tbuckley/cabot-search huggingface dataset:
Abstract 2193: Characterization of the aggresome targeted Q141K ABCG2/BCRP variant.
Authors: Agnes Basseville, Suneet Shukla, Akina Tamaki, Robert Robey, Suresh V. Ambudkar, Susan E. Bates
Journal: Cancer Research (2013)

Abstract ABCG2 is a member of the G subfamily of human ABC transporters. It is an ATP-dependent protein and is a half-transporter that must dimerize for function. In various tumor cell lines, ABCG2 was involved in resistance to chemotherapy, by transporting numerous anticancer agents including tyrosine kinase inhibitors. Studies show the transporter has an important role in normal tissue protection, including the blood-brain and maternal-fetal barriers. It has also been observed that ABCG2 may play a protective role with respect to exposure to smoke or dietary carcinogens. A common variant in human ABCG2, the polymorphism Q141K, impairs expression and function, thereby reducing drug clearance and increasing the toxicity of chemotherapy and other substrate drugs. Although the activity of the Q141K variant is regularly described, biochemical data remain rare. Q141K has an impaired trafficking to cell surface compared to the WT protein and is sequestered in the aggresome. Here we characterized the Q141K and WT protein in human cells, studying post-translational modification, biochemistry, dimerization status, half-life, and endocytosis. Glycosylation and phosphorylation are equivalent, as is ATP binding and hydrolysis, and substrate binding using IAAP competition assays. Cell treatment with romidepsin, an HDAC inhibitor approved by FDA as an anticancer agent, restored the impaired variant trafficking, leading to an increase in drug efflux. The restoration of ABCG2 Q141K function has potential applications in oncology and in medicine, in improving normal tissue protection and drug elimination, as well as in cancer prevention since several carcinogens are substrates for ABCG2. Citation Format: Agnes Basseville, Suneet Shukla, Akina Tamaki, Robert Robey, Suresh V. Ambudkar, Susan E. Bates. Characterization of the aggresome targeted Q141K ABCG2/BCRP variant. [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 2193. doi:10.1158/1538-7445.AM2013-2193
1065 COMBINED TRANSIENT ELASTOGRAPHY OF THE LIVER AND SPLEEN TO ASSESS DISEASE SEVERITY IN CHRONIC VIRAL LIVER DISEASE
Authors: R. Pozzi, M. Fraquelli, M. Giunta, C. Rigamonti, S. Della Valle, S. Massironi, C.B. Conti, A. Aghemo, G. Ronchi, D. Conte, M. Colombo
Journal: Journal of Hepatology (2012)
Induced differentiation of erythroleukemia cells by hexamethylene bisacetamide: a model for cytodifferentiation of transformed cells.
Authors: P A Marks, R A Rifkind
Journal: Environmental Health Perspectives (1989)

There is considerable evidence that malignant transformation need not eliminate the potential for a cell to express its developmental capabilities. This review explores the process whereby polar compounds, hexamethylene bisacetamide (HMBA) in particular, induce murine erythroid leukemoid cells (MELC) to express the differentiated erythroid phenotype, including hemoglobin production and cessation of cell division. This is a multi-step process which, although the mechanisms of action of HMBA are not yet fully understood, is amenable to experimental definition and analysis. Early effects, including changes in protein kinase C activity, in ion transport, and in expression of certain nuclear proto-oncogenes, have been examined in relation to the onset of terminal cell differentiation. This experimental experience has formed the context for initiating preliminary clinical studies designed to examine the pharmacology of HMBA and to explore its potential for modifying the natural history of cancer.
SAT0146 Single nucleotide polymorphisms in the TNF-α gene and efficacy of anticytokine therapy in patients with rheumatoid arthritis
Authors: N. Shkaruba, A. Silkov, J. Sennikova, A. Sizikov, O. Herzsog, S. Dolgikh, V. Mazurov, J. Shulman, L. Sizyakina, T. Kalashnikova, V. Kozlov, S. Sennikov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tumour necrosis factor (TNF-α) is an multifunctional proinflammatory cytokine that plays an important role in systemic inflammatory process, autoimmune diseases and stimulates reactions of inflammation. There is increased level of TNF-α production in many systemic inflammatory processes. It is known that anti-cytokine therapy (infliximab, adalimumab) for rheumatoid arthritis neutralizes the effects of TNF-α. TNF-α is known to have some biallelic single-nucleotide polymorphisms that may associate with response to anti-TNF therapy. <h3>Objectives</h3> The aim of this work was to examine the correlation of -1031T&gt;C, -857C&gt;T, -238G&gt;A and -308G&gt;A polymorphisms of the TNF-α gene with response to anti-TNF therapy with infliximab in patients with rheumatoid arthritis of the Southwest Siberian Population. <h3>Methods</h3> Blood samples were taken from 91 patients with rheumatoid arthritis treated with infliximab. Patients with rheumatoid arthritis treated with infliximab were divided into responders and non-responders according to EULAR response criteria. Evaluation of treatment efficacy was conducted before the sixth infusion of the infliximab. The genetic distribution of SNPs in the promoter site was established by PCR-restriction fragment length polymorphism (PCRRFLP) analysis. For statistical analysis of the data we used the Spearman correlation index, χ<sup>2</sup>-criterion (Pχ) and Fisher’s precise method for small samples. <h3>Results</h3> The non-responders group was 21,98%. It was found statistically significant association between the efficacy of therapy (EULAR response criteria) and the polymorphism at position -857C&gt;T of the TNF-α gene before the sixth infusion of the infliximab. Spearman correlation index was for these parameters R = -0,27 (p=0,01). It was found that the CC genotype presented more frequently in non-responders (χ<sup>2</sup> =5,27, p=0.02, OR=0.1, CI95 0.01272-0.7998). The risk of treatment failure in carriers of genotype -857CC increased by 29.29% compared with carriers of genotypes -857CT and -857TT. In addition it was found that C allele presented more frequently in patients with treatment failure (χ<sup>2</sup> =5,015, p=0.03, OR=0.1851, CI95 0.04226-0.8103). The risk of treatment failure in carriers of allele C at position -857 was higher by 17.14% compared with carriers of the alternative allele. <h3>Conclusions</h3> The polymorphism 857C&gt;T is informative as a molecular marker of the efficacy of anti-TNF-α therapy of rheumatoid arthritis. Work is supported by grants of the RFBR (the grant 09-04-13620 ofi_s) and FTP “Scientific and Scientific-Pedagogical Personnel of the Innovative Russia in 2009-2013” (GC No. 02.740.11.0707). <h3>Disclosure of Interest</h3> None Declared
ASCO and AACR to Undergo "Trial Separation" in 1994
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article ASCO and AACR to Undergo “Trial Separation” in 1994 Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 23, 2 December 1992, Pages 1774–1776, https://doi.org/10.1093/jnci/84.23.1774 Published: 02 December 1992
Choledochoscope-assisted percutaneous fibrin glue sealing of bile leak complicating transarterial chemoembolization of hepatocellular carcinoma after liver transplantation
Authors: V. Cennamo, L. Fuccio, E. Giampalma, E. Terzi, L. Eusebi, C. Mosconi, F. Piscaglia
Journal: Endoscopy (2011)

Transarterial chemoembolization (TACE) is recommended for patients with unresectable hepatocellular carcinoma (HCC); however, it is not a risk-free procedure and biloma may occur as a complication [1].
SAT0447 Changes in treatment and outcomes of ankylosing spondylitis in routine care in germany 2000 to 2010
Authors: D. Huscher, M. Rudwaleit, K. Thiele, S. Bischoff, I. Kötter, K. Fischer, A. Zink
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> For patients with ankylosing spondylitis (AS), new treatment options have changed the therapeutic landscape tremendously during the past decade. In Germany, the first biologic agent was approved for AS in May 2003. <h3>Objectives</h3> To describe changes in treatment and outcome of AS during the past ten years. <h3>Methods</h3> The national database of the German collaborative arthritis centres collects clinical and patient-derived data from unselected outpatients with inflammatory rheumatic diseases. Each patient is recorded once a year. Cross-sectional data from nine years were compared with regard to clinical presentation and quality of life indicators. Due to changes in the documentation routine, the data from 2005 and 2006 are not representative and therefore omitted from the table. Data on BASDAI, BASFI, BASMI and EuroQoL are available from 2007 onwards. <h3>Results</h3> In the individual years, between 33 and 42% of the patients were female. Their mean age was about 49 years, and the mean disease duration about 15 years. From 2007 onwards, nearly half of all patients with AS received biologic agents. The use of synthetic DMARDs decreased significantly (Table), steroids were given to 21% of the patients in 2000 and only 11% in 2010. NSAIDs and Coxibs remain important therapeutic options with 55% of the patients receiving nonselective NSAIDs and 24% Coxibs in 2010.The proportion of patients whose disease was rated severe or very severe by the treating physician decreased from 20% to 12% between 2000 and 2010. The disease specific indices BASDAI, BASFI and BASMI indicate a further improvement during the past years. The proportion of patients reporting no limitations in daily activities and walking in the EuroQoL increased by about 5% since 2007, while almost no patients reported severe physical restrictions (≤2.5%). Significant changes occurred in the working situation: 54% of the patients in the working age were employed in 2000 and 65% in 2010, while early retirement declined to 16%. During this time period the percentage of patients with sick leave during the last 12 months fell from 43% to 33%. <h3>Conclusions</h3> Routine care of patients with AS has changed tremendously during the past decade. Increasingly, these better treatment options are reflected in better clinical outcomes, quality of life and participation in the labor market. <h3>Disclosure of Interest</h3> D. Huscher Grant/Research support from: The database was funded by the German Federal Minister of Research from 1999 to 2007 (grant #01 GI 0344/3). Since 2007 a consortium of 10 pharmaceutical companies has been funding the National Database by an unconditional grant to the German Rheumatological Society., M. Rudwaleit: None Declared, K. Thiele: None Declared, S. Bischoff: None Declared, I. Kötter: None Declared, K. Fischer: None Declared, A. Zink: None Declared
Reply
Authors: Mark H. Kuniholm, Kenrad E. Nelson
Journal: Hepatology (2016)

We appreciate the interest of Spacek and Solga in our article describing hepatitis E virus (HEV) testing of human immunodeficiency virus (HIV)-infected (HIV+) U.S. women and men.1 Because HEV viremia was rare in the populations we studied, we suggested that "widespread screening for HEV in HIV+ U.S. populations is not warranted." We made this suggestion—which represents no change from the current status quo—based on the available data. To date, only our study and one other study systematically screened HIV+ U.S. populations for HEV viremia. This other study did not identify any HEV viremic HIV patients.2 It is entirely possible that new data reported in the future may lead us to reevaluate our suggestion. Indeed, we believe that the evidence base for HEV/HIV clinical decision making in the United States is extremely small—conduct of more studies in diverse HIV+ populations, including populations living in rural areas, is a priority. In past studies conducted by our group and others of the nationally representative National Health and Nutrition Examination Survey (NHANES) III study population (1988-1994), prevalence of immunoglobulin G antibody against HEV (anti-HEV IgG) was higher in participants living in metropolitan versus nonmetropolitan areas.3, 4 In the NHANES 2009-2010 population, however, prevalence of anti-HEV IgG did not differ between participants living in metropolitan versus nonmetropolitan areas.4 Taken together, these data do not support the hypothesis that exposure to HEV is more common in rural versus urban areas of the United States. Acquisition of HEV after consumption of undercooked meat from a hunted deer was observed in Japan,5 but it is unclear whether this also occurs in the United States. Furthermore, it is unclear what fraction of exposures to HEV in the United States are attributable to consumption of undercooked meats versus other confirmed or hypothesized HEV transmission pathways—blood transfusion, consumption of contaminated seafood, produce, drinking water, and contact with pet or pest animals. In conclusion, though we agree with Spacek and Solga that more U.S. HEV/HIV research is sorely needed, we do not believe that current data support widespread screening for HEV in HIV+ U.S. populations. Mark H. Kuniholm, Ph.D.1 Kenrad E. Nelson, M.D.2 1Department of Epidemiology and Population Health Albert Einstein College of Medicine Bronx, NY 2Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore, MD
ET-64 * PRE-CLINICAL ASSESSMENT OF DISSOCIATIVE STEROIDS AS DEXAMETHASONE SUBSTITUTE FOR TREATMENT IN DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)
Authors: E. Wells, M. Khambampati, S. Yadavilli, J. Damsker, E. Hoffman, R. Packer, J. Nazarian
Journal: Neuro-Oncology (2014)

BACKGROUND: Although corticosteroids are widely used to treat cancer, cerebral edema, and other inflammatory disorders, their exact mechanism of action is poorly understood and less toxic alternatives are needed. The purpose of this study was to use a genetically engineered DIPG murine model to conduct pre-clinical testing of a new orally-administered steroid derivative, VBP15, which promises to reduce side effects through dissociating GRE-mediated transcription and NFkB-mediated modulatory actions. METHODS: First, to compare VPB15 to dexamethasone in reducing pro-inflammatory signals in vitro, BSG D10 murine and Control D10 cells were expanded in culture for 24 hours, serum starved and treated at 12 hours with dexamethasone, VBP15 or DMSO (control) and no drug in complete media for two hours. Using extracted RNA from the cells, NanoString evaluated specific inflammatory pathways. Second, in vivo efficacy of VBP15 was assessed. CSPG4+/+ neurospheres were into the brainstem of 18 mice at P2, 7 were treated with oral dexamethasone, 7 with VBP15 and 4 with cherry syrup (control) for up to 45 days. RESULTS: (In Vitro) Compared to DMSO, both dexamethasone and VBP15 given 12 hours into serum starvation decreased cytokine expression of IL10, IL6 and Tnf, which are cytokines in the NfKB pathway. (In Vivo) Post-mortem H&E staining revealed that 17 of 18 mice had developed tumor. Kaplan-Meir survival curves indicated a survival advantage for mice treated with VBP15 compared to dexamethasone or control. CONCLUSIONS: VPB15 has similar or better efficacy vs. dexamethasone (DEX) in reducing pro-inflammatory signals in brainstem glioma cells in vitro, and VBP15-treated DIPG mice show better survival compared to dexamethasone in vivo. These pilot results warrant more extensive pre-clinical testing and possibly development of a clinical trial.
A new suturing procedure for closure of a gastrocutaneous fistula
Authors: Nicolas Flori, Julie Courraud, Eric Assenat, Pierre Senesse
Journal: Endoscopy (2014)

Gastrostomy is a useful technique for feeding patients. Gastrostomy tubes are removed when patients recover an acceptable nutritional status and can eat again. Usually, the puncture site closes spontaneously in a short time; however, in some cases, a gastrocutaneous fistula can persist and may affect the patient's quality of life. Different closure techniques are available, such as clip placement, with or without electrochemical cautery [1], use of biological fibrin glue [2], or complex percutaneous endoscopic suturing [3]. We have developed a novel and easier suturing procedure for closure of a gastrocutaneous fistula.
1193 RESISTANCE ANALYSES USING DEEP AND POPULATION SEQUENCING AFTER 3 DAY MONOTHERAPY WITH GS-9669, A NOVEL NON-NUCLEOSIDE NS5B INHIBITOR IN GENOTYPE 1 HCV PATIENTS
Authors: H. Dvory-Sobol, E.S. Svarovskaia, V. Gontcharova, S. Rossi, E.J. Lawitz, M.D. Miller, H. Mo
Journal: Journal of Hepatology (2013)
Can three-dimensional endoanal ultrasonography detect external anal sphincter atrophy? A comparison with endoanal magnetic resonance imaging
Authors: RL West, S Dwarkasing, JW Briel, BE Hansen, SM Hussain, WR Schouten, EJ Kuipers
Journal: Endoscopy (2006)

Objectives: Anal sphincter atrophy is associated with a poor clinical outcome of sphincter repair in patients with faecal incontinence. Preoperative assessment of the sphincter is therefore relevant. External anal sphincter (EAS) atrophy can be detected by endoanal magnetic resonance imaging (MRI), but not by conventional endoanal ultrasonography (EUS). Three-dimensional EUS allows multiplanar imaging of the anal sphincters and thus enables more reliable anal sphincter measurements. The aim this study was to establish whether 3D EUS measurements can be used to detect EAS atrophy. For this purpose 3D EUS measurements were compared to endoanal MRI measurements.
Abstract 4687: Novel functions of the AMPK pathway to maintain spindle orientation during mitosis
Authors: Jose T. Thaiparambil, Adam I. Marcus
Journal: Cancer Research (2011)

Abstract AMP activated protein kinase (AMPK) functions as an energy sensor that regulates cell signaling. It is phosphorylated by the tumor suppressor, LKB1 at times of energy stress in both the cell polarity and motility pathways. Here we show that phosphorylated AMPKα (Thr-172) localizes to the spindle poles at gamma tubulin sites during mitosis in an LKB1-independent manner and serves as an essential regulator of mitotic spindle orientation. Phosphorylated AMPK levels peak during mitosis and siRNA-based disruption AMPK-α1&amp; α2 function, results in spindles that are mis-oriented relative to the normal spindle axis. This phenotype is accompanied by an aberrant, double-ring actin cage that encompasses the microtubule spindle, as well as reduced astral microtubules. Similar results were obtained by live cell imaging using compound C (AMPK pharmacological inhibitor) treated cells. Molecular studies show that AMPK regulates spindle orientation through a PI3k-AKT pathway at the spindle poles that signals to myosin regulatory light chain (MRLC). We postulate that AMPK is regulating astral microtubule docking onto actin through this pathway and when compromised spindles become misaligned. Taken together, this study reveals a novel PI3K-AKT-p-AMPK-MRLC mitotic signaling axis that regulates spindle orientation during mitosis. 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 4687. doi:10.1158/1538-7445.AM2011-4687
Abstract 87: SULF2 methylation is a prognostic biomarker for lung cancer survival and increases sensitivity to camptothecin analogues via expression of ISG15
Authors: Mathewos Z. Tessema, Christin M. Yingling, Cynthia L. Thomas, Donna M. Klinge, Amanda M. Bernauer, Chris Stidley, Nancy Joste, Suzanne Dahlberg, Joan Schiller, Steven A. Belinsky
Journal: Cancer Research (2011)

Abstract Heparan sulfate proteoglycans (HSPGs) serve as co-receptors for numerous signaling molecules including growth factors and cytokines. The sulfation pattern on the heparan sulfate (HS) motif is central to the interaction between HSPGs and the myriads of molecules including interferon (INF). SULF2 encodes for HS 6-O-endosulfatase enzyme that removes the 6-O-sulfate moieties from HS and regulates the specificity of this interaction. Increased expression of SULF2 promotes angiogenic and oncogenic signaling. In hepatocellular carcinoma higher expression of SULF2 is associated with worse prognosis after resection. Conversely, we recently reported that methylation-mediated SULF2 silencing is associated better survival of resected lung cancer patients. Here we show that SULF2 methylation is also a favorable survival marker in unresectable lung cancer. Furthermore, epigenetic silencing of SULF2 suppresses cell migration and induces the expression of multiple INF-inducible genes. Knocking down 80% of SULF2 expression in Calu-3 cells using siRNA resulted in 7-fold increase in the expression of INF-inducible regulator of ubiquitination, ISG15. Similarly, lung cancer cell lines with methylated SULF2 (SULF2M) on average express 60-fold higher ISG15 than cell lines with unmethylated SULF2 (SULF2U). ISG15 is a key marker for increased sensitivity of cancer cells to topoisomerase-1 inhibitors such as camptothecin and topotecan. In vitro treatment of lung cancer cell lines with camptothecin revealed a 65-fold higher sensitivity in cell lines with SULF2M and ISG15 high (ISG15H) phenotype compared to SULF2U and ISG15 low (ISG15L) cell lines. In nude mice, 10mg/kg/week topotecan treatment dramatically arrested the growth of SULF2M and ISG15H lung cancer xenografts but had no effect on SULF2U and ISG15L xenografts. Heterogeneity for ISG15 expression was also seen in primary tumors. One third of primary lung tumors have ISG15H phenotype with an average of 5-fold higher expression than the remaining 2/3rd tumors in which the ISG15 level is comparable to normal lung. Taken together these results indicate SULF2 methylation is not only a favorable prognostic marker for lung cancer, but through its association with increased expression of ISG15 could indicate a higher sensitivity to topoisomerase-1 inhibitors. 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 87. doi:10.1158/1538-7445.AM2011-87
Bile duct perforation caused by an uncovered metal stent treated by placement of a covered metal stent in a patient with pancreatic cancer
Authors: S. Park, S. Jeong, D. Lee
Journal: Endoscopy (2014)

Endoscopic retrograde biliary drainage (ERBD) using metal biliary stents is widely applied to biliary obstruction resulting from benign stricture or malignancy. The increased use of biliary stents has also been accompanied by an increasing number of cases of complications. Early complications occurring within 2 weeks of treatment by ERBD are not uncommon [1]. Delayed biliary perforation caused by metal stents is very rare [2]. Various methods have been suggested for the management of complications after placement of self-expandable metal stents (SEMSs) including mechanical cleaning, use of a diathermic treatment to remove malignant tissue ingrowth, introduction of a second stent into the primary stent, use of percutaneous transhepatic biliary drainage, cutting the stent using argon plasma, or endoscopic removal of the stent [3] [4].
PRECIPITATING FACTORS FOR HOSPITALIZATION WITH HEART FAILURE AND CLINICAL OUTCOMES: RESULTS FROM THE GULF CARE STUDY
Authors: Amar Salam, Kadhim Sulaiman, Jassim Al Suwaidi, Nidal Asaad, Khalid AlHabib, Wael Almahmeed, Alawi Alsheikh-Ali, Ahmed AL-Motarreb, Haitham Amin, Nooshin Bazargani, Prashanth Panduranga, Hussam AlFaleh, Abdulfatah Elasfar, Mohammad Al Jarallah, Mustafa Ridha, Awad Alqahtani, Rajvir Singh, Robert Bonow, Magdi Yacoub
Journal: Journal of the American College of Cardiology (2015)