tbuckley/cabot-search huggingface dataset:
Abstract 4590: Characterization of an epithelial micro-pattern within ducts and lobules of the human breast: The topography of estrogen receptor expression
Authors: Rene Villadsen, Agla Jael Fridriksdottir, Jiyoung Kim, Lone Rønnov-Jessen, Ole W. Petersen
Journal: Cancer Research (2010)

Abstract Estrogen receptors (ERs) function as relays between oscillating levels of circulating estrogen and micro-environmental cues for growth and differentiation during breast development, function and carcinogenesis, yet the cells that express ERs are poorly understood. Using an antibody library and multicolour imaging, we have found that ERs, which are expressed in an apparently unpredictable manner throughout ducts and lobules of the human breast, are in fact patterned by an underlying compartment of cells with a unique differentiation program and topography. Furthermore, we show that while ER-occupancy of this compartment is highly variable from zero to full between individual ducts and lobules, its average size is relatively constant. Moreover, vacancy is associated with a slightly higher proliferative activity as revealed by staining for Ki-67 and the ER-compartment cells are able to form acinus-like colonies inside a reconstituted basement membrane. In human breast cancers staining for the ER-compartment program revealed that fifty percent of a sample of apparently ER-negative tumors in reality was composed of ER-compartment cells. These results establish an anatomical foundation for the expression of ER in the human breast and a link between a broader sense, normal ER-compartment and a subset of ER-negative albeit luminal human breast carcinomas. 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 4590.
Blood Transfusion as a Risk Factor for Cirrhosis and Liver Cancer: A Matched Case-Control Study
Authors: A. FUKUDA, K. SUGIMACHI, S. TOKUDOME, M. IKEDA, S. KOGA, T. HIROHATA
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Blood Transfusion as a Risk Factor for Cirrhosis and Liver Cancer: A Matched Case-Control Study Get access ATSUSHI FUKUDA, ATSUSHI FUKUDA * *Correspondence to: Dr. Atsushi Fukuda, Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Senda-machi 1-9-6, Nakaku, Hiroshima 730, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar KEIZO SUGIMACHI, KEIZO SUGIMACHI Department of Surgery II, Faculty of Medicine, Kyushu UniversityFukuoka, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar SHINKAN TOKUDOME, SHINKAN TOKUDOME Department of Community Health Science, Saga Medical SchoolSaga, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar MASATO IKEDA, MASATO IKEDA Department of Clinical Epidemiology, University of Occupational and Environmental HealthKitakyushu, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar SHIGEMASA KOGA, SHIGEMASA KOGA Department of Surgery I, Faculty of Medicine, Tottori UniversityTottori, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar TOMIO HIROHATA TOMIO HIROHATA Public Health, Faculty of Medicine, Kyushu UniversityFukuoka, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 15, 2 August 1989, Pages 1189–1190, https://doi.org/10.1093/jnci/81.15.1189 Published: 02 August 1989
Human Immunodeficiency Virus Type 1 in the Semen of Men Receiving Highly Active Antiretroviral Therapy
Authors: Hui Zhang, Geethanjali Dornadula, Maria Beumont, Lawrence Livornese, Bonnie Van Uitert, Kelly Henning, Roger J. Pomerantz
Journal: New England Journal of Medicine (1998)

Highly active antiretroviral therapy can effectively decrease the levels of human immunodeficiency virus type 1 (HIV-1) virions in peripheral plasma and seminal fluid of infected men. Whether the genital tract of HIV-1–infected men who are receiving highly active antiretroviral therapy and who have no detectable virus in the peripheral plasma harbors replication-competent virus is not known.
Sequential Injection of Cationic Liposome and Plasmid DNA Effectively Transfects the Lung with Minimal Inflammatory Toxicity
Authors: Yadi Tan, Feng Liu, Zhiyu Li, Song Li, Leaf Huang
Journal: Molecular Therapy (2001)

A major hurdle to lipoplex-based systemic gene delivery is acute inflammatory toxicity. In this study, a safe, simple, and effective alternative to lipoplex administration, specifically, sequential injection of cationic liposome and plasmid DNA, was evaluated. When plasmid DNA was injected into the tail vein of mice 2–5 min after the injection of cationic liposomes, 50–80% lower levels of proinflammatory cytokines, including TNF-α, IL-12, and IFN-γ, were observed compared to lipoplex injection. The sequential injection technique yielded a two- to fivefold higher level of transgene expression in the lung and was more effective in repeated dosing than lipoplex. Other types of lipoplex-associated toxicities, such as neutropenia, lymphopenia, thrombocytopenia, and complement depletion, were also significantly reduced with sequential injection. The reduction in cytokine release was observed with several different liposome formulations and appeared to be a general phenomenon. A major hurdle to lipoplex-based systemic gene delivery is acute inflammatory toxicity. In this study, a safe, simple, and effective alternative to lipoplex administration, specifically, sequential injection of cationic liposome and plasmid DNA, was evaluated. When plasmid DNA was injected into the tail vein of mice 2–5 min after the injection of cationic liposomes, 50–80% lower levels of proinflammatory cytokines, including TNF-α, IL-12, and IFN-γ, were observed compared to lipoplex injection. The sequential injection technique yielded a two- to fivefold higher level of transgene expression in the lung and was more effective in repeated dosing than lipoplex. Other types of lipoplex-associated toxicities, such as neutropenia, lymphopenia, thrombocytopenia, and complement depletion, were also significantly reduced with sequential injection. The reduction in cytokine release was observed with several different liposome formulations and appeared to be a general phenomenon.
Treatment of Hemophilia with Glycine-Precipitated Factor VIII
Authors: Charles F. Abildgaard, Joseph V. Simone, James J. Corrigan, Ruth A. Seeler, Gerald Edelstein, Jane Vanderheiden, Irving Schulman
Journal: New England Journal of Medicine (1966)

EFFECTIVE hemostasis can be achieved in most simple bleeding episodes of classic hemophilia by the use of fresh, fresh-frozen or lyophilized plasma as the source of antihemophilic factor (AHF, factor VIII). In the event of major trauma or surgical procedures sustained levels of 20 to 30 per cent of factor VIII are necessary to provide hemostasis. Such levels are often impossible to achieve with the use of plasma, and attempts to maintain hemostasis with repeated infusions may lead to congestive heart failure owing to the resulting overexpansion of total plasma volume. Recently, concentrated forms of factor VIII that provide safer . . .
Abstract 942: Effects of maternal and postnatal folic acid supplementation on genomic DNA methylation in the mammary glands in a chemical rat model of mammary tumorigenesis
Authors: Anna Ly, Hanna Lee, Jianmin Chen, Kyoung-Jin Sohn, Karen K. Sie, Ruth Croxford, Richard Renlund, Lilian Thompson, Young-In Kim
Journal: Cancer Research (2010)

Abstract Background: Widespread loss of genomic DNA methylation is an early and consistent epigenetic event in cancer development including breast carcinogenesis. Folate, an essential co-factor in the transfer of one-carbon units, has been shown to modulate both cancer risk and genomic DNA methylation. We recently observed that folic acid (FA) supplementation provided in utero and in early postnatal life significantly increased risk of mammary tumors in the offspring in the dimethylbenzanthracene (DMBA) rat model. To determine a potential underlying mechanism of FA-mediated mammary tumor development, we investigated the association between global DNA methylation, DNA methyltransferase (DNMT) activity, FA supplementation, and mammary tumor status in the offspring. Methods: Female Sprague-Dawley rats were placed on a control diet (2 mg FA/kg diet) or a supplemented (5 mg) diet for 3 weeks prior to breeding and throughout pregnancy and lactation. At weaning, female pups were randomized to the control or supplemented diet. At 7 weeks of age, all pups received a single intragastric dose (5 mg) of DMBA to induce mammary tumors. At 28 weeks of age, plasma, mammary gland and liver folate and plasma homocysteine concentrations were determined and mammary tumors were enumerated and histologically confirmed. Genomic DNA methylation and DNMT activity were determined in non-neoplastic mammary glands. Results: Plasma, liver, and mammary folate and homocysteine concentrations accurately reflected dietary FA levels at weaning and 28 weeks of age (p&amp;lt;0.05). A significant interaction was observed between genomic DNA methylation and mammary adenocarcinoma status in the offspring (p&amp;lt;0.001), indicating that among tumor-free offspring, genomic DNA methylation was significantly decreased by maternal FA supplementation. In addition, in offspring bearing at least one adenocarcinoma, genomic DNA methylation was significantly decreased regardless of dietary FA intervention. Postweaning FA supplementation independently decreased DNMT activity in the offspring (p=0.05). Conclusions: Our data suggest that decreased genomic DNA methylation and DNMT activity associated with maternal and postweaning FA supplementation might be a mechanism by which maternal and postweaning FA supplementation increased mammary tumorigenesis in the offspring. Given the drastic increase in FA intake among women of childbearing age in North America, future studies are need to determine whether or not FA supplementation increases the risk of breast cancer through epigenetic mechanisms. 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 942.
COAGULATION PROCESS AND FIBRINOGEN GENETIC VARIABILITY ARE STRONG RISK FACTORS FOR ATHEROGENESIS, MYOCARDIAL INFARCTION AND THE EXTEND OF THE DISEASE IN SUBJECTS SUSPECTED FOR STABLE ANGINA
Authors: Nikolaos Papageorgiou, George Hatzis, Maria Kozanitou, Emmanouel Androulakis, Marietta Charakida, Antigoni Miliou, Gerasimos Siasos, George Latsios, Andreas Synetos, Konstantinos Toutouzas, Spyridon Papaioannou, Zoi Pallantza, Christodoulos I Stefanadis, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2015)
Case 18-1998
Authors: Fred S. Rosen, Atul K. Bhan
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 54-day-old girl was admitted to the hospital because of recurrent respiratory distress and failure to gain weight.She had been born to a 38-year-old woman (gravida 2, para 0) who had group B, Rh-positive blood. The mother was immune to rubella and had a negative serologic test for syphilis. Because her obstetrician had concluded that her vaginal mucus was lethal to her husband's sperm, he had administered clomiphene and inserted sperm directly into the uterus. Conception occurred on the fourth attempt. The pregnancy was complicated by the mother's smoking (less than one pack of cigarettes per . . .
Abstract 3158: Transcription factor SOX11 decreases viability in ovarian carcinoma cells.
Authors: Caryn M. St. Clair, Stephanie L. Wethington, Maria Bisogna, Fanny Dao, Petar Jelinic, Douglas A. Levine
Journal: Cancer Research (2013)

Abstract Objective: The Cancer Genome Atlas (TCGA) evaluated nearly 500 advanced serous ovarian carcinomas and identified four gene expression subclasses. The transcription factor SOX11 was markedly overexpressed in the proliferative subtype and associated with phosphorylation of other cell cycle related proteins including CHEK2, WWTR1, and EIF4EBP1. We tested the hypothesis that over-expression of SOX11 will decrease proliferation of ovarian cancer cells through transcriptional repression. Methods: SOX11 was overexpressed via lipofectamine transfection in the TP53 wild-type ovarian cancer cell line SKOV3 and the TP53 mutated ovarian cancer cell line OVCAR3. Cell proliferation was assessed 48 hours after transfection using the VisionBlue fluorescence-based viability assay. Cell cycle analysis was performed utilizing a propidium iodide (PI) assay followed by fluorescence-activated cell sorting (FACS). Finally migration of SOX11-transfected cells was analyzed in comparison to mock-transfected controls via monolayer scratch assay. Results: Successful overexpression of the SOX11 protein was confirmed using GFP fluoroscopy and western blot 24 and 48 hours following transfection. Cell viability was reduced by 14-63% at 48 hours in SOX11-transfected SKOV3 cells compared to mock controls (P = 0.01) in a dose dependent fashion. Cell cycle was unaffected by SOX11 overexpression. Finally, the monolayer scratch assay demonstrated that cells overexpressing SOX11 migrated more slowly than mock controls (median velocity 3.92 vs. 6.19 um/hr, P = 0.001). Data from OVCAR3 cells are currently being analyzed and will be presented. Conclusions: Overexpression of SOX11 resulted in decreased cell viability without affecting cell cycle. Further studies will assess the mechanism of this decreased viability which may involve diversion toward an apoptotic pathway when SOX11 is overexpressed or regulation by transcription repressors such as WWTR1. SOX11 suppression has been shown in lymphoma to be associated with more aggressive tumors through mechanisms associated with lysophosphatidic acid growth regulation, offering mechanistic associations with ovarian cancer. Ongoing work will determine the relationship between SOX11 and TP53 mutation frequently found in high-grade serous carcinoma. These studies will help to explain the differential outcomes seen across high-grade serous ovarian carcinoma. Citation Format: Caryn M. St. Clair, Stephanie L. Wethington, Maria Bisogna, Fanny Dao, Petar Jelinic, Douglas A. Levine. Transcription factor SOX11 decreases viability in ovarian carcinoma 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 3158. doi:10.1158/1538-7445.AM2013-3158
Abstract 762: ONT-10, a liposomal vaccine targeting hypoglycosylated MUC1, induces a potent cellular and humoral response and suppresses the growth of MUC1 expressing tumors
Authors: Linda A. Pestano, Brenda Christian, Sandy Koppenol, Jeff Millard, Gary Christianson, Kevin Klucher, Rob Rosler, Scott R. Peterson
Journal: Cancer Research (2011)

Abstract MUC1 is highly expressed in multiple tumor histologies and is hypoglycosylated relative to normal tissue, with prematurely terminated carbohydrate modifications including αN-acetylgalactosamine (Tn). The aberrant glycosylation state of MUC1 makes this antigen immunologically distinct in tumor relative to normal tissues and an attractive vaccine target. ONT-10 is a liposomal formulated vaccine that incorporates a synthetic glycopeptide antigen that includes two complete 20 amino acid tandem repeats from human MUC1, including six glycosylated sites modified by Ser- or Thr-O- Tn, and is incorporated into the liposomal drug product via two C-terminal lipid serines. The ONT-10 drug product is formulated with the novel, fully synthetic lipid A adjuvant, penta erythritol lipid A (PET Lipid A). PET Lipid A displays a similar spatial distribution of lipid chains as natural Lipid A, but is composed of pure 6-acyl moieties, resulting in enhanced potency as an activator of Toll-like Receptor 2 and 4 (TLR2, TLR4). In preclinical studies, immunization of mice with ONT-10 induces a prominent T cell and antibody response to MUC1 and results in a substantial growth inhibition of MUC1 expressing tumors. T cell recall assays show a Th1 cytokine pattern with strong IFNγ production in spleen derived CD4 and CD8 cells in response to Tn-MUC1. At doses as low as 5μg/mouse ONT-10 results in a high titer anti-MUC1 antibody response composed principally of IgG2b and IgG3 that show preferential binding to Tn-MUC1 and selectively target tumor cells that express human MUC1. In a preventative B16-MUC1 tumor model, vaccination with 5μg ONT-10 potently suppresses tumor growth, resulting in 99% mean tumor growth inhibition relative to controls with 9/12 animals tumor free four weeks after tumor cell implantation. Similarly, in a MC38-MUC1 tumor model 5μg ONT-10 results in an 90% reduction in tumor growth relative to controls. Based on these preclinical data, we propose that the combination of the glycopeptide antigen structure and improved Lipid A adjuvant in ONT-10 offer advantages relative to previous MUC1 targeted vaccines by potently activating both humoral and cellular immunity against hypoglycosylated MUC1 and that these features may provide additional therapeutic benefit to patients with MUC1 expressing cancers. 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 762. doi:10.1158/1538-7445.AM2011-762
Insulin Signaling and Heart Failure
Authors: Christian Riehle, E. Dale Abel
Journal: Circulation Research (2016)

Heart failure is associated with generalized insulin resistance. Moreover, insulin-resistant states such as type 2 diabetes mellitus and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes mellitus alters the systemic and neurohumoral milieu, leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead box O transcriptional signaling or glucose transport, which may also impair cardiac metabolism, structure, and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed.
IM-14 * IMMUNOLOGIC TARGETING OF MEDULLOBLASTOMA SUBTYPES USING DEVELOPMENTALLY REGULATED ANTIGENS
Authors: C. Pham, C. Flores, Y. Pei, R. Wechsler-Reya, D. Mitchell
Journal: Neuro-Oncology (2015)

INTRODUCTION: Medulloblastoma (MB) remains incurable in one third of patients despite aggressive multi-modality standard therapies. Immunotherapy represents a promising strategy by specifically targeting cancer cells. To date, there have been no successful immunologic applications targeting MB. Evidence from integrated genomic studies suggests MB subtypes arise from deregulation of pathways affecting proliferation of progenitor populations within the developing cerebellum. Using total embryonic RNA as a source of tumor rejection antigens is attractive because it can be delivered as a single vaccine, target both known and unknown fetal proteins, and be refined to preferentially treat distinct MB subtypes. METHODS: We have created two transplantable, syngeneic animal MB models recapitulating human SHH and Group 3 variants to investigate the immunologic targeting of different MB subtypes. We generated T cells specific to the developing mouse cerebellum (P5) and tested their reactivity to target cells pulsed with total RNA from two MB subtypes and the normal brain. Immune responses were evaluated by measuring cytokine secretion following re-stimulation of activated T cells with both normal and tumor cell targets. In vivo antitumor efficacy was also tested in survival studies of intracranial tumor-bearing animals. RESULTS: We generated T cells specific to the developing cerebellum in vitro, confirming the immunogenicity of developmentally regulated antigens. Additionally, we have shown that developmental antigen-specific T cells produce high levels of Th1-type cytokines in response to tumor cells of two immunologically distinct subtypes of MB. Interestingly, developmental antigen specific T cells do not show cross reactivity with the normal brain or subsequent stages of the developing brain after P5. Targeting developmental antigens also conferred a significant survival benefit in a treatment model of Group 3 tumor bearing animals and 60% survivors in SHH tumor bearing animals. CONCLUSIONS: Developmental antigens can safely target multiple MB subtypes with equal effectiveness compared to previously established total tumor strategies.