tbuckley/cabot-search huggingface dataset:
Abstract 1393: CD44 has dual functions to enhance the hyaluronan-induced chemokinesis in cancer cells as an associated molecule of hyaluronidase2-mediated HA catabolism and a hyaluronan receptor for RhoGTPase activation
Authors: Kenichi Harigaya, Teruyoshi Saito, Kazuhiko Azuma, Toshifumi Umemiya, Akihiro Toyoda, Yuki Shida, Motoo Kitagawa
Journal: Cancer Research (2011)

Abstract Major oncogenic signaling pathways are involved in the alteration of hyaluronan (HA) metabolism of cancer cells, such as Erb B, Wnt, TGF-β and p53 signalings. HA is a widely distributed extracellular matrix glycosaminoglycan and changes biological activities depending on its molecular sizes. Our recent study has shown that fragmented low molecular weight (LMW) HA (approximately 20 kDa) is an autocrine chemokinetic motility factor supported by the HA synthethase2-hyaluronidase2 / CD44 system on the plasma membrane of the cancer cells. In HeLaS3 cells, LMW-HA stimulation effectively enhanced cell spreading and random cell movement (chemokinesis) among different molecular sizes of HA (3, 23, 230, 940-kDa). Biochemically, LMW HA effectively provoked a RhoA activation, recurrent Cdc42 and Rac1 activation, and sustained phosphorylation of ERK1/2. Constrastly, 220 kDa HA did not enhance chemokinesis of HeLaS3 cells with similar activation profiles of Rac1 and ERK 1/2 except for the progressive decrease of Cdc42 and RhoA activation. The transfection of CD44 si-RNA to HeLaS3 cells abolished the enhanced chemokinesis with the remarkable decrease of Rho GTPase activation even in LMW HA stimulation. Accordingly, our study showed that CD44 has dual functions to enhance the HA-induced chemokinesis in cancer cells as an associated molecule of hyaluronidase2-mediated HA catabolism and a HA receptor for RhoGTPase activation. 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 1393. doi:10.1158/1538-7445.AM2011-1393
Whole-Body Positron Emission Tomographic Scanning in Patients with Adrenal Cortical Carcinoma
Authors: Mohammed Ahmed, Abdulaziz Al-Sugair, Abdullah Alarifi, Abdulraof Almahfouz, Saif Al-Sobhi
Journal: Clinical Nuclear Medicine (2003)

AHMED, MOHAMMED F.A.C.P.*; AL-SUGAIR, ABDULAZIZ M.D.†; ALARIFI, ABDULLAH F.R.C.P.*; ALMAHFOUZ, ABDULRAOF M.D.*; AL-SOBHI, SAIF F.R.C.S.‡ Author Information
Abstract 761: The development of cell permeable Shp2 PTP inhibitors
Authors: Harshani R. Lawrence, Liwei Chen, Daniele Pernazza, Latanya Scott, Yaun Ren, Yunting Luo, Xin Wu, Sung Shen-Shu, Wayne Guida, Said M. Sebti, Nicholas J. Lawrence, Jie Wu
Journal: Cancer Research (2010)

Abstract Protein tyrosine phosphorylation affects cellular activities that control tumor growth and progression. Protein tyrosine phosphorylation, a key regulatory process of signal transduction pathways, is controlled by the action protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Kinases are now a clinically proven anticancer drug target. The development of PTP inhibitors is, by comparison, a relatively new field. Since PTPs do not require a small molecule cofactor they generally show a low propensity to bind a small molecule inhibitor. Nevertheless there are now examples of highly potent PTP inhibitors that provide promising proof-of-principle that PTPs are druggable. Most PTP inhibitors have a charged or highly polar functional group that mimics the phosphotyrosine residue, that often leads to poor ADME and cell permeability properties. We will report our efforts to address the problems of cell permeability we have encountered in our Shp2 PTP inhibitor program. We have previously reported a series of isatin based Shp2 inhibitors based on a compound (NSC-117199) identified from screen of the NCI Diversity Set. We synthesized &amp;gt;100 analogs of NSC-117199 in our lead optimization effort, which yielded several compounds with approximately 50-fold increase in potency and &amp;gt; 10-fold increase in selectivity (Shp2 versus Shp1). However, these Shp2 PTP inhibitors have either a polar nitro or carboxyl group and have no detectable cellular activity. We will report three approaches to address this problem. The first approach was to prepare neutral ester prodrugs. Several compounds have clearly demonstrable activity against Shp2 in cells. A series of esters has also been designed to also improve the water solubility of the PTP inhibitor. A second approach taken was to further modify the isatin scaffold that does not necessitate the use of a prodrug strategy. We will report the discovery of new isatins related to NSC-117199 that have new modifications that result in cell active Shp2 inhibitors. Finally we will report the discovery and preliminary optimization of new classes of cell active Shp2 inhibitors based on alternative scaffolds. 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 761.
SAT0445 Risk of Cardiovascular Disease in Patients with Osteoarthritis: Results from the Must-Heart Study
Authors: I.K. Eeg, S. Rollefstad, I.K. Haugen, I.C. Olsen, N. Østerås, B. Slatkowsky-Christensen, H.B. Hammer, L. Nordsletten, B. Natvig, T.K. Kvien, A.G. Semb
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Controversies exist regarding whether patients with osteoarthritis (OA) have an increased risk of cardiovascular (CV) disease. <h3>Objectives</h3> Our aim was to evaluate the CV risk in a population-based OA cohort. <h3>Methods</h3> The Musculoskeletal pain in Ullensaker STudy (MUST) is a cross-sectional investigation comprising a thorough clinical examination, recording of CV risk factors in addition to radiographic evaluation of hands, hips and knees of persons with self-reported OA (The MUST-Heart study). Of the 604 persons examined, 438 fulfilled the ACR classification criteria for OA in the hand, knee and/or hip joints. The study population was divided into: 1) generalized OA, defined as bilateral hand OA or involvement of ≥3 out of 6 sites (bilateral hand/hip/knee); 2) focal OA; or 3) non-OA. CV risk was calculated by the SCORE algorithm<sup>1</sup> for persons without CV disease, not using lipid lowering and/or antihypertensive medication (OA n=200 and non-OA n=87). An estimated CV risk &lt;5% for experiencing a fatal myocardial infarction coming 10 years is defined as low to medium risk, while ≥5% is the cut off for initiation of CV preventive pharmacotherapy. Comparisons between groups were done by using independent samples T-test, Mann Whitney-U and χ<sup>2</sup> as appropriate. <h3>Results</h3> The median CV risk for patients with OA [1.40 (IQR 0.65, 2.92)] was significantly higher compared to non-OA [0.99 (IQR 0.52, 1.92)] (p=0.02). The difference in the CV risk was related to higher age (p&lt;0.001), but not to total cholesterol (p=0.07), systolic blood pressure (p=0.13) or to the OA diagnosis. Only 17/200 (8.5%) of the OA patients and 3/87 (3.4%) of the non-OA persons had a CV risk ≥5% (p=0.12). The presence of established CV disease was comparable for those with (n=72/438, 16.8%) and without OA (n=34/166, 21.1%) (p=0.23). Dividing the OA group into focal and generalised OA, did not reveal any further differences regarding estimated CV risk or CV disease compared with non-OA. Inflammatory biomarkers (erythrocyte sedimentation rate and C-reactive protein) were in the normal range for the whole study population, with no difference between OA and non-OA (p=0.30 and 0.10, respectively). <h3>Conclusions</h3> Inhabitants with OA in a Norwegian municipality had an overall low risk of CV disease and did not have higher prevalence of established CV disease compared to non-OA. <h3>References</h3> Perk J, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Atherosclerosis 2012; 223(1):1-68. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2479
Does drug mis-instrumentalization lead to drug abuse?
Authors: Tod E. Kippin
Journal: Behavioral and Brain Sciences (2011)

Abstract Understanding the perceived benefits of using drugs to achieve specific mental states will provide novel insights into the reasons individuals seek to use drugs. However, the precision of attempts to instrumentalize drugs is unclear both across drugs and individuals. Moreover, mis-instrumentalization , defined as discrepancies between such endpoints, may have relevance to understanding the relation among use, abuse, and addiction.
RISK OF CONTRAST INDUCED NEPHROPATHY DURING COMPLETE REVASCULARIZATION COMPARED TO INFARCT-RELATED ARTERY REVASCULARIZATION IN THE SETTING OF ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: A META-ANALYSIS
Authors: Bertrand Njume Mukete, Russell Riehl, Owen Mogabgab, Rohan Samson, Abhishek Jaiswal, Asif Anwar, Thierry Le Jemtel
Journal: Journal of the American College of Cardiology (2016)
Abstract 481: METCAM promotes <i>in vitro</i> motility, invasiveness and colony formation, and <i>in vivo</i> tumorigenesis of human breast cancer cells
Authors: Guang-Jer Wu
Journal: Cancer Research (2010)

Abstract METCAM (alternative names are MUC18, CD146, S-endo 1, MelCAM, and MCAM) is an integral membrane CAM in the Ig-like gene super-family because it has an immunoglobulin-like extra-cellular domain and a cytoplasmic domain, which contains five consensus sequences potentially to be phosphorylated by PKA, PKC, and CK2. METCAM, as predicted from the protein structure, is capable of performing typical functions of CAMs, such as cell-cell interaction, cell-extracellular matrix interaction, and cross-talk with many signaling pathways. Thus altered expression of METCAM should change cell motility and cellular invasiveness, alters angiogenesis, and affects cellular survival and growth. Consistent with this notion, aberrant expression of METCAM positively associates with the malignant progression of melanoma and prostate cancer. However, the role of METCAM in the progression of human breast cancer cells has been controversial. Two groups suggest that METCAM plays a tumor suppressor role in the development of breast cancer. Two other groups suggest the opposite role. To resolve this controversy, we reinvestigate the role of METCAM in the progression of breast cancer cells. We transfected the METCAM cDNA gene into two breast cancer cell lines, MCF-7 and SKBR3, and isolated G418-resistant clones, which expressed high levels of the protein, for testing the effect of enforced expression of the protein on their in vitro and in vivo cellular behaviors. We have found that METCAM is not expressed or very weakly expressed in five luminal breast cancer cell lines, MCF-7, T47D, BT-10, BT474, and SK-BR-3, but moderately expressed in two basal cell-like breast cancer cell lines, MDA-MB231 and 468. Enforced expression of METCAM in two breast cancer cell lines, MCF-7 and SKBR3, increased their in vitro motility and invasiveness and in vitro anchorage-independent colony growth, and promoted disorganized growth in 3D basement membrane culture. Enforce expression of METCAM also increased the in vitro motility and invasiveness of MDA-MB231 and MDA-MB-468 cells. Furthermore, the growth of MDA-MB231 and MDA-MB-468 in the 3D embedded basement membrane culture is inhibited by the anti-huMETCAM antibodies. Furthermore, enforced expression of METCAM dramatically promoted the tumor formation of SK-BR-3 cells in nude mice, but slightly promoted the tumor formation of MCF7 cells in SCID mice via orthotopic injection into mammary fat pads. Taken together, we concluded that over-expression of METCAM in breast cancer cell lines appeared to promote the tumorigenesis of breast cancer cells, suggesting its positive association with the progression of breast cancer cells, similar to melanoma and prostate cancer. 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 481.
INTRAVENTRICULAR PRESSURE DIFFERENCES AT LATE DIASTOLE DURING ISCHEMIA: A DOG STUDY BY THE NEW ECHOCARDIOGRAPHIC METHOD OF RELATIVE PRESSURE IMAGING
Authors: Marie Stugaard, Toshiki Kamimukai, Kasumi Masuda, Daisuke Sakurai, Toshihiko Asanuma, Satoshi Nakatani
Journal: Journal of the American College of Cardiology (2016)
Re-evaluating the inpatient use of routine diphenhydramine transfusion premedication practices.
Authors: Ida Wong-Sefidan, Eric Roeland
Journal: Journal of Clinical Oncology (2013)

164 Background: Routine diphenhydramine premedication to prevent allergic transfusion reactions is common practice despite lack of evidence. First-generation antihistamines are associated with a number of anticholinergic side effects such as sedation and cognitive impairment that impact patient care and increase cost. Because premedication should be evidence-based and patient-specific, the University of California, San Diego (UCSD) inpatient Bone Marrow Transplant (BMT) service implemented a transfusion premedication protocol, specifically addressing antihistamine use. Methods: To revise the protocol, a committee was formed. The committee reviewed evidence-based practices, challenges, pharmacology, and costs of antihistamines, and developed an inpatient BMT antihistamine premedication protocol that omitted pre-ordered diphenhydramine and offered cetirizine as a first-choice premedication. Antihistamine premedication was encouraged for high risk patients only. A retrospective comparison of antihistamine prophylaxis pre (2010-2011) and post (2011-2012) protocol implementation was completed. The number of antihistamine doses and transfusions was computed by a count from the electronic medical records. Results: Despite a 14% increase in transfusions, the number of BMT inpatient antihistamine premedication orders decreased by 26%. Diphenhydramine use decreased from 85.9% to 34.2%, while cetirizine use increased from 3.3% to 55.9%. Conclusions: The evidence-based, risk-stratified antihistamine premedication protocol decreased the use of diphenhydramine. Limitations include the retrospective design and lack of data comparing reactions in patients who did and did not receive premedication. Our institution plans to expand this study and complete a prospective evaluation of safely and rationally administered transfusion premedication with the goal to evaluate premedication-related toxicity and methods to improve the quality of life in our patients. [Table: see text]
AB0660 Prevalence of migraine in iraqi systemic lupus erythematosus patients
Authors: F.I. Gorial, A.M. Al-Mahdawi, A. Shaker
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a relapsing-remitting autoimmune disease characterized by wide range of organ involvement and clinical symptoms (1). Headache is one of the common neurological findings in SLE (2). Migrainous headache is one of the most common neurological disorders and causes substantial levels of disability (3, 4). <h3>Objectives</h3> To assess prevalence, type,severity, and predictors of migraine in Iraqi systemic lupus erythematosus (SLE) patients <h3>Methods</h3> A case control study was conducted on patients attending Medical Department, Rheumatology unit&amp; Neurological Department in Baghdad Teaching Hospital. Fifty patients with SLE diagnosed by rheumatologist according the American College of Rheumatology Revised criteria for the classification of systemic lupus erythematosus (5) were compared with 50 healthy control group matched for age and sex. The International Headache Society (IHS) classification (6) was used for diagnosis of migraine type.Migraine Disability Assessment (MIDAS) headache questionnaire was used to assess severity of migraine (7). <h3>Results</h3> There were 15 (30%) migrainous subjects in SLE group compared with 6 (12%) migrainous subjects in the control group (P=0.027). In migrainous SLE patients, 80% have migraine without aura, 13.3% migraine with aura, and 6.7% retinal migraine. The moderately severe migraine was commonly observed (53.3%). There were significant associations between migraine and Raynaud’s phenomenon, neurosis, and anticardiolipin antibodies (p&lt;0.05). <h3>Conclusions</h3> There is high prevalence of migraine in Iraqi SLE patients. The common type and moderately severe migraine most commonly observed. Raynaud’s phenomenon, neurosis, and anticardiolipin antibodies are significant associates with migraine. <h3>References</h3> Benedict RHB, Shucard JL, Zivadinov R, and Shucard DW. Neuropsychological Impairment in Systemic Lupus Erythematosus: A Comparison with Multiple Sclerosis. Neuropsychol Rev 2008 June; 18(2): 149–66. doi:10.1007/s11065-008-9061-2. Lessa B, Santana A, Lima I, et al. Prevalence and classification of headache in patients with systemic lupus erythematosus. Clin Rheumatol 2006;25:850-3 Andlin-Sobocki P, Jönsson B, Wittchen H U, and Olesen, J. Cost of disorders of the brain in Europe. Eur. J. Neurol. 2005; 12: 1–27. Wang SJ, Fuh JL, Young YH, Lu SR, and Shia B C. Prevalence of migraine in Taipei, Taiwan: a population-based survey. Cephalalgia 2000; 20: 566–72. Hochberg, MC. Updating the American College of Rheumatology Revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40:1725. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004; 24 Suppl 1:9-160. Migraine Disability Assessment (MIDAS) headache questionnaire. (© Innovative Medical Research 1997. <h3>Disclosure of Interest</h3> None Declared
Abstract 882: Copy number variation analysis identified multiple genetic variants related to nasopharyngeal carcinoma predisposition
Authors: Wen-Hui Su, Ka-Po Tse, Min-lee Yang, Yin Yao Shugart, Yu-Sun Chang
Journal: Cancer Research (2011)

Abstract Nasopharyngeal carcinoma (NPC) is a multi-factorial malignancy closely associated with genetic factors and Epstein-Barr virus infection. Recently, we have conducted a genome-wide association study (GWAS) in 277 NPC patients and 285 healthy controls within the Taiwanese population, analyzing 480,365 single-nucleotide polymorphisms (SNPs). Twelve statistically significant SNPs were identified and mapped to chromosome 6p21.3 in the major histocompatibility complex region. In addition to HLA-A gene, we detected novel significant associations between NPC and two genes: specifically, gamma aminobutyric acid b receptor 1 and HLA-F. To our knowledge, it is the first GWAS report of NPC showing that multiple loci (HLA-A, HLA-F, and GABBR1) within chromosome 6p21.3 are associated with NPC. Following the GWAS study, we made an effort to search systematically for copy number variations (CNVs) that confer increased risk to NPC using the same dataset. We generated CNV calls using four different softwares and used 15 internal duplicated samples to look for best filtering criteria. CNVs were selected if same CNVs were identified from two independent softwares to increase credibility of prediction. We identified eight CNVs that overrepresented in NPC patients compared to healthy controls. Six deletions on chromosomes 3, 6, 7, 8 and 19, as well as 2 duplications on chromosomes 7 and 12 were found. One of the most significant CNV on chromosome 6p21.3 was further replicated in an independent case-control dataset, using a deletion-specific polymerase-chain reaction. To the best of our knowledge, it is the first study of genome-wide constitutional CNV in NPC. 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 882. doi:10.1158/1538-7445.AM2011-882
SAT0337 Adipokines related to biochemical and radiographic measures of burden, incidence, and progression in early-stage knee osteoarthritis: Data from check
Authors: W.E. van Spil, P.M. Welsing, F.P. Lafeber
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The association between obesity and knee OA has classically been attributed to biomechanical mechanisms, but more recently also metabolic mechanisms have been implied to be involved. Key mediators in this metabolic link between obesity and OA could be the adipokines (leptin, adiponectin, resistin, and others) that are mainly secreted by adipose tissue. <h3>Objectives</h3> To investigate cross-sectional and predictive associations between plasma adipokines and biochemical and radiographic measures of (very) early-stage knee osteoarthritis (OA). <h3>Methods</h3> Baseline pLeptin, pAdiponectin, and pResistin, and uCTX-II, sPIIANP, sCS846, sCOMP, sHA, and sPIIINP were assessed by ELISA or RIA in CHECK (Cohort Hip and Cohort Knee), a cohort of 1002 participants with symptoms related to (very) early-stage knee and/or hip OA. Knee radiography was performed at baseline and after 2 and 5 years. Knee OA burden was defined as the summed Kellgren &amp; Lawrence (K&amp;L) grade of both knees at baseline. Five-year knee OA incidence and progression were defined as the area under the curve (AUC) of summed K&amp;L grade progression. <h3>Results</h3> pLeptin showed positive associations with uCTX-II, sCOMP, sPIIANP, sHA, and sPIIINP. Furthermore, pLeptin was positively associated with knee OA burden and progression. Associations largely disappeared after adjustment for BMI. pAdiponectin showed positive associations with uCTX-II and sCOMP, but no association with any radiographic OA measure. pResistin was positively associated with sPIIINP and with knee OA burden and incidence. Although statistically significant, all associations were weak. <h3>Conclusions</h3> Especially leptin and resistin showed positive associations with multiple biomarkers of synovial and cartilage metabolism and with radiographic knee OA burden, incidence, and progression. This might indicate that these adipokines play aggravating roles in knee OA, possibly (also) mediated through synovitis. However, since associations were only weak, another conclusion should be that these systemic adipokines generally do not play a major role in early-stage knee OA. <h3>Acknowledgements</h3> This study was funded by CHECK, an initiative of the Dutch Arthritis Association. <h3>Disclosure of Interest</h3> None Declared
740 THE FEASIBILITY STUDY OF ALLOGENEIC BONE MARROW MESENCHYMAL STEM CELLS TRANSPLANTATION IN ACUTE-ONCHRONIC LIVER FAILURE PATIENTS CAUSED BY HEPATITIS B
Authors: J. Chen, H. Cao, D. Xie, W. Weng, J. Li, Y. Mei, Z. Gao, B. Lin
Journal: Journal of Hepatology (2013)
Atypical Mycobacteriosis Caused by Mycobacterium haemophilum in an Immunocompromised Patient
Authors: Silvia Münster, Jozef Zustin, Thorsten Derlin
Journal: Clinical Nuclear Medicine (2013)

We report a rare case of atypical mycobacteriosis diagnosed by 18F-FDG PET/CT. A 28-year-old man with a history of kidney transplantation presented with fever, painful nodular skin lesions, and elevated inflammatory markers. FDG PET/CT demonstrated multiple subcutaneous, cutaneous, and osseous areas of increased tracer uptake. Histopathologic and microbiological evaluation revealed disseminated infection with Mycobacterium haemophilum. FDG PET/CT is a valuable tool for early and correct diagnosis of occult sources of infection in immunocompromised patients.