tbuckley/cabot-search huggingface dataset:
Abstract 877: Identification of novel genes critical to survival of MPNST cells via medium throughput screening using lentiviral shRNA
Authors: Ami Patel, Nancy Ratner
Journal: Cancer Research (2012)

Abstract Malignant peripheral nerve sheath tumor (MPNST) is a soft tissue sarcoma that is highly invasive and eventually lethal. About 50% of MPNSTs have mutation and/or loss of the NF1 gene, while the rest are spontaneous. Many MPNST also show mutations in p53 and/or homozygous deletion of CDKN2. In an effort to identify novel genes that play key roles n MPNST tumorigenesis, we performed a genome wide micro-array analysis using human neurofibroma and MPNST (Miller et al., 2009). This analysis identified 130 genes that are up-regulated &amp;gt;3 fold in MPNSTs as compared to normal human Schwann cells. Over expression of these genes in tumors as compared to normal cells suggested that some might be critical for survival of MPNST cells. This hypothesis was directly tested by studying effects on survival of MPNST cells in vitro post down regulation of the 130 genes using lentiviral short hairpin (sh) RNA. For each shRNA experiment a sh non-targeting lentivirus was used as a negative control and shSOX9, a construct previously shown to kill MPNST cells in vitro, was used as a positive control for an effect on cell survival. Screening was performed sequentially allowing for selection of genes with significant effects on survival. In screen I, T265 MPNST cells were exposed to each shRNA virus. In screen II, shRNAs were tested for effects on adenocarcinoma cells (A549) vs T265 cells. These two round of screens identified 10/130 genes specific for survival of T265 cells. Screen III was performed on four different MPNST cell lines, including T265 (NF1-/-), 8814 (NF1-/-), S462TY (NF1-/-) and SSTS26T (sporadic MPNST wild-type for NF1), to identify shRNA's with similar or different effects on cell survival in the presence or absence of wild-type NF1 gene. No significant difference in survival was observed for NF null MPNST cells vs sporadic MPNST cell line for any gene. This approach facilitates a streamlined pathway from genome wide gene expression analysis to identification of novel genes critical to survival of cancer cells in vitro. Future studies will be directed toward testing the identified genes for roles in tumor formation and growth, and as potential MPNST therapeutic targets. 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 877. doi:1538-7445.AM2012-877
Management of Malignant Hypertension Complicated by Renal Insufficiency
Authors: James W. Woods, William B. Blythe
Journal: New England Journal of Medicine (1967)

BEFORE the introduction of hypotensive drugs malignant hypertension uniformly resulted in early death. In 2 large series 79 per cent and 90 per cent of patients died in the first year after diagnosis.1 , 2 In contrast, a one-year survival rate of 85 per cent and a twelve-year survival rate of 38 per cent were recently reported in treated nonazotemic patients.3 There is general agreement that the main factor influencing length of survival is the state of renal function at the time of diagnosis. When this study was begun, the results from most published experience suggested that lowering of blood pressure in . . .
Abstract 2740: Decision tree-based modeling of androgen pathway genes and prostate cancer risk
Authors: Jill S. Barnholtz-Sloan, Xiaowei Guan, Charnita Zeigler-Johnson, Neal J. Meropol, Timothy Rebbeck
Journal: Cancer Research (2011)

Abstract Background: Inherited variability in genes that influence androgen metabolism has been implicated in the etiology of prostate cancer. However, joint effects of these genes have not been fully defined in terms of risk. Objective: The objective of this analysis was to evaluate gene-gene and gene-environment interactions for prostate cancer risk using classification and regression tree (CART) models (i.e. decision trees), and to evaluate whether these interactive effects add information about prostate cancer risk prediction beyond that of “traditional” risk factors. Methods: We compared CART models to traditional logistic regression models for associations of factors with prostate cancer risk using 1084 prostate cancer cases and 941 controls. All analyses were stratified by race. We used unconditional logistic regression (LR) to complement and compare to the race-stratified CART results using the area under curve (AUC) for the receiver operating characteristic (ROC) curves. Results: In European Americans, single SNP or haplotype associations were found with CYP3A5 (OR=2.11 (1.13, 3.97)); increasing number of CAG repeats in the AR gene (OR=0.90 (0.83, 0.98)); and the CYP3A4/CYP3A5 AG haplotype (OR=2.86 (1.15, 7.12)). No significant single SNP or haplotype associations were found in African Americans. The CART modeling of prostate cancer risk showed different interaction profiles by race. For European Americans, interactions among CYP3A43 genotype, history of BPH, family history of prostate cancer and age at consent revealed a distinct hierarchy of gene-environment and gene-gene interactions. While for African Americans, interactions among family history of prostate cancer, individual proportion of European ancestry, number of GGC AR repeats and CYP3A4/CYP3A5 haplotype revealed distinct interaction effects from those found in European Americans. For European Americans the CART model had the highest AUC while for African Americans, the LR model with the CART discovered factors had the largest AUC. Conclusion: These results show novel gene-gene and gene-environment interactions specific for European Americans and African Americans discovered using CART as compared to standard LR techniques. 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 2740. doi:10.1158/1538-7445.AM2011-2740
Partial Reduction of Blood Pressure and Prevention of Complications in Hypertension
Authors: James Taguchi, Edward D. Freis
Journal: New England Journal of Medicine (1974)

The data obtained in the Veterans Administration Cooperative Study on patients with prerandomization diastolic blood pressures averaging 90 to 114 mm Hg were analyzed to ascertain the importance of reducing blood pressure to normal in prevention of major complications. Of 380 patients 186 were randomly assigned to active drug treatment. Blood pressures recorded at the visit four months after randomization were used to select two subgroups of treated patients: Subgroup A comprised 67 patients who exhibited diastolic blood pressures of 90 mm Hg or higher, whereas Subgroup B included 62 patients with diastolic levels of 80 mm Hg or less. Over an average follow-up period of 3.2 years cardiovascular complications developed in 14.9 per cent of Subgroup A and 9.7 per cent of Subgroup B. The attack rates in Subgroup A were significantly less (p<0.05) than the 28.9 per cent of patients in the untreated group in whom morbid events developed. The results suggest that although normalization of blood pressure with antihypertensive drugs is desirable, considerable therapeutic benefit is still obtained with lesser degrees of pressure reduction. (N Engl J Med 291:329–331, 1974)
FRI0358 Impaired endothelial function in patients with takayasu’s arteritis
Authors: F. Alibaz-Oner, S. Yurdakul, S. Aytekin, H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Takayasu' s arteritis (TAK) is a chronic, inflammatory, large-vessel vasculitis. In the present study we aimed to evaluate vascular endothelial function in patients with TAK compared to systemic lupus erythematosus (SLE), another inflammatory, autoimmune disorder. <h3>Methods</h3> We studied 33 patients with TAK, 18 patients with SLE and 20, age and sex-matched healthy controls. Brachial artery Doppler ultrasonography (USG) and bilateral carotid artery intima-media thickness (CIMT) measurements were performed. <h3>Results</h3> Basal diameter and nitrate- induced dilatation (NID) values of the brachial artery were similar between the three groups. However, flow-mediated dilation (FMD) was markedly reduced in patients with TAK (Table 1). Carotid artery intima-media thickness (CIMT) was also significantly increased in TAK group, compared to the controls (0.11±0.03 vs to 0.07±0.009 cm, respectively, p=0.0001). Presence of hypertension had no association with FMD and CIMT measurements. In the SLE group, a marked impairment in FMD % was obtained (8.85±2.8, p=0.0001). % NID and CIMT measurements was observed to be similar between the patients with SLE and the healthy controls (p=0.60 and p=0.05, respectively). <h3>Conclusions</h3> In the present study, we detected significantly decreased FMD and increased CIMT in TAK patients, suggesting a marked endothelial dysfunction. Chronic inflammation and vascular fibrosis might lead to increased atherosclerosis in TAK. <b>Disclosure of Interest</b>: None Declared
Abstract 5412: CCR4+CCR6+Th17 cells suppress autologous CD8+ T cell responses in patients with hepatocellular carcinoma
Authors: Fei Zhao, Bastian Hoechst, Jaba Gamrekelashvili, Lars Ormandy, Torsten Voigtländer, Heiner Wedemeyer, Kris Ylaya, Stephen Hewitt, Xin Wang, Michael Manns, Firouzeh Korangy, Tim Greten
Journal: Cancer Research (2012)

Abstract The role of Th17 cells in cancer patients remains unclear and controversial. We have noticed an increase in Th17 related cytokines (IL-17 and IL-23) in tumor supernatants derived from primary liver cancer, which prompted us to examine Th17 cells in patients with hepatocellular carcinoma (HCC). First we analyzed the frequency of CD4+IL-17+ cells in peripheral blood from patients with HCC, which was increased in comparison to healthy controls. In order to further analyze the function of these cells, we generated Th17 cells in vitro in the presence of IL-1beta, IL-6 and IL-23 cytokines, anti-IL-4 and anti-IFN-gamma antibodies. Th17 cells were than stained using an IL-17 capture antibody and purified by FACS sorting. In vitro primed Th17 cells were further purified into CCR4+CCR6+ and CCR4negCCR6+ Th17 cells. When cultured with autologous CD8+ T cells, CCR4+CCR6+Th17 cells suppressed the lytic function, proliferation and cytokine secretion of both antigen specific and CD3/CD28/CD2 stimulated autologous CD8+ T cells. In contrast, CCR4negCCR6+ CD4+ T cells, which also secrete IL-17, did not affect the CD8+ T cells. Suppression of CD8+ T cells by CCR4+CCR6+Th17 cells was partially dependent on TGF-beta, since neutralization of TGF-beta in cocultures reversed their suppressor function. Based on these findings we evaluated the frequency CCR4+CCR6+Th17 and CCR4negCCR6+Th17 cells in patients with HCC separately. Our analysis revealed also an increase in the frequency of CCR4+CCR6+Th17 cells but not CCR4negCCR6+Th17 cells in peripheral blood of HCC patients and ex vivo isolated CCR4+CCR6+CD4+ T cells from peripheral blood of patients. Finally we demonstrated the suppressor activity of freshly isolated CCR4+CCR6+T cells on autologous CD8+ T cell proliferation. In summary our study not only underlies the importance of analysis of subsets within Th17 cells to understand their function, but also suggests Th17 cells as yet another immune evasion mechanism in HCC. This has important implications when studying the mechanisms of carcinogenesis as well as designing effective immunotherapy protocols for patients with cancer. 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 5412. doi:1538-7445.AM2012-5412
Reply to Saritas et al.
Authors: V. Moritz
Journal: Endoscopy (2012)

I appreciate the constructive comment from Saritas and Ustundag on our article exploring the role of withdrawal time as a quality indicator in colonoscopy. We chose to adhere to the generally accepted definition of polyp detection rate (PDR) as the percentage of colonoscopies with findings of one or more polyps performed by an individual endoscopist. This enabled us to compare our results with other studies based on the same PDR definition. Counting numbers of polyps would make the analysis vulnerable to outliers due to patients with polyposis syndromes and extremely high polyp numbers.
THU0104 No expression of an alternative CD20 transcript variant in B cells from patients with rheumatoid arthritis
Authors: M. Deschamps, B. Gaugler, P. Saas, C. Ferrand, E. Toussirot
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Targeting B cells is an effective therapy in rheumatoid arthritis (RA). Rituximab (RTX) is a chimeric monoclonal antibody directed against the membrane CD20 protein present on B cells. Predictive factors for good response to RTX therapy in RA have been identified and included the presence of rheumatoid factors and anti -CCP antibodies. Recently, a spliced mRNA transcript of CD20 (ΔCD20) has been identified in B cell lines from patients with lymphoma and leukaemia (ref.). This transcript is coding for a non anchored membrane protein and its expression is associated with resistance to RTX in patients with haematological malignancies. <h3>Objectives</h3> to determine whether ΔCD20 is expressed by circulating B cells from patients with RA and whether it could be a factor for non response to RTX therapy. <h3>Methods</h3> 23 RA patients (17 F, age (mean ± SEM): 60.1±2.7 years; disease duration: 13.3±1.7 years, positive rheumatoid factors:19/23; positive anti- CCP antibodies: 19/23) and 20 healthy controls (15 F, age: 59.6±2.5 years) were evaluated. Patients were under DMARDs, low corticosteroids (&lt;10 mg/j) or anti TNFa agents but none received or had received RTX. CD20 mRNA expression study was performed using RT-PCR assay allowing first to discriminate full length CD20 (membrane CD20) from ΔCD20 transcripts. A more sensitive RT-PCR assay, using a specific primer spanning the splice fusion area was then used to detect specifically only the ΔCD20 transcript. <h3>Results</h3> RA patients had mild active disease (DAS28 score: 3.3±0.3; CRP levels: 6.8±1.9 mg/l). Number of circulating B cells per μl was not different between RA patients and controls (mean ± SEM, range: 184±22, 18-437 <i>vs</i> 211±27, 63-408, respectively). Among all the 23 RA samples, although full length CD20 expression was always detected, we were unable to detect ΔCD20, even with the more sensitive RT-PCR assay permitting to identify the spliced transcript form. <h3>Conclusions</h3> The present study showed that, on the contrary of leukemic or lymphoma B cells, RA B-cells do not express ΔCD20, suggesting that this transcript may be a molecular marker of malignancies rather than of auto-immune diseases like RA. Study of RTX-non responders or -escaping RA patients may be relevant to know if ΔCD20 expression may be detected under the pressure of RTX therapy. <h3>References</h3> Henry C et al., Blood, 2010;115:2420-9 <h3>Disclosure of Interest</h3> None Declared
Abstract 4921: Essential role of MMP-2 in carbon nanotube-induced invasion of human pleural mesothelial cells.
Authors: Warangkana Lohcharoenkal, Yuxin Liu, Todd A. Stueckle, Cerasela-Zoica Dinu, Liying Wang, Yon Rojanasakul
Journal: Cancer Research (2013)

Abstract Carbon nanotubes (CNTs) have increasingly been used in a wide variety of applications. However, because of their needle-shape morphology, biopersistence and mode of exposure similar to those of asbestos which is a known carcinogen causing lung mesothelioma, there has been a great concern about their potential carcinogenicity. In this study, we investigated the effect of long-term exposure of CNT on proliferative and invasive properties of human pleural mesothelial cells. We found that chronic exposure of human mesothelial Met5A cells to low-dose non-cytotoxic concentration of single-walled CNT (0.02 μg/cm2 for 25 weeks) in culture induced malignant transformation of the cells as indicated by their increased cell invasion and migration. Analysis of gene expression by real-time PCR array showed a 50-fold increase in MMP-2 expression in CNT-transformed cells as compared to passage-matched control cells. Western blot analysis of the protein expression confirmed the upregulation of MMP-2 in the transformed cells. Downregulation of MMP-2 in the transformed cells by short-hairpin RNA stable transfection effectively inhibited the MMP-2 activity in these cells as well as their invasive and migratory activities. These results indicate MMP-2 as a key regulator of the aggressive phenotype of mesothelial cells after chronic CNT exposure. This study fortifies the carcinogenic potential of CNT and reveals a novel mechanism that may be important in CNT-induced mesothelioma. Citation Format: Warangkana Lohcharoenkal, Yuxin Liu, Todd A. Stueckle, Cerasela-Zoica Dinu, Liying Wang, Yon Rojanasakul. Essential role of MMP-2 in carbon nanotube-induced invasion of human pleural mesothelial cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4921. doi:10.1158/1538-7445.AM2013-4921
THE IMPACT OF ELECTROLYTE IMBALANCE ON INHOSPITAL MORTALITY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION: SUBANALYSIS FROM JAPANESE REGISTRY OF ACUTE MYOCARDIAL INFARCTION DIAGNOSED BY UNIVERSAL DEFINITION (J-MINUET)
Authors: Hitoshi Takano, Masaharu Ishihara, Masashi Fujino, Hisao Ogawa, Koichi Nakao, Satoshi Yasuda, Teruo Noguchi, Yukio Ozaki, Kazuo Kimura, Satoru Suwa, Kazuteru Fujimoto, Yasuharu Nakama, Takashi Morita, Yoshihiko Saito, Atsushi Hirohata, Yasuhiro Morita, Teruo Inoue, Atsunori Okamura, Masaaki Uematsu, Kazuhito Hirata, Kengo Tanabe, Yoshisato Shibata, Mafumi Owa, Takeshi Yamamoto, Wataru Shimizu
Journal: Journal of the American College of Cardiology (2016)
A unique measles B3 cluster in the United Kingdom and the Netherlands linked to air travel and transit at a large international airport, February to April 2014
Authors: Laura Nic Lochlainn, Sema Mandal, Rita de Sousa, Karthik Paranthaman, Rob van Binnendijk, Mary Ramsay, Susan Hahné, Kevin E. Brown
Journal: Eurosurveillance (2016)

This report describes a joint measles outbreak investigation between public health officials in the United Kingdom (UK) and the Netherlands following detection of a measles cluster with a unique measles virus strain. From 1 February to 30 April 2014, 33 measles cases with a unique measles virus strain of genotype B3 were detected in the UK and the Netherlands, of which nine secondary cases were epidemiologically linked to an infectious measles case travelling from the Philippines. Through a combination of epidemiological investigation and sequence analysis, we found that measles transmission occurred in flight, airport and household settings. The secondary measles cases included airport workers, passengers in transit at the same airport or travelling on the same flight as the infectious case and also household contacts. This investigation highlighted the particular importance of measles genotyping in identifying transmission networks and the need to improve vaccination, public health follow-up and management of travellers and airport staff exposed to measles.
1202 ORAL ANTI-CD3 IMMUNOTHERAPY FOR HCV-NON-RESPONDERS IS SAFE, PROMOTES REGULATORY T CELLS, AND DECREASES VIRAL LOAD AND LIVER ENZYME LEVELS: RESULTS OF A PHASE-2a PLACEBO-CONTROLLED TRIAL
Authors: W. Halota, P. Ferenzi, D. Kozielewicz, D. Dybowska, N. Lisovoder, S. Samira, I. Shalit, R. Ellis, Y. Ilan
Journal: Journal of Hepatology (2013)
Abstract 4383: Regulation of cancer cell differentiation in vivo by delta-like 1 homolog (Drosophila) DLK1
Authors: Asma Begum, Yuri Kim, Qun Lin, Zhong Yun
Journal: Cancer Research (2011)

Abstract Malignant tumor progression from a benign growth to metastasis is often accompanied by an accumulation of multiple genetic and epigenetic changes occurring over a course of more than a decade. The stem cell-like characteristics, especially the self-renewal capacity, of tumor cells is essential for uninterrupted inheritance of these disparate genetic and epigenetic changes in the same originating tumor cell. Like normal stem cells, cancer cells can lose their stemness or self-renewal potential in response to environmental stresses. Therefore, tumor cell stemness needs to be actively maintained. However, the underlying mechanisms remain to be clearly understood. Our previous studies and others have suggested that the tumor microenvironment, including hypoxia, plays a significant role in the regulation of cancer stem cell characteristics. We have identified a previously uncharacterized stem cell pathway mediated by DLK1 or delta-like 1 homolog (Drosophila) that is upregulated by hypoxia and enhances cancer cell stemness and tumorigenicity in neuronal tumors. In this study, we investigated the role of DLK1 in the regulation of cancer cell differentiation in vivo using neuroblastoma (NB) xenografts as a model. Our findings have revealed that overexpression of DLK1 promotes tumor growth by increasing the number of mitotic or proliferative cells and inducing angiogenesis. On the other hand, tumors derived from NB cells with down regulation of DLK1 expression by RNA interference or with overexpression of dominant negative mutants of DLK1 sensitize NB cells to undergo differentiation, as shown by increased expression of neuronal and glial differentiation markers. These results demonstrate that DLK1 plays an important role in the maintenance of undifferentiated, stem cell-like phenotype of NB cells in vivo. Our findings also indicate that the tumor microenvironment, especially hypoxia, can exert a profound impact on the tumor cell fate in vivo by regulating specific stem cell pathways. 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 4383. doi:10.1158/1538-7445.AM2011-4383
SP0070 The Impact of Foot Issues Experienced by People with Inflammatory Arthritis – A Patient View
Authors: R. Schulterobben
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> For 34 years arthritis has been a part of my life. The onset of my RAled to a rapid change and deterioration of my feet. I have been benefitting from biologicals since 2008and have had many operations on my feet. <h3>Objectives</h3> My main objective is to be independent as far as possible even with all these physical restrictions. An individual´s mobility makes a significant contribution to quality of life with RA. <h3>Methods</h3> For me, the most important thing is to have good orthopaedic shoes which are individually made by a qualified orthopaedic shoe maker. The shoes must be functional and, at the same time, wearable and fairly stylish. My feet benefit from regular care routines such as bathing, frequent reflex zone massages and a daily application of cream. <h3>Results</h3> As a result, I mostly can walk, ride my bicycle, drive my car and enjoy the freedom of movement relatively well. <h3>Conclusions</h3> It is also important for me to sometimes do things which are not recommended. From time to time, for example, I go dancing or do a lot of walking and I then have to take extra painkillers. I know that afterwards my feet will be more painful than usual but it reminds me what even my very rheumatic feet can still do. <h3>Disclosure of Interest</h3> None Declared