tbuckley/cabot-search huggingface dataset:
Abstract IA02: Precision medicine in acute lymphoblastic leukemia
Authors: Charles G. Mullighan
Journal: Clinical Cancer Research (2016)

Abstract Acute lymphoblastic leukemia (ALL) is the commonest childhood tumor. Despite overall favorable treatment outcomes in children, relapsed ALL remains a leading cause of cancer death in young people. Current treatment regiments are mostly non-targeted and accompanied by significant toxicities, and new treatments tailored to patient-specific tumor vulnerabilities are required to further improve treatment outcomes. ALL has long been known to be genetically diverse. Recent genomic sequencing efforts have provided multiple new insights into the classification and genetic basis of ALL. ALL is now known to comprise multiple subtypes that have distinct constellations of chromosomal rearrangements, DNA copy number alterations and sequence mutations that perturb a limited number of key cellular pathways including lymphoid development, Ras and kinase signaling, tumor suppression drug metabolism and epigenetic regulation. These findings have several implications for precision medicine approaches. First, different subtypes have distinct associations with relapse risk that will enable tailoring of the intensity of therapy, the requirement for intensive treatment approaches such as transplantation, and the potential for pathway-directed approaches such as BCL2 inhibitors, PI3K inhibitors and Ras inhibitors. Secondly, several subtypes have genetic alterations that are logical candidates for genomic testing and individualized targeted therapy. An important recent advance has been the identification of Ph-like ALL, a common high risk subtype of leukemia characterized by a range of genetic alterations activating cytokine receptor and kinase signaling amenable to ABL-class and JAK-STAT inhibitors. Large precision medicine trials identifying Ph-like ALL, the underlying genetic alterations, and directing patients to targeted kinase inhibitor therapy are currently in development. Thirdly, studies sequencing sequential samples obtained during therapy have identified several genes and pathways selectively mutated at relapse, including epigenetic regulators, that are logical targets for therapeutic intervention. Finally, genome sequencing is being used to develop highly sensitive approaches to detect and track response to treatment. Examples of each of these paradigms will be presented that highlight the potential of precision medicine to further improve treatment outcomes in ALL. Citation Format: Charles G. Mullighan. Precision medicine in acute lymphoblastic leukemia. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr IA02.
Abstract 5250: The role of tumor associated macrophage on drug resistant in non-small cell lung cancer .
Authors: Wen-Chien Huang, Yu-Jen Chen
Journal: Cancer Research (2013)

Abstract Increased evidence suggests that chronic inflammation is associated with cancer development, metastasis, invasion and drug resistant. The possible mechanisms by which inflammation can contribute to carcinogenesis include lymphocytes infiltration, cytokines and chemokines secretion, tissue remodeling and angiogenesis, etc. The inflammatory mediators facilitate the communication between tumor cells and tumor-associated host stromal tissue, thereby accelerating tumor progression. Tumor-associated macrophages (TAM) are key regulators of the link between inflammation and cancer. Previous studies found macrophage in non-small cell lung cancer (NSCLC) specimens by immunohistochemistry staining, and also discovered interplay of cancer cells and macrophages would induce secretion of certain cytokines and chemokines. However, the mechanism of cytokines and chemokines involved with tumor drug resistant in NSCLC is still obscure. It is also unclear the regulatory mechanisms in change of macrophages from M1 to M2 phase affected by tumor cells. In this study, we attempt to investigate the roles of TAM-mediated molecules using different characteristics of NSCLC cell lines (H2126, CL1-1, H1437, H23, H838, CL1-5, and H2009) as the study model. We will explore TAM mediators in NSCLC cell lines to detect and compare the phenotypic characteristics; then, we may investigate the transcriptional signaling pathways that are associated with expression of TAM mediators. Finally, we will correlate the expression of TAM mediators/proteins that are associated with TAM-mediated regulatory signaling in tumor drug resistant to the outcome of NSCLC patients. We believe that these proteins may serve as therapeutic targets for NSCLC patients in the future. In our pilot study, we analyzed the secretion stimulation of cytokines (MCP-1, IL-6, IL-7, IL-8, IL-10, and TNF-a) and MMPs (MMP-8, MMP-9, MMP-10 and TIMP-1) from cancer cells under the effect of macrophages. In the current study, we will deeply concern that the ambivalent interactions between TAM phenotypes and biological behavior of cancer cells, because the paradoxical responses between cancer cells and TAMs in a to and fro way are potentially evident. Citation Format: Wen-Chien Huang, Yu-Jen Chen. The role of tumor associated macrophage on drug resistant in non-small cell lung cancer . [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 5250. doi:10.1158/1538-7445.AM2013-5250 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Clinical Characteristics of Patients with Ventricular Fibrillation during Antiarrhythmic Drug Therapy
Authors: J D Minardo, J J Heger, W M Miles, D P Zipes, E N Prystowsky
Journal: New England Journal of Medicine (1988)

We retrospectively studied 28 patients with 38 episodes of newly occurring ventricular fibrillation during antiarrhythmic drug therapy. Twenty-six of these patients, who had ventricular fibrillation during single-drug therapy with quinidine, procainamide, or disopyramide, were compared with a control group of 62 patients who had been treated similarly for ventricular arrhythmias but did not have ventricular fibrillation during treatment. The median duration of therapy before ventricular fibrillation was three days. The left ventricular ejection fraction of the study group was lower than that of the control group (0.29 vs. 0.43; P less than 0.0001), and concomitant treatment with digitalis and diuretic agents was more common in the study group. The base-line QT interval (corrected for heart rate) was slightly longer in the study group than in the controls (0.47 vs. 0.44; P less than 0.005), although both groups had similar degrees of QT prolongation during drug therapy. Four of 13 patients (31 percent) who underwent multiple trials of antiarrhythmic drugs had recurrent episodes of ventricular fibrillation. Six patients died suddenly after a mean follow-up of 18 months--four who were receiving antiarrhythmic therapy and two who were not. We conclude that drug-associated ventricular fibrillation is an early event, that there may be an increased risk of its recurrence with subsequent trials of antiarrhythmic drugs, and that left ventricular dysfunction and concomitant therapy with digitalis and diuretic agents may predispose patients to this complication.
GLYCEMIC VARIABILITY PREDICTS LEFT VENTRICULAR REVERSE REMODELING IN PATIENTS WITH ST-SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION
Authors: Yugo Minamimoto, Noriaki Iwahashi, Masaomi Gohbara, Shunsuke Kataoka, Eiichi Akiyama, Nobuhiko Maejima, Kengo Tsukahara, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Satoshi Umemura, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2016)
Abstract P6-05-12: Lack of Frequent Estrogen Receptor Mutation in Primary Breast Tumors
Authors: S Oesterreich, C Kitchens, P Gavin, C-C Wu, K Riehle, C Coarfa, D Edwards, R Schiff, A Milosavljevic, A Lee
Journal: Cancer Research (2012)

Abstract The estrogen receptor alpha (ESR1) is a critical driver of breast tumorigenesis, and as such has been a target for therapy for many years. Early reports using Sanger sequencing and conformational assays reported that there were little if any mutations in ER-positive tumors, although a few somatic mutations have recently been described in tumors and cell lines. We set out to validate the authenticity of these reported somatic mutations by performing analysis of ER DNA sequence variants (DSVs) in 66 ER+ breast tumors, and 39 breast cancer cell lines. We utilized a combined approach of target capture sequencing of ESR1, and subsequent testing for novel and previously identified DSVs using an orthogonal mass spectrometry based sequencing approach. A DNA capture approach was designed to capture all exons, flanking splice sites, and the 3′ UTR of ESR1. DNA was captured and sequenced using SOLiD. Using stringency with a cut-off with at least 2 variant reads, variants in at least 20% of the reads, and requiring evidence for the variants in both strands, we identified 4 previously reported SNPs (rs2077647; rs46432; rs1801132; rs2228480), and two previously reported somatic mutations H6Y and N532Y. We developed mass-spectrometry assays, including controls, for these DSVs, and in addition, we included 10 DSVs which had previously been reported as somatic mutations in breast (and other) cancer. Applying mass-spec based analysis to breast tumors and cell lines, we were able to confirm previously reported SNPs, and one previously reported mutations (H6Y). This mutation was found in one breast tumor and one cell line. None of the other reported somatic mutations could be confirmed in tumors or cell lines. Functional assays on the ESR1H6Y DSV failed to identify differences to wildtype receptor. The lack of a phenotype, and the infrequent occurrence of this DSV do not support a major driver role for ESR1H6Y. This analysis suggests that ESR1 mutations are a rare event in ER+ primary breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-12.
SP0188 Statistical Interaction, Friend or Foe?
Authors: A. Tobias
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> The understanding of the interaction term probably presents one of the greatest challenges for the clinical researcher. The <i>foe</i> arises from its application, since it could refer different situations. Firstly, we could mean interaction when assessing for the joint influence of two, or more, exposure causes on their risk of disease, which is a biological or causal interaction. It could also refer the variation in the effect measure for the exposure cause under study across levels of another factor, which is an effect modification. Finally, we could also refer the necessity for a product term in a linear-based regression model, that is the statistical interaction. Usually, both, biological interaction and effect modification are addressed for by fitting an interaction term in a chosen regression model. This would imply that the relation between the response variable and the cause exposure and/or other factor variables is no longer additive. However, this departure from additivity could also depend on the statistical model used. The aim of this presentation is to emphasize the <i>friendly</i> use of statistical interactions as the basis for assessing biological interactions and/or effect modifications. Practical examples will be used to illustrate the proper use of linear-based regression models for both situations in rheumatology research. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6202
EORTC Fellowships Broaden European Clinical Research Base
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article EORTC Fellowships Broaden European Clinical Research Base Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 9, 3 May 1995, Pages 639–641, https://doi.org/10.1093/jnci/87.9.639 Published: 03 May 1995
Protease inhibitors may cause fat abnormalities and heart disease
Authors: A. Berger
Journal: BMJ (1998)

Disturbing changes in body fat distribution and rising cholesterol concentrations are being blamed on protease inhibitors, one of the most common class of drugs taken by people infected with HIV.

Data presented by several groups at the 12th world AIDS conference in Geneva confirms earlier reports that some people taking protease inhibitors are developing “buffalo humps” on their backs and truncal obesity (lipodystrophy), in addition to wasted limbs. The same drugs also seem to be affecting lipid concentrations, leading to a greater risk of premature heart disease. The two protease inhibitors which are most implicated in these metabolic changes …
LAS PRÓTESIS METÁLICAS CUBIERTAS (PMC) BILIARES EN POSICIÓN TRANSHILIAR AUMENTAN EL ALCANCE TERAPÉUTICO DE LA CPRE EN PATOLOGÍA BILIAR BENIGNA
Authors: P Gil Simón, N Alemán, I Peñas, R Sánchez-Ocaña, A Vargas García, H Núñez, P Díez Redondo, J Barrio, C De La Serna Higuera, M Pérez-Miranda
Journal: Endoscopy (2013)

Introducción: Las PMC son útiles en el tratamiento de la patología biliar benigna, aunque se desaconseja su uso por encima del confluente biliar. Objetivos: Evaluar la viabilidad del uso de PMC proximales al confluente biliar. Material y Método: Análisis retrospectivo, datos prospectivos entre septiembre 2011-junio 2012, 34 pacientes (17 mujeres; edad 59 [32 – 87] años) consecutivos con PMC biliares transhiliares mediante CPRE por patología biliar benigna. Resultados: Etiología: 28 estenosis biliares, 13 post-colecistectomía, 11 post-trasplante, 4 indeterminadas, 6 miscelánea (2 fugas de alto débito, 2 decúbito de prótesis embebidas 1 sumidero, 1 colangitis esclerosante,). En 19.4% se colocaron 2 ó 3 PMC transhiliares. En el 80.6% el hepático contralateral se tutorizó con prótesis plásticas. Las PMC se utilizaron como primera opción en 14, y como rescate tras fracaso del tratamiento convencional en 20. Tipos de PMC: Hanaro 23, Wallflex 8, Bonastent 2, Taewoong 1. Complicaciones inmediatas atribuibles a PMC en 2 casos: colangitis por oclusión rama intrahepática y persistencia fístula alto débito. Tiempo medio de permanencia de la PMC 5.3 (1 – 15) meses, con retirada exitosa en todos, a pesar de 4 migraciones relativas (3 proximal/1 distal), con 2 colangitis. Retirada PMC con resolución definitiva en 64.3%, 35.7% en programa de recambio, pendientes de completar tratamiento endoscópico. Ensanchamiento transitorio de vía intrahepática, sin correlato clínico, documentado en 12. Conclusiones: Si se tiene la precaución de no ocluir ramas segmentarias y de drenar el hepático contralateral con prótesis plásticas o metálicas, pueden utilizarse (y retirarse luego electivamente) PMC biliares en posición transhiliar.
IS THERE AN IMPACT ON POSTOPERATIVE MORBIDITY AND LONG TERM SURVIVAL AFTER MINIMAL ACCESS AORTIC VALVE REPLACEMENT
Authors: Sven Lehmann, Denis Merk, Sergey Leontyev, Christian Etz, Martin Misfeld, Anne Funkat, Jens Garbade, Friedrich Mohr
Journal: Journal of the American College of Cardiology (2016)
RESYNCHRONIZATION RESPONSE EVALUATED BY SPECKLE-TRACKING RADIAL STRAIN IS ASSOCIATED WITH MYOCARDIAL AUTOPHAGY IN SUBJECTS UNDERGOING CARDIAC RESYNCHRONIZATION THERAPY
Authors: Xu Jianfeng, Daoyuan Ren, Li Lin, Yangang Su, Yueguang Chen, Dadong Zhang
Journal: Journal of the American College of Cardiology (2015)
P1-11-08: Breast Cancer Screening Resources and Stage at Diagnosis in Appalachia: A Geospatial Perspective.
Authors: N Yao, MM Hillemeier, RT Anderson
Journal: Cancer Research (2011)

Abstract Background: National Cancer Institute has designated Appalachia as a priority area characterized by significant disparities in cancer outcomes. However, little research focuses on the availability of cancer care resources in this region and how resource availability may relate to cancer outcomes. This paper will describe the distribution of breast cancer screening resources in Appalachia and examine the relationship between the screening resources and breast cancer stage at diagnosis at the population level. Method: Percentages of early stage breast cancer incidence are computed based on the county-level data from the four Appalachian state cancer registry data from 2000 to 2008. Per capita breast cancer screening providers or facilities are computed for these Appalachian states. Descriptive analysis, exploratory spatial data analysis, and spatial regression were conducted. Results: Appalachian counties had significantly fewer primary physicians, OB/GYN specialists, and diagnostic radiologists per capita than non-Appalachian counties. Spatial analysis demonstrates moderate clustering of scarce breast cancer screening resource and low percentage of early stage breast cancer incidence in West Virginia and Appalachian Kentucky. Those diagnosed at early stages were 67.92% of Appalachian vs. 68.34% of non-Appalachian breast cancer patients. The number of diagnostic radiologists per capita is significantly associated with the percentage of early stage breast cancer incidence when controlling for covariates such as county level poverty rates, uninsurance rate, percentage of adults with college degree, and per capita primary care resources. Conclusions: Fewer diagnostic radiologists in West Virginia and Appalachia Kentucky are associated with lower percentage of early stage breast cancer incidence in the Central Appalachia region. Public health intervention could include policies and regulations to improve breast cancer screening resources in this region. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-08.
QUALITY OF LIFE IS DIMINISHED IN PATIENTS WITH TETRALOGY OF FALLOT WITH MILD RESIDUAL DISEASE: A COMPARISON OF TETRALOGY OF FALLOT AND ISOLATED VALVAR PULMONARY STENOSIS
Authors: Shivani M. Bhatt, Amy Cassedy, Bradley Marino, Elizabeth Goldmuntz, Laura Mercer-Rosa
Journal: Journal of the American College of Cardiology (2016)
The HLA System
Authors: Jan Klein, Akie Sato
Journal: New England Journal of Medicine (2000)

A man dies because his body has rejected a heart transplant; a woman is crippled by rheumatoid arthritis; a child goes into a coma that is brought on by cerebral malaria; another child dies of an infection because of an immunodeficiency; an elderly man has advanced hepatic cirrhosis caused by iron overload. These five clinical situations are as diverse as can be, yet all have one thing in common: the cause of all of them involves the human leukocyte antigen (HLA) system, the human version of the major histocompatibility complex (MHC). Malfunction of the HLA system, which is at the . . .
A6.02 Somatic mutations in clonally expanded CD8<sup>+</sup>T cells in patients with newly diagnosed rheumatoid arthritis
Authors: T Kelkka, P Savola, H Rajala, A Kuuliala, K Kuuliala, S Eldfors, P Ellonen, S Lagström, RK Khajuria, T Jaatinen, R Koivuniemi, H Repo, J Saarela, K Porkka, M Leirisalo-Repo, S Mustjoki
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Clonally expanded CD8<sup>+</sup> lymphocytes are known to exist in patients with rheumatoid arthritis (RA). Interestingly, in large granular lymphocyte (LGL) leukaemia (a haematological malignancy with indolent disease course), CD8<sup>+</sup> lymphocytes expand and the expanded clones harbour somatic mutations. LGL leukaemia patients with <i>STAT3</i> mutated CD8<sup>+</sup> lymphocytes have significantly increased risk of developing autoimmune manifestations, RA being a common autoimmune co-morbidity. As somatic mutations in CD8<sup>+</sup> lymphocytes associate with autoimmunity in LGL leukaemia, we wanted to examine if similar phenomenon exists in newly diagnosed RA patients without known LGL lymphoproliferation. <h3>Materials and methods</h3> Lymphocyte clonality was analysed by flow cytometry using vbβ -staining kit (Beckman Coulter) and the major clones were confirmed by TCR deep sequencing. Deep sequencing of 986 selected immune-related genes was performed from CD8<sup>+</sup> T cells using CD4<sup>+</sup> lymphocytes as germline control. The coverage was 200–6000x enabling reliable calling of low frequency mutations. Candidate mutations were validated using targeted deep amplicon sequencing. <h3>Results</h3> 43% (n = 31) of the newly diagnosed RA patients in our patient cohort (n = 68) had CD8<sup>+</sup> lymphocyte expansions exceeding 10% of the total CD8<sup>+</sup> T cells. The largest clones were subjected to targeted deep sequencing. We identified somatic gene variants in five (n = 5) patients and in one healthy control. Most of these variants were non-synonymous coding single nucleotide changes in genes important for immune functions (<i>C5</i>, <i>PADI4</i>, <i>IRF1</i>, <i>SLAMF6</i>, <i>BST1</i> and <i>CLEC10A</i>), or proliferation (<i>PTPRO</i>, <i>PADI4, PROM1</i>, <i>CDK12</i> and <i>CLIP2</i>). Sequencing of FACS sorted CD8<sup>+</sup> lymphocytes confirmed that the expanded clone harboured the identified mutations. <h3>Conclusions</h3> In RA patients, somatic mutations accumulate in the CD8<sup>+</sup> T cells during clonal expansion. Related findings have recently been reported in the myeloid lineage, where somatic variants are found to accumulate even in healthy subjects in a process called clonal haematopoiesis. Importantly, we focused on CD8<sup>+</sup> lymphocytes that have undergone thymic education and thus we report acquired somatic variants in mature cytotoxic lymphocytes in a non-malignant set-up. Although more research is needed to address the possible pathogenicity of the identified mutations, these findings provide an interesting link between autoimmunity and cancer.
States Begin CDC-Sponsored Breast and Cervical Cancer Screening
Authors: Tom Reynolds
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article States Begin CDC-Sponsored Breast and Cervical Cancer Screening Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 1, 1 January 1992, Pages 7–9, https://doi.org/10.1093/jnci/84.1.7 Published: 01 January 1992