tbuckley/cabot-search huggingface dataset:
Abstract 1804: Integrative genomics and expression analysis reveals enhanced SENP2-mediated desumoylation and a crosstalk with Neddylation pathway in squamous cell carcinoma of the lung.
Authors: Jun Qian, Jing Wang, Megan D. Hoeksema, Yong Zou, Allan V. Espinosa, Jamshedur Rahman, Bing Zhang, Pierre P. Massion
Journal: Cancer Research (2013)

Abstract Chromosome 3q26-29 amplification is a critical genomic alteration in squamous cell carcinomas (SCC) of the lung. There remains no consensus on what driver genes may carry this amplicon throughout tumor progression and their functional implications. We hypothesized that the amplification level of a predefined amplicon in a tumor sample can be inferred based on gene expression data. The hypothesis was tested using the TCGA dataset with paired copy number and gene expression data and achieved an accuracy of 90%. Based on the TCGA dataset and six other independent gene expression datasets (GSE4573, GSE8894,GSE2109,GSE3141 and GSE17710), we inferred candidate 3q26-29 drivers by searching for genes that were consistently over-expressed in SCCs with a high-level of 3q26-29 amplification in all seven datasets. The top 20 candidate driver genes includes PSMD2, DCUN1D1,SENP2, ZNF639, FXR1, SENP5,PRKCI, PIK3CA and UBXN7, et al. Using NetWalker we further identified a potential driver network consisting of SENP2, DCUN1D1, UBXN7 and DVL3, which are involved in SUMOlyation and Neddylation pathway. The amplification and overexpression of four genes were confirmed by performing genome-wide Agilent 244k CGH profiling and 44k gene expression profiling on twenty-four SCC tumors. Knocking down using siRNA against SENP2 resulted in greatest cell growth inhibition on 3q26-28 amplified SCC cell line H520. Immunoprecipitation assay showed that SENP2 binds to endogenous MDM2 in H520 cells. Loss of SENP2 leads to increased SUMO1 expression and elevated p53 expression associated with a decrease in MDM2 expression. Furthermore, knocking down SENP2 reduced the expression of DCUN1D1 and DVL3 but not UBXN7 in H520 cells. Together these data suggest that SENP2-mediated desumoylation and crosstalk with the Neddylation pathway contribute to lung SCC progression. Citation Format: Jun Qian, Jing Wang, Megan D. Hoeksema, Yong Zou, Allan V. Espinosa, Jamshedur Rahman, Bing Zhang, Pierre P. Massion. Integrative genomics and expression analysis reveals enhanced SENP2-mediated desumoylation and a crosstalk with Neddylation pathway in squamous cell carcinoma of the lung. [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 1804. doi:10.1158/1538-7445.AM2013-1804
P32 Liver mobilisation during liver resection induces immediate and profound hepatocellular damage and inflammation in humans
Authors: M. A. J. van den Broek, R. Shiri-Sverdlov, J. J. W. Schreurs, J. G. Bloemen, V. Bieghs, W. A. Buurman, C. H. C. Dejong, S. W. M. Olde Damink
Journal: Gut (2011)

<h3>Introduction</h3> In a recent study we coincidentally showed that mobilisation of the liver was a major cause of liver surgery-induced damage. The magnitude of and mechanisms by which this damage occurs are unknown. <h3>Aim</h3> (A) To determine the relative contribution of mobilisation during liver surgery to liver damage and (B) To examine whether there is an association between mobilisation-induced liver damage and liver inflammation. <h3>Method</h3> Consecutive patients undergoing liver surgery requiring full mobilisation of the right hemi-liver were included. Plasma samples and liver biopsies were obtained immediately after induction, prior to and directly after liver mobilisation, and after liver transection. Liver Fatty Acid Binding Protein (L-FABP) and alanine aminotranferase (ALAT) were analysed as markers of hepatocyte injury. Specimens were stained by immunohistochemistry for myeloperoxidase (MPO), human neutrophil peptide (HNP), and caspase-3-mediated cleavage generated neo-epitope of CK18 (M30). Gene expression of interleukin (IL) 1β, 6 and 8, and intercellular adhesion molecule (ICAM) were analysed by q-RT-PCR. <h3>Results</h3> Nineteen patients were included (11M/8F, median age 64 years [30–79]) who underwent major liver surgery. L-FABP levels increased significantly during liver mobilisation (from 91.7 ng/ml [11.4–2212.5 ng/ml] to 1014.4 ng/ml [141.4–8986.1 ng/ml], p&lt;0.001) and did not increase significantly thereafter (1315.2 ng/ml [67.0–20 099.2 ng/ml], p=0.75). L-FABP levels after ≥60 min mobilisation time were significantly higher when compared to ≥60 min mobilisation (1679.7 ng/ml vs 645.9 ng/ml, p=0.04). ALAT levels increased significantly from 26 IU/l [13–147] before to 130 IU/l [74–813] after liver mobilisation and to 275 IU/l [13–1352] after transection (all p&lt;0.05). Liver mobilisation increased the numbers of positive cells in staining for MPO (p=0.0007), HNP (p=0.03), and M30 (p=0.01), whereas transaction led to no further increase thereafter. Liver mobilisation increased the gene expression of IL1b (p=0.01), IL-6 (p=0.08), IL-8 (p=0.02) and ICAM (p=0.007). Expression increases ranged from 2.8-fold in ICAM to 130-fold in IL-6. After transection, mRNA levels increased even further in IL-6 (p=0.004), IL-8 (p=0.0004) and ICAM (p=0.02), but not IL1b (p=0.32). <h3>Conclusion</h3> Mobilisation of the liver during surgery induces profound hepatocellular damage and inflammation, which is associated with activation and/or infiltration of immune cells. Given the short half-life of L-FABP (14 min), hepatocyte damage predominantly occurred during mobilisation of the liver and not during transaction. These data produce insight into the mechanisms of mobilisation-induced liver damage, and provide indications for designing interventions aiming at prevention of surgery-induced liver damage in the future.
P456 SYSTEMS BIOLOGY ANALYSIS OF PROBIOTIC LACTOBACILLUS GG IN CIRRHOTIC PATIENTS WITH MINIMAL HEPATIC ENCEPHALOPATHY: A RANDOMIZED DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
Authors: J.S. Bajaj, D. Heuman, P. Hylemon, A. Sanyal, R. Sterling, R. Stravitz, P. Puri, M. Sikaroodi, L.R. Thacker, J. Wade, P.M. Gillevet
Journal: Journal of Hepatology (2014)
Abstract 844: Tumor cell detection in autologous stem cell harvests in patients with high risk neuroblastoma
Authors: Janine Stutterheim, Florentien M. Vree, Lily Zappeij-Kannegieter, Huib N. Caron, C. Ellen van der Schoot, Godelieve A.M. Tytgat
Journal: Cancer Research (2010)

Abstract Introduction The presence of minimal residual disease (MRD) detected by real-time quantitative (RQ)-PCR in autologous stem cell harvests (ASCH) in children with high risk neuroblastoma (NBL) seems to be associated with an unfavourable outcome. However, to date only small studies have been performed, which suffered from lack of specificity of the assay due to background amplification in normal bone marrow (BM) and peripheral blood stem cells (PBSC). We previously developed a new panel of specific neuroblastoma RQ-PCR markers for MRD testing. The goal of this study was to determine the incidence of harvest contamination using this panel of markers and to investigate whether reinfusion of contaminated harvests was associated with poor outcome. Methods In this single center study, RQ-PCR was performed with six NBL-specific markers: homeobox2b (PHOX2B), tyrosine hydroxylase (TH), dopamine decarbohydroxylase (DDC), growth associated protein 43 (GAP43), cholinergic receptor3 (CHRNA3), and dopamine beta-hydroxylase (DBH) on 40 BM and 38 PBSC harvests of 70 high risk patients. The prognostic impact of MRD in reinfused autologous harvests (n=50) was assessed using Kaplan-Meier plots and log-rank tests. Results NBL mRNA was detected in 42% (18/40) of BM harvests and in 13% (5/38) of PBSC harvests of which in total 50 harvests were reinfused. In reinfused patients, 30% (15/50) received a MRD positive harvest, which was associated with poor outcome (5-y-OS 20±11.8 versus 62.3%±8.8;p=0.02). This association was more pronounced in patients reinfused with BM harvests than in patients reinfused with PBSC harvests, since more BM harvests were MRD positive. Remarkably, overall there was no difference in survival between patients reinfused with PBSC or BM harvest (p=0.7). Conclusion The presence of NBL mRNA in stem cell harvests, as reliably measured by a panel of NBL specific-PCR targets, is significantly associated with an unfavourable outcome. This could either mean that the amount of tumor cells reinfused in the graft influences relapse rate or that the stem cell graft reflects remission status. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 844.
Abstract 107: miR-200a targets SIRT1 for malignant transformation
Authors: Gabriel Eades, Yuan Yao, Qun Zhou
Journal: Cancer Research (2011)

Abstract Evidence supports a critical role for microRNAs in regulation of tissue specific differentiation and development. Signifying a disruption of these programs, miRNA profiling has revealed extensive dysregulation in tumors compared with healthy tissue. The malignant contribution of some miRNAs is understood, however, in other instances the pathways affected by aberrant miRNA expression have yet to be characterized. The miR-200 family has been established as a key regulator of epithelial phenotype and as such, is deeply involved in EMT-like processes in cancer. While exploring a model of transformation of normal mammary epithelium we observed epigenetic silencing of the miR-200 family- as was previously identified in breast cancer cell lines. Here we show the class III histone deacetylase SIRT1 overexpression in a TGF-β driven model of transformation as well as in patient samples of early stage breast cancer. We establish SIRT1 transcript as subject to novel regulation of the miR-200 family, through miR-200a / miR-141 targeting. Moreover, we demonstrate that downregulation of miR-200 family members contributes at least in part to the overexpression of SIRT1, a proposed oncogene in breast cancer. Restoration of miR-200a or knockdown of SIRT1 results in decreased growth in soft agar and decreased invasion. These observations provide further evidence of the important tumor suppressive role of miR-200 family members in breast epithelium, as well as identifying a novel regulatory mechanism that may contribute to SIRT1 upregulation early in breast tumorigenesis. 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 107. doi:10.1158/1538-7445.AM2011-107
Abstract LB-326: Elucidating significant genetic associations between genes and lung cancer
Authors: Anthony M. D'Amelio, Carol J. Etzel
Journal: Cancer Research (2012)

Abstract Introduction: To further understand and elucidate the genetic risk factors for Lung Cancer (LC) will substantially improve cancer prevention, screening programs, and treatment options for this insidious disease. However, our previous attempts to increase the discriminatory power in an existing risk model with the inclusion of SNPs identified via GWAS have not been very successful. In this analysis, we reassess the increase in discriminatory power by including haplotypes based on existing GWAS-identified SNPs and additional single SNPs. Methods: Cases included 1154 histological-confirmed Caucasian lung cases from MD Anderson Cancer Center in Houston, Texas, and controls included 1137 individuals recruited through the Kelsey-Seybold Clinics in Houston, Texas. Genetic information from both populations was selected for 157 SNPs that exist in the Texas GWAS and were part of the top 200 SNPs as determined by a previously published meta-analysis of 10 different lung cancer GWAS datasets (Landi et al. 2009). Plink and Haploview were used to determine the top SNPs and top haplotype blocks respectively. Then, univariate logistic regression was used to determine the best genetic model for the top SNPs. Joint logistic risk model regression was used to determine haplotype risk for each individual haplotype block. Finally, multivariate logistic regression was used to develop the final extended model that included the original set of risk factors from the Spitz model plus additional haplotypes and SNPs. We evaluated increase in discriminatory power by evaluated change in the area under the receiver-operating characteristic curve and the net reclassification index. Results: The discriminatory power for the original Spitz model was 66.1% (95% CI = 0.638-0.683). With the inclusion of only single SNPs in to the model, the discriminatory power increased by 4.5% to 70.6% (95% CI = 0.684-0.727, p-value = &amp;lt;0.0001). Adding the top 6 haplotypes further increased the discriminatory power to 71.9% (95% CI = 0.697-0.739). The net reclassification index results show that this increase in discriminatory power is evident for both cases (23.47%) and controls (23.43%). Conclusions: Inclusion of genetic variants into an established epidemiologic risk model can substantially increase the discriminatory power; however, selection and modeling of these variants needs to be carefully done. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-326. doi:1538-7445.AM2012-LB-326
CLINICAL INFLUENCE OF REPEAT ENDOVASCULAR THERAPY ON OUTCOMES OF CRITICAL LIMB ISCHEMIA WITH TISSUE LOSS
Authors: Norihiro Kobayashi, Keisuke Hirano, Masatsugu Nakano, Yoshiaki Ito, Toshiya Muramatsu, Reiko Tsukahara, Hiroshi Ishimori
Journal: Journal of the American College of Cardiology (2015)
Special Rapporteur's reply to Summerfield
Authors: J. E. Mendez
Journal: BMJ (2014)

In March 2013, I communicated a response, via the Office of the High Commissioner for Human Rights, with regard to the allegations brought to the attention of my mandate by Dr Summerfield.1 These and additional allegations provided were not taken up because they referred to the conduct of the Israeli Medical Association (IMA) and the World Medical Association (WMA), entities that are civil society organisations. My mandate …
RESECCIÓN DE PÓLIPOS PEDICULADOS (PARIS Ip) GRANDES DE COLON
Authors: M Alburquerque, A Smarrelli, L Vidal, C Ledezma, J Chevarria, M Figa, F Gonzalez-Huix
Journal: Endoscopy (2014)

Objetivo: Comparar la seguridad de las técnicas de resección de pólipos de colon Paris Ip ≥20 mm según las características del pedículo.
Abstract P5-18-23: The prognosis of T1a, T1b N0 M0, HER2+ patients in Korea.
Authors: JW Lee, H-G Moon, W Han, D-Y Noh
Journal: Cancer Research (2012)

Abstract Backgrounds: Increased expression of HER-2 or amplification of the HER-2/neu gene has been associated with a worse prognosis than with other breast cancer phenotypes. Especially in cases of size of 0.5∼1cm and node-negative status, adjuvant chemotherapy with or without Trastuzumab treatment is suggested by recent National Comprehensive Cancer Network(NCCN) guidelines. In Korea, the breast cancer patient pool is more younger than western data, and there could be some ethnic differences. Methods: The Korean Breast Cancer Society (KBCS) has been collaborating with the Korean Central Cancer Registry (KCCR) to improve the completeness and validity of the breast cancer registry and the mortality data. Data of T1a, bN0M0 breast cancer patients from 1999 to 2006 from KBCS on-line registry was obtained, and a total of 2,962 patients were included for survival analysis. Results: 711 patients (24.0%) was HER-2 positive. Hormone receptor and HER2 status was used to classify 4 molecular subtypes; Hormone receptor(HR)+/HER2−, HR+/HER2+, HR−/HER2+, HR−/HER2−. The median follow-up was for 55.82 month (±24.196). Breast cancer specific survival rate was lowest at HR−/HER2+ subtype(97.9%). It's 1.0∼1.8% lower than other subtypes. Between all T1N0M0 cases, especially T1b HR−/HER2+ cases showed lowest survival of 96.4%. Conclusion: This study calculated the nationwide survival rates of Korean breast cancer patients with T1a, bN0M0 disease for the first time. HER2 gene positivity was associated with worse prognosis and it's concordant with western studies. But prognosis of T1N0M0 lesion is much better than that of other nations. So, the usage of chemotherapy and Trastuzumab treatment should be considered more carefully in Korea. Further analysis of the long-term survival and a nationwide collaborative study should be performed to estimate the survival trend of Korean breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-23.
Daniel Sutton, a forgotten 18th century clinician scientist
Authors: Arthur Boylston
Journal: Journal of the Royal Society of Medicine (2012)

The 1760s saw an explosion in the numbers of individuals inoculated for smallpox. This was largely due to the innovations of the Sutton family, which made the procedure almost painless, much safer, and much more convenient. While Robert Sutton Senior modified inoculation technique so that it involved only a tiny stab just through the skin with a sharp lancet, it was the combination of skill and business genius of his son Daniel which really drove the expansion of inoculation. Daniel, with his brothers and several other partners, set up a chain of franchises across England and parts of Europe and North America which offered the now famous ‘Suttonian Method’. Daniel himself inoculated 22,000 people between 1763 and 1766 with only 3 deaths and made a great deal of money from his practice. His contemporaries in the Royal College of Physicians struggled to emulate his approach and often condemned him and his family as ‘men of confined abilities’. But Daniel Sutton was a great deal more than that.

In 1796, Daniel Sutton published a collection of his observations and ideas concerning inoculated smallpox in his autobiography, ‘The Inoculator’.1 He intended it as an instruction manual for young practitioners and hoped that they would benefit from his years of experience. He warned his readers that many of his practices appeared trifles but: 

Despise not trifles, tho they small appear:
Sands rise to mountains, moments make the year;
and trifles life. Your time to trifles give,
or you may die before you learn to live.
DEPRESSION AND OUTCOME OF PATIENTS WITH ACUTE CORONARY SYNDROME: A 3 YEAR FOLLOW-UP STUDY
Authors: Parloop Bhatt, Aditi Patel, Parth Parikh, Jawahar Mehta, Piyush Thakar, Aditi Nanavati, Roosha Parikh, Apurva Patel, Keyur Parikh
Journal: Journal of the American College of Cardiology (2015)
SP0088 Advances in Systemic Vasculitis
Authors: S. De Vita
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Some major advances on the different systemic vasculitides during the past year will be analyzed. A key point to improve the management of any systemic vasculitis is a deeper knowledge of the major pathogenetic events implicated. Genetic predisposition and antigenic stimulation of the immune system by exogenous triggers and/or autoantigens have been intensively investigated. In HCV-related cryoglobulinemic vasculitis the identification of a key infectious trigger, and the possible treatment with antiviral agents or immunosuppressors, proved useful to better dissect the role of treatments acting on upstream or downstream pathogenetic events. However, in this disease we learnt that it is the clinical picture, i.e., disease severity, the main discriminant for treatment decisions, at present. There are different novel treatments proposed for different vasculitides, and major points include the the optimal induction therapy and treatment of refractory cases, the optimal maintenance regimen, and strategies for glucocorticoid sparing. Laboratory and imaging examinations not only for the diagnosis, but also for the monitoring of the disease, and to better predict treatment response and the risk of relapse, are relevant. Both the prompt diagnosis and the proper classification of the type of primary or secondary vasculitis are crucial, and criteria to facilitate both of them are then important. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6348
The ACA and High-Deductible Insurance — Strategies for Sharpening a Blunt Instrument
Authors: J. Frank Wharam, Dennis Ross-Degnan, Meredith B. Rosenthal
Journal: New England Journal of Medicine (2013)

By mandating insurance coverage and requiring affordable premiums but not enacting other cost-control mechanisms, the Affordable Care Act will cause a major shift toward high-deductible health plans — increasing the urgency of determining such plans' consequences.
AB0702 IGG and IGM anti-DSDNA isotypes in patients with systemic lupus erythematosus
Authors: B. Keiserman, O.A. Monticielo, M.R. Ronchetti, H.L. Staub
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease, where renal involvement is common, being a determinant for bad prognostic. Lupus nephritis is generally associated to the presence of anti-dsDNA. The IgM isotype of this autoantibody, unlike the IgG isotype, seems to be nephroprotector. <h3>Objectives</h3> To study the influence of isotypes IgG and IgM anti-dsDNA antibodies on clinical and laboratory manifestations of SLE. <h3>Methods</h3> We conducted a cross-sectional study with 137 patients with SLE, in which we explored the presence of isotypes IgG and IgM anti-dsDNA antibodies. The research of anti-dsDNA was performed by indirect immunofluorescence with Crithidia luciliae (CLIF). <h3>Results</h3> Fifty-eight (42%) patients had IgG anti-dsDNA reagent and were selected for the study of the IgM isotype. The group of patients who had anti-dsDNA IgG alone (n=43) compared with the group who had concomitant isotypes IgG and IgM (n=15), showed a higher frequency of active urine sediment (34.9% versus 6.7%, p=0.046). Analysis of the median distribution of IgG/IgM anti-dsDNA ratio, according to the presence or absence of clinical and laboratory features, showed a trend of the IgG/IgM ratio be greater in the presence of arthritis and leukopenia/lymphopenia [4 (2-8)versus 1 (1-2), p=0.070 and 4 (3-8) versus 1 (1-4), p=0.066, respectively]. <h3>Conclusions</h3> Our study showed that the concomitance of the isotypes IgM and IgG anti-dsDNA inhibited the effect of the isotype IgG isolated in association with active urinary sediment. Future studies are needed to clarify the role of anti-dsDNA isotypes in SLE. <h3>References</h3> Bootsma, H., et al., The predictive value of fluctuations in IgM and IgG class anti-dsDNA antibodies for relapses in systemic lupus erythematosus. A prospective long-term observation. Ann Rheum Dis, 1997. 56(11):661-6. Witte, T., et al., IgM anti-dsDNA antibodies in systemic lupus erythematosus: negative association with nephritis. SLE Study Group. Rheumatol Int, 1998. 18(3):85-91. Forger, F., et al., Clinical significance of anti-dsDNA antibody isotypes: IgG/IgM ratio of anti-dsDNA antibodies as a prognostic marker for lupus nephritis. Lupus, 2004. 13(1):36-44. Munoz, L.E., et al. Predictive value of anti-dsDNA autoantibodies: importance of the assay. Autoimmun Rev, 2008. 7(8):594-7. Atta, A.M., et al., Anti-dsDNA antibodies in Brazilian patients of mainly African descent with systemic lupus erythematosus: lack of association with lupus nephritis. Clin Rheumatol, 2009. 28(6):693-7. <h3>Disclosure of Interest</h3> None Declared