tbuckley/cabot-search huggingface dataset:
Abstract 5410: Down regulating heavy chain ferritin gene increasesthe radiation therapeutic efficacy for treatment of glioma
Authors: Xiaoli Liu, A.B. Madhankumar, Jonas Sheehan, Becky Slagle-Webb, James R. Connor
Journal: Cancer Research (2011)

Abstract Gliomas, especially glioblastoma multiforme are resistant to radiation and chemotherapy. Therefore, efforts to develop new course of therapy to enhance efficacy of treatment strategies are obviously critical. We hypothesized that disrupting iron homeostasis in malignant tumor cells could prove effective at negatively affecting tumor growth because cancer cells have a robust iron requirement consistent with their rapid growth and high metabolic rates. The high levels of iron uptake require a mechanism to limit iron induced oxidative damage. This function is the responsibility of ferritin; an iron storage protein with 24 subunits of two types of chains light and heave chains. Heavy chain ferritin (H-ferritin) has been found in the nucleus of tumor cells where it appears to protect DNA from oxidative damage and promote transcription. We hypothesized that silencing the H-ferritin gene could increase the sensitivity of tumors cells to radiation. On the other hand, our previous data already demonstrated that silencing the H-ferritin gene increased chemotherapeutic efficacy for treating gliomas. To test our present hypothesis, the H-ferritin gene will be silenced via a cationic liposome carrying siRNA. We have chosen glioma cell lines (U251, U87 and MNSF) as our in vitro model. Subcutaneous glioma tumor in mouse model (athymic nude mice) was chosen as our in vivo model. Our preliminary in vitro data demonstrated silencing the H-ferritin gene in U251 cells leads to a 50% increase in cell death at 20 Gy for 24, 48 and 72 hours post radiation. Intratumoral injections of cationic liposomes containing H-ferritin siRNA reduced the effective in vivo dose of radiation for tumor suppression by more than 90% at 7 weeks. A supercoil relaxation assay demonstrated that H-ferritin, but not L-ferritin directly protects DNA from radiation by maintaining DNA in a relaxed from. We will further test our hypothesis in glioma-U87, neurofibroma-sNF96.2 and breast cancer-MCF-7 cells. As of now our data shows that silencing the H-ferritin gene appears to be an effective way to increase the sensitivity of the glioma tumors to radiation, which sheds light on increasing the radiation therapeutic efficacy for treatment of malignant tumors. 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 5410. doi:10.1158/1538-7445.AM2011-5410
ORAOV1 is Amplified in Esophageal Squamous Cell Cancer and Related to Tumor Growth and Poorly Differentiated Tumor
Authors: Y. Togashi, T. Arao, H. Kato, K. Matsumoto, M. Terashima, H. Hayashi, Y. Fujita, T. Yasuda, H. Shiozaki, K. Nishio
Journal: Annals of Oncology (2013)
Abstract P2-01-05: Parallel DNA and RNA profiling of EpCAM-positive cells in blood of metastatic breast cancer (MBC) patients confirm their malignant nature
Authors: MJM Magbanua, L Hauranieh, EV Sosa, P Pendyala, JH Scott, HS Rugo, JW Park
Journal: Cancer Research (2012)

Abstract Background: Molecular studies of EpCAM-positive cells found in the blood of cancer patients have been limited to immuno-enriched samples containing a high background of leukocytes. We developed a process to isolate rare EpCAM-positive cells and subjected them to DNA and RNA profiling. Methods: Blood was subjected to immunomagnetic enrichment using EpCAM beads followed by fluorescence activated cell sorting (IE/FACS) to isolate EpCAM-positive cells away from leukocytes (CD45+). Duplicate samples of 20 cells were isolated from the same enriched blood from 53 MBC patients and then subjected to DNA and RNA profiling in parallel. For DNA profiling, sorted cells were subjected to BAC array comparative genomic hybridization analysis following whole genome amplification. For RNA profiling, QPCR analysis was performed on sixty four (64) cancer-related genes using Taqman® low density arrays. For non-tumor controls, RNA profiling was performed on matched leukocytes (CD45+) isolated from the same enriched blood samples from 44 of the 53 patients. Results: Differential gene expression analysis between EpCAM-positive cells and matched leukocytes confirmed the up-regulation of EPCAM and other genes including MUC1 and KRT19 (adjusted p &amp;lt;0.05). In addition, EpCAM-positive cells showed a significant down-regulation of the leukocyte-specific marker PTPRC (encodes CD45) as well as CD44 and VIM, markers associated with stem cellness and epithelial to mesenchymal transition, respectively. Unsupervised hierarchical clustering analysis of RNA profiles showed that EpCAM-positive cells clustered away from the leukocytes. Genome-wide copy number analysis of EpCAM-expressing cells revealed gains (e.g. 1q and 8q), losses (e.g. 8p and 16q), and focal amplifications (e.g. on 8q and 11q including CCND1) frequently seen in primary breast cancers. Discussion: We demonstrate the feasibility of isolation and molecular analysis of highly pure EpCAM-positive cells in the blood. Our results strongly suggest that epithelial cells captured from blood of MBC patients are malignant in nature and are therefore circulating tumor cells. This approach can serve as a non-invasive source of highly pure metastatic tumor tissue for further molecular characterization. This study was supported by CALGB and BCRF. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-05.
Abstract 3093: Gene regulation induced by constitutive expression of HIF-1α in transgenic mice
Authors: Masaru Ide, Naoko Sueoka-Aragane, Akemi Sato, Tomomi Nakamura, Masako Yokoo, Shinya Kimura, Keiji Tanimoto, Eisaburo Sueoka
Journal: Cancer Research (2011)

Abstract Hypoxia-inducible factor-1α (HIF-1α) has a central role on regulation of various genes under hypoxic condition linked to regulation of angiogenesis, metabolism and tumor development. Expression of HIF-1α was reported in many cancers associated with tumor progression, invasion and metastasis. We reported that constitutive expression of HIF-1α in transgenic mice induced tumors in lymphoid, lung and breast tissues in last this meeting. The incidence of tumors in transgenic mice was up to 90% until 18 months after birth. To clarify the molecular mechanism of lymphomagenesis in the transgenic mice, lymphocyte subsets, gene expression and mitogenic responsiveness on lymphoid tissues were analyzed. Although population of T and B cell subset in spleen, maturation pattern of T cells in thymus, or cell growth rate after treatment with various mitogens were not changed by HIF-1α overexpression, the lymphocytes from transgernic mice showed longer survival than those from wild mice. The lymphocytes also showed resistance for genotoxic stimuli like topoisomerase inhibitors. We next compared gene expression profile on lymphocyte from transgenic mice and wild mice by cDNA microarray and RT-PCR. The expression of over a hundred of genes including HIF-1α itself was altered on T and B cells in transgenic mice. Among them the gene associated with cell survival and cell transformation-related genes were further analyzed by validation study. In this paper, we present the results concerning the role of HIF-1α in lymphoma occurrence, and will discuss the contribution of the transcription factor in human cancer development. 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 3093. doi:10.1158/1538-7445.AM2011-3093
THE CHADS2 SCORE PREDICTS ISCHEMIC STROKE IN CHRONIC HEART FAILURE PATIENTS WITHOUT ATRIAL FIBRILLATION: COMPARISON TO OTHER STROKE RISK SCORES
Authors: Takumi Kondo, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Masashi Ishimi, Hideyuki Hakui, Tatsuhisa Ozaki, Yoshihiro Sato, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2016)
The Diagnosis of Brain Death
Authors: Eelco F.M. Wijdicks
Journal: New England Journal of Medicine (2001)

Physicians, health care workers, members of the clergy, and laypeople throughout the world have accepted fully that a person is dead when his or her brain is dead. In the United States, the principle that death can be diagnosed by neurologic criteria (designated as brain death) is the basis of the Uniform Determination of Death Act,1 although the law does not define any of the specifics of the clinical diagnosis. There is a clear difference between severe brain damage and brain death. The physician must understand this difference, because brain death means that life support is useless, and brain death . . .
Abstract 1171: Identification of p53 target genes by ChIP-Seq and transcriptome analysis combined with genome-wide p53-binding motif analysis <i>in silico</i>
Authors: Masashi Idogawa, Yasushi Sasaki, Yasuhisa Shinomura, Kohzoh Imai, Takashi Tokino
Journal: Cancer Research (2012)

Abstract p53 is one of the most important tumor suppressor genes. In approximately half of all human cancers, p53 is inactivated as a direct result of mutations in the p53 gene. Furthermore, mutation or deletion of p53 is related to poor prognosis and resistance to chemotherapy and radiation. The activation of p53 is induced by a variety of cell stresses, such as DNA damage, oncogene activation, spindle damage and hypoxia. Activated p53 transactivates a number of genes, many of which are involved in DNA repair, cell cycle arrest and apoptosis. In this study, we tried to identify novel p53 target genes by the combination of chromatin-immunoprecipitation, transcriptome analysis and a search of p53 binding motif in silico. We infected lung cancer cell, H1299 (p53 null) with adenovirus vectors expressing FLAG-tagged p53, p63g and p73b, and then performed chromatin-immunoprecipitation (ChIP) with FLAG antibody. The immunoprecipitated DNA was subjected to next-generation sequencing (ChIP-Seq). The short sequences generated by ChIP-Seq were aligned to the human genome sequence and peaks which indicate the binding of p53 family protein were detected by several algorithms. We also searched p53 binding motif, RRRCWWGYYY appeared inside genes and 10k base upstream from its transcription start site, and selected ChIP-Seq peaks of which genomic positions include p53 binding motif. Furthermore we analyzed mRNA expression of H1299 cells by cDNA microarray including several long intergenic non-coding RNAs (lincRNAs) and next-generation sequencing (RNA-Seq). We combined three categories of data, mRNA expression, ChIP-Seq peaks and p53 binding motif in silico. As a result, we found several genes which are upregulated by p53 family proteins and have ChIP-Seq peaks with p53 binding motif in promoter regions or gene bodies. These genes included not only well-known p53 target genes such as p21 and MDM2 but also novel candidate genes. In addition, ChIP-PCR and reporter assay confirmed the binding and responsiveness to p53. Thus, our approach identified several novel target genes induce by p53. We are now analyzing the role of these genes in p53 response pathway. 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 1171. doi:1538-7445.AM2012-1171
FRI0086 The effect on smoking cessation on disease activity in rheumatoid arthritis (RA). Data from barfot, a multicenter study of early RA
Authors: M. Söderlin, M. Andersson, S. Bergman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It is not known if smoking cessation after onset of rheumatoid arthritis (RA) has effect on disease activity. <h3>Objectives</h3> To assess the effect of smoking cessation on disease activity in patients with RA in a 15-year follow up. <h3>Methods</h3> Between 1992 and 2005, 2800 adult patients were included in the BARFOT early RA study in Sweden. Disease Activity Score 28 joints (DAS28), C-reactive protein (CRP), Health Assessment Questionnaire (HAQ), rheumatoid factor (RF), anti-CCP, general health and pain visual analog scales (VAS), EULAR response and remission criteria and treatment were registered at inclusion and at follow-up, 3 and 6 months, 1 year, 2, 5, 8 and 15 years. In 2010, a self-completion postal questionnaire was sent to 2102 patients enquiring about life style factors, inclusive demographics, such as socioeconomic class (SEI), and smoking habits including smoking cessation. <h3>Results</h3> A total of 1460 adult RA patients with disease duration ≤24 months were included in this study. A total of 17% smoked in 2010. A total of 127 patients stopped smoking after inclusion in the study. Smoking cessation after inclusion in the study was negatively associated with EULAR outcome at 8 years (N=560, OR 0.44, 95% CI 0.22-0.86, p=0.02), adjusted for age, disease duration, sex, socioeconomic class, smoking status, RF and DAS28. Higher DAS28 and male sex predicted better EULAR response at 8 years and SEI class “Other” and RF predicted poor EULAR response. <h3>Conclusions</h3> A total of 17% of the RA patients smoked in 2010 in this large Swedish RA cohort. Smoking cessation after RA onset did not change the poor prognosis of smokers in RA. This could be due to a selection effect. Our data needs to be confirmed in larger studies <h3>Disclosure of Interest</h3> M. Söderlin Consultant for: Pfizer &lt;$5000, Speakers Bureau: MSD&lt;$2000, Abbott&lt;$5000, Pfizer&lt;$5000, M. Andersson: None Declared, S. Bergman: None Declared
Abstract LB-142: Induced expression and activation of oncogenes in NSCLC (non-small cell lung cancer) in the absence of activating mutations of EGFR and k-Ras
Authors: Gokhan Gorgisen, Derya Ozes, Suray Pehlivanoglu, Abdullah Erdogan, Levent Dertsiz, Gulay Ozbilim, Irem Hicran Ozbudak, Osman N. Ozes
Journal: Cancer Research (2012)

Abstract Induced expression and activation of oncogenes in NSCLC (non-small cell lung cancer) in the absence of activating mutations of EGFR and k-Ras Background: Activating mutations in exon 18,19 and 21 of EGFR and changes in codons 12,13 and 61 of k-RAS are blamed for the development of NSCLC in 88% of patients. Therefore, it is suggested that the use of tyrosine kinase (TK) inhibitors, Erlotinib or Gefitinib, can be very useful to treat NSCLC patients. NSCLC patients harboring activating mutations of EGFR are very responsive to TK inhibitors; while, patients who do not have these mutations are unresponsive to these treatment. Therefore, it is recomended that before initiating therapy with these TK inhibitors, mutation status of EGFR must be determined. Methods: The protein lysates of tumor samples and DNA have been isolated from tumor and corresponding normal tissues of 16 NSCLC patients who underwent surgery. Genomic-DNA is used to sequence exons 18, 19 and 21 of EGFR1 as well as the second exon of k-RAS. Protein lysates have also been used to determine the expression or phosphorylation levels of EGFR and down-stream elements such as, STAT3, ERK and AKT. The expression levels of metastatic factors TWIST1 and GAPDH have also been determined. Results: Even though sequence analysis of indicated regions of EGFR and k-RAS reveal no mutation, the protein analysis of 16 tumor samples show remarkable changes in the activation or expression levels of above mentioned oncogenes. Among the patients different levels of induced phosphorylation have been found; these levels are, 2 to 23 fold induced phosphorylation of ERK, 1.5 to 20 in AKT, 2 to 10 in EGFR, and 2 to 24 in TWIST1 and 2-450 in GAPDH. These results indicate that even in the absence of any activating mutations of EGFR or k-Ras, the EGFR pathway is still very active in some NSCLC patients. Conclusion: If activating mutations of EGFR is considered the main reason for TK therapy, then TK use may not be the optimal decision to make. Results clearly indicate that NSCLC patients who do not show any activating mutations of EGFR may benefit from TK therapy. Even though, activating mutations of EGFR is the “gold standard” for TK therapy, surgery materials of NSCLC patients must be examined for oncogene activation. This is especially true for the EGFR pathway since, as shown in this work, the tumor micro-environment created by the tumor or surrounding cells can be as important as the activating mutations of EGFR. 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-142. doi:1538-7445.AM2012-LB-142
Critical Care Medicine — A New Specialty?
Authors: Mark A. Kellley
Journal: New England Journal of Medicine (1988)

Recently, controversy has surrounded the field of critical care medicine, as major medical specialties have competed for the rights to this new discipline. Critical care medicine attracted attention in the early 1980s, when more stringent regulations of third-party reimbursement and health care motivated physicians to protect their access to the resources of the intensive care unit (ICU). But no one then or now has had a clear vision of whether critical care medicine involves a distinct group of physicians. Critically ill patients account for a substantial percentage of hospital practice, and critical care medicine has therefore been considered an extension . . .
Abstract 4335: The genomic landscape of childhood pre-B acute lymphoblastic leukemia
Authors: Jean-François Spinella, Virginie Saillour, Chantal Richer, Manon Ouimet, Pauline Cassart, Jasmine Healy, Eric Bareke, Mathieu Larivière, Pascal St-Onge, Stephan Busche, Bing Ge, Alexandre Montpetit, Tomi Pastinen, Daniel Sinnett
Journal: Cancer Research (2012)

Abstract Precursor B-cell acute lymphoblastic leukemia (pre-B ALL) is the most frequent pediatric cancer. Increased understanding of the pathobiology of B-cell ALL has led to risk-targeted treatment regimens and increased survival rates. However, the underlying causes of this pediatric cancer are still unclear. We are using next-generation sequencing technology to better understand the genomic landscape of pre-B ALL and to build a catalogue of variations involved in pediatric ALL onset and/or progression. Using a unique “quartet” design that involves matched tumor (at diagnosis) and normal (remission) samples, as well as DNA from both parents, we will be able to identify somatic mutations driving the leukemic process. Here, we report the deep-sequencing of the whole exomes, and the partial miRNomes, of over 60 childhood B-cell ALL quartets. Using ABI SOLiD technology, we captured over 4.0 Gb of sequence on average per sample with a mean coverage of 40X. Genome-wide genotyping (Illumina's Omni 2.5 array) was also for quality control and structural variant identification. For each individual, approximately 97% of the targeted region was covered α1X and 80% of the targeted bases passed our thresholds for variant calling (≥ 5X coverage, MQV ≤ 20). According to these criteria, about 25,000 SNPs were found per individual. Using this quartet design we were able to incorporate parental sequence information to reduce sequencing errors and facilitate the identification of true variants within a given family, and of leukemia-specific variants within the ALL cohort. We investigated the somatic mutation profiles of the ALL genomes and identified both recurrent and private leukemia-specific mutations, and highlighted genes/pathways with an increased burden of somatic loss of function variants. Our goal now is to validate potential driver mutations that could play a direct role in leukemogenesis through functional assessment. Ultimately, this work will provide invaluable insights to understand the genetic mechanisms underlying pediatric ALL which could lead to the development of powerful clinical tools to improve detection, diagnosis and treatment of this childhood 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 4335. doi:1538-7445.AM2012-4335
AB0706 Capillaroscopy: a useful tool for primary raynaud identification
Authors: C. Molina, M. D. Garcia-Armario, J. Ivorra, I. Martinez-Cordellat, J. L. Valero, E. Grau, I. Chalmeta, R. Negueroles, L. Gonzalez-Puig, M. L. Muñoz, C. Nuñez-Cornejo, C. Alcañiz, J. A. Roman-Ivorra
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The identification of individuals with primary Raynaud's likely to develop scleroderma or other connective tissue diseases is of great importance in order to have an early control and therapeutic management of the disease, with great influence on the patient's prognosis. The most appropriate methodology for this would be the capillaroscopy, as it is an affordable, non-invasive and easy to use method. <h3>Objectives</h3> Evaluate the correlation between clinical diagnosis and capillaroscopic pattern in patients with Raynaud's phenomenon both primary and secondary. <h3>Methods</h3> We performed a descriptive observational study comprising 116 capillaroscopies performed in the H.U.P. La Fe in 2012. All were conducted on patients with Raynaud's phenomenon both primary and secondary. Rheumatologists ignored the clinical diagnosis for each case and based on observed characteristics a capillaroscopic pattern was assigned to each patient. We performed a biostatistical analysis using multinomial logistic regression model in order to estimate the likelihood of each diagnosis based on a given capillaroscopic pattern. <h3>Results</h3> The results obtained in the capillaroscopies are: heterogeneous capillary disposition (30%); visible venous plexus (44%) maintained capillary density (78%), decreased (15%), greatly decreased (7%); elongated capillary morphology (24%), lack of dilatation (22%), isolated dilatation (40%), diffuse dilatation (38%); existence of megacapillaries (28%); existence of bleeding (56%), presence of avascular areas (8%), absence of windings (10%), presence of grade I tortuosities (29%), grade II (38%), grade III (22%); angiogenesis (47%). According to these results the patients were classified according to the capillaroscopic pattern and clinical diagnosis. See Table 1. <h3>Conclusions</h3> Our results showed that a high percentage of cases with a regular capillaroscopic pattern had a high probability of presenting/displaying Primary Raynaud's diagnosis. Thus, capillaroscopy could be useful in primary Raynaud's discrimination based on the pattern found. <h3>Disclosure of Interest</h3> None Declared