjens M., Avezaat E, Hakkinen A, Klaver R, van der Leeden M. et al. Restrictions and contraindications for exercise therapy in patients with hip and knee osteoarthritis and comorbidity. Physical Therapy Reviews 2013;18:101-11. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6120
PWE-310 Extramural vascular invasion is a more powerful predictor of prognosis than tumour regression grade in rectal cancer
Authors: E Palkhi, D Harji, S Pathak, D Burke, P Sagar
Journal: Gut (2015)

<h3>Introduction</h3> There are a number of pathological predictors of adverse outcome in rectal cancer which includes positive resection margin, extramural vascular invasion (EMVI) and tumour regression grade (TMG). The aim of this study is to elicit the prognostic significance of EMVI and TMG for primary rectal cancer. <h3>Method</h3> All patients undergoing surgery for primary rectal cancer were identified from a prospectively maintained database between 2004 and 2012. Tumours were graded using a quantitative 5-grade Mandard TRG classification and the presence of EMVI was histologically studied. <h3>Results</h3> A total of 342 patients were identified, of which 99 patients had a complete dataset for EMVI and TRG. The 5-year overall survival (OS) was 38% with a disease-free survival (DFS) of 72%. Poor TRG grades and EMVI positivity were found to prognostically significant for OS (p values 0.01 and 0.05, respectively) and DFS (p values 0.02 and 0.001, respectively) at univariate analysis. However, EMVI positivity remained statistically significant for OS (p = 0.05) and DFS (p = 0.01) at multivariate analysis over TRG (OS, p = 0.46 and DFS, p = 0.17). <h3>Conclusion</h3> The presence of EMVI is a more powerful prognostic factor than TRG in rectal cancer and should be taken into account during the risk stratification process when considering adjuvant chemotherapy. <h3>Disclosure of interest</h3> None Declared.
Échoendoscopie de contraste harmonique (EECH) pour le diagnostic d'adénocarcinome (ADK) pancréatique: résultats de la première étude prospective multicentrique avec évaluation de la concordance inter- et intra-observateur
Authors: R Gincul, L Palazzo, B Pujol, F Tubach, C Lefort, M Palazzo, F Fumex, A Lombard, D Ribeiro, V Hervieu, M Labadie, JY Scoazec, M Fabre, T Ponchon, B Napoléon
Journal: Endoscopy (2011)

Introduction: L'anatomo-pathologie est le gold standard diagnostique des tumeurs solides pancréatiques. Cependant, la VPN de la ponction guidée sous échoendoscopie (PG/EE) pour le diagnostic d'ADK est <75%. Dans la série pilote française*, la performance de l'EECH pour le diagnostic d'ADK est de 88% pour l'efficacité globale, de 88,5% pour la VPN. Ces résultats nécessitent d'être confirmés par une large étude multicentrique. Buts de l'étude: 1) Comparer dans une étude prospective multicentrique, la VPN de l'EECH à la PG/EE pour le diagnostic d'ADK du pancréas. 2) Evaluer la concordance inter et intra-observateur de l'EECH pour le diagnostic d'ADK du pancréas.
PREDICTORS OF LEFT ATRIAL THROMBI AND SPONTANEOUS ECHOCARDIOGRAPHY CONTRAST IN PATIENTS WITH ATRIAL FIBRILLATION TAKING NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS
Authors: Hideyuki Kishima, Takanao Mine, Kenki Ashida, Takeshi Kodani, Tohru Masuyama
Journal: Journal of the American College of Cardiology (2015)
1003 IMPACT OF MAA SPECT/CT IN THE PREDICTION OF RESPONSE, SURVIVAL AND IN THE TREATMENT PLANNING FOR HEPATOCELLULAR CARCINOMA PATIENTS TREATED BY 90Y-LOADED GLASS MICROSPHERES
Authors: E. Garin, L. Lenoir, J. Edeline, Y. Rolland, M. Pracht, S. Laffont, J.-L. Raoul, B. Clement, E. Boucher
Journal: Journal of Hepatology (2012)
Abstract 4131: Alternative splicing changes during the acquisition of anoikis resistance.
Authors: Quoc Huynh, Charles E. Chalfant, Margaret A. Park
Journal: Cancer Research (2013)

Abstract Breast cancer is the most common cancer in women and the second leading cause of cancer-related death among women in the U.S. Metastases from the primary tumor are common and are the main cause of mortality in this population. Therefore, it is imperative to identify therapeutic molecules that target mechanisms specific to metastatic cells. One such mechanism to target is anoikis, a specialized form of programmed cell death that prevents epithelial cells shed from basement membranes from colonizing distant organs. Circulating tumor cells (CTCs) become anoikis-resistant, which is an essential early step in the development of distant metastases in many types of cancer including breast cancer. Recent studies have implicated RNA splicing dysregulation in a number of cancer phenotypes (e.g. oncogenesis). In these studies, we have developed anoikis-resistant (AnR) breast cancer cell lines, which grow unattached to hydrophilic surfaces. We then performed a preliminary intron / exon array screen comparing parental and AnR breast cancer cell lines. This approach identified a novel splice variant of Non-catalytic region of tyrosine kinase associated protein 1 (NckAP1), in which the 15-18 cassette is deleted. This splice variant is dysregulated in both AnR cells and in relevant samples from breast cancer patients. NckAP1, along with Nck and Ras-related C3 botulinum toxin substrate (Rac), are found in a complex with the actin-polymerization protein Wiskott Aldrich syndrome protein verprolin homologous 1 (WAVE1). After dissociation from this complex, WAVE1 is able to induce polymerization of actin during lamellipodia formation, and is thus a mediator of migration. Hence, splicing of NckAP1 may help mediate migratory capacity of breast cancer cells. These studies also suggest a major role for splicing regulation in metastasis. Citation Format: Quoc Huynh, Charles E. Chalfant, Margaret A. Park. Alternative splicing changes during the acquisition of anoikis resistance. [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 4131. doi:10.1158/1538-7445.AM2013-4131
Role of Transforming Growth Factor β in Human Disease
Authors: Gerard C. Blobe, William P. Schiemann, Harvey F. Lodish
Journal: New England Journal of Medicine (2000)

In human tissues, normal homeostasis requires intricately balanced interactions between cells and the network of secreted proteins known as the extracellular matrix. These cooperative interactions involve numerous cytokines acting through specific cell-surface receptors. When the balance between the cells and the extracellular matrix is perturbed, disease can result. This is clearly evident in the interactions mediated by the cytokine transforming growth factor β (TGF-β).TGF-β is a member of a family of dimeric polypeptide growth factors that includes bone morphogenic proteins and activins. All of these growth factors share a cluster of conserved cysteine residues that form a common cysteine . . .