tbuckley/cabot-search huggingface dataset:
Abstract 5293: CCN3 increases motility of human chondrosarcoma via PI3K, AKT and NF-κB pathways
Authors: Ruei-Ching Chen
Journal: Cancer Research (2010)

Abstract Nephroblastoma overexpressed (Nov; CCN3), from the CCN gene family, which is involved in many cellular activities such as growth and differentiation. Most of the CCN family can regulate the cell motility, adhesion and division. Here, we found that CCN3 increased the migration and expression of matrix metalloproteinase (MMP)-13 in human chondrosarcoma cells (JJ012 cells). Activations of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), Akt and NF-κB pathways after CCN3 treatment was demonstrated, and CCN3-induced expression of MMP-13 and migration activity was inhibited by the specific inhibitor of PI3K, Akt and NF-κB cascades. Transfection of cells with FAK, p85, Akt, IKKα and IKKβ mutant also reduced CCN3-mediated cancer migration. Taken together, our results suggest that CCN3 acts through FAK/PI3K/Akt, which in turn activates NF-κB, resulting in the activation of MMP13 andcontributing to the migration of human chondrosarcoma cells. 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 5293.
AB0436 Anca associated vasculitis in a teaching hospital
Authors: A. Alarfaj, N. khalil
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The antineutrophil cytoplasmic autoantibody (ANCA) - associated vasculitis (AAV) include granulomatosis with polyangitis GPA (Wegener’s), microscopic polyangitis (MPA), allergic granulomatosis and angitis (CSS) (Churg-Strauss syndrome) and renal - limited vasculitis (RLV) [1]. The strong association of proteinase 3 ANCA (PR3 ANCA) / myeloperoxidase ANCA (MPO ANCA) with the AAV has led to assumption that ANCAs are directly involved in the pathogenesis of these diseases [2]. PR3-ANCAs are mainly detected in GPA, whereas MPO-ANCAs are predominantly found in MPA and CSS. In GPA, PR3-ANCA is positive at &gt;90% [3]. <h3>Objectives</h3> To study the profile of ANCA in ANCA associated vasculitis (AAV). <h3>Methods</h3> A review of ANCA tested patients at KSU clinics, Riyadh, Saudi Arabia during the period 1980-2012. <h3>Results</h3> Out of 459 patients tested for ANCA, 330(71.9%) were positive for ANCA. Patterns were: P-ANCA in 167 (36.4 %), C-ANCA in 103 (22.4%) and Atypical in 60(13.1%). Among these 459 ANCA tested patients, Twenty three cases of ANCA associated vasculitis (AAV) were identified. The diagnoses in these 23 cases were: GPA in 16/23(69.6%), CSS in 5/23(21.7%) and MPA in 2/23(8.7%) cases. With regard to 16 GPA cases, the results showed that 14 (87.5%) were ANCA positive and 2 (12.5%) were ANCA negative. Pattern of ANCA was C- ANCA in 11 (68.75 %) and P- ANCA in 3 (18.75 %). Ten of the 16 GPA cases were analyzed for MPO and PR3 specificity. None showed specificity for MPO, while 8 (80.0%) showed PR3 specificity and 2 were without PR3 specificity. <h3>Conclusions</h3> In all ANCA tested patients for various diagnoses, P-ANCA (36.4%) was more frequent compared to C-ANCA. However GPAwas the most common vasculitis[16/23 (69.6%)]. We found that 87.5 % of GPA cases were positive for ANCA, most of them (68.8 %) were C-ANCA positive and mostly (80.0%) showed PR3-ANCA specificity. <h3>References</h3> Kallenberg CG, Heeringa P, Stegeman CA: Mechanisms of disease: pathogenesis and treatment of ANCA-associated vasculitis. Nat Clin Pract Rheumatol 2006, 2:661–670. van der Woude FJ, Rasmussen N, Lobatto S <i>et al</i>. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener’s granulomatosis. <i>Lancet</i> 1985; 1:425-429. Specks U, Wheatley CL, McDonald TJ et al. Anticytoplasmic autoantibodies in the diagnosis and follow up of Wegener’s granulomatosis. Mayo Clin Proc 1989; 64: 28–36. <h3>Disclosure of Interest</h3> None Declared
Prolonged Extracorporeal Oxygenation for Acute Post-Traumatic Respiratory Failure (Shock-Lung Syndrome)
Authors: J. Donald Hill, Thomas G. O'Brien, James J. Murray, Leon Dontigny, M. L. Bramson, J. J. Osborn, F. Gerbode
Journal: New England Journal of Medicine (1972)

Abstract A 24-year-old man sustained subadventitial transection of the thoracic aorta and multiple orthopedic injuries resulting from blunt trauma. The aortic injury was repaired. Because respirato...
Abstract P4-08-08: Cross Reactivity of Clinically Validated Anti-HER2 Antibodies
Authors: A-S Schrohl, SS Jensen, HC Pedersen, SL Nielsen, N. Brunner
Journal: Cancer Research (2010)

Abstract Background: Human epidermal growth factor receptor (HER-) 2 belongs to the family of epidermal growth factor receptors (EGFRs) with homology to HER1, HER3 and HER4. HER2 is over-expressed in approximately 20% of invasive human breast cancers (Wolff, Hammond et al. 2007). Over-expression of HER2 is associated with a poor prognosis; however, the protein can be targeted by anti-HER2 therapy (trastuzumab, Herceptin®) (Slamon, Leyland-Jones et al. 2001). Trastuzumab therapy is offered only to patients whose tumors over-express HER2 protein and/or show amplification of the HER2 gene. Accordingly, the expression level of HER2 protein and/or amplification of the HER2 gene are determined routinely in all newly diagnosed breast cancers. Essential to this testing of HER2 expression at the protein level is the availability of specific antibody-based test systems. Aim: The aim of the present study was to investigate the specificity of three clinically approved commercially available anti-HER2 antibodies towards members of the EGFR-family. Methods: We studied the antibody used in the Herceptest™ (Dako), the PATHWAY® antibody (Ventana Medical Systems, Inc.) and the Oracle™ antibody (Leica Microsystems). Antibody specificity was investigated by manually performed immunohistochemistry (IHC) and in competitive ELISAs. For IHC, Chinese Hamster Ovary (CHO) cells were transiently transfected with the intracellular domain of respectively HER1, HER2, HER3 and HER4 and all three antibodies were applied to sections of formalin-fixed paraffin-embedded (FFPE) transfected cells. In ELISA, cross reactivity towards HER1 and HER4 was tested with peptides corresponding to the C-terminal part of HER1 and HER4. Results: In IHC experiments, all three antibodies stained cells transfected with HER2. Binding of the antibodies to HER2 was confirmed bycompetitive ELISA. However, in IHC experiments the PATHWAY® and the Oracle™ antibodies also stained cells transfected with HER4. Competitive ELISAs confirmed binding of the PATHWAY® antibody to HER4, whereas binding of the Oracle™ antibody to HER4 could not be confirmed in a competitive ELISA. None of the antibodies cross reacted with HER1 and HER3 homologous to the HER2 binding site of the antibodies. Conclusions: Two out of three clinically validated anti-HER2 antibodies were shown to cross react with HER4 in FFPE cells. As determination of HER2 over-expression and/or amplification guides therapy with trastuzumab, a valid test result by the use of specific antibodies is crucial to ensure proper personalized therapy with HER2-targeted therapy. These results warrant further investigation of anti-HER2 antibodies and of the procedures for clinical determination of HER2 protein expression. References: Slamon DJ et al. (2001) J Med 344:783 Wolff AC et al. (2007) J Clin Oncol 25:118 Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-08.
A role for GATA-3 in control of estrogen receptor alpha expression.
Authors: C Hostetter, LA Licata, JC Keen
Journal: Cancer Research (2009)

Abstract Abstract #3050 Expression of the GATA-3 binding protein correlates with estrogen receptor (ER) alpha expression in primary and cultured breast cancer cells. While the significance of this correlation and role of GATA-3 in breast cancer remains unclear, GATA-3 may serve as a good prognostic indicator in breast tumors. Recently, a reciprocal interaction between GATA-3 and ER has been demonstrated. GATA-3 may regulate ER levels through binding to an enhancer region upstream of the ER gene while ER can associate with and regulate GATA-3 expression. Meta-analyses of several cancer microarrays indicate that GATA-3 is co-expressed with ER and other ER responsive genes, further suggesting a role of GATA-3 in the ER signaling pathway. Our laboratory has been investigating the role of the RNA binding protein HuR/ELAV1 in control of mRNA stability in breast cancer cells. We have previously reported that ER mRNA stability is increased through binding of HuR to the 3'UTR. Microarray analysis of those transcripts associated with HuR in MCF7 cells showed that GATA-3 mRNA associates with HuR compared to an IgG control. Biotin pulldown assays using a biotinylated GATA-3 RNA probe confirmed that HuR binds to the GATA-3 3'untranslated region (UTR). Inhibition of HuR using siRNA probes decreased GATA-3 mRNA and protein expression, further indicating a role for HuR in regulation of GATA-3 mRNA stability. siRNA mediated inhibition of GATA-3 expression significantly reduced ER mRNA and protein levels. Surprisingly, we found that GATA-3 bound to the ER mRNA by binding to two out of four regions within the ER 3'UTR, suggesting that while GATA-3 may play a role in upregulation of ER mRNA transcription through the enhancer interaction, GATA-3 may stabilize ER mRNA once transcribed by binding to the ER 3'UTR. Studies are ongoing to fully characterize this role of GATA-3 in control of ER mRNA stability. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3050.
Stat Bite: Cancer in Children by Race
Authors: L. A. G. Ries
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Stat Bite: Cancer in Children by Race Get access Lynn A. Gloeckler Ries Lynn A. Gloeckler Ries Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 6, 17 March 1993, Page 425, https://doi.org/10.1093/jnci/85.6.425 Published: 17 March 1993
AB0291 Therapy response in rheumatoid arthritis patients and concomitant fibromyalgia
Authors: I. Cojocaru-Gofita, P. Ciurea, A. Rosu, A. Musetescu, F. Vreju, M. Florea, A. Barbulescu, C. Hoanca
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It has been stated that rheumatoid arthritis (RA) and fibromyalgia (FM) can simultaneously affect patients. At the same time DAS28 values tend to be higher in RA patients whom have also developed FM and this might cause a more aggressive therapeutic approach and further misinterpretation of the clinical outcome in this group of patients. <h3>Objectives</h3> To study the effect and beneficial outcome of remissive therapy in a Romanian RA cohort diagnosed with concomitant FM <h3>Methods</h3> The initial group included 34 established RA female patients with a disease duration of minimum 12 months (diagnosed between 2006-2008) and a mean age of 41.3±4 years which were also diagnosed with FM within 3 to 6 months prior to inclusion. A second group consisting of 20 RA female patients with no clinical signs of FM was chosen as controls. All patients were started on a stable Methotrexate dose of 7.5-15mg/week for the first 12 weeks. Both groups were evaluated every 3 to 6 months between 2009-2011 through the Disease Activity Score on 28 joints (DAS284v) <h3>Results</h3> The first group showed little if no DAS28 improvement with a mean value of 5.1±0.7 (p&lt;0.001) after 3 months of MTX therapy leading towards dosage increasing while the controls showed a mean value of 4.2±0.5 (p&lt;0.001) thus avoiding dosage adjustments. After the second evaluation point at 6 months, 7 out of the initial 34 patients included in the study group needed a higher MTX dosage showing a mean value of DAS28 of 4.5. After the first 12 months 11 patients from the study group and 3 controls were administered a different remissive therapeutic agent due to their disease activity score – a mean value of DAS28 of 4.8±0.7 (p&lt;0.001) <h3>Conclusions</h3> In the analyzed groups fibromyalgia showed itself to be an aggravating factor adding to the rheumatoid arthritis. Furthermore patients diagnosed with both RA and FM needed a more aggressive change in their treatment regimen showing that an extremely careful approach is needed in the RA cases where a concomitant FM may develop simultaneously <h3>Disclosure of Interest</h3> None Declared
Inherited Hemorrhagic Disorder with Antihemophilic Globulin Deficiency and Prolonged Bleeding Time (Vascular Hemophilia)
Authors: Carroll L. Spurling, Milton S. Sacks
Journal: New England Journal of Medicine (1959)

SINCE 1953 a number of reports seem to have established as a clinical entity a hereditary hemorrhagic disorder characterized by deficiency of antihemophilic globulin and a prolonged bleeding time. Despite the deficiency of antihemophilic globulin, the disease differs from classic hemophilia in several important ways: it occurs commonly in both sexes and thus follows an obviously different genetic pattern; the type of bleeding differs in that it is most often into the skin or from mucous membranes and rarely involves the joints; and the bleeding time is characteristically prolonged.Alexander and Goldstein,1 in 1953, first described the dual hemostatic defect . . .
Abstract 4997: The isolation of miRNA targeting EGFR gene in lung cancer
Authors: Gaku Yamaguchi, Norihiko Ikeda, Masahiko Kuroda, Tatsuo Ohira, Osamu Uchida, Naohiro Kajiwara, Jitsuo Usuda, Masatoshi Kakihana, Hisashi Saji, Masakatsu Takanashi, Kohji Fujita, Kohichi Yoshida, Hiroaki Kataba, Kentaro Iwasaki, Masami Tanaka
Journal: Cancer Research (2011)

Abstract MicroRNAs (miRNAs) belong to a class of the endogenously expressed non-coding small RNAs which primarily function as gene regulators. Growing evidence suggests that microRNAs have a significant role in tumor development. Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains the leading cause of cancer related deaths worldwide. Although EGFR signaling is important and well studied with respect to NSCLC progression, little is known about how miRNAs mediate EGFR signaling to modulate tumorigenesis. In this study, we identified miRNAs that directly regulate the EGFR gene expression. We employed computational tools such as Pictar and Target Scan, and putative targets of 88 miRNAs were identified within the EGFR mRNA. Then, we analyzed the expression of EGFR in miRNAs-transfected human lung cancer cells (H3255, A549, Hcc827) by real time-PCR methods. In addition, we performed argonaute (AGO) IP experiments to ascertain whether these algorithmically predicted miRNA targets are biologically true targets in EGFR. Convincingly, we found that two miRNAs directly regulated the EGFR and both of these miRNAs also inhibited cell growth in cell viability assays. Identifying microRNA regulators of EGFR may contribute in development of novel therapeutics, and non-invasive early detection biomarkers for NSCLC. 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 4997. doi:10.1158/1538-7445.AM2011-4997
FDA reveals new initiatives to deal with drug shortages
Authors: M. McCarthy
Journal: BMJ (2013)

Under proposed rules announced on 31 October by the US Food and Drug Administration, drug makers will be required to notify the government at least six months in advance, or as far in advance as practical, if they intend to stop making a medically important drug. This rule will also apply to any interruption in a drug’s manufacture that is likely to lead to a disruption in supply.1 

The rules were drawn up to deal with shortages of drugs that have sent doctors and hospitals in the US scrambling to find new suppliers or alternatives. Shortages peaked in 2011, when more than 250 drugs and biological products were reported to …
O6.02 * ANALYSIS OF PD1 AND PD-L1 EXPRESSION IN GLIOBLASTOMA
Authors: A. S. Berghoff, B. Kiesel, G. Widhalm, A. Wohrer, K. Dieckmann, M. Filipits, C. Marosi, J. A. Hainfellner, M. Preusser, W. Wick
Journal: Neuro-Oncology (2014)

BACKGROUND: Immune checkpoint inhibitors targeting programmed cell death (PD)1 and PD-ligand (L)1 show promising clinical activity in various solid extracranial cancers. Expression of PD1 on tumor infiltrating T lymphocytes and PD-L1 expression on tumor cells were postulated to have predictive value for the response to PD1/PD-L1 targeting immune checkpoint inhibitors. METHODS: 135 specimens of 117 patients (median age 60, range 21-80); median KPS 90 (range 10-100) with glioblastoma were included. In 18 patients, resection specimens of the first local recurrence in addition to tumor tissue from the initial resection were available. Analyses of PD1, PD-L1, CD3 and CD8 expression were performed by immunohistochemistry and previously published semiquantitative evaluation criteria. O6-methylguanine DNA methyltransferase (MGMT) promoter methylation was analyzed using pyrosequencing and a cut-off at 8%. RESULTS: Sparse to moderate density of tumor-infiltrating lymphocytes (TILs) in a total of 100/135 (74.1%) cases (CD3+ 92/135, 68.1%; CD8+ 64/135, 47.4%) was observed. PD1 expression was found on scattered TILs, both within the tumor tissue and in the perivascular compartment, in 20/135 (14.8%) cases. PD-L1 expression was evident on tumor cells and macrophages/microglial cells throughout the tumor tissue with occasional focal accentuation in 116/135 (85.9%) specimens, with 44.5% showing PD-L1 staining of more than 50% of the viable tumor tissue. MGMT methylation was found in 37/99 (37.4%) analyzed specimens. No significant correlation of expression of PD1 or PD-L1 with the density of TILs or MGMT methylation status (p > 0.05) was observed. Younger age (p = 0.009), high KPS (p = 0.035) and MGMT hypermethylation (p = 0.008) showed a significant correlation with favorable overall survival, while TIL density or expression of PD1 (p = 0.783) and PD-L1 (p = 0.866) did not associate with patient outcome. CONCLUSION: PD1 and/or PD-L1 are immunohistochemically detectable in a majority of glioblastoma samples. A clinical study with specific immune checkpoint inhibitors seems to be warranted in glioblastoma.
IMPROVEMENT IN PSORIASIS SKIN DISEASE SEVERITY IS ASSOCIATED WITH REDUCTION OF CORONARY PLAQUE BURDEN
Authors: Joseph Lerman, Aditya Joshi, Justin Rodante, Tsion Aberra, Mohammad Tarek Kabbany, Taufiq Salahuddin, Qimin Ng, Joanna Silverman, Marcus Chen, David Bluemke, Martin Playford, Nehal Mehta
Journal: Journal of the American College of Cardiology (2016)
Screening for Carriers of Tay-Sachs Disease among Ashkenazi Jews
Authors: Barbara L. Triggs-Raine, Annette S.J. Feigenbaum, Marvin Natowicz, Marie-Anne Skomorowski, Sheldon M. Schuster, Joe T.R. Clarke, Don J. Mahuran, Edwin H. Kolodny, Roy A. Gravel
Journal: New England Journal of Medicine (1990)

The prevention of Tay-Sachs disease (GM2 gangliosidosis, type 1) depends on the identification of carriers of the gene for this autosomal recessive disorder. We compared the enzyme-based test widely used in screening for Tay-Sachs disease with a test based on analysis of DNA. We developed methods to detect the three mutations in the HEXA gene that occur with high frequency among Ashkenazi Jews: two mutations cause infantile Tay-Sachs disease, and the third causes the adult-onset form of the disease. DNA segments containing these mutation sites were amplified with the polymerase chain reaction and analyzed for the presence of the mutations.
S51 Reducing intracellular aggregation and improving the secretion of Z alpha-1 antitrypsin
Authors: S. Alam, J. Wang, S. Janciauskiene, R. Mahadeva
Journal: Thorax (2011)

The Z variant (Glu342Lys) of α<sub>1</sub>-antitrypsin (AT) is one of the serpinopathies; it polymerises and accumulates in the hepatocyte endoplasmic reticulum (ER) resulting in neonatal hepatitis and liver cirrhosis. The secretory defect leaves the lungs vulnerable to elastolysis and early-onset emphysema. Prevention of polymerisation of Z-AT can be achieved in vitro by targeting strand 4a of the AT molecule. Here we evaluate whether an inhibitor of polymerisation; Ac-TTAI-NH<sub>2</sub> (4M) would inhibit Z-AT polymerisation in a cell model. HEK293 cells were transfected with Z-AT (Z-AT cells) or control M-AT (M-AT cells). ELISA demonstrated significantly reduced Z-AT secretion, 242(SEM±63) ng/ml compared to M-AT, 2449±130 ng/ml (p≤0.001), due to retention of Z-AT polymers in inclusion bodies. This was confirmed by electron microscopy demonstrating distension of the rough ER, and ELISA and Immunoblot with a polymer specific antibody (ATZII). 4M significantly reduced the amount of polymers in inclusions in a dose-dependent manner; no peptide, 2468.5±μg/ml, 5 mg, 2181.7±26.2 ng/ml (p=0.006), 10 mg, 1576±164.7 ng/ml (p=0.001), and 20 and 30 mg completely prevented polymer formation in inclusions (p≤0.001). Unrelated peptides had no effect. Elastase activity of AT in the supernatant from Z-AT cells was significantly reduced compared to M-AT cells; p≤0.001, in keeping with the secretory defect due to retention of Z-AT in inclusion bodies. The elastase activity (and AT concentration) in the supernatant from Z-AT cells was restored by 20 mg 4M, O.D. 405 nm, Z-AT vs Z-AT + 20 μg 4M, 0.129±0.009 vs 0.788±0.054 respectively, (p≤0.001), where a higher O.D. represents higher elastase activity. Functional activity of secreted AT following treatment with 4M was confirmed by its ability to form an SDS-stable complex with elastase as shown by immunoblot. RT-PCR showed that the ER accumulation of Z-AT induced cell stress; NF-κB activation, expression of protein kinase RNA (PKR)-like ER kinase (<i>PERK</i>), and IL-6 (100.4±16 pg/ml) and IL-8 (2592.5±575 pg/ml), all of which could be abrogated effectively by 20 mg 4M (IL-6, 45.8±28 pg/ml, p≤0.001 and IL-8, 184.3±29 pg/ml, p=0.014). These findings are the first evidence that inhibitors of Z-AT polymerisation targeting s4A can prevent its cellular accumulation and deleterious effects. Importantly, this strategy was also able to improve plasma concentration of Z-AT.