tbuckley/cabot-search huggingface dataset:
Abstract 930: A simple and inexpensive approach to allelotyping the HLA region in a case-control study of non-Hodgkin lymphoma
Authors: Nicholas K. Akers, John D. Curry, Martyn T. Smith, Lucia Conde, Paige M. Bracci, Christine F. Skibola
Journal: Cancer Research (2010)

Abstract Background: Non-Hodgkin lymphoma (NHL) is a heterogeneous malignancy of B- and T-cells. NHL is the fifth most common cancer in the US and NHL incidence rates are increasing, having doubled since the 1970s. As a result, finding causative factors, whether genetic or environmental, remains an important task. The human leukocyte antigen (HLA) region has a long track record of genetic association with autoimmune disease. Our group has recently published findings that indicate a genetic link between follicular lymphoma and a locus at chr6p21.33, in the HLA Class 3 region. Extended haplotypes are typical in this region, and the overall data implicate a possible genetic association between NHL and distant, yet linked, HLA alleles. Due to high genetic complexity, it is difficult to assess allelotype information in the HLA region without using genetic sequencing approaches. However, sequencing is expensive both in terms of dollars and DNA, making it unfeasible for pilot study work. To circumvent these research limitations and quickly and easily explore our hypothesis, we set out to create an assay that is high-throughput, inexpensive, uses minimal DNA, and gives meaningful HLA allelotype information. Results: Using multiplexed ligation-dependent probe amplification (MLPA) we have developed an assay that is able to obtain specific allelic information for one complex HLA gene. One to two digit, bi-allelic typing requires only 100ng of genomic DNA and can be run on 96-well plates over the course of 2 days. Samples are run through an Applied Biosystems 3730xl capillary DNA analyzer to obtain raw data. Analysis is simple relative to sequencing-based typing approaches; there is no need for expensive computer programs and translating raw data to allelotypes is trivial. Compared to sequencing, this is a very affordable assay that gives broad indications of allele associations, making it an ideal methodology for pilot studies. We are currently applying MLPA technology to screen for HLA allelotypes associated with risk of NHL. Discussion: MLPA is a useful tool that can be applied to conduct HLA allelotyping. This technology is an economically feasible approach for large-scale genotyping of closely related alleles and represents a key intermediate research tool that is more specific than genome-wide analysis and more affordable than sequencing. This assay may aid in the discovery of key HLA allelotypes associated with lymphoma, as well as help to eliminate false positive results. 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 930.
THU0141 Painless Synovitis – A Silent Enemy? A Controlled, Ultrasound, Radiographic, Clinical Trial
Authors: D. F. Pereira, J. Natour, A. L. Buosi, F. Ferreira, A. Fernandes, R. N. Furtado
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Some rheumatoid arthritis (RA) patients exhibit persistent chronic synovitis marked by joint swelling that may or may not be accompanied by pain. <h3>Objectives</h3> The aim of the present study was to compare painless and painful chronic synovitis in established RA with regard to clinical, ultrasonography (US), radiography and laboratory outcomes. <h3>Methods</h3> A cross-sectional study was carried out involving 60 patients with RA and synovitis in the metacarpophalangeal joints (MCPs): 30 patients without pain and 30 patients with pain for at least 6 months. The radiocarpal, distal radioulnar joints and MCPs were evaluated using US gray scale (US-GS), power Doppler (US-PD) and radiography. Past and present clinical and laboratory findings were also evaluated. <h3>Results</h3> No statistically differences between groups were found for the most of outcomes analyzed. Worse scores on the disease activity indices (DAS 28 and SDAI) (p&lt;0.001), questionnaires of function (HAQ and Cochin) and pinch strength (p &lt; 0.001 to 0.039) were found in the group with pain. The logistic regression analysis revealed that the use of an immunobiological agent was associated with a threefold greater chance of belonging to the group with pain (p = 0.049). No statistically significant differences were found for the majority of variables analyzed by radiography and US (including PD assessment). However, worse joint damage scores (erosion and cartilage) were found in the group without pain. <h3>Conclusions</h3> Patients with RA and painless chronic synovitis exhibited similar disease progression, radiographic and US findings to those with painful chronic synovitis. Although similar between groups, the US evaluation demonstrated worse joint damage scores in patients with painless synovitis. <h3>References</h3> Bugatti S, Manzo A, Caporati R et al. Assessment of synovitis to predict bone erosions in rheumatoid arthritis. Ther Adv Musculoskeletal Dis 2012; 4(4):235-244. Naredo E, Bonilla G, Gamero F et al. Assessment of inflamatory activity in rheumatoid arthritis: a comparative study of clinical evaluation with gray scale e power Doppler ultrasonography. Ann Rheum Dis 2005;64:375-381. Brown AK, Quinn MA, Karim Z, Conaghan PG, Peterfy CG, Hensor E, Wakefield RJ, O'Connor PJ, Emery P. Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission – Evidence from an imaging study may explain structural progression. Arthritis Rheum. 2006;54(12):3761-3773. Filippucci E, da Luz KR, Di Geso L, et al. Interobserver reliability of ultrasonography in the assessment of cartilage damage in rheumatoid arthritis. Ann Rheum Dis 2010; 69(10):1845-8. <h3>Disclosure of Interest</h3> None Declared
Abstract 4377: The Golgi protein GLG1 coordinates ARF3 activation in tumor cells.
Authors: Anne Planche
Journal: Cancer Research (2013)

Abstract Increasing evidence suggests that endocytosis and membrane trafficking are deregulated in cancer cells. Because of their dependence on selected signaling pathways, tumor cells may need to rely on accelerated receptor recycling and increased secretion of a variety of molecules such as matrix components, adhesion molecules and growth factors. Mass spectrometry analysis of proteins associated with separase, recently shown to be an important regulator of membrane trafficking, identified the Golgi apparatus protein 1 (GLG1). GLG1 is primarily known as an E-selectin ligand that mediates the initial step of tethering and rolling of leukocytes on vascular endothelium. We therefore addressed the possibility that GLG1 could play a similar role in circulating tumor cells, facilitating arrest and extravasation into adjacent tissues. Consistent with this possibility, tail vein injection of stably GLG1-depleted tumor cells into NOD/SCID mice resulted in reduced numbers of metastatic nodules. Moreover, metastatic tumor growth was almost exclusively intravascular, indicating impaired extravasation of tumor cells. Further investigation, however, showed that, in tumor cells, GLG1 is almost exclusively localized to the Golgi apparatus, challenging the notion that it plays a direct role in mediating tumor cell adhesion to endothelium as in leukocytes. To elucidate the molecular mechanisms by which GLG1 could affect tumor cell migration through interactions at the Golgi level, we conducted various experiments using GLG1-depleted human tumor cell lines. Transient silencing of GLG1 by siRNA was observed to modify cell shape (elongated morphology), to reduce migration of a range of tumor cell lines and to markedly alter Golgi architecture. Interestingly, subsequent experiments led to the identification of a new interactor of GLG1, the Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1), an ARF-GEF required to initiate membrane vesicle formation at the trans-Golgi compartment by promoting guanine-nucleotide exchange on ARF1 and ARF3. GLG1 was shown to participate in BIG1 and ARF3 recruitment to the Golgi membrane and subsequent ARF3 activation. Surprisingly, the observed morphological disruption of the Golgi apparatus and reduced ARF3 activation did not affect the secretory pathway in general, but rather seemed to impair secretion of selected molecules including MMP-9. Taken together, our observations provide insight into a novel and specific role of GLG1 in tumor progression by affecting, thanks to its privileged position in the secretory pathway, trafficking of key molecules implicated in cell migration. Citation Format: Anne Planche. The Golgi protein GLG1 coordinates ARF3 activation in tumor cells. [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 4377. doi:10.1158/1538-7445.AM2013-4377
Lagos state doctors are sacked for striking over pay
Authors: C. Odigwe
Journal: BMJ (2012)

The government of Lagos state in Nigeria has sacked nearly 800 doctors for going on an indefinite strike over pay, accusing them of being insensitive to patients’ needs. It says that it cannot afford to pay the salaries it agreed to two years ago.

The sacked doctors have been striking for the past three weeks in protest at the failure of the Lagos state government to implement the consolidated medical salary scale, a …
Measurement of Serum DNA-Binding Activity in Systemic Lupus Erythematosus
Authors: Theodore Pincus, Peter H. Schur, James A. Rose, John L. Decker, Norman Talal
Journal: New England Journal of Medicine (1969)

Antibodies to DNA were demonstrated in the serums of patients with systemic lupus erythematosus (SLE) by ammonium sulfate precipitation. DNA is soluble in 50 per cent saturated ammonium sulfate, whereas immunoglobulins and immunoglobulin-bound DNA are insoluble. When ammonium sulfate is added to a mixture of radioactive DNA and serum, the precipitate contains radioactivity if DNA is bound to immunoglobulins. Abnormal binding was found in serum of 75 per cent of unselected patients with SLE, 25 per cent with Sjögren's syndrome, 5 per cent with related disease and 2 per cent of normal subjects. All of 52 selected SLE serums with positive, as well as 21 of 32 SLE serums with negative, complement-fixation tests for anti-DNA antibodies had abnormal binding. Binding activity was associated with immunoglobulin G of serum. High binding values were seen chiefly in patients with active SLE renal disease; marked reductions accompanied clinical improvement. The test overcomes problems inherent in other methods to detect anti-DNA antibodies, is easy to perform and is useful in the diagnosis and assessment of the course of SLE.
Hepatic Failure and Lactic Acidosis Due to Fialuridine (FIAU), an Investigational Nucleoside Analogue for Chronic Hepatitis B
Authors: Robin McKenzie, Michael W. Fried, Richard Sallie, Hari Conjeevaram, Adrian M. Di Bisceglie, Yoon Park, Barbara Savarese, David Kleiner, Maria Tsokos, Carlos Luciano, Timothy Pruett, Jennifer L. Stotka, Stephen E. Straus, Jay H. Hoofnagle
Journal: New England Journal of Medicine (1995)

We describe severe and unexpected multisystem toxicity that occurred during a study of the antiviral nucleoside analogue fialuridine (1-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)-5-iodouracil, or FIAU) as therapy for chronic hepatitis B virus infection.
Abstract 4406: Multiple organic anion transporting polypeptides (OATPs) contribute to the in vitro and in vivo disposition of docetaxel
Authors: Richard H. Ho, Brenda F. Leake, Wendy Teft, Richard B. Kim
Journal: Cancer Research (2011)

Abstract Docetaxel is one of the most widely used antineoplastic agents and is approved for the treatment of breast, lung, ovarian, prostate, gastric, and head and neck cancers. It is a semisynthetic taxane derived from an extract of the needles of European yew tree (Taxus baccata). Docetaxel promotes the assembly of microtubules and stabilizes their formation by inhibiting depolymerization and cell death results from inhibition of normal microtubule processes. While it is known that docetaxel is a substrate of efflux transporters such as P-glycoprotein (P-gp), less is known regarding transporters that could mediate its cellular uptake. Accordingly, an array of drug uptake transporters, including organic anion, organic cation and bile acid transporters, were evaluated for radiolabeled docetaxel transport utilizing a recombinant vaccinia-based method in a heterologous cell system. Screening transport experiments and kinetic analysis in HeLa cells demonstrated that multiple organic anion transporting polypeptides (OATPs), including OATP1A2, OATP1B1, and OATP1B3, were capable of docetaxel transport in vitro. In addition, after intravenous administration, in vivo docetaxel transport experiments in Oatp1b2-/- mice (ortholog to hepatic OATP1B1/OATP1B3) revealed ∼5-fold higher plasma concentrations of docetaxel in Oatp1b2-/- mice versus their wild-type counterparts. The liver to plasma ratio of docetaxel was ∼3-fold increased in wild-type mice versus Oatp1b2-/- mice. Furthermore, the pharmacokinetic profile of docetaxel is characterized by substantial interindividual variability, with an up to tenfold difference in drug clearance, even in patients with normal hepatic function. A panel of single nucleotide polymorphisms (SNPs) in OATPs was assessed for docetaxel transport. Multiple SNPs in SLCO1A2, 1B1 and 1B3 were associated with impaired docetaxel transport in vitro. In conclusion, multiple OATPs were capable of transporting docetaxel in vitro and in vivo, suggesting these transporters are important to docetaxel disposition. A number of OATP variants were associated with significantly impaired docetaxel transport, which may have important toxicological and therapeutic ramifications. 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 4406. doi:10.1158/1538-7445.AM2011-4406
846 DISCOVERY OF A NEW SERIES OF POTENT, MULTI-GENOTYPE HCV NS5B INHIBITORS: IN VITRO ACTIVITY AND PRE-CLINICAL PHARMACOKINETIC RESULTS
Authors: S. Bond, J. Cianci, A. Draffan, A. Luttick, M. Frazetto, B. Frey, R. Halim, S. Hamilton, M. Harding, R. Hufton, S. Jahangiri, T. Jeynes, B. Lin, M. Lilly, C. Morton, T. Nero, V. Nguyen, M. Parker, B. Pool, K. Porter, M. Pryor, J. Thomas, D. Tilmanis, S. Tucker, J. Wielens
Journal: Journal of Hepatology (2012)
AB0783 Medical costs associated with rheumatoid arthritis in turkey: an analysis of real-world data
Authors: O. Baser, A. Burkan, E. Baser, R. Koselerli, E. Ertugay, A. Altinbas
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Health Transformation Programme implementation by the Turkish Ministry of Health resulted in significant health system changes in Turkey.<sup>1</sup> Recognizing the importance of information technology and health technology assessment, Turkey invested in stronger systems and data collection. MEDULA, a nationwide integrated system between health insurance and healthcare providers, was built to collect e-invoice information electronically in 2007. Rheumatoid arthritis (RA) costs in Turkey were analyzed for the first time using real-world data. <h3>Objectives</h3> Estimate and identify medical cost determinants associated with RA in Turkey using nationwide real-world data. <h3>Methods</h3> Data was obtained from MEDULA (2009-2011). Adult RA patients (ages 18-99) were identified (01JUN2010-31DEC2010), and were required to have two RA diagnoses ≥60 days apart, and were grouped as prevalent and incident cases. The first RA claim date was designated as the index date. Healthcare costs were examined following the index date. Descriptive and multivariate analyses are provided. Pharmacy, outpatient and inpatient claims were compiled. Generalized linear models were used to calculate expected annual costs after controlling for age, gender, region, comorbid conditions and medication. <h3>Results</h3> A total of 2,613 patients met all inclusion criteria (693 incident; 1,920 prevalent patients). Prevalent patients were older, less likely to reside in the Marmara region, had higher comorbidity index scores and were more likely to be prescribed non-steroidal anti-inflammatory drugs, biologics and disease-modifying anti-rheumatic drugs relative to incident patients. Average annual costs were €2,000 (incident) and €2,386 (prevalent), due to pharmacy costs (73%, incident; 60%, prevalent). For both groups, inpatient and outpatient costs were mostly due to physician costs. Costs did not significantly differ in terms of age or region, prior comorbid conditions and medication use significantly affected cost estimation. <h3>Image/graph</h3> <h3>Conclusions</h3> RA annual costs were found to be lower in Turkey relative to estimates in Europe, yet a significant portion was due to pharmacy costs. Comparative effectiveness analyses may be useful to decrease RA pharmacy costs. <h3>References</h3> Akdag R. Progress Report 2008 Health Transformation Programme: Ministry of Health, Ankara; 2008. <h3>Disclosure of Interest</h3> None Declared
Vincent DeVita Receives First Pezcoller Award
Authors: H. R. Neville
Journal: JNCI Journal of the National Cancer Institute (1988)

Vincent DeVita Receives First Pezcoller Award Heather R. Neville Heather R. Neville Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 10, 20 July 1988, Page 719, https://doi.org/10.1093/jnci/80.10.719 Published: 20 July 1988
Abstract 4778: Resveratrol suppresses constitutive activation of AKT via generation of reactive oxygen species and induces apoptosis in diffuse large B cell lymphoma cell lines
Authors: Zeenath Jehan, Azhar R. Hussain, Maqbool Ahmed, Saeeda O. Ahmed, Fouad Al-Dayel, Prashant Bavi, Shahab Uddin, Khawla S. Al-Kuraya
Journal: Cancer Research (2011)

Abstract We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in the pathogenesis of diffuse large B cell lymphoma (DLBCL). In an attempt to identify newer agents that can be utilized to target these deregulated pathways, we found that Resveratrol (trans-3,4′, 5-trihydroxystilbene) is a naturally occurring polyphenolic compound that has an antioxidant and chemopreventive effects on various cancer cells. In the current investigation, we therefore investigated the role of resveratrol-mediated chemopreventive effect on various DLBCL cell lines. Resveratrol caused a dose dependent inhibition of cell viability in DBCL cell lines. To see whether this inhibition was due to cell cycle arrest or apoptosis, we found that resveratrol induced apoptosis in all DLBCL cell lines. We next investigated the action of resveratrol on PI3-kinase/AKT pathway and found that resveratrol treatment resulted in inhibition of constitutively activated AKT and its downstream targets, p-FOXO1, p-GSK3 and p-Bad via generation of reactive oxygen species (ROS). Inactivation of Bad led to conformational changes in Bax protein causing loss of mitochondrial membrane potential and release of cytochrome c to the cytosol. This led to activation of caspase-9, caspase-3, and poly-(ADP)-ribose polymerase cleavage leading to caspase-dependent apoptosis. In addition, resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; however, this up-regulation did not result in apoptosis. Finally, co-treatment of DLBCL with sub-toxic doses of TRAIL and resveratrol induced efficient apoptosis. Altogether, these data suggest a novel function for resveratrol, acting as a suppressor of AKT/PKB pathway via generation of ROS in DLBCL cells, and raise the possibility that this agent may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway either alone or in combination with other chemotherapeutic agents. 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 4778. doi:10.1158/1538-7445.AM2011-4778
Abstract P2-02-10: Clinical Utility of MRI before Re-Lumpectomy in Breast Conserving Operation
Authors: C Jeon, JS Lee, S Kim
Journal: Cancer Research (2010)

Abstract Background: It was necessary to know the resection margin status for breast conserving operations after diagnostic excisional biopsies. The purposes of this study were to assess the accuracy of breast MRI in detecting residual tumor extent around excisional biopsy or mammotome biopsy sites with unknown resection margin status and evaluate the impact of MRI on surgical treatment planning for breast conserving operation. Material and Methods: Preoperative breast MRI was performed in 47 breast cancer patients who underwent mammotome biopsy and excisional biopsy with unknown resection margin status. All subjects underwent breast MRI and ultrasonography for extent of residual tumor, and were evaluated by experienced two diagnostic radiologists, followed by immediate curative operation. We investigated the correlation between radiologic and pathologic finding and the radiologic decision's effect on further surgical treatment. Results: 28 patients(59.6%) were taken by excisional biopsy, 13 patients by mammotome biopsy(27.7%), and 6 patients(12.8%) by lumpectomy. Twenty-five patients (53.1%) underwent re-lumpectomy, while 19 patients (40.4%) mastectomy, and 3 patients(6.3%) only sentinel lymph node biopsy. Residual tumor was present in 33 patients (70.3%) and multifocal breast cancer was found in 12 patients (25.5%). In terms of the accuracy of MRI in detecting residual tumor, the sensitivity was 63.6%, specificity was 45.5% and the positive predictive value was 77.7%. In that of ultrasonographies, the sensitivity was 52.3%, specificity was 88.8%, and the positive predictive value was 91.6%. Pathologic finding of residual tumor showed that ductal carcinoma in situ was most common (57.1%) in not only radiologic-pathologic concordant cases, but also in radioloigc-pathologic discordant cases (58.3%). But 5 patients (10.6%) with invasive ductal carcinoma in residual tumor were not detected by MRI. Positive predictive value was not associated with residual tumor sizes. The MR findings of residual tumor changed the next procedure from re-lumpectomy to mastectomy (10 patients), additional biopsy of suspicious lesion in ipsilateral breast (2 patients), and second-look ultrasonography (4 patients). Discussion: Preoperative MRI was not critical effect on evaluating the margin status around excisional biopsy sites. An important clinical role of MRI is to identify a subset of patients with extensive residual or multifocal breast cancer who would be better served by undergoing mastectomy rather than breast conserving operation. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-02-10.
INCREASED THROMBIN GENERATION IN BOTH STABLE AND UNSTABLE CORONARY HEART DISEASE DESPITE DUAL ANTIPLATELET THERAPY
Authors: Aruni Seneviratna, Christina Yip, Thet Khaing, Sock Hwee Tan, Sock Cheng Poh, Zhen Long Teo, Yap Eng Soo, Mark Chan
Journal: Journal of the American College of Cardiology (2016)
IMPACT OF ONSET TO BALLOON TIME AND SHORT-TERM MORTALITY IN PATIENTS WITH CARDIOGENIC SHOCK COMPLICATING ACUTE CORONARY SYNDROME TREATED WITH PRIMARY PERCUTANEOUS CORONARY INTERVENTION FROM JCS SHOCK REGISTRY
Authors: Hideki Ebina, Matoba Tetsuya, Mohri Masahiro, Tanaka Nobuhiro, Hokama Yohei, Fukutomi Motoki, Hashiba Katsutaka, Fukuhara Rei, Ueki Yasushi, Suwa Satoru, Matsuura Hirohide, Tachibana Eizo, Yonemoto Naohiro, Nagao Ken
Journal: Journal of the American College of Cardiology (2016)