tbuckley/cabot-search huggingface dataset:
Abstract 248: Functional characterization of MED29 gene in pancreatic cancer
Authors: Riina Kuuselo, Kimmo Savinainen, Anne Kallioniemi
Journal: Cancer Research (2010)

Abstract Pancreatic cancer is a highly aggressive malignancy characterized by rapid progression and an extremely poor prognosis. More knowledge is needed to better understand the mechanisms of the disease pathogenesis. Identification of new disease genes can improve our understanding about the biology of pancreatic cancer and might provide us tools for improving both diagnostics and treatment. Previously, we performed a detailed characterization of the 19q13 locus, one the recurrently amplified regions in pancreatic cancer, and identified a set of putative amplification target genes that showed consistent overexpression in amplified cell lines versus non-amplified cell lines. Subsequent high-throughput RNAi screen targeting genes within the amplified region revealed a number of genes whose downregulation led to decreased cell viability in the amplified but not in the non-amplified cells. Of these, the mediator complex subunit 29 (MED29) was consistently overexpressed in all amplified cell lines and had the most dramatic effect on cell viability. By flow cytometry analysis, we showed that MED29 silencing resulted in G0/G1 cell cycle arrest and increased apoptosis in the amplified PANC-1 cells. MED29 is a subunit of a large multiprotein complex that is involved in transcriptional regulation and may function both as a transcriptional repressor and enhancer. To further define the function of MED29 we constructed a lentiviral vector for MED29 gene delivery. Mouse embryonic fibroblasts (NIH/3T3) and two pancreatic cancer cell lines with low basal MED29 expression (MIAPaCa2 and Hs700T) were transduced with a lentivirus vector containing MED29. Stable MED29 expression was confirmed in all three cell lines by quantitative RT-PCR and western blot analysis. MED29 expression led to statistically significant changes in proliferation and/or survival in both the NIH/3T3 cells and the pancreatic cancer cells. Finally, MED29 overexpressing human pancreatic cancer cell lines were subcutaneously inoculated into immunocompromized mice to follow tumor growth in vivo. Significant growth difference was observed between MED29 expressing cancer cells compared to control cells when injected into mice. To conclude, our results implicate MED29 as an important regulator of growth and survival in pancreatic cancer both in vivo and in vitro. 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 248.
Hemorrhagic gastritis at the excluded stomach after Roux-en-Y gastric bypass
Authors: Adriana Safatle-Ribeiro, Emanuele Lima Villela, Eduardo Guimarães Hourneaux de Moura, Paulo Sakai, Klaus Mönkemüller
Journal: Endoscopy (2014)

Anemia frequently occurs in patients after Roux-en-Y gastric bypass. The causes are usually related to surgery, anastomotic site lesions, or malabsorption of nutrients caused by altered anatomy and physiology [1]. A 57-year-old man underwent an uncomplicated laparoscopic Roux-en-Y gastric bypass for morbid obesity and experienced melena and anemia 10 years after surgery. His medical history included hypertension and insulin-dependent diabetes mellitus that disappeared after surgery. Laboratory findings revealed a hemoglobin level of 5.9 g/dL and iron deficiency (iron, 47 µg/dL; ferritin 11 ng/mL; iron saturation, 8.6 %). His medications included vitamin B12 and omeprazole (20 mg/day). Endoscopy, colonoscopy, and abdominal computed tomography showed no abnormalities apart from anatomical changes related to surgery.
AB0759 Management of giant cell arteritis: Audit of BSR guidelines:
Authors: K. Scott, S. Pathare
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The British Society of Rheumatology guidelines for the diagnosis and management of giant cell arteritis (GCA), published in 2010<sup>1</sup>, recommend temporal artery biopsy (TAB) in all suspected cases. Sample length should be over 1cm, with longer samples showing a greater positive predictive value for a positive TAB<sup>2</sup>. <h3>Objectives</h3> To audit these guidelines at JCUH looking at clinical presentation, and details of biopsy sampling. <h3>Methods</h3> All TABs in the year 2009-2010 in were identified through pathology records. Information was collated on symptoms, the dose and timing of steroids, TAB length and result. The final diagnosis was also established. <h3>Results</h3> 60 TABs were obtained for suspected GCA, mean age 68 years (40 women). For further analysis, the results were separated by TAB result. See table. All 13 TAB-positive an further 18 TAB-negative patients were treated as GCA. Non-GCA final diagnoses included: one ANCA positive small vessel vasculitis; one later developed aortitis; 11 other causes of headache; 6 other causes of visual disturbance; 2 malignancies; one TMJ dysfunction; and 7 uncertain diagnoses. <h3>Conclusions</h3> 60 TABs were performed with 13 positive results. 31 patients were treated as GCA. ACR classification criteria predicted final diagnosis of GCA with sensitivity 84%, specificity 72%. TABs were performed rapidly with minimal pre-TAB steroids exposure. Those performed less than 2 weeks after starting steroids had 100% sensitivity for a positive result. The length of the TAB and the speciality or seniority of the surgeon did not predict a positive result in our sample. Ophthalmologists seem to have a lower threshold for TAB. The final clinical diagnosis was GCA is only 50% of their patients compared to 80% and 73% of patients seen by rheumatology and general physicians, respectively. Our results would support the use of a rapid access rheumatology-led GCA clinic, where by some unnecessary TABs may be avoided. <h3>References</h3> Dasgupta B et al. BSR and BHPR guidelines for the management of giant cell Arteritis. Rheumatology (Oxford). 2010 Aug;49(8):1594-7. Mahr A, Saba M, Kambouchner M et al. Temporal artery biopsy for diagnosing giant cell arteritis: the longer, the better? Ann Rheum Dis 2006;65:826-8. <h3>Disclosure of Interest</h3> None Declared
The need to develop occupational health services for doctors with ill health
Authors: Drushca Lalloo
Journal: BMJ (2016)

While I accept the points raised in Oxtoby’s articles,1 2 doctors’ attitudes and behaviours are gradually changing over time. As highlighted, a key concern for most doctors who become ill is the potential impact on their ability to do their job, and for those off sick, when they will be able to return to work. NHS occupational health services can therefore play an important role in …
THU0327 The Spectrum of Inflammatory Ocular Involvement in Systemic Lupus Erythematosus in a Multidisciplinary Uveitis Unit
Authors: G. Espinosa, L. Pelegrin, A. Montehermoso, M. Figueras, M. T. Sainz de la Maza, B. Sanchez-Dalmau, B. Molins, V. Llorens, M. Mesquida, A. Adan, R. Cervera
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) can affect all structures of the eye and ocular adnexa. The most common ocular findings include dry eye and retinal vascular changes. <h3>Objectives</h3> To describe the inflammatory ocular manifestations of patients with systemic lupus erythematosus (SLE) at a multidisciplinary uveitis unit. <h3>Methods</h3> Retrospective chart review of patients with SLE in a tertiary referral center between 2007 and 2012 was performed. All patients have undergone complete rheumatologic and ophthalmic examination including visual acuity, slit-lamp examination of the anterior segment and fundus examination. Fluorescein angiography and optical coherence tomography were performed if they were required. <h3>Results</h3> Twenty-three patients presented inflammatory ocular manifestations related to SLE. Patients complained of ophthalmologic disturbances with blurry vision and ocular redness as the most common symptoms. A decrease in the visual acuity was detected in 16 patients (69.6%) mostly due to retinal involvement, optic neuritis and anterior uveitis. Anterior uveitis was found in 8 patients (34.8%), peripheral ulcerative keratitis in 1 patient and diffuse scleritis in 4 patients (17.4%). Changes in retina were found in 7 patients (30.4%); the most frequent was retinal vein occlusion (central retinal vein occlusion in 2 patients and branch retinal vein occlusion in 2 patients) followed by hypertensive retinopathy with serous retinal detachment in 1 patient, occlusive vasculopathy in 1 patient and central serous choroidopathy due to corticosteroids in 1 patient. Three patients (13%) showed neuro-ophthalmological symptoms, 1 patient showed rotatory nistagmus related to central nervous system involvement, 1 patient showed optic neuritis and the remaining presented bitemporal hemianopsy. <h3>Conclusions</h3> Ocular manifestations in SLE can affect any structure in the eye. The most visually devastating damage occurs secondary to optic nerve involvement and retinal vaso-occlusion. Anterior uveitis is not an uncommon manifestation of SLE; physicians must be aware of this involvement since it can be treated without serious visual loss. <h3>Disclosure of Interest</h3> None Declared
FRI0018 Type I interferone inducible gene signatures in pregnant women with rheumatoid arthritis
Authors: F. Förger, J. Weix, T. Häupl, P.M. Villiger
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pregnancy is a state of natural immunomodulation during which most patients with rheumatoid arthritis (RA) experience spontaneous improvement of their disease. In our previous studies, genes of the innate immune cells were shown to be up-regulated during pregnancy (1). Important players of the innate immune response are type 1 interferons (IFN) (2). <h3>Objectives</h3> To investigate whether type I IFN inducible gene signatures are modified during pregnancy in patients with RA. <h3>Methods</h3> Peripheral blood mononuclear cells (PBMC) of patients with RA and healthy women who were recruited during and after pregnancy were evaluated for type I IFN inducible genes by GeneChip analysis. Candidate genes were further investigated by quantitative real-time PCR (qPCR) in pregnant and non-pregnant RA patients and healthy women. The influence of pregnancy serum on the expression of the pre-selected type I IFN candidate genes was measured upon stimulation with IFN-alpha or IFN-beta. <h3>Results</h3> GeneChip analysis showed an up-regulation of most type I IFN inducible genes during the third trimester in both healthy controls as well as in RA patients. In pregnant RA patients, the gene expression of IFI35, IFI44, IFI44L, IFIT3, OAS1 and SICLEC1 peaked at the second trimester and decreased postpartum. Moreover, pregnant RA patients showed significantly higher levels of IFI44 and SICLEC as compared to pregnant healthy women. Pregnancy serum was able to induce IFI44L and IFIT3 in PBMC of non-pregnant RA patients. This effect could be increased by the addition of IFN-alpha. <h3>Conclusions</h3> Pregnancy and RA give rise to an increased expression of type I IFN inducible genes reflecting an up-regulation of the innate immune system by both conditions. <h3>References</h3> Häupl T, Østensen M, Grützkau A, Radbruch A, Burmester GR, Villiger PM. Reactivation of rheumatoid arthritis after pregnancy: increased phagocyte and recurring lymphocyte gene activity. Arthritis Rheum. 2008;58(10):2981-92. Van Holten J, Plater-Zyberk C, Tak PP. Interferon-beta for treatment of rheumatoid arthritis. Arthritis Res 2002;4:346-52 <h3>Disclosure of Interest</h3> None Declared
Abstract 2887: From fruit extract to structure activity relationship studies: Alpha-mangostin promotes G1 cell cycle arrest in PC3 cells and inhibits tumor formation in athymic nude mice
Authors: Jeremy J. Johnson, Deeba N. Syed, Vaqar Adhami, John T. Rasmussen, Imtiaz A. Siddiqui, Harleen Handa, Hasan Mukhtar
Journal: Cancer Research (2010)

Abstract The angosteen fruit (Garcinia mangostana) is native to southeast Asia and has been receiving increased attention for its health promoting properties that include antioxidant, anti-inflammatory, anit-microbial and anti-diabetic properties. The principle constituents isolated from the mangosteen fruit are the xanthones with alpha-mangostin being the most abundant. Here we report on the properties of dietary xanthones for cancer chemoprevention using prostate cancer (PCa) as a model disease. In a separate abstract we provide promising results suggesting that a standardized mangosteen fruit extract promotes cell cycle arrest and decreases tumor formation in an athymic nude mouse model. To gain an understanding of the pharmacology of xanthones in cancer inhibition we selected alpha-mangostin as the lead compound and evaluated it against fifty different protein kinases deregulated in cancer in a cell free kinase assay. A kinase that is often deregulated in a variety of cancers including prostate is cyclinD1/CDK4 where alpha-mangostin was found to significantly inhibit the activity. Using two different cells lines (PC3 and CWR22) we have evidence suggesting alpha-mangostin promoted G1 cell cycle arrest by flow cytometry and western blot analysis of cyclins and CDKs with observed effects in the range of 5-10 μM. Further confirmatory studies were performed by western blot analysis. A preliminary pharmacokinetic analysis of mice administered 1 mg of alpha-mangostin intraperitoneally resulted in a plasma concentration of 7.3 μM - within the concentration of in vitro mechanistic studies. Next, using an athymic nude mouse model implanted with CWR22Rv1 cells we randomized mice to receive intraperitoneally the alpha-mangostin (&amp;gt;95%) or placebo two times weekly with tumors measured twice weekly. At the conclusion of the study the treatment group had a significantly smaller tumor with an average tumor volume of (400 mm3) compared to the placebo group (1225 mm3) representing a 69% smaller tumor in the treatment group. Based on these promising results we used purified xanthones from the mangosteen fruit and selected 9 xanthones for structure activity relationship studies against cyclinD1/CDK4 using cell free biochemical assays and molecular modeling. Collectively these data indicate that the purified xanthone alpha-mangostin could be a promising agent for PCa prevention. 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 2887.
P313 AMIODARONE HEPATOTOXICITY IS MEDIATED VIA INDUCTION OF STEATOSIS, ER STRESS AND mTOR ACTIVATION IN-VIVO AND IN-VITRO
Authors: N. Erez, R. Cohen, D. Uzi, V. Scaiewicz, T. Meuller, B. Tirosh, O. Shibolet
Journal: Journal of Hepatology (2014)
Efficacy of rociletinib (CO-1686) in plasma-genotyped T790M-positive non-small cell lung cancer (NSCLC) patients (pts).
Authors: Lecia V. Sequist, Jonathan Wade Goldman, Heather A. Wakelee, D. Ross Camidge, Helena Alexandra Yu, Andrea Varga, Ben Solomon, Geoffrey R. Oxnard, Sai-Hong Ignatius Ou, Vassiliki Papadimitrakopoulou, Bo H. Chao, Stephen V. Liu, Karen L. Reckamp, Alexander I. Spira, Zofia Piotrowska, Darrin Despain, Chris Alan Karlovich, Sergey Yurasov, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2015)

8001 Background: Rociletinib is an oral inhibitor of mutant EGFR, including the T790M resistance mutation. We reported robust activity in T790M positive pts identified by tumor genotyping treated at 500mg-1000mg BID (active doses) [NCT01526928]. We now present data from the pt subset with T790M detected by plasma genotyping. Methods: For the overall phase 1/2 study, pts had EGFR-mutant NSCLC and treatment with ≥ 1 EGFR inhibitor, ECOG PS 0-1. Brain metastases were allowed. In phase 2, T790M pos by central tumor genotyping was required. Plasma EGFR status was assessed by BEAMing (Sysmex), a quantitative assay using emulsion PCR then flow cytometry. Results: 345 pts were enrolled at active doses, median age 62 yrs, 66% female, 69% ECOG 1, 87% from US sites, median prior therapies 3 (45% ≥ 2 prior TKIs). Response data are available for 219 with tissue genotyping and 113 with plasma genotyping. The RECIST objective response rate (ORR) was ~48% in T790M pos pts, regardless of genotyping method. ORR was 33-36% among T790M neg pts, (see Table). There were 17 pts T790M pos in plasma but with neg (9) or failed (8) tissue genotyping, and 5/17 responded. There were 16 pts T790M pos in tissue but with neg plasma genotyping and 6/16 responded. 3/8 who were neg by both methods responded. The majority of T790M negative responders were on an EGFR TKI immediately before rociletinib (10/12 tissue and 10/10 plasma). Serial plasma data typically showed a decrease in the levels of T790M over time. Related all grade AEs in ≥ 15% patients were: hyperglycemia (40%), diarrhea (28%), nausea (23%), fatigue (21%), decreased appetite (17%). Conclusions: Rociletinib is associated with durable response and is well tolerated in pts with EGFR mutant T790Mpos NSCLC. One-third of T790M neg pts also respond, which cannot be explained by retreatment effect. Serial plasma data shows T790M decrease in most pts, including non-responders, suggesting T790M is not always the dominant growth driver. Plasma genotyping by BEAMing may be a complementary method to select patients. Clinical trial information: NCT01526928. Table: Outcome by genotype/ biopsy type T790M + T790M - Tissue genotype ORR (%) ORR: 91/186 (49) 12/33 (36) DoR (days) 1-394+ 1-283+ Plasma genotype ORR 40/83 (48) 10/30 (33) DoR 1-394+ 74-329
An Unusual Cluster of Cases of Castleman's Disease during Highly Active Antiretroviral Therapy for AIDS
Authors: Christian Zietz, Johannes R. Bogner, Frank-Detlef Goebel, Udo Löhrs
Journal: New England Journal of Medicine (1999)

To the Editor: Castleman and coworkers first described a lymphatic hyperplasia now called Castleman's disease, which has two forms, the hyaline vascular type (found in 90 percent of cases) and the plasma-cell type (found in 10 percent).1,2 Patients may present with a multicentric lymphadenopathy and progressive systemic symptoms or with a more localized, indolent disease that can often be cured by local excision. The majority of patients with so-called multicentric Castleman's disease have the plasma-cell–rich variant with an interfollicular predominance of plasma cells on histologic analysis.2,3 Multicentric Castleman's disease is associated with infection with human herpesvirus 8 (HHV-8) . . .
Familial Aggregation of Blood Pressure in Childhood
Authors: Stephen H. Zinner, Paul S. Levy, Edward H. Kass
Journal: New England Journal of Medicine (1971)

The familial aggregation of blood pressure is well known in adults. To determine if this familial effect is detectable in childhood, blood pressures of 721 children two to 14 years of age were taken in the homes of 190 families. A portable, automated blood-pressure recorder was used, and scores adjusted for age and sex were expressed in standard-deviation units. For both systolic and diastolic pressures, variance of blood-pressure scores was significantly less within families than among all children in this age group (p less than 0.01). Sib-sib and mother-child regression coefficients were 0.34 and 0.16 for systolic pressure and 0.32 and 0.17 for diastolic pressure respectively. The clustering effect was measurable at all levels of blood pressure. Thus, a familial influence on blood pressure can be detected in children, and it is possible that factors responsible for essential hypertension are acquired in childhood.
Diagnosing trees and men
Authors: G. Dunea
Journal: BMJ (1997)

Trees are to be enjoyed, admired, worshipped, climbed on, cut down for pulp or furniture, or ground up to cure malaria and cancer. Their infinite variety and complicated taxonomy require the aspiring diagnostician to study them long and hard, along majestically lined avenues, on country roads, in green parks, and arboretums. Like reading Proust, you travel but never arrive. Like learning medicine, the task is never completed. You alternate forever between the ecstasy of an astute diagnosis and the crushing humiliation of a diagnostic blunder. Maples and oaks, willows and chestnuts are easy, stuff for beginners.

But there are treacherous trees that look like one thing and turn out to be another. What you take for …
Prevention of stricture after large esophageal endoscopic submucosal dissections
Authors: Tsuneo Oyama
Journal: Endoscopy (2015)

Ten years have passed since the esophageal endoscopic submucosal dissection (ESD) technique was first developed. ESD is a useful treatment for superficial esophageal cancers, its advantages being high R0 resection rate, more precise histological examination, and low local recurrence rate [1]. However, in situations where semicircumferential or circumferential ESD is performed for esophageal lesions, severe strictures occur, which worsen the subsequent quality of life of the patients.
P194 THE RISK OF HEPATITIS B-RELATED HEPATOCELLULAR CARCINOMA (HCC) IS REDUCED WITH ANTIVIRAL THERAPY: EVIDENCE FROM 3 HCC PREDICTION MODELS
Authors: M. Abu-Amara, O. Cerecchi, G. Mahli, S. Sharma, C. Yim, H. Shah, D.K. Wong, H.L.A. Janssen, J.J. Feld
Journal: Journal of Hepatology (2014)
FRI0292 Efficacy of A Conjugated Pneumococcus Vaccine in Rheumatoid Arthritis Patients Treated with Etanercept
Authors: Έ. Rákόczi, B. Perge, E. Végh, P. Csomor, A. Pusztai, S. Szamosi, N. Bodnár, S. Szántό, G. Szücs, Z. Szekanecz
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> <i>Streptococcus pneumoniae</i> is the most common cause of pneumonia. Prevenar 13, a conjugated vaccine has been developed and has been widely used int he adult population due to its high immunogenicity. In the general population, its efficacy has been proven at all ages, however, little information has become available regarding the efficacy of Prevenar 13 in biologic-treated rheumatoid arthritis (RA) patients. <h3>Objectives</h3> Immunogenicity of Prevenar 13 was assessed in a cohort of RA patients treated with etanercept. <h3>Methods</h3> In this prospective study, 22 RA patients already treated with weekly 50mg sc etanercept in combination with methotrexate (n=15) or in monotherapy (n=7) for at least one year were included (mean age 55.1 years). Altogether 24 osteoarthritis patients not receiving biological therapy served as controls (mean age 63.9 years). Prevenar 13 vaccination was performed in all RA patients (±5 days before/after etanercept treatment) and controls and Pneumococcus antibody levels were assessed at baseline, as well as 4 and 8 weeks after vaccination. <h3>Results</h3> At baseline, Pneumococcus antibody levels in RA patients and in controls were 110.1±68.2 mg/l and 124.0±99.0 mg/l, respectively. Four weeks after vaccination, antibody levels significantly increased in both groups (RA: 247.7±155.6 mg/l; controls: 417.7±198.3 mg/l vs baseline) (p&lt;0.001). There was significant difference between the two groups (p=0.002). At week 8, antibody levels somewhat decreased in both groups, however, still remained significantly higher compared to baseline (RA: 207.6±127.6 mg/l; control: 356.4±171.2 mg/l) (p&lt;0.001). In RA, increases in antibody levels at week 8 compared to baseline exerted a negative correlation with age (Spearman9s R=-0,431; p=0.045). Combination with methotrexate had no effect on pPneumococcus antibody levels as compared to patients treated with etanercept monotherapy. <h3>Conclusions</h3> In RA patients treated with etanercept, vaccination with Prevenar 13 is effective, resulting in a two-fold increase in Pneumococcus antibody levels. The efficacy of Prevenar 13 vaccination may be more pronounced in younger patients. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2652